Handbook of Poisons [1 ed.]

Citation preview

ve oy

HANDBOOK of

POISONS

ROBERT

H. DREISBACH, M. D., Ph. D. Professor of Pharmacology, Stanford University School of Medicine, San Francisco, California

Lange Wcdical Publications Los Altos, California

1955

Copyright 1955

by Lange Medical Publications Library

of Congress

Catalog

Card

No. 55-12323

Lithographed in U. S. A. A Concise Medical Physician’s

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Summer,

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Summer,

Illustrated Review F. L. Liebolt

of Fracture

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Review of Medical Microbiology E. Jawetz, J. L. Melnick, E. A. Adelberg Handbook

1955

$4.00 Summer, 1954

$4.50 Fall, 1954

of Poisons

$3.00

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1955

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Years

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Altos, California

PREFACE The purpose

summary

of this handbook

is to provide a concise

of the diagnosis and treatment of clinically import-

ant poisons. Many other potentially poisonous agents that have not been important clinically are included in tabular form. The necessity for such a book has grown out of the rapidly expanding importance of chemical products in industrial, agricultural,

and

domestic

processes.

These

substances

have

been introduced commercially in a bewildering variety of new preparations whose nature is often disguised by a coined name. Poisons have been organized into industrial, agricultural, household,

medicinal,

allows considerable

and natural hazards,

since

this method

correlation of poisons with types of ex-

posure. In some cases, chemically similar agents with varied uses appear in more than one section. Insofar as is possible or feasible,

chemically

and,

in some

cases,

pharmacologically

related agents have been grouped together. In order to enable the physician to identify the toxic principle in a given proprietary preparation, brand names have been freely used and are included in the general index. Only those likely to be important clinically or those whose composition is not obvious are included. This group comprises many insecticides and medicinal agents. Others will undoubtedly be added in future editions. The author hopes that in striving for brevity and clarity he has not oversimplified or been unduly dogmatic. References have been almost entirely omitted; anyone interested in references on any subject discussed in this book can find them in Chemical Abstracts or the Current List of Medical Literature.

Since this book is new and nothing similar of comparable scope is available, any suggestions for increasing its usefulness will be appreciated. Information about toxic agents not included which have been found to have clinical significance will be especially helpful. The author wishes to thank Drs. Otto E. Guttentag, Paul Sanazaro,

and

Mr.

Avram

Lowell

Goldstein,

Bradford

while in preparation;

Mr.

Charles

Hine,

Hamilton

Anderson,

for critically reading the manuscript

J. R. Slevin,

of the California

Academy of Sciences, for reviewing the section on reptiles; Arthur Furst, for reviewing the chemical formulas; Miss Claire

Forster,

Miss Rowena Sweet, editor,

for her work

Reilly,

and encouragement

in typing the initial manuscript;

for preparing the final copy;

for his illustrations; Mr. James Ransom,

Dr.

Mr.

Ralph

and Dr. Jack D. Lange and his for their criticisms, assistance,

during the preparation

of the manuscript.

Robert H. Palo Alto,

Dreisbach California,

1955

Digitized by the Internet Archive in 2022 with funding from Kahle/Austin Foundation

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TABLE

OF CONTENTS

Section I - General Considerations of Poisons and Poisoning Chapter Chapter Chapter Chapter

1- Emergency Management of Poisoning. .. . 2 - General Principles in the Treatment of Acute Poisoning 27 4.5 ,c.l-er bo eh oee » > 3 - Prevention of Poisoning. . ~ changes,

give t0-~

Gm. potassium chloride by gastric tube. Do not \give potassium in presencé of acute renal failure ithout laboratory

study of the precise degree

of

erum potassium deficiency. C. Specific Measures: If coma persists as a result of drug ingestion, consider use of artificial kidney or peritoneal dialysis to remove the drug (see p. 31).

ACUTE

RENAL

FAILURE

Acute renal failure may occur in poisoning from carbon tetrachloride, mercurials, arsenicals, sulfonamides, and

hemolytic

substances

(naphthalene,

either produce

castor bean,

These

lesions

in the tubule cells or block the tubules by hemoglobin

or crystalline

substances

benzene,

etc.).

focal degenerative

precipitates.

Part of the renal shutdown is the result of edema and swelling of tubule epithelial cells with blockage of the excretory ducts; when edema and swelling subside, renal function can return almost completely to normal if cellular damage has not been extensive.

i |

30

Renal

Failure

Clinical and Laboratory Findings: A. Initial Period: The patient may be asymptomatic, with a urine output of up to 300 to 400 ml. per day. Blood pressure may be normal or low. The urine examination reveals hemoglobin, albumin, and red blood cells. B. Period of Renal Shutdown: The patient may continue asymptomatic until signs of uremia appear, at which time weight gain, edema, and rales indicate fluid retention from overhydration. If this state of overhydration is permitted to continue, the patient will drown. During this period, the blood N.P.N. rises rapidly. C. Recovery Period: The diuresis which attends recovery from renal shutdown leads to dehydration and electrolyte imbalance. Muscular weakness can occur as a result of loss of potassium; tetany can occur as a result of a loss of calcium. Treatment: A. Emergency Measures: 1. Treat shock (see p. 25). 2. In hemolytic reactions, give sodium bicarbonate, 5 Gm. (75 gr.), every one to two hours as necessary to maintain an alkaline urine. B. General Measures During Period of Renal Shutdown: 1. Weigh patient Gaily - Weight gain indicates fluid retention,

2. Restrict

be avoided.

which

must

fluids

- In presence

of vomiting,

replace in-

sensible water loss with 10 to 15 ml. /Kg. of 20%

dextrose in distilled water by I. V. catheter. Replace the fluid lost from vomiting or diarrhea by an additional amount of 20% dextrose equal to that lost in vomiting or diarrhea. The patient can be maintained on this empirical basis for about two weeks. 3. Diet - If the patient is not vomiting, a high-carbohydrate, high-calorie diet can be given to slow the breakdown of endogenous protein. A diet made up of 120 Gm. (4 oz.) of salad oil, 120 Gm. (4 oz.) of lactose,

4 ml.

of a vitamin

to 15 ml. /Kg.

2 to 5 ml.

of water

of Tween 80®.

B complex

mixture,

is emulsified

and

in a blender

10

with

The total volume is divided

into 24 parts and given hourly by syringe through a polyethylene tube passed through the nose into the stomach. 4.

Blood

chemistry

- Serum

sodium,

serum

potassium,

and blood carbon dioxide combining power should be determined daily and deficiencies corrected by oral administration of the appropriate electrolytes. 5. Digitalization - Cardiac failure is indicated by pulmonary

venous

congestion,

longed circulation

time,

cardiac

tender

enlargement,

enlargement

of the

pro-

Pulmonary

Edema

31

liver, or increased venous pressure. If any of these develop, digitalize immediately. 6. Dialysis methods - If diuresis has not returned at the end of ten days, consideration should be given to the use of an artificial kidney (hemodialysis) or peritoneal dialysis (peritoneal irrigation). The artificial kidney is preferred, and equipment is now available ina number of centers. The patient should be moved to such a center before he becomes moribund. C. Period of Recovery: During this period, rapid blood electrolyte changes are likely to take place; daily serum

electrolyte determinations trolling therapy.

are of great value in con-

The type of diuresis may vary from one patient to another. The following are examples:

1. If the return of tubular function is delayed, the patient’s urine may be essentially a glomerular filtrate. In these patients, the urine contains large amounts of potassium, sodium, and other ions. Adequate management requires collection of daily 24-hour urine samples. The urine is then analyzed for total sodium and potassium, and these amounts are replaced by oral administration in the next 24 hours. The diuresis may be accompanied by retention of sodium and consequent

rapid rise in serum

sodium

and chloride.

Treatment in this case consists of forcing fluids and restricting sodium. 2. Specific loss or retention of sodium, potassium, or calcium is best revealed by daily serum electrolyte determinations. Deficiencies are then corrected by the oral administration

of the appropriate

PULMONARY

salts.

EDEMA

Pulmonary edema from poisoning is usually the result of the inhalation of irritants, with injury to the pulmonary epithelium followed by exudation into the alveoli. Ingestion, injection, or skin absorption of parasympathetic stimulants or cholinesterase

inhibitors

(phosphate

esters)

causes

pul-

monary edema by stimulating increased bronchial secretion. Pulmonary edema is dangerous because it interferes with oxygen exchange in the lungs and eventually drowns the patient in his own secretions.

Clinical Findings: Symptoms and signs of pulmonary edema include dyspnea, rales at the bases of both lungs, cyanosis, and rapid respiration. In extreme cases, gurgling respirations and foaming at the mouth may occur.

32

Cardiac

Arrest

Treatment:

A. Emergency Measures: 1. Postural drainage - Place the patient in the Trendelenburg position to allow fluid to drain from the chest.

2. Relieve anxiety - Give morphine sulfate, gr.),

to depress

rapid,

10 mg.

(1/6

inefficient respiration.

3. Give 60 to 100% oxygen by face mask.

4. Give aminophylline,

0.5 Gm.

(74/2 gr.) I. V. to relieve

associated bronchial constriction. B. General Measures: Relieve pulmonary

foaming by replacing the water in the oxygen humidifier with 50 to 70% ethyl alcohol. Evidence shows that oxygen saturated with

ethyl alcohol helps to collapse the foam in the bronchi and alveoli and permits better oxygen exchange. The oxygen should be given at slightly increased pressure, either by placing the outlet tube from the face mask under approximately 5 cm. (2 in.) of water or by using a positivepressure face mask (see p. 403).

CARDIAC

Cardiac

ARREST

arrest may occur as a result of general anesthe-

sia, asphyxia from carbon monoxide or other gases, inhalation of chlorinated hydrocarbons, injection of local anesthetic

agents, drugs,

ingestion of cardiac asphyxia

tion of irritants, procaine phylline,

from

drugs,

pulmonary

overdosage

edema

of cardiac

following the inhala-

and drug idiosyncrasy (especially quinidine,

or other local anesthetics, procaineamide, aminoand iodides). The possibility of cardiac arrest must

be anticipated in order to give effective treatment. Clinical Findings: A presumptive

diagnosis of cardiac

arrest is made when

pulse and blood pressure suddenly disappear and no heart sounds are audible on auscultation. Upon opening the chest, the heart is usually not completely quiescent, but is either

beating feebly with a normal rhythm or is fibrillating. The type of rhythm present is of great importance in determining what drugs should be given, Treatment:

A. Emergency Measures: Preparations must be made ahead of time so that suitable equipment and surgical kits will be available

cardiac

for use

arrest

within

seconds

after the diagnosis

is made.

1. Cardiac massage - Make an incision on the left side through the fourth interspace and rhythmically and

firmly squeeze the heart 80 to 100 times per minute. 2. Maintain artificial respiration by squeezing a

of

Cardiac

Arrest

33

rebreathing bag connected through a carbon dioxide Oxygen should be supplied absorber to a face mask. to the bag at a rate of 500 to 1000 cc. per minute; (see p. 403). 3. Maintain an adequate airway - Use a pharyngeal or laryngeal airway (see p. 17). B. General Measures: 1. Defibrillation of ventricular fibrillation -

a. Apply 2 0.1 sec. pulse of 110 volts a.c. to the If the first shock is not effective, a reheart. peated shock at 220 volts may be tried. A simple defibrillator has been described by R. S. Mackay in J.A.M A. 154:1421, 1954. b. If ventricular fibrillation does not respond to electric shock, inject procaine hydrochloride, 10 ml. into atrium or 50 to 100 ml. LV.

1%,

5%, 0.5 ml. LV. 2 to 4 ml. of 10% solution,

c. Inject potassium chloride,

Inject calcium chloride,

into the left ventricle to improve tractions.

Inject epinephrine,

of 1:10, 000 solution,

1 ml.

left ventricle if cardiac

cardiac tone and con-

massage

and calcium

into the chloride

injections are ineffective in restoring normal con-

Avoid injections into the ventricular tractions. muscle or injection of more concentrated solutions.

1 ml. of 1:1000 solution, into the left ventricle to block vagus inhibition. 5. Temporarily clamp the descending aorta in order to improve circulation to the brain and coronaries. C. Equipment which should be available at each nursing

4. Inject atropine,

station,

in each patient’s room after cardiac surgery,

and in every emergency room and operating room: 1. Oxygen tank, reducing valve, humidifier, tight-fitting

face mask,

carbon dioxide absorber,

laryngoscope, Instructions

mouth

gag,

rebreathing bag,

and intratracheal catheters.

in the use of this equipment should be

given to physicians and nurses periodically. Sterile surgical scalpel. Sterile self-retaining rib retractor. Pharyngeal airways of different sizes. Sterile gloves. D. Equipment which should be available on operating floor, central supply room, andemergency room*: § Drugs -

a. Procaine hydrochloride, b. Epinephrine,

©. Calcium chloride, ee Leeds, Sanford E.: 152-1409,

1953.

1% solution.

1:10, 000 solution.

Cardiac

10% solution. ee Resuscitation.

a ay ae J.A.M.A.

uado

‘doip

Bur /

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34

Convulsions

d. Atropine,

1:1000

35

solution.

2. Syringes with needles. 3. Defibrillator unit, including sterile electrodes covered with gauze or felt and connecting wires. 4. Sterile surgical equipment for use after circulation and respiration are established by artificial means a.

Skin antiseptics

and towels,

drapes,

and gloves.

b. Instruments to control bleeding from chest wound when pulse and blood pressure have returned: hemostats,

c.

absorbable

surgical

sutures,

forceps,

and scissors. Long forceps with teeth and long scissors to open pericardium if necessary to improve massage, to verify presence or absence of ventricular fibrillation,

or to permit

application

of electrodes

directly to the epicardium. d.

Instruments,

suture

material,

and

used in closing the thoracotomy

catheter

to be

wound.

CONVULSIONS Drugs cause convulsions by direct effect on the C.N.S., by reflex effects from the stimulation of peripheral receptors (e.g., the carotid sinus), or by producing asphyxia. The immediate treatment is the same for convulsions of any etiology, i.e., to suppress the convulsion until a diagnosis can be made and specific treatment instituted. Convulsions are dangerous to life in two ways. First, the patient may die of anoxia during prolonged spasm of the respiratory muscles; second, death may occur from respiratory failure during the depression which follows a convulsive episode. Because convulsions are followed by coma and respiratory depression, antidotes which may also cause coma and respiratory depression must be used cautiously; drugs which have easily controllable effects are preferable. include ether, pentobarbital, and thiopental.

These

Clinical Findings: Substances amphetamine,

which act primarily caffeine,

on the cerebrum

and atropine)

cause

(e.g.,

hyperactivity,

restlessness, and mania. Substances such as pentylenetetrazol (Metrazol®) and picrotoxin, which act primarily on

the brain stem, cause clonic convulsions. Strychnine acts primarily on the spinal cord to produce typical tonic extensor spasms. Other agents such as veratrum, cyanide, and nicotine may cause convulsions by a combination of reflex, C.N.S.,

and anoxic

effects.

36

Dermatitis

Treatment:

A. Emergency Measures: di Give artificial respiration

- Muscle

spasm

may re-

quire mouth-to-mouth insufflation if a resuscitator is not available (see p. 353). When the respiratory muscles are in spasm, the Nielsen method of artificial respiration is likely to be ineffective, and may precipitate convulsions. 2. Restrain patient during convulsions to prevent injury. 3. Maintain the patient in quiet, darkened surroundings and avoid disturbing him any more than necessary. 4. Do not attempt emesis or gastric lavage if the patient is twitching or hyperirritable. B. General Measures: ie Administer anticonvulsants

(see chart

on p.

34).

2. Maintain hydration by oral or subcut. fluids. The urine output should be 1 to 3 L. daily. . Maintain an adequate airway (see p. 17). A mouth and a clamp on the tongue may be necessary. Reduce elevated temperature by tepid sponges. on Remove secretions from the pharynx by suction. . Give positive-pressure

vulsions

oxygen

therapy

gag

during con-

(see p. 353).

DERMATITIS

FROM

CONTACT

WITH

CHEMICALS

Dermatitis from chemicals may arise as result of primary irritation or from sensitization. Diagnosis:

A. Primary Irritants: Dermatitis from primary irritants is characterized by the following: alts The site of maximum involvement is the site of maximum exposure. The site of maximum exposure is the site of first appearance. . Other workers exposed have similar involvement. . The time relationship between the beginning of exposure and the onset different workers.

B. Allergic

Reactions:

of dermatitis

Dermatitis

from

is similar

in

sensitizing

materials is characterized by the following: 1 The site of maximum involvement may be different from

the site of maximum

exposure.

. The time relationship between and the onset

. Other tions.

workers

of dermatitis

the onset of exposure

is variable.

exposed may not have similar

erup-

Dermatitis

37

Evaluation of Dermatitis From Contact With Chemicals: A. Contact Dermatitis From Direct Irritants: Approximately 80% of contact dermatitis is the result of primary irritation. A primary or direct irritant is an agent which is capable of injuring the skin at the site of the first application if the concentration and duration of exposure sufficient. Examples of primary irritants are:

are

1. Solvents - Volatile oils, gasoline, kerosene, benzene, or other fat solvents. 2. Acids - Even dilute solutions will cause primary irritation. 3. Alkalies - Prolonged contact will dissolve fats and lead to primary irritation even in dilute solutions. 4. Soaps - These dissolve or emulsify fats from the skin and thus cause direct irritation. 5. Other corrosives and irritants - See p. 130. B. Sensitization Dermatitis: Dermatitis from sensitizers occurs only after repeated contact. The dermatitis is not necessarily limited to the site of contact but may involve large areas of skin. The diagnosis of sensitization to a chemical can be made by means of the diagnostic patch test. The technics are as follows*: 1. Covered patch test - A small amount of the suspected sensitizer is applied to an area of the normal skin of the patient. Concentration of chemical should begin at 1:100, 000 and should be increased to 1:1000 if no reaction occurs. In using liquid or ointment test substances, a three-quarter-inch square of absorbent fabric (e.g., four-ply gauze or flannel) is saturated with the appropriate concentration of liquid or ointment. The excess is removed and the patch applied to

the test site of the skin, ordinarily the volar surface of the forearm. The contact material is next covered with a one-and-one-half-inch square of noncoated cellophane. Finally a three-inch square of adhesive plaster is used to seal the test material and the cellophane to the skin. Solid test substances may be soluble or insoluble in water. If insoluble in water they should be dissolved in an appropriate solvent. The absorbent fabric is then immersed in the solution, the solvent allowed to evaporate, and the impregnated fabric applied to the skin. Solid objects such as coins, metals, jewelry, plastics, and wood can be applied directly to the skin and covered with cellophane and adhesive tape. Powders or crystals should be applied to the test site.

*J.

G. Downing,

Dermatitis.

et al.:

J.A.M.A.

As

in patch testing with

other

Role of the Patch Test in Contact 156:497,

1954.

38

Dermatitis

materials, caution must be used in order to avoid concentrations which will produce serious reactions. The patch test material should be left in place for 24 to 48 hours. On occasion, as in testing with fabrics or wearing apparel, prolonged contact (72 hours) may be indicated. 2. Open patch test - The open patch test is indicated when a patient has been in contact with a volatile substance and presents a history of an eruption following exposure

to vapors,

mists,

fumes,

or gases

sus-

pected of inducing specific sensitization. One procedure consists of exposing the forearm of the patient to an open vessel containing the suspected sensitizer such as the vapor from paint or lacquers. After an exposure of a few seconds to two hours, the vessel removed and the reaction observed for the next

is

several days. Another method of open patch testing employs an uncovered patch. In this instance, certain substances

such

as nail polish,

shellac,

paint,

are applied to the skin and left uncovered hours.

If the test material

the duration

is a low-grade

or

dyes

for 24 to 48 sensitizer,

of contact can be longer than would be

used for a sensitizer

known

to be potent.

3. Precautions in patch testing a. Do not use adhesive tape if the patient is sensitive to it. In this case the cellophane can be held in place by elastic bandages. b. Never use an unknown substance for patch testing.

Severe burns

or exfoliative dermatitis

may result.

c.

Instruct the patient to remove the patch at the first sign of irritation or discomfort. d. Apply patch tests cautiously to patients with acute skin diseases. e. Avoid using primary irritants in patch testing; if testing is necessary, use these substances in concentrations weak enough not to cause irritation. 4. Interpretation - Test sites should be examined 15 minutés, 24 hours, 48 hours, and 72 hours after the removal of the test material. At each examination the test site is graded for redness, swelling, papules, vesiculation, desquamation, oozing, and necrosis. a. Positive reactions - A positive reaction is the

result of primary

irritation or sensitization.

reaction which is still present 15 minutes moval of the patch test, or which appears b.

Any

after reat sub-

sequent examinations, indicates a positive test. False-positive reactions - False-positive reactions

may occur (1) when primary irritants are used for patch testing and (2) when a patient reacts to a substance to which he has previously been sensitized

Dermatitis

39

even though he has had no recent contact with the material. c. Negative reactions - A negative reaction is one which shows no skin reaction 15 minutes or longer after removal of the test material. 5. Reasons for failure a. The patch test may not have been performed with the actual offending agent. b. The test substance may not have equalled the offending substance in strength or quantity. ce. Adjuvant physical or mechanical factors may be necessary to produce the dermatitis. d. Hyposensitivity may have developed since the patient contracted the original dermatitis. e. In local sensitivity the appropriate testing agent may fail to elicit a reaction in areas far removed from the site of dermatitis. Pro phylaxis: CA. Use of impervious

and,

gloves, masks, gauntlets, aprons, clothing may help to reduce the inof dermatitis.

if necessary,

cidence

. Workmen

should use mild soap frequently.

. Avoid the use of degreasing solvents, paint thinner, solvent, and harsh cleaning agents for cleaning the skin. _ Protective creams or ointments may be useful preventives

but are not likely to gain favor with workers. . A high incidence of dermatitis in a plant may personal inspection by the physician. Tre atment:

require

using any irritating or sensitizing medications.

A. Discontinue

sulfonamides, include all mercurial antiseptics, phenols, resorcinol, nitroantibiotics, local anesthetics, Ointments adhesive tape, and various dyes. furazone, These

sometimes

contain a sensitizing

mercurial

as a pre-

servative.

. Moist,

oozing

wet dressings

are

lesions

which

treated by application

of mild

should be replaced every two to

Impervious coverings prevent the cooling three hours. The effects of evaporation and should not be used.

can be used without fear of aggra-

following medications vating the irritation:

1. Aluminum 2. Magnesium 3.

Sodium

acetate,

1% solution.

sulfate,

half-saturated

bicarbonate,

solution. 4. Starch or oatmeal

saturated

solution

solution.

or half-saturated

(can be used as a bath and

repeated every two to four hours). 5. Normal

pint,

saline

or 1 lb.

solution

(1 tsp.

in 12 gallons).

of sodium

chloride

per

40

Liver Damage

6. Potassium permanganate, 1:10,000 solution. (Leaves a stain, but otherwise excellent. ) C. Fissured, thickened, scaling eruptions are treated by

mild ointments,

of which the following are satisfactory:

1. Zine oxide ointment. 2. Zine oxide (Lassar’s)

paste.

3. Hydrophilic ointment (Aquaphor®).

LIVER

DAMAGE

Acute liver damage may be caused by any of a large number of chemicals. Exposure to any of the following may cause acute or chronic liver damage: chlorine-containing organic

compounds,

sulfonamides

cincophen,

(rarely),

alcohol,

neocincophen,

gold salts,

arsenicals,

mushrooms,

amino or nitro compounds (trinitrotoluene, etc.), castor beans, chromium compounds, lead, and phosphorus.

Clinical Findings: A. Acute Poisoning: Nausea, vomiting, anorexia, headache, malaise, lethargy, abdominal pain, fever, jaundice, and enlarged, tender liver. B. Chronic Poisoning: Weight loss, weakness, pallor, hematemesis, palmar erythema, enlarged or atrophic liver, jaundice, ascites, dependent edema, hemorrhoids, pruritus.

C. Laboratory Findings in Hemolytic Jaundice From Poisons: 1. Bilirubin is present in the urine. 2. Urinary urobilinogen is increased. 3. Fecal urobilinogen is increased. 4. Blood bilirubin is increased, indicating the inability of the liver to remove bilirubin as fast as formed. The degree of the accompanying anemia indicates the

severity of the process. D. Laboratory

Findings

in Suspected Hepatic Cell Injury

From Poisons: 1. Bilirubin is present

in the urine. 2. Urinary urobilinogen is increased. 3. Fecal urobilinogen is decreased. 4. Blood bilirubin is increased, indicating the inability A of the liver to remove bilirubin as fast as formed. gradual increase in bilirubinemia indicates progression of the lesion; reduction of the bilirubinemia indicates healing of the cellular injury. 5. Sulfobromophthalein (B.S. P.) excretion test - Sulfobromophthalein can be used to test minimal impair-

ment of the excretory capacity of the hepatic cells

when function is sufficient to prevent bilirubinemia. More than 5% retention 45 minutes after administration

Liver Damage

of 5 mg./Kg.

41

1.V. indicates hepatic cell disease.

. The synthetic and conjugative functions of the liver can be tested by a variety of methods. While reduced function indicated by these tests is important diagnostically, the presence of liver injury cannot be excluded by a normal test. Severe injury may be present in the absence of alterations of these function tests. The following tests are used: a. Altered serum albumin- globulin ratio can be shown by (1) positive cephalin flocculation, (2) positive thymol turbidity, (3) positive colloidal gold tests, and (4) positive zine turbidity test. Serum albumin is decreased and serum globulin is normal or in-

creased.

These tests may show little correlation

with clinical findings and are poor indicators of prognosis or of over-all liver function. However, they are useful in following the effect of treatment on impaired liver function or to indicate adverse effects of new drugs. Changes in such tests are of more importance diagnostically and prognostically than are isolated positive tests. b. A low plasma

prothrombin

concentration

24 hours

after vitamin K administration (10 to 100 mg. I.V. or I.M.) indicates the inability of the liver to synthesize prothrombin from vitamin K. Persistence of low plasma prothrombin in the absence of obstruction indicates a poor prognosis. ec. Diminished serum cholesterol or cholesterol esters indicates severe injury to hepatic cells. Prognosis is poor if low levels persist. Serum cholesterol

should be 150 to 240 mg. /100 ml.,

of which 60%

should be esterified. Treatment: A. Emergency Measures for Acute Form: 1. Discontinue all drugs and chemicals, alcohol,

barbiturates,

salicylates,

arsenicals

sulfonamjdes,

and other

especially narcotics,

metals,

and

anti-

histamines. Maintain complete bed rest. Avoid unnecessary transportation. Avoid anesthesia or surgical procedures. B. ener Measures in Acute or Chronic Liver Damage: Qrwonw = . Avoid dehydration - If vomiting is severe and oral

fluids are not retained, give 1 L. of 5% dextrose or invert sugar in normal saline plus 1 to 3 L. of 10% dextrose or invert sugar in distilled water I. V. each 24 hours. Replace vomitus with an additional equal quantity

2. Calcium

of 10% dextrose in normal saline. gluconate - Give 10 ml. of 10% solution

42

Acidosis

slowly I. V.

twice daily as a nonspecific

cellular pro-

tectant.

3. As soon as possible, feed patient through a Levine tube or polyethylene tube at hourly intervals, supplementing all feedings with 1 to 4 ml. of multivitamin drops. Feedings should consist of 60 to 240 ml. (2 to 8 oz.) of the following in alternation: a. Fruit juice fortified with dextrose, 60 Gm. (2 oz.)

{Vee

4.

b. Fortified milk, made by blending 120 Gm. (4 oz.) dry skimmed milk with 60 Gm. (2 oz.) dextrose in 1 L. of water; let stand in the refrigerator until used. When vomiting is under control, give frequent oral feedings of a high-carbohydrate, high-protein diet to

at least 3500 Calories daily. made to make fully. 5.

Vitamin

50 mg. 6.

Blood

K - Give

I.M.

Every effort should be

the diet palatable. menadione

Record

sodium

intake care-

bisulfite,

10 to

daily.

transfusion

- If anemia

is severe,

replace

blood

by transfusion. 7.

Lipotropic

agents

methionine

is still controversial.

up to 10 Gm.

- Use of choline,

cystine,

and

If available,

give

daily orally.

ACIDOSIS Acidosis

in poisoning may be caused by either of two

mechanisms: (1) Loss of base with reduction in pH and carbor dioxide combining power may be caused by vomiting, diarrhea, or urinary excretion during alkalosis from respiratory stimulation. (2) Increase in acid with reduction of pH may be caused by metabolism of a poison to an acid intermediate

(e.g.,

methanol

to formic

acid),

retention of carbonic

acid

during respiratory depression, and retention of metabolic acids during anuria from renal damage. In either case the pH is less than the normal 7. 4. Clinical Findings:

A. Symptoms and Signs: 1. If acidosis is caused by carbon dioxide retention, respiratory inadequacy is apparent and cyanosis is present. 2. If caused by loss of base or increased organic acids, the respirations will be increased in rate and depth; dehydration, stupor, or coma will be evident. B. Laboratory Findings: 1. The fall in carbon dioxide combining power reveals the magnitude of base loss.

Methemoglobinemia 2.

The

hematocrit

indicates

hemoconcentration

43

in de-

hydration. Treatment: A. Of Carbon Dioxide Retention: Maintain an adequate airway (see p. 17). Give oxygen therapy (see p. 24). B. Of Loss of Base or Increase in Organic Acids: (Presence of anuria must be recognized and treated accordingly; seep. 29. 1. If carbon dioxide combining power is below 20 mEq. / L.

(45 Vol.%),

give sodium

bicarbonate,

5 Gm.

(75

gr.) orally every 30 minutes until the urine is alkaline or until the carbon dioxide combining power is above 20 mEq. /L. 2. If carbon dioxide

combining power

is below

L. (22 Vol. %), give M/6 sodium lactate,

10 mEq. /

60 ml. /Kg.,

or sodium bicarbonate, slowly. In the absence

0.8 Gm./Kg. orally or I.V. of special solutions, 50 Gm.

sodium

be dissolved

bicarbonate

can

in 1 L.

of

of 5%

dextrose. 3. As

soon

as oral

medication

is possible,

continue

giving 5 to 10 Gm. (75 to 150 gr.) sodium bicarbonate orally every hour until the urine becomes alkaline or until the carbon dioxide combining power remains

above 20 mEq. /L. C. Treat Dehydration: to maintain

hydration

Give up to 4 L. and adequate

of fluids orally daily urine output.

METHEMOGLOBINEMIA Methemoglobin

is formed by the oxidation of the ferrous

‘et*) iron of hemoglobin to the ferric (Fe+++) form by the stion of a number of chemicals including nitrites, chlorates, -i1ethylene blue, and amino and nitro organic compounds. For ample, sodium nitrite is used in meat curing. It may be present in excess in home-cured meat, or the meat-curing

salt may be used to take the place of table salt.

In infants or

children, nitrate contamination in well water from agricultural use of fertilizers or from bismuth subnitrate may be reduced to nitrites in the intestine and absorbed to cause methemoglobinemia. Organic nitrates and nitrites, including glyceryl trinitrate,

amyl nitrite,

and other vasodilating

all capable of causing methemoglobinemia.

nitrates

are

Acetanilid,

sacetophenetidin, aniline, nitrobenzene, and other nitro and ‘amino organic compounds are also powerful methemoglobin

formers. The ferric iron of methemoglobin

ferrous

iron (hemoglobin)

(of methylene blue.

can be reduced to most promptly by the administration

Although methylene blue in large doses is

44

Methemoglobinemia

itself capable of causing methemoglobinemia, a point of equilibrium is reached when not more than 5 to 10% of the After adminhemoglobin has been changed to methemoglobin. istration, the colored methylene blue is rapidly converted leuko base by the coenzyme diphosphopyridine nucleotide

(DPN).

ferric iron (Fet**)

This leuko base rapidly reduces

to ferrous

The reactions

iron (Fett).

Reduced

DPN

Leuko methyl-

Methylene

4

blue

‘2

SSS

ee al

are as follows:

DEN.

Leuko

a

methylb

ene blue

Methemoglobin

Hemoglobin

(Fett)

(Fett)

ene blue

to a

2

Methyl-

ene blue

The reaction continues in the presence of reduced DPN. Ascorbic acid is also capable of reducing the ferric iron

of methemoglobin to the ferrous iron of hemoglobin, but the action is slower than that of methylene blue. Without treatment, methemoglobin levels of 20 to 30% will revert to normal in one to three days. Clinical Findings:

A. Cyanosis occurs

when

15% of hemoglobin has been con-

verted to methemoglobin, but symptoms of headache, dizziness, weakness, and dyspnea are not likely to occur

until the concentration

reaches

30 to 40%.

At levels of

60%, stupor and respiratory depression occur. B. Laboratory Findings: 1. Spectrophotometric analysis will give the concentration of methemoglobin in the blood. 2. A concentration of methemoglobin above 40% indicates that treatment by means of methylene blue is neces-

sary. Treatment:

A. Emergency Measures: 1. Give 100% oxygen by mask to increase the oxygen saturation of unchanged hemoglobin if the patient shows dyspnea or air hunger. 2. Remove ingested poison by gastric lavage or emesis followed by catharsis; terminate skin contact by washing the skin thoroughly with soap and water. B. Antidote: (When methemoglobin concentration is over 40% or in presence

of symptoms. )

1. Give methylene blue,

5 to 50 ml. of 1% solution slowly

is Vis 2. If methylene 1 Gm.

blue is not available,

(15 gr.) slowly 1.V.

give ascorbic

acid,

Agranulocytosis,

Blood Dyscrasias

45

C. General Measures: 1. Absolute bed rest must be enforced if methemoglo-

binemia is above 40%. 2. Continue oxygen therapy for at least two hours methylene blue has been given.

AGRANULOCYTOSIS

AND

BLOOD

after

DYSCRASIAS

A large number of nitrogen compounds and metals are capable of causing blood dyscrasias, including agranulocytosis, leukopenia, aplastic anemia, and thrombocytopenia. The incidence of these reactions varies from approximately one case in 100 to one in 1000 patients receiving aminopyrine, phenylbutazone, thiouracil, allyl-isopropyl-acetylurea (Sedormid®), gold salts, arsenicals, and sulfonamides; the incidence is less than one case in 10, 000 users of antihistamines, antibiotics, anticonvulsants, and thiouracil derivatives (see table below). Almost all blood dyscrasias

appear

to be on the basis of

In tests on patients who have had such reactions sensitivity. to drugs, doses of a few mg. were capable of reproducing the syndrome. INCIDENCE

OF

BLOOD

DYSCRASIAS Estimated Incidence per

Drug

100,000

Aminopyrine

Phenylbutazone (Butaz olidin®) Thiouracil Allyl-isopropyl-acetylurea

(Sedormid®)

Users

Produced

1,000

Agranulocytosis

1,000

Thrombocytopenia Agranulocytosis Agranulocytosis, aplastic anemia Aplastic anemia, agranulocytosis

100

¥.

Type of Blood Dyscrasias Agranulocytosis Agranulocytosis

Propylthiouracil Gold salts

Sulfonamides

DRUGS

; 1,000

hg

Arsenicals

FROM

10

Agranulocytosis, thrombocytopenia, aplastic

Trimethadione

Agranulocytosis,

10 10

Agranulocytosis Hemolytic anemia,

10

Thrombocytopenia

aplastic anemia

(Tridione®)

Diphenylhydantoin (Dilantin®) Ethylmethylphenylhydantoin

(Mesantoin®) ia

Quinidine

|

Antihistamines Streptomycin,

anemia

10

dihydro-

streptomycin Chloramphenicol

aplastic anemia

1

Agranulocytosis

1

Agranulocytosis

1

Aplastic anemia

46

Metal Poisoning

Clinical

Findings:

A. Agranulocytosis of the mouth

or Leukopenia:

and throat,

fever,

Symptoms malaise,

are infections

and pneumonia.

The blood examination reveals a decrease or disappearance of granulocytes. B. Aplastic Anemia: Severe anemia which does not respond to any type of treatment. The bone marrow is aplastic. C. Thrombocytopenia: The disappearance of thrombocytes leads to frequent purpuric or massive and severe internal hemorrhages. Treatment:

A. Emergency Measures: Discontinue the use of the offending drug at the first symptom. B. General Measures: 1. Prophylactic chemotherapy - Give penicillin, one million units I.M., in divided doses every 24 hours. 2. Give repeated blood transfusions.

SPECIAL IN

DIMERCAPROL

“COMPOUNDS POISONINGS

"USED

(BAL®) IN METAL

POISONING

Metals such as mercury and arsenic apparently combine with -SH groups in enzyme systems to cause inactivation of the enzymes. Dimercaprol, containing two -SH groups, is an ideal compound to prevent this inactivation. It combines with metals in the following manner. CHyCHCH,OH

SH SH

HC ——CHCH.OH

‘edad

aaa a

s

eS

Hg Dimercaprol

Such cyclic combinations

are soluble in body fluids and

appear to be more stable than the monothio- compounds formed between metals and the cellular enzymes. The metals thus removed from combination in or on cells

are then excreted In overdoses,

rapidly. dimercaprol

latory effects on the C.N.S. localized.

produces

a variety of stimu-

which have not as yet been

EDTA

47

Treatment With Dimercaprol: A. The prompt use of dimercaprol

is important. It should be given within the first four hours after poisoning to obtain the maximum benefit. B. Dimercaprol is available as a 10% solution in oil for I. M. administration. Each ampul contains 5 ml., or 500 mg. This amount supplies two-and-one-half doses for an adult of average size. C. Dosage: Give 3 to 4 mg./Kg. (or 0.3 to 0.4 ml. /10 Kg.) every six hours for the first two days and then twice daily

for a total of ten days.

The larger dose is used when the

estimated amount of poison is larger. D. Ephedrine: If unpleasant reactions are severe, give ephedrine sulfate, 25 mg. (3/g gr.), orally, prior to administration

EDATHAMIL

of each

dose

CALCIUM

of dimercaprol.

DISODIUM

Sequestrine®) IN METAL

(EDTA,

Versenate®,

POISONING

Metals such as lead and iron can be effectively detoxified by chelation. This is the formation of stable ring compounds by the coordination of electrons from the metallic element with an unshared

pair of electrons

from

a member

of the

organic compound. An effective chelating agent is edathamil (ethylenediamine tetra-acetic acid), which forms readily soluble,

un-ionized

compounds

with

metals.

Its usefulness

as an antidote, however, is limited to those metals which are bound more tightly than is calcium. At the present time, lead,

iron,

and copper

are

the only common

metals

which

have been demonstrated to form compounds with ethylene diamine tetra-acetic acid which cannot be displaced by calcium.

c—c&2°

[*

ee By

cH,

CH,

Te

OH

ze

i

C—OH

Edathamil

(Ethylene diamine acid)

fo)

a

Ve Ca

0.

' N—C— Cy PRs Se HyC—C—ONa

j

Edathamil calcium disodium (Calcium disodium ethylene diamine tetra-acetate)

afe)

eela

ONa

fT edth ado evi 5

COW ug CB

ay On N—C— CC | ) CHy

tetra-acetic

BZ c—c&

ve

OH

N

pee a haa

cht,

7 Ph

cH

a

Tes 0.

!

N—c—c=o | Hy

HC

a

oot

Edathamil

oO lead

(Lead ethylene diamine tetra-acetate)

48

EDTA

Effects of EDTA: A. Administration of calcium edathamil has apparently produced only transient fall of blood pressure without other signs of toxicity. A prolonged course of administration would remove other metals such as magnesium from the body, and it is advisable to interrupt treatment frequently so that loss of minerals can be corrected. B. Laboratory Findings: Studies on the use of calcium edathamil in lead poisoning indicate that a large increase in lead excretion occurs on the first day or two of administration. This indicates that the drug should be given in repeated short courses interrupted by rest periods.

Treatment with Calcium Edathamil: A. Edathamil calcium disodium (calcium disodium ethylene diamine tetra-acetate) is available as a 20% solution in 5 ml.

(1 Gm.) ampuls

Beverly Blvd.,

from Riker

Los Angeles 48,

B. Give 1 Gm. /20 Kg.

in 100 ml.

Laboratories,

8480

California.

5% dextrose I. V. overa

one- to two-hour period twice daily. The maximum dose should not exceed 5 Gm. per day. The drug should be given in courses of two to five days with a rest period of equal duration between courses.

Chanter3

PREVENTION

OF POISONING

AGRICULTURAL POISONS (Insecticides, Rodenticides, Fungicides,

etc.)

Persons two groups.

exposed to agricultural poisons are divided into The first group includes those who work with agricultural poisons during manufacture, preparation for use, storage, or application. The second group includes those who

some in contact with these chemicals accidentally, either through improper storage, by entering sprayed areas, or by eating sprayed foods from which spray residues have not been removed. Poisoning can be prevented by attention to the following:

Storage of Poisons: A. Poisons

must

be stored

in well-marked

containers,

preferably under lock and key. B. Mixtures of poisons with flour or cereals must not be stored near food. Sweet mixtures are the most danger-

ous. C. Emptied

containers

must be burned to destroy residual

poisons.

Protective Clothing and Equipment*: A. Use masks and exhaust ventilation during dry mixing. B. Wear protective clothing, goggles, and oil-resistant neoprene gloves when prolonged handling of poisons in petroleum oils or other organic solvents is necessary. Protective clothing should be removed and exposed skin washed thoroughly before eating. C. Wear respirators, goggles, protective clothing, and gloves during preparation and use of sprays, mists, or aerosols when skin contamination or inhalation may occur. Protective equipment should be made of rubber when handling chlc.sinated hydrocarbons and of neoprene or other oil-resistant materials when handling poisons in organic solvents. The phosphate esters (see p. 71) ‘References

to safety equipment

are listed under Safety Equip-

ment in the yellow sections of the telephone books of larger ities.

49

50

Prevention

of Poisoning

and indane ous. Other

derivatives

Protective

A. Always

(see p. 69) are especially danger-

Measures:

spray downwind.

B: Avoid exposure for more than seven or eight hours per 24 hours in a closed area where thermal insecticide Such vaporizers MUST be vaporizer is being operated adjusted to release not more than 1 Gm. (15 gr. ) of DDT or Lindane® per 15, 000 cubic feet per 24 hours at a rate No other insecticides are safe for constant within 25%. use in vaporizers.

Thermal

used in living quarters

should never

vaporizers

or where

food is stored,

be

prepared,

or served.

PREVENTION OF POISONING FROM INDUSTRIAL CHEMICALS Provision of Adequate Environmental Controls: TN Dust-forming operations must be conducted in closed General room systems with local exhaust ventilation. ventilation is never sufficient to control air contamination. . Hoods

for local

exhaust

ventilation

should

enclose

the

process as completely as possible to prevent dispersion of contaminants toward the operator or into the room. . Materials should be transported by enclosed mechanical conveyors whenever possible. ._ Areas

where

hazardous

materials

are

used

should

have

impervious floors and work tables to allow adequate cleaning and to prevent accumulations of hazardous dusts or liquids. Drains should be provided to allow frequent and thorough flushing. . Spilled dusts should be removed by vacuum cleaning. . Sweeping should be done only with wet or oiled sweeping ey compounds. . Spilled liquids should be removed by flushing. . General room ventilation should be provided by fresh air and not by recirculating room air. Less toxic substances should be substituted wherever _ possible. Control of temperature should be provided where position to dangerous byproducts is possible.

decom-

Instructions and Provision of Safety Equipment: A. Workers should be trained to understand the hazards volved and to avoid exposure

by proper

in-

use of safety

equipment.

B. Gloves, goggles, aprons, and protective clothing should be used wherever necessary.

Prevention

of Poisoning

51

. Eye fountains and showers must be provided for rapid removal of corrosive materials. . If protective clothing is necessary, it should be laundered

daily. . For operations where local control of contaminants is impractical, supplied-air masks, gas masks, or selfcontained oxygen helmets should be provided. . Supplied-air masks or gas masks should be provided for emergency use wherever dangerous substances are being used. A safety harness and life-line should be available for evacuation of personnel from areas which may become dangerously contaminated. . Workers handling poisonous substances should be required to wash properly before eating or smoking. A change of clothing on leaving work should be required in such instances. . Workers

should

be instructed

to report

for examination

at the first evidence of injury. Adequate Medical Program: A. Workers in hazardous occupations must be examined every six months to one year as a check against failures in control measures.

. Facilities should be inspected weekly or monthly in order to detect failures or inadequacies in control Adequate inspection may require continuous

methods. or inter-

mittent sampling of air. . Pre-placement physical examinations should be used to detect chronic respiratory, kidney, or other systemic diseases. Individuals with these diseases should not be exposed to any toxic fumes.

PREVENTION

OF HOUSEHOLD

POISONING

Adequate Storage:

A. All medicines should be stored in locked cabinets. Bi. Lye, polishes, kerosene, and other household chemicals should never be left on a low shelf or on the floor. solutions should never be left in drinking glasses or in soda pop bottles. iD Insecticides and rodenticides should be stored under lock and key. E. Combustion devices should be adequately vented.

Cc. Dangerous

|Education:

A. Parents must be educated to the dangers present in medicines and household chemicals. A poison label should appear on all dangerous medicines, including aspirin, soluble iron salts, and barbiturates.

52 CHECK

LIST OF HOUSEHOLD

POISONS

House: Insecticides - All ant and roach poisons. Inflammables and Extinguishers Kerosene and gasoline

Fire lighter - Methyl alcohol, denatured alcohol Fire

-

starting tablets

petroleum hydrocarbons,

Metaldehyde,

methenamine

Fire extinguishers - Carbon tetrachloride, methyl bromide Cleaning Equipment Drain cleaner - Lye, sodium acid Carbon tetrachloride sulfate Solvent distillate Rug cleaner - Chlorinated hydro(Stoddard solvent) Lye (sodium hydroxide) carbons Ammonia Wallpaper cleaner - Kerosene, Bleach - Sodium hypopetroleum hydrocarbons chlorite, oxalic acid Laundry ink - Aniline Medicines Salicylates - Aspirin, methyl salicylate Sedatives

- Barbiturates,

bromides

Anti-epileptic agents Antihistamines (‘‘cold’’ tablets) and seasickness pills Cathartic pills - Strychnine, atropine, drastic cathartics Cough mixtures - Codeine, methadon, other opiates

Nose drops - Ephedrine,

Privine®,

Neo-Synephrine®,

Reducing or slimming tablets - Amphetamines, Cardiac drugs - Digitalis, quinidine, veratrum Antiseptics

- Boric

Hematinics Cosmetics Hair

dye - Silver

Cold wave

acid,

- Ferrous

- Solvents,

lead,

iodine,

phenol

anilines

bromate

Storeroom: Paints and Painting Supplies Paint

chloride,

sulfate

salts,

- Potassium

mercuric

others

thyroid preparations

-

arsenic,

chlorinated

hydrocarbons

Paint remover - Chlorinated hydrocarbons, acids, alkalies Lacquer - Ethyl acetate, amyl acetate, methyl alcohol Shellac - Methyl alcohol Wood bleach - Oxalic acid Pesticides - Moth balls (naphthalene)

Yard or Storage (Garage): Insecticides - (Organic solvents used in some of these are also poisonous. ) Benzene hexachloride Tetraethylpyrophosphate Chlordane and lindane Parathion and malathion DDT and toxaphene Dichloroethyl ether in soil Arsenic and lead fumigants arsenate Nicotine Rodenticides

-

Sodium fluoracetate Phosphorus Strychnine Plants Fox glove - Digitalis Cherry - Cyanide

Methyl bromide Thallium and barium Cyanides Thorn apple - Atropine Mushrooms

Oleander Poison ivy

Prevention

of Poisoning

53

B. Parents must begin to teach their children at an early age the danger of touching, eating, or playing with medicines, pesticides,

household

PREVENTION

chemicals,

or plants.

OF SUICIDAL

POISONING*

Recognition of Suicidal Tendencies: A. Symptoms and Signs of Depression: 1. Insomnia - True insomnia is frequently an early symptom of depression. The patient is unable to go to sleep at night or may awaken during the night or early in the morning and be unable to go back to sleep. 2. Anorexia - The patient may complain that food no longer ‘‘tastes good’’ or that it ‘‘tastes like straw’’ and that he is gradually losing weight. 3. Lack of interest in surroundings - The patient shows no interest in his occupation, friends, or hobbies. He may quit his job and at the same time profess that he is still interested in the same type of work. 4. Chronic fatigue. B. Actual Suicidal Attempts May Be of Two Types: 1. Benign - Attempts by the use of aspirin, Lysol®, or wrist-slashing may be only for the purpose of gaining attention. 2. Malignant - If patient uses firearms, barbiturates, carbon monoxide, or throat-cutting he must be considered dangerously ill and hospitalized under psychiatric care. C. Psychiatric evaluation should be done on every patient who mentions suicide or is depressed. Hospitalization may

be necessary

Prevention: A. The physician

for proper

evaluation.

should avoid prescribing barbiturates

for

depressed or possibly suicidal persons. Barbiturates are responsible for at least 20% of suicidal deaths. Relatives should be apprised of possible suicidal tendencies

in a patient.

B. Persons who have made unsuccessful attempts at suicide should have adequate follow-up psychiatric therapy.

*Bennett, A. E.: 81:396, 1954.

Prevention

of Suicide,

California

Medicine

Chapter 4

THE PHYSICIAN’S LEGAL AND MEDICAL RESPONSIBILITY IN POISONING Written Records: In any case of poisoning in which there is a possibility of legal action at a later date, the physician must keep careful A history written records of his observations and findings. obtained from another party must be carefully noted as such in the records. Since court action may begin as late as a year or more afterward, written records are essential to maintain the physician’s position as an unbiased observer.

Preservation

of Evidence:

If the physician suspects pojsoning in any patient he is called upon to see, he must be careful to save evidence that may be important for identification of the poison, The bottles used for storing specimens should be clean and free from con-

tamination by chemicals

or metals.

It is best not to use

bottles that have been previously used for chemicals or for pathologic specimens. A clear glass bottle with a plastic or metal cap with a heavy waxed paper liner is adequate. The container should be sealed with a glue-paper label extending

over the cover and down onto the jar.

The physician’s sig-

nature should be affixed to the label at the juncture between the cap and the bottle. Avoid using a seal such as adhesive tape, which can be removed and replaced. If the analysis

cannot be done immediately, the material should be stored by freezing. Preservatives should not be used since they may mask material of toxicologic importance. If shipping is necessary,

the container

should be wrapped

with paper

and placed

in a carton with dry ice. A. Evidence to Be Saved in Nonfatal Poisoning: 1. Prescription bottles or other bottles from which the poison was obtained, 2. Urine

- 24-hour

specimen.

(Lead,

biturates, alkaloids. ) 3. Blood - 10 to 50 ml. (Barbiturates, insecticides. )

4. Vomitus

mercury,

alkaloids,

and first two gastric washings.

gestion of poison but not necessarily ing. ) 5. Feces. (Arsenic. )

54

bar-

lead,

(Indicates in-

systemic

poison-

Legal and Medical

Responsibility

55

Body fat (obtained by biopsy). (Insecticides. ) Hair clippings. (Arsenic. ) orn Clippings of fingernails and toenails. (Arsenic. ) 9. Food. (Bacterial food poisoning, arsenic, pesticides. )

B. Evidence to Be Saved in Fatal Poisoning:

Autopsy must

be performed prior to embalming. Blood collected at the time of embalming will be contaminated by embalming fluid. In taking pathologic specimens, be certain that gloves and instruments are not contaminated by disinfectants or chemicals which may be transferred to specimens. Specimens should be placed directly in containers known to be clean; do not allow them to become contaminated on a table or sink. No preservatives should be used. In addition to the above, the following should be collected and stored: 1. The stomach and contents. 2. 3.

Liver, at least one-half. Kidneys, at least one.

4. Blood, er.) 5. Bone,

50 to 100 ml.

100 Gm.

(Should completely

fill contain-

(4 oz.).

6. Lungs. 7. Brain,

at least one-half.

C. In cases of poisoning in which specimens are of medicolegal importance, the physician must use care to establish a legal chain of custody in such a way that each person having responsibility for the material can state that it has not been contaminated or changed.

SPECIAL Attempted

PROBLEMS

Suicide:

In treating a patient who has attempted suicide, the physician’s main responsibility is to treat the patient adequately and to prevent him from repeating the attempt. The patient must be placed in quiet, protected surroundings, preferably away from his family. Hospitalization is frequently necessary. After the patient recovers from the immediate symptoms,

he should

psychiatrist, suicide.

be carefully

to make

evaluated,

preferably by a

certain that he will not again attempt

Successful Suicide: If a physician is called upon to treat a patient who dies in a suspected suicidal attempt, the physician is legally responsible for reporting the death to the police and to the coroner. Proof of suicide may have considerable legal and financial importance,

and the physician will be called upon to justify

| his statements

by careful observations

and written records.

56

Legal and Medical Responsibility

Homicidal

Poisoning:

Although homicidal poisoning appears to be rare, in view of the frequent newspaper accounts of poisoners being discovered only after they have successfully poisoned as many as six or eight of their relatives, many cases must go unrecog-

nized even today.

If homicide is considered as a possible

cause of poisoning, the patient must be removed to a hospital until he recovers and the circumstances reported to the police. Further proof of homicidal poisoning must be left to the police. If a patient dies from a suspected homicidal poisoning, the

physician is legally bound to report the death to the police and to the coroner. Carefully written records of all observations will aid the physician in court appearances.

Accidental

Poisoning:

In accidental poisoning, the first responsibility of the physician is to give proper treatment. The frequency of litigation involving poisoning indicates that treatment must be thorough and personal; suggestions over the telephone are not sufficient even if the poisoning is apt to be inconsequential.

The physician must see the patient immediately, carry out the necessary emergency measures even if these seem superfluous, and continue observing the patient during the time when the maximum effects of the poison are calculated to

occur. This may require 24 hours of observation. Of all nonoccupational poisonings, food poisoning resulting from eating in a public restaurant is the only type that must be reported. Such cases must be reported to the local public health officer. Fatalities from suspected accidental poisonings must be reported to the police and to the coroner,

Occupational Poisoning: If poisoning has resulted from occupational exposure, a report must be sent to the proper authorities if the poisoning is reportable. The table on pp. 57 and 58 lists the reportable occupational poisons by states. The table on pp. 59 and 60 gives the addresses of authorities to whom such occupational poisonings must be reported.

57 SPECIFIC REPORTABLE OCCUPATIONAL POISONS OR DISORDERS DUE TO POISONS*

POISON OR DISORDER

Ss =

Alabama Arkansas Colorado Connecticut

Cancer

(contact,

x

Acetaldehyde and aldehydes Acids, organic and inorganic

Alcohols Alkalis Ammonia

aniline Arsenic

ista [rn [ee] a= ocou Ce ee Cs ee fife aN cis SEDI ie xe Us

ABHBHs etal |e[| ls a

Antimony

Benzene (benzol), benzene derivatives, and other cyclic

hydrocarbons Beryllium

ie oad

*

ea

4

xix

ey a i es a Ne Sh

(metal fume

Cadmium Carbon dioxide Carbon disulfide (bisulfide)

Se Carbon

Washing

(industrial)

Dermatoses industrial)

Brass

g

monoxide

TELE ELL x

chloride Chlorinated naphthalene and chlorinated diphenyl Chlorine Chromium, chrome, chromates, chromic acid, bichromates

Cutting compounds Cyanide Dinitrobenzene

xy

br

*

a

x Eee icihe: x x

x a

*

a

eSpresaco aie

aaa GE a at anar Pulm

Fluorides

ea

Se TTT pene cee] | 1s OE Formaldehyde Fumes alides carbons

carroting

solutions

*For other states,

x

see pp.

59 and 60.

|

58 SPECIFIC REPORTABLE OCCUPATIONAL POISONS OR DISORDERS DUE TO POISONS (CONT'D. )*

w Iu a

POISON OR DISORDER

a3 & Be o

ot os Le OL Sh. ©ge paakw

6S

o a Cee Connecticut Colorado

Hydrochloric acid Hydrocyanic acid Hydrofluoric acid Hydrogen sulfide Industrial solvents Insecticide sprays Lead Lead

dioxide

Mercury Metal fumes Metals Methanol chloride

Methyl (wood) alcohol

Nitric acid Nitric oxides Nitrobenzene

es

ee

=

o

ee

=

o

ee

He =

o

ae

aera arta cco Ez

Nitrogen oxides Nitroglycerine Nitrous

IMS

a

ot

Alea eb |

fumes

Organic solvents Petroleum and products, and all aliphatic hydrocarbons Phenols Phosphorus Pitch Selenium Solvents

Sulfide Sulfur dioxide Sulfuric Tar

acid

Tetraethyl Tetryl

lead

Trinitrotoluene Vanadium Wood alcohol or its compounds Zine

*For other states,

tet «

a

©

x

arsenate

Methyl chloride Natural gas

a

Ss

Ci)

c

x

Manganese Manganese

3

S

eetnit aie Ln ee |

TEES CIE ESE

see pp.

59 and 60.

59 STATE

REQUIREMENTS FOR REPORTING OCCUPATIONAL POISONING AND THE AGENCY RESPONSIBLE

State Alabama Arizona

Remarks County Health Officers or Dept. of Public Health, Montgomery 4. State Industrial Commission,

|See p. 57.

Phoenix.

only.

Report for compensation

r:

Arkansas

See p. 57.

California

available. All reportable.

Colorado

Connecticut

Delaware District of Columbia Florida

Dept. of Industrial Relations, Division of Labor Statistics, Berkeley 4. Local Health Officer and State Board of Health, Denver 2.

State Dept.

of Health,

Hartford.

State Board of Health, Dover. District Industrial Commission. Florida Industrial Tallahassee.

Commission,

See p. 57. telephone,

Report card

Report by in person, or

by writing. [See p. 57. report form, hours. Lead only.

Special within 48

|Report for compensation only. | Report for compensation only. available.

Boise.

Illinois Indiana

lowa

Kentucky

Louisiana Maine

Maryland

Massachusetts

Michigan

Minnesota

[Beles

No report required.

Division of Industrial Hygiene, All reportable. State Board of Health, Indianapolis. Local Health Officer or State See p. 57. By special Dept. of Health, Des Moines 19. |form, or personal communication. Lawrence. County Health Officer, or the Division of Industrial Health, Kentucky State Dept. of Health, Louisville. State Dept. of Health, New Orleans. State Dept. of Health and Welfare, Augusta.

State Board of Health, Annapolis; also to Baltimore City Health Dept. Dept. of Labor and Industries, Division of Occupational Hygiene, Boston 10. Dept. of Health, Lansing.

State Industrial St. Paul.

Commission,

Mississippi Missouri

Local City, County or District Health Dept., Division of Health of Missouri, Jefferson City.

All reportable on occupational disease report | card, within 48 hours. All reportable. All reportable on special forms within days.

10

All reportable.

All reportable.

All are reportable on occupational disease forms, Report for compensation only.

All reportable.

See p. 57. available,

Report

cards

60 STATE REQUIREMENTS FOR REPORTING OCCUPATIONAL POISONING AND THE AGENCY RESPONSIBLE (CONT'D. ) State Montana

Agency

Remarks

State Board of Health, Helena. Repo rt may be requested by Division of Industrial Hygiene.

Nebraska Nevada

New

Hampshire

New

Jersey

New

Mexico

New

York

North

Carolina

North Dakota Ohio

State Industrial Commission, Carson City. State Health Dept., Concord State Dept. of Health, Trenton State Dept. of Labor. State Dept. of Public Health, Santa Fe. Dept . of Labor, Division of Industrial Hygiene, New York City and New York City Health Depa rtment. State Industrial Commission, Raleigh State Dept. of Health, Division of Industrial Hygiene, Columbus Copy to Factory Inspector.

Oklahoma

Oklahoma Oregon

Pennsylvania

City 5.

State Industrial Accident Commiss ion, Portland 1, Dept. of Health, Bureau of In-

dustrial Hygiene, Rhode

Island

Harrisburg. Division

State Dept. of Health, of Industrial Hygiene, Providence.

South Carolina South

Dakota

Tennessee

exas

Columbia 1. State Industrial Pierre, State Industrial

sity or

Jtah

County

tate Dept.

Vermont

Virginia

Commission,

Commission,

Health Officer

of Health,

City. State Industrial Montpelier. State Industrial Richmond.

Salt Lake

Commission,

Commission,

Washington

State Dept.

West

State Industrial Commission, Charleston State Board of Health, Madison.

Virginia

Wisconsin yoming

State Dept. Cheyenne.

of Health,

of Public

Seattle 4.

Health,

All reportable.

Report for compensation only. Report for compensation only. See p. 57. Certificate of occupational disease. Lead only. See p. 57. By telephone or on special form. See p. 57. Occupational disease report form.

Report for compensation only. No report required. All reportable on occupational disease report form, All reportable on occupational disease report form. Report for compensation only. Report for compensation only. All reportable on occupational disease report form. All reportable. Report for compensation only. Report for compensation only. All reportable. All reportable on reportable disease record card. Report for compensation only. Report for compensation only. See p. 57. Report for compensation only. Report any causing 4 days or more lost time. All reportable.

Section II

Pesticides and Other Agricultural Poisons Chapter 5 INSECTICIDES

CHLORINATED DDT,

CHLOROBENZENE DERIVATIVES: TDE, DFDT, METHOXYCHLOR, DIMITE, NEOTRAN®,

OVOTRAN®,

Cl

Cl

PED rp

H

cl

cl

H

PE

H

TDE Tetrachlorodiphenylethane

o

i C1— pe

Cc rok—Cl -_ i

Cl

da

DDT Dichlorodiphenyltrichloroethane

F

DMC,

DILAN

OCH3

oa ¢ag?

HCO

H

H

DFDT Difluorodiphenyltrichloroethane

Methoxychlor

5ts Hg

ce Cl

Cl

a

H

16) H

Dimite Dichlorodiphenylethanol

DMC Dichlorodipheny] Methyl Carbinol

4 cl

Cl

CI

a

meee

Cl

Cl-

i]

go oO

H

Ovotran®

Neotran®

61

Cl

62

Chlorobenzene

Derivatives

Dilan

Chlorobenzene derivatives are synthetic chemicals which are stable for weeks to months after application. They are soluble in fat but not in water. Commercial insecticide formulas consist either of insecticides in technically pure form, dry mixtures of several insecticides, or solutions of one or more insectici des in various organic solvents, especially kerosene, benzene, or other petroleum derivatives. These organic solvents are themselves toxic. (See pp. 121 and 122.) : DDT appears to be the most toxic of these chemical s, at least in experimental animals. In human beings, ingestion of 20 Gm. (2/3 oz.) of DDT in the form of a 10% dry mixture with

flour has induced

severe

symptoms

which

persisted

for more

than five weeks, with gradual recovery. Virtually all fatalities reported in the literature have resulted from ingestion of DDT in various solvents. The toxicity of these solutions is greater than that of DDT or the solvent alone. The m.a.c. of chlorobenzene derivatives in food is? 7p. Pp.m:, with the exception of methoxychlor (14 p.p.m.), Lack of reported instances of human poisonin g from TDE,

DFDT, methoxychlor, dimite, DMC, Neotran®, Orotran®, and dilan and the reduced toxicity for laboratory animals indicate that these agents are not dangerous to life. Only dimite has a toxicity in animals approaching that of DDT. Low toxicity for mammals of these substances is presuma bly accounted for by lack of absorption, Although the mechanism of poisoning by these agents is not known, it has been postulated that they act by interfering with nerve function as a result of their breakdo wn to trichloroethane and chlorobenzene. DDT acts chiefly on the cerebellum and motor cortex of the C.N.S., causing a characteristic hyperex citability, tremors, muscular weakness, and convulsions. The myocardium becomes sensitized so that, at least in experimental

animals,

injection of epinephrine may induce ventricular

fibrillation. TDE is reported to induce adrenal atrophy in experimental animals.

hypoactivity and

Chlorobenzene

Inasmuch the presence

as most deaths from DDT of other

insecticides

are

centrolobular

data ob-

In DDT-poisoned

necrosis

63

are complicated by

and of solvents,

tained at autopsy are not reliable. the findings

Derivatives

of the liver,

animals, vacuoli-

zation around large nerve cells of the C.N.S., fatty change of the myocardium, and renal tubular degeneration. The most characteristic finding in experimental animals exposed to the other chlorobenzene derivatives is liver damage.

Clinical Findings: The principal manifestations of poisoning with these agents are vomiting, tremors, and convulsions. A. Acute Poisoning: (Results only from ingestion. ) 1. Ingestion of 5 Gm. (75 gr.) or more of dry DDT Severe vomiting begins within 30 minutes to one hour; weakness and numbness of the extremities have a more gradual onset. Apprehension and excitement are marked,

and diarrhea

may

occur.

2. Ingestion of more than 20 Gm.

(2/3 oz.) of dry DDT -

Twitching of the eyelids begins within eight to 12 hours; this is followed by muscular tremors, first of the head and neck and then more distally, involving the extremities in severe clonic convulsions similar to those seen in strychnine poisoning. The pulse is normal; respiration is accelerated early and slowed later. 3. The organic solvents present in many commercial insecticides decrease the convulsive effects of DDT and increase the depression of the C.N.S. Onset of slow, shallow breathing within one hour after inhaling, in-

gesting,

or absorbing a DDT

implicates

the solvent

rather

solution through the skin than the DDT.

B. Chronic Poisoning: (From ingestion, inhalation, or skin contamination by solvent formulations.) There have been few reported instances of chronic poisoning from DDT not complicated by simultaneous exposure to other insecticides or organic solvents. In these few instances, intoxication has been manifested by gradually progressive malaise, numbness and weakness of the extremities, mild tremors, mild anemia, slight leukocytosis, and

weight loss. These symptoms disappeared completely upon removal from further exposure for one to two months. Reports ascribing dermatitis, agranulocytosis, thrombocytopenic purpura, anaphylaxis, rhinitis, anda vague C.N.S. disease to DDT exposure are complicated by simultaneous exposure to other chemicals and cannot be evaluated at present. Workers with a history of many months’ exposure to DDT and having up to 68 p.p.m. of DDT in their body fat have remained completely well. These insecticides are all stored for long periods in the body fat; in animals,

rapid metabolism

of fat

64

Chlorobenzene

Derivatives

containing a large amount of insecticide will induce poisoning

even in the absence

of previous

symptoms.

The same mechanism is possible in human beings. Liver damage from DDT exposure might be expected from evidence obtained in experimental animals, but no such reports have appeared in the literature. Methoxy-

chlor,

TDE,

DFDT,

dimite,

DMC,

Neotran®,

Orotran®,

and dilan have apparently not produced chronic poisoning in human

beings.

C. Laboratory Findings: 1. A high urine level of organic chlorine or especially of bis(p-chlorophenyl)acetic acid (DDA) indicates exposure to DDT or to one of the analogous compounds. However, urine levels are not indicative of the severity of the exposure. 2. Lowered red cell count and elevated white cell count indicate exposure to DDT, but both counts may be within normal ranges in severe exposure or may result from exposure to the various solvents with which insecticides are formulated. 3. In suspected chronic poisoning, the liver function may be impaired as revealed by appropriate tests (see p. 40). 4. In suspected chronic poisoning, analysis of a fat biopsy may be necessary for diagnosis. A biopsy can be conveniently collected from the anterior part of the abdomen, above or below the belt-line. About 2.5 Gm. (37.5 gr.) of fat should be obtained and immediately blotted with paper toweling, weighed to at least two decimal places, and placed in carbon tetrachloride, C.P., ina small container which can be tightly closed. The container is then carefully labelled with the patient’s name, weight of sample, date of collection, and name and address of physician. The sample is then sent to Technical Development Laboratories, Technology Branch, Communicable Disease Center, U.S. Public Health Service, P. O. Box 769 Savannah, Georgia. Containers and further directions are obtainable from the Technical Development Laboratories. Treatment

of Chlorinated Insecticide

Poisoning:

A. Acute Poisoning: 1. Emergency measures a. Gastric lavage with 2 to 4 L. tap water. b. Emesis - If lavage cannot be given, give 500 ml. (one pint) milk or tap water and induce vomiting by a finger in the throat. c. Catharsis - Give 30 Gm. (1 oz.) sodium sulfate in 250 ml. (1 cup) water. d. Scrub skin with soap and water to remove excessive

skin contamination.

Benzene

Hexachloride

65

e. Artificial respiration with oxygen if respiration is slowed. 2. Antidote - None known. 3. General measures a. Anticonvulsants - Give phenobarbital sodium, 100 mg. (aye gr.) subcut. hourly until convulsions are

controlled or until 0.5 Gm. given; or,

if convulsions

barbital sodium, I.V.,

(11/2 gr.) phenobarbital sodium

as necessary.

b. Calcium gluconate, six hours

give pento-

100 to 500 mg. (11/2 to 71/2 gr.)

then 100 mg.

subcut.

(71/2 gr.) have been

are severe,

(Seep.

10%,

35.)

10 ml.

as a nonspecific

I.V.

every four to

cellular protectant.

c. DO NOT GIVE STIMULANTS,

especially epineph-

rine; these are extremely dangerous. B. Chronic Poisoning: 1. Protective measures - Remove patient from further exposure or require use of protective equipment. 2. Antidote - None known. 3. General measures a. High-calcium, high-vitamin, high-carbohydrate diet to control liver damage.

b. Phenobarbital,

100 mg.

(11/2 gr.) orally every

four hours for tremors. c. If white cell count is depressed below 1000 per cu. mm., give penicillin, one million units I.M. daily as a prophylaxis against infections. Prophylaxis: See p. 49. Prognosis:

A. Acute Poisoning: If convulsions are severe and protracted, recovery is questionable. If symptoms progress only to tremors, recovery is complete within one to two months. B. Chronic Poisoning: C.N.S. symptoms disappear in one to two months after removal from exposure. Hematologic changes disappear within six months.

BENZENE

HEXACHLORIDE

(Gamma isomer = Lindane®) Cl

|

66

Benzene

Hexachloride

Benzene hexachloride (hexachlorocyclohexane) is stable for three to six weeks after application. It is soluble in fat but not in water. Wettable

powders,

organic solvents the technical

emulsions,

dusts,

and solutions

are available for use as insecticides.

preparation

and the gamma

isomer

in

Both

(lindane)

are used in vaporizers. Ingestion of 20 to 30 Gm.

(2/3 to 1 oz.) of technical benzene hexachloride will produce serious symptoms, but death is unlikely unless this amount was dissolved in an organic solvent. In the case of lindane, the gamma isomer, 3.5 Gm. / 70 Kg. is considered a dangerous dose. The m.a.c. of

benzene hexachloride or lindane in food is 7 p. p.m. Reported instances of serious poisoning have been rare and have resulted from accidental or suicidal ingestion. Technical benzene hexachloride and lindane stimulate the C.N.S. to cause hyperirritability, ataxia, and convulsions.

Pulmonary edema and vascular collapse may also be of neurogenic origin. Effects of lindane on experimental animals have their onset within 30 minutes and last up to 24 hours; with the

technical product,

onset of effects may be delayed one to six

hours and then will persist up to four days. Benzene hexachloride is stored in the body fat, being slowly lost through metabolism or excretion in urine, feces, or milk.

Of the various

isomers

of benzene

hexachloride,

lindane is excreted most rapidly. The most prominent feature of benzene hexachloride or lindane poisoning in animals is liver necrosis. Other changes which have been seen in experimentally poisoned animals are hyaline degeneration of renal tubular epithelium and histologic changes in the brain, adrenal cortex, and bone marrow. Clinical Findings: The principal manifestations of poisoning with benzene hexachloride or lindane are vomiting, tremors, and convulsions.

A. Acute

Poisoning:

tamination

solvent.) posure.

Symptoms Vomiting

to convulsions. contains

cyanosis,

(From

ingestion or massive

with a concentrated

solvent,

appear

first and progress

is likely unless in which

case

the material dyspnea,

and circulatory failure may progress

Exposure

skin con-

in an organic

begin one to six hours after ex-

and diarrhea

Recovery

an organic

solution

to smaller

amounts

rapidly.

by skin contamination

by ingestion leads to dizziness, headache, nausea, tremors, and muscular weakness. In addition to these symptoms, exposure to vaporized benzene hexachloride or lindane will produce irritation of eyes, nose, and throat. Such symptoms disappear rapidly upon removal from further exposure.

or

Toxaphene

67

B. Chronic Poisoning: True systemic chronic poisoning has not been reported from any of the isomers of benzene hexachloride. Dermatitis from skin contamination with benzene hexachloride has occurred elimination of exposure.

but has improved

rapidly upon

C. Laboratory Findings: 1. Clinical laboratory tests are noncontributory. 2. Liver function may be impaired as revealed by appropriate tests (see p.

40).

3. Specific examination of feces,

urine,

or fat may reveal

presence of benzene hexachloride. For method of collection and analysis of the fat specimens, see p. 64. Treatment:

See p. 64.

Prophylaxis: See p. 49.

Prognosis: A. Acute Poisoning: In acute poisoning not complicated by ingestion of an organic solvent, recovery is likely. Progression of symptoms to pulmonary edema and vascular collapse following ingestion of benzene hexachloride or

lindane in an organic solvent may make recovery unlikely. B. Mild Exposure: Symptoms from slight exposure to benzene hexachloride or lindane vaporizers or ingestion of small amounts of benzene hexachloride have lasted not more than two weeks.

TOXAPHENE® (Chlorinated Camphene)

—6H + 8Cl = Toxaphene®

Toxaphene is stable for one to six months cation. It is fat-soluble and water-insoluble.

after appli-

68

Toxaphene

Toxaphene is available for insecticidal use in the form of wettable powders, dusts, emulsion concentrates, and concen-

trated solutions in oil. The fatal dose for an adult is estimated to be around

2 Gm. (30 gr.). Several members of one family were nonfatally poisoned after eating greens contaminated with toxaphene to The maximum dose inthe extent of 3 Gm. /Kg. of greens. gested by one person was thought to be in the neighborhood of Several fatalities in children have followed 1 Gm. (15 gr.). ingestion of larger but undetermined amounts. The m.a.c. of toxaphene in foods is 7 p. p.m. Approximately three fatalities from toxaphene ingestion have been reported.

Toxaphene induces convulsions by diffuse stimulation of Convulsions are clonic in charthe brain and spinal cord. acter; salivation, vomiting, and auditory reflex excitability indicate medullary stimulation comparable to that induced by camphor. Pathologic findings in acute poisoning are petechial hemorrhages and congestion in the brain, lungs, spinal cord, heart,

and intestines.

Pulmonary

edema

and focal areas

of

degeneration in the brain and spinal cord are also present. In experimentally induced chronic poisoning, degenerative changes were found in the liver parenchyma and renal tubules. Clinical Findings: The principal manifestations vomiting and convulsions.

A. Acute Poisoning:

(From

of toxaphene

are

ingestion or skin absorption. )

frequently begin without

Convulsions

poisoning

toms but may be preceded by nausea

premonitory

and vomiting.

symp-

In

fatal poisoning, convulsions occur at decreasing intervals until respiratory failure supervenes, almost always In nonfatal within four to 24 hours after poisoning.

poisoning,

cessation of convulsions

is followed variably

by a period of weakness, lassitude, and amnesia. B. Chronic Poisoning: (From ingestion, inhalation, or skin absorption.) Instances of chronic poisoning have not apExperiments in animals inpeared in the literature. dicate that toxaphene is less apt to cause chronic toxicity

than DDT are

but that similar changes in the liver and kidneys

possible.

C. Laboratory Findings: 1. Usual clinical laboratory tests are noncontributory. 2. Liver function may be impaired as revealed by appropriate tests (see p. 40). 3. No chemical procedure for determining toxaphene in body tissues is available. Determination of the organi: chlorine content of tissues will indicate exposure to chlorinated hydrocarbons.

Indane Treatment: See p.

Derivatives

69

64.

Prophylaxis: See p.

49.

Prognosis: In acute poisoning, recovery is likely unless convulsions are progressive and cannot be controlled by barbiturates. Most dangerous is the interval from four to 24 hours after poisoning.

INDANE DERIVATIVES: CHLORDANE, HEPTACHLOR, ALDRIN, DIELDRIN, ENDRIN, AND DIENDRIN

Cl

Cl

Cl Cl

—Cl

Cl

Fame Ot

Cl

Cl

Cl

Chlordane

Cl

Heptachlor

’

cl

H H

Ci Cl

H H

H Cl

Dieldrin

H Aldrin

The indane derivatives are synthetic fat-soluble but water‘insoluble chemicals. Aldrin is stable for one to three weeks after application. The others are stable for months to a year

or more.

These chemicals, either singly or in mixtures in the form of dusts, wettable powders, or solutions in organic sol-

vents, are used as insecticides qQuitoes, and field insects,

for the control

of flies,

mos-

Aldrin is the most toxic of the indane derivatives, being two to four times as toxic in animals as chlordane. The other derivatives have approximately the same toxicity as chlordane. In an average adult, severe symptoms will follow ingestion or

70

Indane

Derivatives

skin contamination with 15 to 50 mg.

(1/4 to 3/4 gr.)/Kg.

or 1

{n one in3Gm. (15 to 45 gr.) of any indane derivative. to stance, accidental skin contamination with 30 Gm. (2 02:.) of chlordane as a 25% solution in an organic solvent was fatal to an adult in 40 minutes. Residual amounts of these indane chemicals in food should not exceed 0.1 p.p.m. One or two instances of severe or fatal poisoning are reported yearly. Convulsions from the indane derivatives apparently originate in the C.N.S., presumably in the cerebral cortex. Characteristic changes in experimental animals are found In the liver, hepatic cell enlargeliver and kidneys. and peripheral margination of basophilic granules are inby feeding the various indane derivatives at levels of At higher doses, degenerative changes are 200 p.p.m.

in the ment duced 10 to found

in the hepatic

cells and renal tubules.

Clinical Findings: The principal manifestations of poisoning with the indane derivatives are tremors and convulsions. A. Acute Poisoning: (From ingestion, inhalation, or skin contamination of any indane derivative, even in the ab-

sence of solvent.) tremors,

ataxia,

to six hours which

may

Symptoms

of hyperexcitability,

and convulsions

begin

within

and are followed by C.N.S. terminate

in respiratory

30 minutes

depression

failure.

In one

persor

who ingested 25 mg. (3/g gr.)/Kg. of chlordane, evidence of renal damage was indicated by albuminuria and hematuria.

B. Chronic Poisoning: (From ingestion, inhalation, or skin contamination. ) Reports of chronic poisoning have not appeared

in the literature.

All the indane

impair liver function in animals lethal levels. C. Laboratory Findings:

at dosages

derivatives

well below

1. Clinical laboratory tests are normal. 2. Liver function may be impaired as revealed by appropriate tests (see p. 40). 3. A fat biopsy may reveal the presence of indane derivatives. (See p. 64 for method of collection.) Treatment:

Prophylaxis:

See p. 64,

See p. 49.

Prognosis: If the liver has previously been damaged, the toxicity of indane is greatly increased. Recovery is likely if onset of convulsions is delayed more than one hour and if convulsions are readily controlled.

Chapier 6

PHOSPHATE

ESTER

INSECTICIDES

TEPP, HETP, PARATHION, EPN, OMPA, SYSTOX, MALATHON, AND METACIDE CoH-O ya

C,H;O

CyH-O 25

Sp=o0

Za

|

cyngo|_ P= C,H,O

ON

TEPP (Tetraethyl Pyrophosphate) Liquid, water-soluble, decomposes

p=s

CyH5O

——()

Parathion

(Diethyl-p-nitrophenyl Thiophosphate) Liquid, water-insoluble, stable for

within six hours.

one to three weeks

= OC9Hs

=P

(CH3)o Toei SP Nate tatvaste

—

Za sh Ss Jams (CHy))—N (CH3)p

—N
R’O

Esters

ROH + R’'O—P=O

xs

R’O /

HO.

/

’

R’ O—P=O

‘

This reaction may occur

la

+ AChE

R”O

The rapidity of the reaction and the stability of the final cholinesterase-phosphate combination are influenced marked-

ly by the structure of the phosphate ester. The inactivation of cholinesterase by phosphate esters allows the accumulation of large amounts of acetylcholine with resultant widespread effects which may be conveniently

separated into three categories: (1) Potentiation of post- ganglionic parasympathetic ictivity. The following structures are affected: pupil (constricted), intestinal muscle (stimulated), secretory glands stimulated), bronchial muscles (constricted), urinary bladder contracted), cardiac sinus node (slowed), and cardiac atriorentricular node (blocked). (2) Persistent depolarization of skeletal muscle, resulting n initial tremors followed by neuromuscular block and aralysis. (3) Initial stimulation followed by depression of cells of

ne C.N.S.,

resulting in inhibition

of the inspiratory center

depression of phrenic discharge) and convulsions of central rigin. No specific anatomic changes are found in acute poisoning. he usual postmortem findings are pulmonary edema, and apillary dilatation and hyperemia of lungs, brain, and other

rgans. In delayed paralysis of the extremities induced by paralion, the findings are demyelinization of ascending and decending spinal tracts, with degeneration of motor horn cells. linical Findings: The principal manifestations

1ate

ester

insecticides

are

visual

of poisoning with the phosdisturbances,

respiratory

fficulty, and gastrointestinal hyperactivity. A. Acute Poisoning: (From inhalation, skin absorption, or ingestion.) The following symptoms and signs, listed in approximate order of appearance, begin within 30 to 60 minutes and are at maximum in two to eight hours: 1. Mild - Anorexia, headache, dizziness, weakness,

74

Phosphate

Esters

anxiety,

tremors

of the tongue

and eyelids,

and impairment of visual acuity. 2. Moderate - Nausea, salivation, tearing, cramps, vomiting, lar tremors. 3. Severe - Diarrhea,

sweating,

miosis,

abdominal

slow pulse,

and muscu-

pinpoint and nonreactive pupils, respiratory difficulty, pulmonary edema, cyanosis, loss of sphincter control, convulsions, coma, and heart block. B. Chronic Poisoning: The cholinesterase-inhibiting effects of phosphate ester poisoning persist in the body for four to six weeks. This means that absorption of small amounts daily may eventually induce symptoms. In such instances,

symptoms

are

similar

to those

of mild

acute

poisoning; if a moderate exposure follows a number of slight exposures, serious poisoning may result. Evidence indicates that parathion may induce delayed peripheral weakness and paralysis similar to that from triorthocresyl phosphate (see p.116). Signs of this type of poisoning are bilateral ankle and wrist weakness and loss of the Achilles tendon and plantar reflexes. Paralysis may progress rapidly to involve not only the ex-

tremities but also the respiratory muscles. C. Laboratory Findings: 1. The usual clinical laboratory tests are noncontributory 2. Cholinesterase levels of red blood cells and plasma are reduced markedly, as determined by special technics. Levels 30 to 50% of normal indicate exposure,

although

symptoms

may

not appear

until the

level falls to 20% or less. Wide normal variation of the cholinesterase level requires that a determination be made upon all individuals prior to exposure. Re-

peated determinations should then be made at weekly intervals during exposure. Directions for collecting and shipping blood samples for cholinesterase the nearest

Technical

P.O.

State

Development

Box 769,

Station,

determination Public

P.O.

Health

Laboratories,

Savannah, Box

3. Urine p-nitrophenol

73,

may

be obtained

Laboratory;

Georgia;

Wenatchee,

from

from the

U.S.P.H.S.,

or from

the Field

Washington.

may also be used as an indication

of parathion exposure. The procedure is given by Waldman and Kraus, Occupational Health 12:37, 1952. Treatment:

A. Acute Poisoning: 1. Emergency measures a. Give atropine in large doses

(see Antidote,

below).

b. Artificial respiration and oxygen - Convulsions respiratory difficulty are treated by forced

and

Phosphate

Esters

75

ventilation artificial respiration. This type of ventilation is easily carried out by applying intermittent compression to a rubber rebreathing bag attached to a tight-fitting face mask of the anesthesia type

(see p. 353). Air or oxygen must be supplied continuously. A resuscitator, bellows respirator, or face mask and demand flow regulator may also be used (see p.

353).

All such

fitted with a safety valve,

c.

d.

e.

equipment

limiting

must

be

the maximum

pressure developed to 20 mm. Hg. In an emergency, mouth-to-mouth insufflation should be used. Be prepared to maintain artificial respiration for many hours. The patient must be watched constantly so that artificial respiration may be administered when necessary. Necessary equipment must be at hand for the first 48 hours after poisoning. Wash skin - Before symptoms appear or after they are controlled by atropine, the skin and mucous membranes are decontaminated by washing with copious amounts of tap water and soap. Lavage or emesis - If symptoms have not appeared,

remove ingested material by lavage with tap water. If equipment for lavage is not available, removal is attempted by giving one liter (1 qt.) of water or milk and stimulating the pharynx to induce vomiting. Catharsis - After vomiting or lavage, ingested material is removed from the intestine by gastric administration of 30 Gm. (1 oz.) of sodium sulfate in 250 ml. (1 cup) water.

2. Antidote

sulfate,

- In the presence

2 mg.

of symptoms,

(1/30 gr.) 1.M.

30 minutes until signs of atropinization face, dry mouth, widely dilated pupils,

Repeat 2 mg.

give atropine

and repeat every 15 to appear (flushed fast pulse).

(1/30 gr.) atropine frequently to main-

tain marked signs of atropinization. As much as 12 mg. (Ys gr.) of atropine has been given safely in the first two hours. Lapse in atropine therapy may be rapidly followed by fatal pulmonary edema or respiratory failure. 3. General measures a. Suction - Pulmonary secretions are removed by postural drainage or by catheter suction. b.

Avoid

morphine,

aminophylline,

barbiturates,

and

other respiratory depressants. B. Chronic Poisoning: Absorption of phosphate esters as detected by a decrease in blood cholinesterase (see p.

indicates necessity for avoidance until cholinesterase is normal.

of further exposure

74)

76

Phosphate

Esters

Prophylaxis: See p.

49.

Prognosis: The first four to six hours are most critical in acute poisoning. Improvement of symptoms upon treatment indicates survival if adequate treatment is continued. In delayed paralysis resulting from demyelinization, damage is permanent.

Chapter 7

MISCELLANEOUS

PESTICIDES

NICOTINE . es H Cc

oe

ry

Ps CH2

N Nicotine

\Exposure to nicotine occurs during processing or extraction of tobacco; during the mixing, storage, or application of insecticides containing nicotine; or during smoking. Nicotine is available in conc entrates as a free base, which is volatile, or as the sulfate. Both are liquids, even in pure form. In addition to concentrates, nicotine is also present in a large number of insecticid e mixtures in concentrations of 1% or more.

The fatal dose of pure-nicotine_is about 40 mg. (1 drop, 2/3 gr.), a quantity contained in 2 Gm. (30 gr.) of tobacco two cigarettes). However, tobaccois much less poisonous than wouldbe expected on th é basis of its nicotine content. When smoked, most of the n icotine is burned; when ingested,

nicotine is poorly absorbed from the tobacco. Ten

to 50 deaths

from

a oe

exposure

to nicotine i=

Nicotine first atluliaion, 7am depresses and paralyzes the cells of the peripheral autonomic ganglia, brain (especially midbrain), and spinal cord. Skeletal muscle, including the diaphragm, is paralyzed. No specific histologic changes are found after nicotine poisoning. After ingestion, the mouth, pharynx, esophagus, | / and stomach may show evidence of the caustic effect of nicotine.

Clinical Findings: The principal manifesta tions of nicotine poisoning are respiratory stimulation and gastrointestinal hyperactivity.

77

78

Nicotine

A. Acute Poisoning: 1. Small doses - (From skin contamination or inhalation of tobacco’ smoke, tobacco dust, or insecticide sprays.) Respiratory |stimulation, nausea, headache, diarrhea, tachycardia,

pressure, sweating,

vomiting, dizziness, elevation of blood

and salivation.

Gradual

recovery

followsa period of weakness. 2. Large doses - (From ingestion or skin contamination with insecticide concentrates.) Initially there is burning

of the mouth,

by rapid progression into prostration,

throat,

and

of the above

convulsions,

stomach,

followed

symptoms,

respiratory

passing

slowing,

cardiac irregularity, and coma. Death occurs within five minutes to four hours. B. Chronic Poisoning: No cumulative effect from exposure to small

amounts

However,

of nicotine

habitual

smoking

insecticides is reported

has

been noted.

to produce

the

following: A syndrome simulating coronary heart disease, with precordial pain, ectopic beats and paroxysmal tachycardia, dyspnea, and Ecg. changes; an increase in the incidence of cardiovascular disease of 50 to 75% in any particular age group; impairment of vision (tobacco lamblyopia); occlusive thromboangiitis obliterans; an in\crease in the incidence of lung cancer. Nonthrombocytopenic purpura has been reported after smoking men-

tholated cigarettes; mentholated

C. Laboratory

recovery followed when the use of

cigarettes

Findings:

was

stopped.

Noncontributory.

Treatment: A. Acute Poisoning: 1. Emergency measures

a. Wash skin - Remove nicotine from the skin by flooding with water and scrubbing vigorously with soap. b. Lavage - Remove ingested nicotine by thorough gastric lavage with tap water containing, if readily available, one of the following: (1) Activated charcoal (five heaping tsp. ). (2) Universal antidote (five heaping tsp. ).

(3) Potassium

permanganate

diluting 5 ml.

(1:10, 000,

made

(1 tsp.) of 1% in 500 ml.

or

by

1

pint of water).

c. Emesis patient

- If gastric lavage is not possible, to swallow

up to one

quart

force

of tap water

or

milk and induce vomiting by forcing a finger well back in the throat. Repeat administration of fluids and stimulation of vomiting at least once. d. Catharsis - Give 30 Gm. (1 oz.) of sodium sulfate in 250 ml. (1 cup) water.

Thiocyanate

Insecticides

79

e. Give artificial respiration, using oxygen if available (see p. 18). 2. Antidote - None known. 3. General measures - Control convulsions with sodium

pentobarbital,

100 to 500 mg.

with ether (see p. 35). B. Chronic Poisoning: Remove dust or smoke.

(14/2 to 71/2 gr.) I.V.

from further exposure

or

to

Prophylaxis: See p. 49. Prognosis: Survival for more complete recovery.

than four hours is usually followed by

THIOCYANATE THANITE®,

INSECTICIDES: LETHANES

CH 3 |

CH, CH,OC 4H,

a

H

O

i

—™~O— C — CHg

— SCN

fe)

CH yCH SCN

Thanite

o=C—

CgHig

Lethane

~ 384

to Cy7H35

Cratos Oo SCN CH,CH,SCN B-thiocyanoethyl esters of 10-16 carbon aliphatic acids

Thiocyanate

mixtures =mulsion cides.

insecticides

Lauryl

Thiocyanate

are ordinarily available

in

as concentrated solutions in an organic solvent, as concentrates, or in combination with other insecti-

The toxicity of these compounds

is moderate

compared

with that of nicotine. One adult patient died after ingesting a mixture containing approximately 5 Gm. (75 gr.) of lethane-

384 and 14 Gm.

(1/2 oz.) of lauryl thiocyanate.

Other fatal-

ties have been reported following ingestion of similar juantities.

80

Thiocyanate Insecticides

, The thiocyanate insecticides induce coma, cyanosis from dyspnea, and tonic convulsions in rats at doses ranging

90 mg. /Kg. (lethane-384) to 1000 mg. /Kg. (thanite).

Pathologic examinations of animals poisoned by thiodamage. cyanate insecticides have not revealed specific organ Clinical Findings: The principal manifestations of poisoning with the thios. cyanate insecticides are respiratory difficulty and convulsion conA. Acute Poisoning: (From ingestion or excessive skin Respiratory difficulty and convulsions. tamination.) No instances of chronic poisoning B. Chronic Poisoning: have been reported.

C. Laboratory Findings: 1. The blood thiocyanate poisoning. 2. After acute poisoning

ing,

is likely to be elevated in acute or in suspected

chronic

poison-

renal injury may be revealed by appearance

of

albumin, casts, and cells in the urine, as well as by a rise in blood nonprotein nitrogen. 3. Liver damage may be revealed by appropriate tests (see p. 40).

Treatment: A. Acute Poisoning: 1. Emergency measures a. Wash skin - Remove skin contamination bing with soap and water.

by scrub-

b. Lavage - Remove swallowed poison by thorough gastric lavage with tap water. c. Emesis - If gastric lavage cannot be accomplished immediately, give up to 1 L. of tap water or milk and induce vomiting by pharyngeal stimulation. Repeat

at least once.

d. Catharsis - Give 30 Gm. (1 oz.) sodium sulfate in 250 ml. (1 cup) water. e. Maintain artificial respiration in spite of convulsions or respiratory difficulty. 2. Antidote - None known. 3. General

measures

- Anticonvulsants

B. Suspected Chronic Poisoning: 1. Remove from further exposure. 2. In the presence of liver damage, hydrate,

high-calcium,

low-fat

(see p.

give high-carbodiet.

Prophylaxis: See p.

35).

49.

Prognosis:

If adequate gastric lavage and catharsis can be

{

Dinitro-ortho-cresol,

accomplished

before onset of symptoms,

DINITRO-ORTHO-CRESOL,

Dinitrophenol

81

recovery is likely.

DINITROPHENOL

NOo

NO»

|

|

—NO2

H3C —

—NOo

|

|

OH

OH

2, 4-Dinitrophenol

4, 6-Dinitro-o-cresol

Dinitro derivatives of phenol and cresol are used as insecticides and herbicides. Dinitrophenol was formerly used medically as a metabolic stimulator to aid in weight reduction. The acute

fatal dose of dinitrophenol

is approximately

1

Gm. (15 gr.); the acute fatal dose of dinitro-ortho-cresol is 0.2 Gm. (3 gr.). Danger is greatest during hot weather, when loss of body heat is impaired. One to ten deaths occur yearly. The dinitro derivatives of various phenols apparently act by inhibiting the synthesis of certain phosphate bonds which are important in conserving energy utilization in the cell. In the absence of this mechanism, cellular respiration is markedly increased. Postmortem examination reveals degenerative changes of the heart, liver, and kidneys in patients dying from exposure

to dinitro

Clinical Findings: The principal

derivatives

derivatives.

manifestation

of poisoning

with the dinitro

is elevation of body temperature.

A. Acute Poisoning: (From skin contamination, ingestion, or inhalation.) Symptoms are frequently of sudden onset up to two days after cessation of exposure and include high fever, prostration, thirst, nausea, vomiting, excessive perspiration, and difficulty in breathing. Later, symptoms progress to anoxia with cyanosis and lividity, and finally muscular tremors and coma. B. Chronic Poisoning: Chronic poisoning has not been reported following agricultural exposure. Medicinal use to induce weight loss has been accompanied by the following toxic reactions: skin eruptions, peripheral neuritis, liver damage, kidney damage, granulocytopenia, and, rarely,

cataract

formation.

82

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83

84

Dinitro-ortho-cresol,

Dinitrophenol

C. Laboratory Findings: 1. In exposed workers, blood concentrations of dinitro derivatives should not exceed 10 y. (See the method of Harvey,

Lancet

1:796,

1952.)

2. Usual clinical laboratory examinations are noncontributory in acute poisoning. During prolonged exposure, white blood count may indicate leukopenia.

Treatment: A. Acute Poisoning: 1. Emergency measures as Lavage - Remove ingested poison by thorough gastric lavage with saturated bicarbonate solution. b. Emesis - If gastric lavage cannot be accomplished immediately, give up to one quart of tap milk and induce vomiting by pharyngeal Repeat at least once. . Catharsis - Give 30 Gm. (1 oz.) sodium 250 ml. (1 cup) water. . Clean skin - Remove skin contamination

water or stimulation. sulfate in

by scrubbing with soap and water after removal of clothing. . Cool patient - If the body temperature is elevated, reduce to 98.6°F. (37°C. ) by immersion in cool water or by applying cold packs. If the body temperature

is above

104°F.

(40°C.) ice water

is neces-

sary. ts Oxygen inhalations for respiratory distress or cyanosis. 2. Antidote - None known. 3. General measures a.

Glucose

- I. V.

or oral administration

of 5% glucose

or 10% invert sugar in saline at the rate of 1 L. every two hours until body temperature is readily controlled. . Feedings - Frequent administration of readily digested food to aid in maintaining

an adequate

source of energy for the increased metabolism. Give sodium chloride to supply loss in sweat. B. Chronic Poisoning: The patient should be removed from further

exposure

to dinitro derivatives.

Prophylaxis: See p. 49. White blood count should be repeated monthly intervals during exposure.

at

Prognosis: Recovery from severe poisoning is likely if body temperature can be kept below 104°F. (40°C. ) and if adequate nutrition is supplied.

Chapter &

RODENTICIDES”

THALLIUM Thallium

is used

as a rodenticide,

as a depilatory,

and to

ill ants. Poisoning most frequently results from the acciental ingestion of thallium rodent or ant baits, which consist f thallium sulfate or acetate mixed with grain, cookie crumbs, racker crumbs, honey, or sweetened water. The most commonly available salts of thallium are the

ulfate,

acetate,

and carbonate.

Thallium

sulfide

and iodide

re appreciably less soluble than the other salts. The fatal dose is approximately 1 Gm. (15 gr.) of aborbed thallium. Approximately one death per year has been eported in the recent literature.

Thallium

induces

10st susceptible

are

degenerative

changes

in all cells.

The

the cells of the hair follicles; next most

usceptible are the cells of the nervous system. Pathological findings include pneumonitis and vacuoliation and degenerative changes in the cells of the hair

yllicles, linical

adrenal

cortex,

thyroid,

and C.N.S.

Findings:

The principal manifestations of thallium poisoning are »9ss of hair and pains in the extremities. A. Acute Poisoning: (From ingestion or skin absorption. ) Evidences of poisoning appear in one to ten days and include pains and paresthesias of the extremities, bilateral ptosis, ataxia, loss of hair, fever, coryza, conjunctivitis, abdominal pain, and nausea and vomiting. Progression of poisoning is indicated by the appearance of lethargy, jumbled speech, tremors, choreiform movements, con-

vulsions,

and cyanosis.

bronchopneumonia failure.

may

Signs of pulmonary precede

death

edema

and

in respiratory

B. Chronic Poisoning: (From ingestion or skin absorption. ) If absorption of thallium occurs over an extended period, the earliest indications

changes in the skin, ther

rodenticides

of poisoning are alopecia,

atrophic

and occasionally salivation and blue

are listed in the tables

85

on pp.

82 and 83.

86

Thallium

line on the gums.

If absorption continues,

and functional changes

of the endocrine

rhea and aspermia) may appear signs as in acute poisoning.

renal damage

system (amenor-

along with symptoms

and

C. Laboratory Findings: 1. Urine examinations may reveal albuminuria and increase in cells and casts. 2. Increase in the eosinophils, lymphocytes, or polymorphonuclear leukocytes may occur. 3. Other clinical laboratory tests are noncontributory. Treatment: A. Acute Poisoning: 1. Emergency measures a. Lavage - Remove ingested poison by thorough gastric lavage with tap water or milk. b. Emesis - If gastric lavage cannot be accomplished immediately, give up to one quart of tap water or milk and induce vomiting by pharyngeal stimulation. Repeat at least once. c. Catharsis - Give 30 ml. (1 oz.) castor oil orally as a cathartic. After catharsis, give a high enema. Repeat both after 12 hours.

d. Scrub skin - Remove

skin contamination

by scrub-

bing with soap and water.

2. Antidote - Dimercaprol (BAL®) is reported to be effective as a specific scribed on p. 46. 3. General measures -

antidote.

Administer

as de-

a. Sodium thiosulfate,

10 ml.

may be effective. b. Vasopressor agents

of 10% solution 1.V.,

- Maintain blood pressure by

5% glucose in saline I. V.; add levarterenol (Levophed®), 4 ml. of 0.2% solution per liter if necessary. c.

Maintain warmth and adequate fluid intake and nutrition. d. Urine output should be maintained at 1000 ml. or more daily unless renal insufficiency appears, in

which contingency only sufficient fluid to replace losses

is given (see p. 29).

B. Chronic Poisoning: Remove from further exposure. symptoms are severe, give dimercaprol as directed above.

If

Prophylaxis: A. Thallium should never be used as a depilatory. BF Adequate precautions must be taken in storing or using rodenticides or insecticides containing thallium to prevent accidental ingestion.

Barium

87

Prognosis: If the progression of signs of cerebral damage (lethargy, delirium, and muscular twitchings) can be halted, recovery is possible. Complete recovery may require two months or

more.

BARIUM Absorbable salts of barium such as the carbonate, hydroxide, or chloride are used in pesticides. The sulfide sometimes is used in depilatories. A soluble barium salt

such as the carbonate

or hydroxide

taminant in the insoluble contrast media.

barium

may be present as a con-

sulfate used as a radiopaque

The fatal dose of absorbed barium is approximately

1 Gm.

(15 gr.). Approximately one fatality is reported per year. Barium ion presumably induces a change in permeability or polarization of the cellular membrane which results in

stimulation of all muscle cells indiscriminately. This effect is not antagonized by atropine but is antagonized by magnesium ions. No specific histologic changes are seen. Clinical

Findings:

The principal manifestations tremors and convulsions.

of barium

poisoning are

A. Acute Poisoning: (From ingestion or, rarely, from inhalation.) Symptoms and signs include tightness of the muscles of the face and neck, vomiting, diarrhea, fibrillary muscular tremors, anxiety, weakness, difficulty in breathing, irregularity of the heart, convulsions, and death from cardiac and respiratory failure. B. Chronic Poisoning: Absorption of an amount less than necessary to cause acute poisoning is without effect. C. Laboratory Findings: 1. The Ecg. will show ectopic beats. 2. The red blood cell count may be increased as a result of dehydration from vomiting and diarrhea. 3, Other laboratory tests are noncontributory. Treatment of Acute Poisoning: A. Emergency Measures: 1. Give sulfates (see Antidote, below). 2. If respiration is affected, give artificial respiration, using oxygen if available, until a sulfate antidote can be given and normal respiration has returned. B. Antidote: Give 10 ml. of 10% sodium sulfate slowly I. V. and repeat every 15 minutes until symptoms subside. Give also 30 Gm. (1 oz.) sodium sulfate in 250 ml. (1 cup) water and repeat in one hour. Give by gastric tube if symptoms have appeared.

88

Fluoroacetate

C. General Measures: 1. Atropine, 1 mg.

2. Give morphine,

(4/60 gr.) subcut.

16 mg.

for abdominal

(4/4 gr.) subcut.

pain.

for severe

colic.

Prophylaxis: A. Orders for radiologic barium sulfate should never use abbreviated terms. Users must be certain that barium sulfate is not contaminated by soluble barium salts. A convenient test is to shake up a portion with water and to the clear supernatant portion add a small amount of a

solution of magnesium

sulfate or sodium

sulfate in water.

Appearance of a precipitate indicates the presence of a soluble barium salt. B. Adequate precautions must be used in storing and using pesticidal barium salts to prevent accidental ingestion. Prognosis: If a soluble sulfate (e.g., magnesium sulfate or sodium sulfate) is given before symptoms become severe, then recovery will occur. Survival for more than 24 hours has always been followed by recovery.

FLUOROACETATE The sodium salt of fluoroacetic acid (CHgFCOON,) isa water-soluble, synthetic chemical used as a rodenticide.

The fatal dose is estimated to be 50 to 100 mg. (3/4 to 11/2 gr.). At least one death from sodium fluoroacetate has occurred. Fluoroacetate in the body forms fluorotricarboxylic acid, which blocks cellular metabolism at the citrate stage. The relationship between this metabolic effect and poisoning has not been elucidated. All body cells, and especially those of the C.N.S., are affected by fluoroacetate as shown by depression of oxygen consumption of isolated tissues. No specific histologic changes are seen in fluoroacetate poisoning.

Clinical Findings: The principal manifestations of fluoroacetate poisoning are vomiting and convulsions. A. Acute Poisoning: (From ingestion or inhalation.)

Symptoms

begin within minutes

with vomiting,

regularity

excitability,

of the heart and respiration,

and respiratory depression. failure. B. Chronic

to four or five hours,

tonic-clonic

convulsions,

exhaustion,

Death is from

poisoning has not been reported.

ir-

coma,

respiratory Experimental

Fluoroacetate

89

studies indicate that a dose less than necessary to produce acute symptoms is without effect. C. Laboratory Findings: Noncontributory.

Treatment of Acute Poisoning: A. Emergency Measures: 1. Lavage - Remove ingested poison by thorough gastric lavage with tap water. 2. Emesis - If gastric lavage cannot be accomplished immediately,

give up to one quart of tap water

or milk

and induce vomiting by pharyngeal stimulation.

Repeat

at least once. 3. Catharsis - Give 30 Gm. (1 0z.) sodium sulfate in 250 ml. (1 cup) water. B. Antidote: Monoacetin (commercial 60% glycerol monoacetate) has been found to be the best antidote in animal experiments, but reports of its use in human beings have not appeared. The recommended dose is 0.1 to 0.5 ml. / Kg. of the 60% solution diluted with five parts of sterile saline solution 1.V. C. General Measures: Control convulsions by giving sodium

pentobarbital, slowly.

100 to 500 mg. (11/2 to 74/2 gr.) 1.V.

Do not depress

the respiration.

Seep.

35.

Prophylaxis: Sodium fluoroacetate must be stored and used with extreme care to prevent ingestion by human beings or domestic animals.

Prognosis: Complete recovery may follow repetition of convulsions for several days. Rapid progression of symptoms within one to two hours after poisoning is likely to result in death. Survival for more than 24 hours indicates a favorable outcome.

90 WARFARIN

oa

Solera anon Pots

1s ae

Oo Warfarin 3-(a@-acetonylbenzyl)4-hydroxycoumarin

pWarfarin is used as a rodenticide and also medically as

an anticoagulant.)

It is available commercially

in 0.025% and

0.5%

concentrations for use as a rodenticide. At least two accidental fatalities have been reported from ingesting warfarin. The dangerous dosage is approximately

100 mg. (1/2 gr.) daily. This represents the ingestion of approximately 0.5 Kg. (1 pound) of rat bait (0. 025%). Warfarin inhibits the formation of prothrombin by the liver and incr i jlity. Excessive bleeding is a result of these two effects. Effectiveness, at least in rats, is greatly increased by repeated dosage; the fatal total dosage by repeated ingestion is less than 1/20 that of a single dose. Numerous gross and microscopic hemorrhages are found on pathologic examination. Clinical Findings: The principal manifestation of warfarin poisoning is bleeding. A. Acute Poisoning: A single massive dose is_not likely to cause poisoning. Rat poison (containing warfarin as an active ingredient) has been taken several times in large

SE B.,;Chronic

eT Poisoning:

y ingestion.)

ware If warfarin is in-

gested repeatedly, the following evidences of pathological bleeding appear in one to two weeks: nosebleeds, massive bruises at knees and elbows, pallor, and blood in the urine and stools. C. Laboratory Findings: 1.

Plasma prothrombin determinations will reveal excessive prolongation of the prothrombin time. 2. Bleeding time and clotting time are prolonged in serious poisoning. 3. Red blood cell counts and hemoglobin levels fall if bleeding is serious.

Warfarin

Treatment of Chronic Poisoning: A. Emergency Measures: 1. Gastric lavage - If ingestion of more

91

than 0.5 Gm.

(1/4 lb. of 0.5% concentrate) is discovered within two

hours,

remove

warfarin by gastric lavage with tap

water.

2. Catharsis - Give 30 Gm. (1 oz.) sodium sulfate in 250 ml. (1 cup) water. B. Antidote: If bleeding occurs or if prothrombin time is prolonged more than twice normal (conc. less than 20% of

normal),

give Mephyton Emulsion® (vitamin K,),

100 mg. (3/4 to 1/2 gr.) 1.V. to 100 mg.

(1 to 11/2 gr.) I.M.

50 to

Vitamin K in any form,

50

three times daily is also

effective. C. General Measures: If hemoglobin is below 60% (10 Gm. / 100 ml. blood) or if bleeding is severe, give repeated transfusions

anemia

of 500 ml.

(1 pint) of whole

blood until

is corrected.

Prophylaxis: Warfarin

Sonfusion

concentrates and bait should with food cannot occur.

Prognosis: If ingestion of warfarin is discontinued ince of bleeding, recovery is likely.

be stored

where

upon the appear-

Section

Ill

Industrial Hazards Chapter 9

NITROGEN

COMPOUNDS

ANILINE, DIMETHYLANILINE, NITROANILINE, TOLUIDINE, AND NITROBENZENES

is

Aniline

0-Toluidine

Nitrobenzene

(Liquid)

(Liquid)

(Liquid)

CHg —N CH3

|

NO9g Dimethylaniline (Liquid)

p-Nitroaniline (Solid)

NO»

NO,

|

|

—NO, —NO»9

—NO,

m-Dinitrobenzene (Solid)

1, 2, 3- Trinitrobenzene (Solid)

Aniline is used in printing inks, cloth-marking inks, paints, paint removers, and in the synthesis of dyes. Dimethylaniline, nitroaniline, toluidine, and nitrobenzene are used in the synthesis of other chemicals. 92

Aniline

93

Ingestion of 1 Gm. (15 gr.) of aniline has caused death, although recovery has followed ingestion of 30 Gm. (1 oz.). Toxicity of aniline derivatives is similar. The m.a.c. in air of aniline and its derivatives and nitrobenzene is 5 p.p.m. The m.a.c. for the dinitrobenzenes and nitroanilines is 1 Pp. p. m2. Up to ten deaths per year have been reported from exposure to aniline, nitrobenzene, and their derivatives. Infant deaths have been caused by absorption of aniline from diapers stencilled with cloth-marking ink containing aniline. Aniline and nitrobenzene apparently act through an unknown intermediate to change hemoglobin to methemoglobin. The intense methemoglobinemia produced by all these chemicals may lead to asphyxia severe enough to injure the cells of the C.N.S. Pathologic findings in acute fatalities from aniline and _ nitrobenzene

derivatives

include

chocolate

color

of the blood,

injury to the kidney, liver, and spleen, and hemolysis. Bladder wall ulceration and necrosis may also occur. BNaphthylamine,

which

contaminates

commercial

aniline,

causes bladder papillomas after one to 30 years’ exposure. These papillomas become malignant if not removed.

Clinical Findings: The principal

manifestations

in poisoning

with these com-

pounds are cyanosis and jaundice. A. Acute

Poisoning:

(From

inhalation,

skin absorption,

or

ingestion.) Symptoms and signs include cyanosis, headache, shallow respiration, dizziness, confusion, blood pressure

fall, convulsions, andcoma. Jaundice, on urination, and anemia may appear later.

B. Chronic Weight

Poisoning: loss,

C. Laboratory 1.

Blood

anemia,

(From

inhalation

weakness,

and

pain

or skin absorption.) irritability.

Findings:

methemoglobin,

may reach

as determined

photometrically,

60% of total hemoglobin.

2. Red blood cells may be reduced to 20 to 30% of normal with accompanying poikilocytosis and anisocytosis. 3. Hepatic cell function impairment may be indicated by the appropriate tests (see p. 40). Treatment: A. Acute Poisoning: 1. Emergency measures a. Remove poison from skin by washing with soap and water. b. If poison was swallowed, remove by or emesis and catharsis (see pp. 10 c. Give oxygen if respiration is shallow present (see p. 24).

thoroughly gastric lavage to 13). or if anoxia is

94

Trinitrotoluene

2. Antidote

- For severe

methylene blue,

methemoglobinemia,

10 to 50 ml.

give

of 1% in 1. 8% sodium

sulfite solution I.V., to reverse normal hemoglobin. B. Chronic Poisoning: 1. Remove from exposure. 2. Treat liver damage (see p. 40).

methemoglobin

to

Prophylaxis: Air contamination must be kept below recommended maximum. If this is not feasible, a mask capable of absorbing organic liquids must be worn. Skin contact must avoided.

be

Prognosis:

Survival for 24 hours is usually followed by complete covery.

TRINITROTOLUENE

re-

(T.N.T.)

CH OoN—

—NOp

|

NO9 2, 4, 6- Trinitrotoluene (Solid)

Trinitrotoluene is an explosive used in the munitions industry. The acute fatal dose is estimated to be 1 to 2 Gm. (15 to 30 gr.). The m.a.c. inairis 0.1 p.p.m. At least 22 fatalities from trinitrotoluene absorption occurred in the United States during World War II. Trinitrotoluene injures almost all cells, especially those of the liver, bone marrow, and kidney.

Pathologic

findings are acute yellow atrophy of the liver,

aplasia of the bone toxic nephritis

marrow,

petechial

hemorrhages,

and

Clinical Findings: The principal is jaundice.

manifestation

A. Acute or Chronic sorption,

Poisoning:

or ingestion.)

of trinitrotoluene

(From

Jaundice,

poisoning

inhalation, dermatitis,

skin abcyanosis,

Trinitrotoluene

95

pallor, nausea, loss of appetite, anemia, and oliguria or anuria occur variably. The liver may be enlarged or atrophic. B. Laboratory Findings: 1. In chronic poisoning, hepatic cell injury will be revealed by appropriate tests (see p. 40). 2. RBC may be depressed, with anisocytosis and poikilocytosis. There may be relative lymphocytosis.

3. Urine may of anuria. Treatment

of Acute

show albumin and casts prior to the onset

or Chronic

Poisoning:

A. Emergency Measures: Terminate skin contamination by thorough washing with soap and water. Remove swallowed trinitrotoluene by gastric lavage or emesis and catharsis (see pp. 10 to 13). B. Antidote: None known. C. General Measures: Protect liver by giving 10 ml. of 10% calcium gluconate I.V. three times daily and high-carbohydrate and high-calcium diet, including at least one quart of skimmed milk daily (see p. 40). Give vitamin D in high doses, e.g., 10 drops of viosterol daily.

Prophylaxis: The m.a.c. must be observed at all times. Careful inspection of plants can eliminate poisoning from trinitrotoluene. Prognosis: Approximately

50% of patients

acute yellow atrophy.

with liver damage

die of

96 NITRO AND AMINO COMPOUNDS AND MISCELLANEOUS NITROGEN COMPOUNDS (For treatment, see p. 93.)

“Te2 - Noticeable slight &

3 - Moderate = Strong, 4 -

or

intense effect

4

&

&

lato)

We

S

=

=

cules

nsel

Olea ale)

gf

2

Ao

1H) Ce Sia

gE

He5

Aminodipheny!

ear

& gs

2U0

Acridine

&|a| 8=

=

or

easily apparent

g

Sables,Co 2

Pe

a

P1O1

ey

see es

el

3

mn Bl

|

§

SEI GERI E54]

Qa o

-/A

z|n}anI|Mo|M{/

renee ch |

Aniline dyes Auramine Aurantia

2 Fe pe RE

2 2

Benzidine

i

Aminothiazole [Not est. | itpetliaes 2] 1] Ammonium picrate (eae

te 3 2

| 10-20

eI

oO]

a4

3

airs

1

= =

fl hei

4

to fetal

=

Tt |) 2

2|2

|Heart and kidney damage 3 |Pulmonary

2

Chlorotoluidine

Not est.

Cyclohexylamine Diazomethane

None safe|

lew |

Di-isopropylamine

0.1

Ethylene

5

imine

Hydrazoic acid

Morpholine B-Naphthylamine

Nitroethane Nitroglycerine

Nitromethane Nitronaphthalene

3 4

to

Dinitrotoluene

None safe

edema 4

| 3

=

re

| Chloropicrin

&mt

e

eee gs

ays | ore ad

° o

aleo] oles se]

([elelsslgSlslale (ee ead Re Be ir

ea

Chloronitroparaffins

Ss

oO

alas

isAy

aes

Aminopyridine

Chloroaniline eter Chloronitrobenzenes |Not est.

S|

| & Seon ot al fiat lia

e Stee

ESE ellAP

Aminophenol

Cetacsiale1 a6

Lung and heart damage

[3 |

[Lung damage

3

Lung damage

2 |Anemia i

3

4

Lung damage

4

IC [Not est. |=al || 1] !

I: 3 |Headache,

Notest.

| | |

1 3

2]

ene

2 (ay

BP

fall

Nitropropane 50 ie [3 | Nitrotoluene = LF || pif a] p-Phenylenediamine [Notest. [ [2] [| [1/2]2 | Phenylhydrazine oe tt 3 {sf 2 2 Ss Anemia Phenylhydroxylamine| Not est. Hn Re Ra eak ia

Phenylnaphthylamine|Notest.

[2/3 ][ 1 |

Picric acid Pyridine

flue iH

TetrahydroB-naphthylamine

Tetranitromethane

Teiryl Toluylenediamine

Trinitroanisole Trinitrotriazine

Kylidene

4 3

[2 [2][2 | Estes" [3 | | 3

[Heart damage

Not est.

0.1

mee

ee

nar:

MBmEs

|

a De Ioi)ine 5 NEA osaa: oo} Seals peehealnen|

Heart damage

Not eat.)

RY ary

3

EC RTINEW HMBN NOH

et 3 [3|

FT

Anemia

Chapter 10

HALOGENATED

CARBON

HYDROCARBONS

TETRACHLORIDE

Formula: CCl4; B.p.: 76.7°C.; Vapor pressure at 20°C.: Carbon tetrachloride decomposes to phosgene Hg. 91mm.

(COCl9) on heating. trachloride

is used as a nonfl

able solvent.

Be ctianae in factories, garages, and-household floor waxes. ers. an a anthelmintic.

oz.).

and as an extinguisher It is also used as a fire eee eee

The adult fatal dose by ingestion is410 6 ml. (1/10 to V6 The m.a.c. in air is 25 p.p.m. (1/2 pint evaporated in

a room

50 x 50 x 15 ft.).

One to 25 deaths occur yearly from

exposure to carbon tetrachloride. Carbon tetrachloride depresses and injures almost cells of the body, including those of the C.N.S., liver,

all kidne The heart muscle may be depressed, and and blood vessels. ventricular arrhythmias may occur. poemc orien eee cohol ingestion increases the effect of carbon tetrachloride «on all organs. The kidneys of fatal cases show marked edema and fatty | The liver shows fatty degenerdegeneration of the tubules.

The heart may also show fatty ation and may be enlarged. The endothelium of blood vessels may be indegeneration. jured,

with

resultant

petechiae

or hemorrhages.

Clinical Findings: The principal manifestations in poisoning with carbon andj anuria, dice. tetra hloride are coma,

A. Acute Poisoning: (From inhalation, skin absorption, pain ingestion.) The immediate effect is abdominal nausea,

vomiting,

dizziness,

and confusion,

or

progressing

to unconsciousness, Yespiratory slowing, glowed or ir= regular pulse, and fall of blood pressure. Ifthe-patient recovers consciousness, he may have mild symptoms of

several days to two weeks until evi ence of liver or kidney damage appears. Li indicated b jaundice

an

j

97

damage

is

98

Carbon

Tetrachloride

indicated by

decrease

in urine

output,

edema,

sudden

weight gain, and uremia. Coma, liver damage, or ‘kidney damage may appear independently, or all may occur in the same individual at different times. B. Chronic Poisoning: (From inhalation or skin absorption. ) The above symptoms and signs of acute poisoning occur after repeated exposures to low concentrations but are less severe. Vague symptoms suggestive of poisoning include fatigue, anemia, weakness, nausea, loss of appetite, loss of weight, lowered blood pressure, blurring of vision, and loss of peripheral color vision. Dermatitis follows repeated skin exposure. C. Laboratory Findings: 1. Liver function impairment may be revealed by appropriate tests (see p. 40). 2.

Casts, albumin, and red blood cells may appear in the urine prior to oliguria or anuria. 3. Nitrogen retention is indicated by increase in N.P.N., urea, and creatinine.

Treatment: A. Acute Poisoning: 1. Emergency measures

a.{ If inhaled,

give artificial respiration until con-

sciousness returns (See p. 19). b.| Remove clothing contaminated with carbon tetrachloride. c.}If ingested remove by gastric lavage or emesis and catharsis (see pp. 10 to 13). 2. Antidote - None known. 3.

General measures Maintain blood pressure b. BO NOT VS

a.

c.

by giving 5% glucose :

‘

I_V.

ne or

ephedrine may Indueé-ventricular fibrillation. ff urine output is normal, give 2 to 4 L. fluid daily ither as I. V. glucose or oral fruit juice, broth, r water,

d. Give high-carbohydrate, high-calcium “tect the liver (see p. 40).

diet to pro-

4. Special problems - Acute renal shutdown is treated as described on p. 29. B. Chronic Poisoning: Remove from exposure and treat as indicated for acute poisoning.

Prophylaxis: If air contamination cannot be kept below the m.a.c., a mask capable of absorbing organic vapors must be worn. Skin contamination must be avoided. Carbon tetrachloride workers must not drink alcoholic

beverages and should ee f

ave a twice-yearly physical cece eS

OEE

GATE

x

Methyl Bromide,

Chloride

99

xamination with laboratory evaluation of liver function. { Carbon tetrachloride fire extinguishers should not be sed in enclosed spaces. rognosis:

:

In anuria, spontaneous return of kidney function may egin two to three weeks after poisoning. Complete return of ver and kidney function requires two to 12 months.

METHYL Formula:

BROMIDE,

METHYL

Methyl bromide,

H3Cl; both are gaseous

CH3Br;

CHLORIDE methyl

chloride,

at ordinary temperatures.

Methyl bromide and methyl chloride are used as refrigrants, in synthesis, and as fumigants. Methyl bromide is sed with carbon tetrachloride in fire extinguishers. The m.a.c. is 20 p.p.m. for methyl bromide, 100 p.p.m. yr methyl chloride. One to ten deaths occur yearly from oisoning with these compounds. The fat-soluble methyl bromide or methyl chloride enter ells, where hydrolysis to methyl alcohol and hydrobromic or ydrochloric acids occurs. Pathologic findings are congestion of the liver, kidneys, rain, and lungs, with degenerative changes in the cells. ronchial

pneumonia

[ethyl bromide ells.

and pulmonary

and methyl chloride

linical Findings: The principal manifestations gents are coma

edema

damage

are

common.

almost all body

of poisoning with these

and convulsions.

A. Acute Poisoning:

(From inhalation,

ingestion.) If the concentration methyl chloride is high, nausea,

skin absorption,

of methyl bromide vomiting, vertigo,

or or weak-

ness, oliguria, drowsiness, convulsions, and pulmonary

blood pressure fall, coma, edema progress over four to six hours after a latent period of one to four hours. After exposure to lower concentrations, symptoms may not

appear for 12 to 24 hours. Pulmonary edema, and bronchial pneumonia are most often the cause of death. Skin contact causes irritation and vesiculation. B. Chronic Poisoning: (From inhalation or skin absorption. Repeated exposure to concentrations slightly higher than the m.a.c. will cause visual disturbances, numbness of the extremities,

confusion,

fainting attacks,

and bronchospasm.

hallucinations,

somnolence,

C. Laboratory Findings: 1. Hepatic cell function impairment may be indicated by appropriate

laboratory

tests (see p.

40).

—

100 Trichloroethylene 2. Urine

may

show

casts,

red blood

cells,

and

albumin.

Treatment: A. Acute Poisoning:

1. Emergency measures - Remove from further exposure and observe carefully for the first 48 hours. 2. Antidote - None known. 3. General measures - Treat pulmonary edema (see p. 3 4. Special problems - Bronchospasm complicating pulmonary edema or bronchial pneumonia is treated by epinephrine, 0.3 ml. of 1:1000 solution subcut.; repeat as necessary.

B. Chronic Poisoning: If necessary, give aminophylline, 0.25 Gm. I.V. Remove from further exposure. Prophylaxis: The m.a.c.

should never

be exceeded.

Gas

masks

are

relatively ineffective because methyl bromide and methyl chloride penetrate skin readily. Safety dispensers must always be used when applying methyl bromide Prognosis: Patients completely.

who survive

48 to 72 hours

as a fumigant.

will usually recover

TRICHLOROE THYLENE Formula: CHCl: CCly; B.p.: 88°C.; Vapor pressure at 20°C.: 60 mm. Hg. Tetrachloroethane (see p. 100) may be present

as an impurity

in technical

products.

Trichloroethylene is used as an industrial solvent, in household cleaners (rugs, walls, clothing), and as an inha-

lation analgesic or anesthetic. The m.a.c, is 100 p.p.m. Up to three fatalities per year have been reported from exposure to commercial trichloroethylene. The most striking effect of trichloroethylene is depressic of the C.N.S. Other areas affected (in order of decreasing severity of involvement) include the myocardium, liver, and ktdney.

Trichloroethylene

rhythmias,

will induce

acute ventricular

including ventricular fibrillation,

precipitated by the administration heart rate is slowed.

ar-

or these may be

of epinephrine

while the

Fatalities from exposure to commercial trichloroethylen reveal degenerative changes in the heart muscle, C.N.S., liver, and renal tubular epithelium. The presence of tetrachloroethane as a contaminant in commercial trichloroethyle1 may contribute to the cellular damage.

Trichloroethylene Clinical Findings: The principal manifestation of trichloroethylene

101

poisoning

is unconsciousness. A. Acute Poisoning: (From inhalation, skin absorption, or ingestion.) Depending on concentration, symptoms progress more or less rapidly through dizziness, headache, nausea, vomiting, and excitement, to loss of conscious-

ness. Irregular pulse may indicate ventricular arrhthmia. Recovery of consciousness is rapid, but nausea and vomiting may persist for several hours. B. Chronic Poisoning: (From inhalation or skin absorption.) Symptoms and signs include weight loss, nausea, anorexia, fatigue, visual impairment, painful joints, dermatitis, and wheezing. Jaundice is uncommon. C. Laboratory Findings: 1. Ecg. may reveal ventricular irregularities during acute

poisoning.

2. Trichloroacetic acid excretion, measured by the method of Ahlmark and Forssman (Arch. Ind. Hyg. 3:386, 1951), indicates amount of absorption. Urine levels above precautions.

20 mg./L.

indicate

improper

safety

3. Hepatic cell function impairment may be revealed by appropriate laboratory tests (see p. 40). Treatment:

A. Acute Poisoning: 1. Emergency measures - Move patient to fresh air and give artificial respiration (see p. 19). Remove contaminated clothing. 2. Antidote - No antidote is known. Do not give epinephrine or

B. Chronic

other

stimulants.

Poisoning:

1. Remove patient from further exposure. 2. Treat liver function impairment by giving a highcarbohydrate, high-protein diet (see p. 40).

Prophylaxis: The m.a.c. should never be exceeded. Cross-ventilation should be sufficient to prevent any noticeable odor when trichloroethylene is used as a cleaner in the home. Prognosis: Survival

recovery.

for four hours is ordinarily followed by complete

102 TETRACHLOROE THANE

Formula: ClyCHCHCl,; 20°C oss me ehipy.

B.p.:

146°C. ; Vapor pressure

at

Tetrachloroethane is used as a solvent in industry and occurs as a contaminant in other chlorinated hydrocarbons. It is occasionally present in household cleaners. Tetrachloroethane is the most poisonous of the chlorinated hydrocarbons. Them.a.c. is 5p.p.m. Up to five cases of poisoning from tetrachloroethane are reported yearly. Tetrachloroethane causes a longlasting narcosis with de-

layed onset and severe damage to the liver and kidneys. The pathologic findings include acute yellow atrophy of the liver. If death has been immediate, congestion of lungs, kidneys, brain, and gastrointestinal tract may be the only evidences of poisoning.

Clinical Findings: The principal manifestations of tetrachloroethane poisoning are coma, jaundice, and anuria. A. Acute Poisoning: (From inhalation, ingestion, or skin absorption.) Initially tetrachloroethane causes irritation of the eyes and nose, followed by headache and nausea. Cyanosis and C.N.S. depression progressing to coma appear after one to four hours. Liver and kidney damage, after apparent recovery or

after repeated exposures to cause

immediate

to amounts

symptoms,

less than necessary

is indicated

by nausea,

vomiting, abdominal pain, jaundice, and anuria with uremia. The relative damage to the liver or kidneys is variable. B. Chronic Poisoning: (From inhalation or skin absorption. ) Headache, tremor, dizziness, peripheral paresthesia, hypesthesia, or anesthesia. C. Laboratory Findings: 1. An increase in the large mononuclear cells above 12% in the differential blood smear indicates exposure. 2. Hepatic cell impairment may be revealed by appropriate tests (see p. 40). 3. The urine may show albumin, red blood cells, or casts. Treatment:

Treatment is the same as described chloride poisoning (see p. 97).

for carbon

tetra-

Prophylaxis: Tetrachloroethane should never be allowed in household products. Less toxic solvents should be substituted for tetrachloroethane in industrial processes whenever possible.

Ethylene Chlorohydrin

103

The m.a.c. should never be exceeded. If a contaminated area must be entered, a gas mask with a canister approved

for tetrachloroethylene is safe for 30 minutes if the concentration does not go over 20,000 p.p.m. (2%). Over 20, 000 p-p.m., an air-line hose mask or self-contained oxygen supply is necessary.

Workers

entering a high-concentration

area must wear rescue harness and life-line attended by a responsible person outside the contaminated area. If direct contact is unavoidable, aprons and gloves of solvent-proof synthetics must be worn. Skin creams will not prevent

penetration.

Alcohol ingestion increases chloroethane.

the susceptibility to tetra-

Prognosis: A rapid progression of jaundice indicates a poor out‘come. In some instances mild symptoms will persist up to three months and then progress to acute yellow atrophy and death. Anuria may persist for as long as two weeks and still be followed by complete recovery.

ETHYLENE Ethylene chlorohydrin

CHLOROHYDRIN (CH 9C1CH,OH)

is a colorless

liquid which evaporates appreciably at room temperature. It is used to speed the germination of seeds and potatoes, as a cleaning solvent, and in chemical synthesis. Deaths have occurred from exposure to liquid ethylene chlorohydrin

in the open

to the vapors

exposure

air,

from

skin absorption,

The

in warehouses.

m.a.c.

or from

in air is

2ip.p-m. (6.6 mg./cu.M:). At least seven fatalities are recorded in the recent literature.

Ethylene chlorohydrin presumably irritates and damages cells after hydrolysis to an acid (perhaps hydrochloric acid),

producing pulmonary hibition

of the cardiac

impairment

edema, muscle,

vascular

damage,

depression

direct inand

of the C.N.S.,

of liver and kidney function.

Postmortem

examination

in fatal poisoning has revealed

fatty infiltration of the liver, edema of the brain, congestion and edema of the lung, dilatation of the heart with fatty degeneration

of the myocardium,

cloudy swelling and hyperemia and swollen

congestion

of the spleen,

and

of the kidneys with fat deposits

epithelial cells in the tubules.

Clinical Findings: The principal manifestations

in poisoning with ethylene

chlorohydrin are respiratory and circulatory failure. A. Acute Poisoning: (From ingestion, inhalation, or skin

104

Ethylene Chlorohydrin

absorption.) Symptoms begin one to four hours after exposure and include nausea, retching, headache, abdominz pain, excitability, dizziness, delirium, respiratory slow ing, fall of blood pressure, twitching of muscles, cyanosis, and coma. Death results from respiratory and circulatory failure. Even in dangerous concentrations, ethylene chlorohydrin does not produce warning odor or irritation of the nose or throat. B. Chronic Poisoning: Chronic poisoning has not been reported following exposure to ethylene chlorohydrin. In rats, prolonged ingestion of amounts only slightly less than necessary to induce acute signs of poisoning was without effect. C. Laboratory Findings: Noncontributory.

Treatment of Acute Poisoning: A. Emergency Measures: 1. Remove from exposure - Remove patient from further exposure to ethylene chlorohydrin vapor or liquid. Complete recovery must be assured before patient returns to work. 2. Artificial respiration - Give artificial respiration if respiration is depressed. Give oxygen as soon as possible.

3. Lavage - Remove ingested ethylene chlorohydrin by thorough gastric lavage, using tap water. 4. Emesis - If gastric lavage cannot be accomplished immediately, give up to one quart of tap water or milk and induce vomiting by stimulation of the pharynx. Repeat

at least once.

5. Catharsis - Give 30 Gm. (1 oz.) sodium sulfate in 250 ml. (1 cup) water orally. B. Antidote: None known. C. General Measures: 1. Oxygen - Give alcohol-saturated oxygen by inhalation for dyspnea resulting from pulmonary edema. This is

done by bubbling the oxygen through 50% alcohol in

water prior to entering mask. (See p. 31.) 2. Raise blood pressure - Give epinephrine, 0.2 to 1 mg. (1/300 to Y6o gr.) subcut. as necessary to maintain normal blood pressure. If necessary, levarterenol (Levophed®) is given as a continuous intravenous drip

(4 ml. of 0.2% diluted in one liter of 5% glucose) at a rate of 0.5 to 2.0 ml. /minute (see p. 26).

Prophylaxis:

Ethylene chlorohydrin

should never be used for cleaning

in an open process. Exhaust ventilation in most is insufficient to prevent dangerous exposure.

Treatment

of potatoes

open hoods

or seeds by ethylene chlorohydrin

Chlorinated Naphthalene

and Diphenyl

105

must be in an entirely closed space in which workmen are not allowed until after 24 hours of forced ventilation. The liquid must be sprayed into the fumigating chamber from a totally closed system to prevent any skin contact or inhalation of vapor. Transfer of the liquid from drums to spraying system must be by means of an enclosed system and not by pouring. Prognosis: Survival for 18 hours by complete recovery.

after poisoning has been followed

CHLORINATED NAPHTHALENE CHLORINATED DIPHENYL

AND

Chlorinated naphthalene (Halowax®) and chlorinated diphenyl (Arochlor®) are used as high-temperature dielectrics for electric

wires,

electric

motors,

transformers,

and other

Depending on the amount of chlorinelectrical equipment. ation, the melting point for these compounds varies from 80° to 130°C. The

mg./cu.

m.a.c.

M.

These generation

for industrial

exposure

has been

set at 1

At least seven fatalities have been reported. compounds produce skin irritation and acute dePathologic of the liver after prolonged exposure.

findings include acute necrosis of the liver, cloudy swelling of the kidneys and heart, and in some cases necrosis of the adrenals. Clinical

Findings:

The principal manifestations in poisoning with chlorinated naphthalene and chlorinated diphenyl are acne and jaundice. A. Acute poisoning from single exposures has not been reported. (From exposure to vapors.) The B. Chronic Poisoning: skin shows a pinhead to pea-sized papular, acneform eruption consisting of straw-colored cysts formed by These progress to pustuplugging of sebaceous glands. General symptoms and signs include lar eruptions. drowsiness, indigestion, nausea, jaundice, enlargement of the liver, and weakness progressing to coma. C. Laboratory Findings: Hepatic cell function impairment is revealed by appropriate tests (see p. 40).

Treatment of Chronic Poisoning: A. Remove

from

further

exposure.

B. Antidote: None known. Treat liver damage C. General Measures:

(see p. 40).

106

Chlorinated Naphthalene

and Diphenyl

Prophylaxis: M.a.c. must be observed at all times. Occurrence acne in workers indicates inadequate control of fumes.

of

Prognosis: At least 50% of cases with liver damage from chlorinated naphthalenes or chlorinated diphenyls have died. If workers are removed from exposure at the onset of acne, recovery is likely.

HALOGENATED

HYDROCARBONS

(For treatment,

ier

Legend:

§

1 - Slight

a

2 - Noticeable or easily apparent

a CaS

&

af

o

gS 3c

ee a a

rom) bo = ie]

ORE

Bo

Chloroform

B’-Dichloroethyl

ether

e

os

Ke]

~

Fea

>

anes -

car

aU

SOU 4 4 2

2 2 2

15

die

2

1

al

2

1 2

2 2 4

[et

&

s .

2 2

— Te

ro)

Oia

ps &

=

ts

Methyl iodide

Not est.

I

2

Pentachloroethane osgene Tetrachloroethylene Trichloroethane Vinyl] chloride

Not est. 1 100 183 500

3 2 1 3

3

(3) ra o

bo | 3

o a ee

2 a o

ie

1 1 2 2 3

cs

|S

3

2 2

4

]

2

1

3

2

3

3 3 3

=

|Cardiac damage Cardiac damage

2 3

4

2 4 3

o

3 3

2 2 ] 3 3

1

ie)

o = CI 4

2

200

et

1m K =

PS ee Ma

s

a

oO vols | S

4 3

2

2

ele ce als

[came

1

Ethyl bromide :

=

@

8 Gig

1S

None safe 50 Not est. 75 25

Not est. 500 75

i)

Diast i

o Ho |.n

5 50 | Not est. 75 200

Dichlorohydrin Dichloromethane 1, 2-Dichloropropane

Es

S 3.0

100

Chlorophenol Dichlorobenzene Dichlorodifluoromethane Dichloroethane 1, 2-Dichloroethylene

5

i}

£

as lA 5 = al Saale

eo an

~

98.)

Be

3 =- Moderate

or effect

p.

)

2

4 - Strong, A intense

Allyl bromide Allyl chloride Bromoform Chlorobenzene Chlorobutadiene

B,

see

4

ardiac damage = Cardiac

Chapter 11

ALCOHOLS

AND

METHYL Formula: CH3OH; 20°C..: 94mm. Hg.

GLYCOLS

ALCOHOL 64.5°C.;

B.p.:

Vapor pressure

at

Methyl alcohol (wood alcohol) is used as an antifreeze, paint remover,

in shellac

solvent

and varnish,

and in chem-

ical synthesis. The fatal internal dose is 100 to 250 ml.

(31/2 to 8 Oz.)

More than 100 deaths ina The m.a.c. in airis 200 p.p.m. single year have resulted from ingestion or inhalation of methyl alcohol.

The high oral or inhalation toxicity of methyl alcohol in comparison with that of ethyl alcohol has not been satisfactorily explained. According to some workers, toxicity is due to metabolism of methyl alcohol to formic acid or formalde-

Either of these metabolic

hyde inside body cells.

products

will inhibit cellular metabolism. Methyl] alcohol is distributed in the body according to the The vitreous body and optic nerve, water content of tissues. which have high water content, have high concentrations, and for this reason the retina and optic nerve are specifically damaged. Methyl alcohol is metabolized and excreted at a rate ap-

proximately one-fifth that of ethyl alcohol.

After a single

dose, excretion from the lungs and the kidneys may continue for at least four days. Severe acidosis is produced by the metabolic product, formic acid. The enzyme system which oxidizes methyl alcohol will utilize predominantly ethyl alcohol if both alcohols are available. Administration of ethyl alcohol will thus reduce the

toxicity of methyl alcohol. In fatal cases,

chymatous epithelium, pneumonia.

the liver,

degeneration.

kidneys,

edema, emphysema, The brain may show

The eye shows

degenerative

and edema

of the optic disk,

and there

The corneal

show

paren-

changes in the retina may

be optic nerve

epithelium may show degenerative

changes.

107

of

congestion, and bronchial edema, hyperemia, and

petechiae. atrophy.

and heart

The lungs show desquamation

108

Methyl Alcohol

Clinical Findings: The principal manifestations of methyl alcohol poisoning are visual disturbances and acidosis. A. Acute Poisoning: (From ingestion, inhalation, or skin absorption. ) ake Mild - Fatigue, headache, nausea, and, after a latent

period,

temporary

Moderate

blurring of vision.

- Severe

headache,

dizziness,

nausea,

vom-

iting, and depression of the C.N.S. Vision may fail temporarily or permanently after two to six days. . Severe - The above symptoms progress to rapid, shallow respiration from acidosis, cyanosis, coma, fall of blood pressure, dilatation of the pupils, and hyperemia of the optic disk with blurring of the margin. Death in respiratory failure occurs in about 25% of those with severe poisoning (carbon dioxide combining

power below 20 mEq. /L.). B. Chronic Poisoning: (From inhalation.) Visual impairment may be the first sign of poisoning; this begins with mild blurring of vision progressing to contraction of visual fields and sometimes complete blindness. C. Laboratory Findings: Severe acidosis is indicated by carbon dioxide combining power of the blood below 20

mEq. /L. Treatment: A. Acute Poisoning: Le Emergency measures - Remove poison. If ingestion of methyl alcohol is discovered within two hours, give thorough gastric lavage with 2 to 4 L. of tap water with sodium bicarbonate added (one heaping tsp. per liter). . Antidote

- Give

ethyl alcohol,

5 to 20 ml.,

every

two

to four hours for four days in order to block the metabolism of methyl alcohol and to allow time for the excretion of methyl alcohol. . General measures a. Combat acidosis - (See p.

b. Give up to 4 L. maintain

c.

42.)

of fluids daily by mouth or I.V.

adequate

to

urine output.

Maintain body warmth.

d. Maintain

adequate

nutrition by giving small

meals

at regular three- to four-hour intervals! - Special problems

barbital sodium, hours. B. Chronic

- Control

100 mg.

delirium

by use of pento-

(14/2 gr.) every six to 12

Avoid respiratory depression. Poisoning:

Remove

from exposure.

Prophylaxis: M.a.c.

in work

areas

should not be exceeded.

Poison

Ethyl

Alcohol

109

labels should be placed on all methyl alcohol containers. Workmen should be instructed in the dangers of methyl alcohol ingestion.

Prognosis:

In acute poisoning from methyl alcohol,

25 to 50% of

those with carbon dioxide combining power below 20 mEq. /L. do not recover. Vision is not likely to show much improvement after one week.

ETHYL

mm.

Pure alcohol has a B.p. Hg at 20°C.

ALCOHOL of 78°C.

Vapor pressure,

44

Ethyl (grain) alcohol (C)H5OH) is used as a solvent, antiseptic, chemical intermediate, and beverage. The fatal dose for an average adult is 300 to 400 ml. of pure alcohol if consumed in less than one hour. This amount is represented by 600 to 800 ml. of 100-proof whisky. The m.a.c. inair is 100 p.p.m. The incidence of fatalities from acute or chronic ethyl alcohol ingestion is probably in excess of 1000 per year. Ethyl alcohol, being a small, hydrophilic molecule, is rapidly absorbed from the gastrointestinal tract or alveoli and is distributed according to the water content of tissues. It is oxidized by way of acetaldehyde to carbon dioxide and water at a rate of 10 to 20 ml. per hour. Ethyl alcohol depresses the C.N.S. irregularly in descending order from cortex to medulla, depending on the amount ingested. The range between a dose which produces anesthesia and one which impairs vital functions is small. Thus, an amount which produces stupor is dangerously close to a fatal dose. The pathologic findings in acute fatalities from ethyl alcohol include edema of the brain and hyperemia and edema

of the gastrointestinal tract. Postmortem findings in patients dying after chronic ingestion of large amounts of alcohol include degenerative

changes

atrophic

and cirrhosis

gastritis,

in the liver,

Clinical Findings: The principal manifestation C.N.S. depression.

kidneys,

and brain;

of the liver.

of ethyl alcohol poisoning is

(From ingestion or inhalation.) A. Acute Poisoning: 1. Mild (blood alcohol 0.05 to 0.15%) - Decreased inhibitions, slight visual impairment, slight muscular incoordination,

and slowing

of reaction

time.

Approx-

imately 25% in this group are clinically intoxicated.

110

Ethyl Alcohol

2. Moderate (blood alcohol 0.15 to 0.3%) - Definite visual impairment, sensory loss, muscular incoordination, slowing of reaction time, and slurring of

speech. . Severe

From

50 to 95% are clinically intoxicated.

(blood alcohol

incoordination,

0.3 to 0.5%) - Marked

blurred

or double

vision,

muscular

approaching

stupor. Fatalities begin to occur in this range. . Coma (blood alcohol above 0.5%) - Unconsciousness, slowed

respiration,

decreased

reflexes,

and

complete

loss of sensations. Deaths are frequent in this range. B. Chronic Poisoning: (From ingestion.) alle General - Weight loss. 2. Gastrointestinal - Cirrhosis of the liver and gastroenteritis with anorexia and diarrhea. 3. Nervous system a. Polyneuritis with pain, and motor and sensory loss in the extremities.

b. Optic atrophy. c. Mental deterioration with

memory loss, impaired judgment, and loss or impairment of other abilities. d. Delirium tremens or acute alcoholic mania usually follows a prolonged bout of steady drinking. Symptoms include uncontrollable fear, sleeplessness, tremors, and restlessness progressing to hallucinations,

delirium,

and sometimes

convul-

sions.

e.

Acute

alcoholic

psychosis (Korsakoff'’s

is characterized

by severe

mental

suggestibility, disorientation, memory. C. Laboratory Findings: Ie Blood alcohol

levels

correlate

findings (see paragraph

A,

syndrome)

impairment,

and falsification of

well with clinical

see above).

2. In chronic alcoholism, the liver function should be evaluated by appropriate tests (see p. 40). 3. Urinalysis may be positive for reducing sugar, acetone,

or

diacetic

acid.

Treatment:

A. Acute Poisoning: dis Emergency measures - Remove by gastric lavage with tap water 10 and 11).

unabsorbed alcohol or emesis (see pp.

. Antidote - None known. . General measures -

a.

Maintain

adequate

airway and oxygenation.

b. Maintain normal body temperature. c. Give 2 Gm. (1/2 tsp.) sodium bicarbonate in 250 ml. (1 cup) water every two hours to maintain neutral or slightly alkaline urine.

Ethyl Alcohol

111

d. Avoid administration of excessive fluids. o . Avoid depressant drugs. f. Give caffeine with sodium benzoate, 0.5 Gm. (7/2 gr.) 1.M. or strong coffee orally as a stimulant. g. Treat coma (see p. 27). B. Chronic Poisoning: 1. Emergency measures a.

In acute

alcoholic

5 to 30 ml.

mania,

paraldehyde,

administer

(1 to 6 tsp.) orally or rectally.

b. Avoid physical restraint. Maintain and uniform surroundings. 2. Antidote - None known.

3. General measures

calm,

quiet,

-

a. Give chlorpromazine (Thorazine®), 25 to 100 mg. (3/g to 11/2 gr.) orally one to four times a day to control

mg.

restlessness;

or give phenobarbital,

100

(14/2 gr.) one to four times daily for restless-

ness. b. Give 1 to 2 L. of 5% dextrose in saline 1.V.

if

patient is unable to take fluids orally. c. Give oral fluids to 4 L. per day. d.

Give

ascorbic

acid,

500

mg.;

thiamine,

nicotinic acid, 100 mg.; and riboflavin, orally daily. e. Give high-vitamin, high-protein diet.

100 mg. ;

100 mg.

Prophylaxis: Alcoholics Anonymous (see listing in local phone book) may be able to help those patients who genuinely desire help. Disulfiram

(Antabuse®)

administration

induces

sensitivity

to alcohol and may be helpful in training the patient to avoid alcohol. Prognosis: In acute, uncomplicated alcoholism, survival for 24 hours is ordinarily followed by recovery. In alcoholic psychosis, survival is likely but complete recovery

is rare.

In the presence

complete withdrawal from minimum improvement.

alcohol

of mental

may

deterioration,

be followed

by only

ALCOHOLS AND GLYCOLS (For treatment, see pp. 110 and

113.)

§

Legend: 1 - Slight

4

2 - Noticeable or easily apparent

E oO rs)

uo} a

3 - Moderate 4 - Strong, or

8 oO

Bo

Ke 5

“

kf

g5

oe n

intense effect

atg

aofl shi

= fo}

o £11) We

§ ol

8 ee

E =

i w

ll teeola]. hieheaki |abad

oeE

(Re ls

ae2

eese

8o

2

MUD

Da

a 7)oO

gi | Su|0l|o Selelele|s| & |Z /m}] & ;

= Allyl alcohol

eR

Amy! alcohol

100

Benzyl alcohol

Butyl alcohol

Butyl carbitol Butyl cellosolve

PNote stor

ie age RE ak em! Pe eal [ 3

| 3 [1 |

eu sshaoe)

Niclas aeafens Os Not est. 200

2

||Headache

awe 2

Da

2

Hematuria, heart to roar

Cellosol Per ee oe ere BB Cyelonesytateohot |—sof 7-2 {J

Carbitol

Sher

200%

Cellosolve

acetate

Diacetone alcohol

2

100

50

2

2

ee

eal

eet

2

Ethyl celfosaive | 1000#-[7-7}|— diaceies Pcie] veenof vcucla ns} wife mononcete | | T | || Dipropylene glycol

Ethylene

Not est.

glycol

ot est.

Ethylene glycol

Not est.

Methyl] cellosolve

2

2

25

4

Hemolysis, toxic

acetate

Methyl cellosolve

Methy] cyclohexanol B-Naphthol Propyl alcohol

a

Propylene

*10 ml.

chloro-

9d es[oct] th 25

en-

cephalopathy

3

Not est. Not est.

2. | 22:3) eaanel ene nen | 4 | | [3 | |Hemolysis 1 3 | | [2 [Headache

Not est.

2

eae

safe on skin daily.

3

1

2

|Hemolysis

113 ETHYLENE These tastes.

GLYCOL,

DIETHYLENE

GLYCOL

agents are heavy liquids with sweetish,

Their

vapor

pressures

at room

acrid

temperature

are

negligible. Ethylene glycol: Formula: CHyOHCH)OH; B.p.: 198°C. Diethylene glycol: Formula: HOCH,CH gOCH)CH2OH; B.p.: 245°C. The fatal dose of ethylene glycol is approximately

(34/2 oz.); of diethylene glycol,

100 Gm.

15 to 100 Gm. (1/2 to 31/2 oz.).

Up to 60 deaths in a single year have been reported from ethylene glycol or diethylene glycol. Ethylene glycol and diethylene glycol are metabolized in the body to oxalic acid (see p. 128), which damages the brain and causes impairment of renal function with subsequent uremia. Both ethylene glycol and diethylene glycol depress ‘the C.N.S. as does ethyl alcohol. The pathologic findings are congestion and edema of the brain, focal hemorrhagic necrosis of the renal cortex, and hydropic degeneration of the liver and kidneys. Calcium oxalate

crystals

may

in the brain,

be found

and

spinal cord,

kidneys. Clinical Findings: The principal manifestations agents are anuria and narcosis.

of poisoning with these

(From ingestion.) The initial sympA. Acute Poisoning: toms in massive dosage (over 100 ml. ina single dose) are those of alcoholic intoxication. These symptoms soon progress to prostration, and Death may occur failure or within

vomiting, cyanosis, stupor, anuria, unconsciousness with convulsions. within a few hours from respiratory the first 24 hours from pulmonary edema.

If the ingestion of small amounts

(15 to 30 ml.) is re-

peated daily or if the patient recovers from acute poisoning, oliguria may begin in 24 to 72 hours and progress

rapidly to anuria and uremia. B. Chronic

Poisoning:

(From

inhalation.)

Repeated

ex-

posure to the vapors from a process utilizing ethylene glycol is reported to induce unconsciousness, nystagmus, and lymphocytosis. The urine may show calcium C. Laboratory Findings: oxalate crystals, albumin, red blood cells, and casts.

Treatment: A. Acute Poisoning:

1. Emergency

measures

- Remove

gastric lavage or emesis

ingested glycols by

and catharsis

13). 2. Antidote - Give calcium gluconate,

(see pp.

10 ml.

of 10%

10 to

114

Ethylene and Diethylene Glycol solution I. V., oxalic acid.

to precipitate

3. General measures

the metabolic

product, ,

- Artificial respiration with oxygen

for depressed respiration. 4. Special problems a. Treat pulmonary edema

(see p. 31). b. Treat uremia (see p. 29). B. Chronic Poisoning: Remove from exposure. Prophylaxis: Ethylene glycol and diethylene poisons and stored safely.

glycol should be labeled as

Prognosis:

Complete recovery of renal function may follow two weeks of complete anuria. Cerebral damage may, however, be permanent.

Chapter 12

ESTERS,

ALDEHYDES, KETONES, AND ETHERS DIMETHYL

Formula: 76°C.: 15 mm.

Dimethyl

(CH3)9SO4; Hg.

SULFATE

B.p.:

188°C.;

sulfate is used in organic

Vapor pressure

synthesis.

at

The lethal

dose is 1 to 5 Gm. (15 to 75 gr.). The m.a.c. in air is 1 p.p.m. Up to ten instances of severe poisoning per year have been reported.

Dimethyl sulfate hydrolyzes in the presence of water to methyl alcohol and sulfuric acid. Dimethyl sulfate is caustic to mucous membranes of the eyes, nose, throat, and lungs. Pulmonary edema is the usual cause of death. Pathologic changes are those of extreme irritation. The eyes, nose, mouth, throat, lungs, liver, heart, and kidney are affected.

Clinical Findings: The principal manifestation is extreme irritation.

of dimethyl

sulfate

poisoning

A. Acute Poisoning: (From inhalation, skin absorption, or ingestion.) The immediate symptoms are irritation and erythema of the eyes progressing to lacrimation, blepharospasm, and chemosis. Cough, hoarseness, edema of tongue, lips, larynx, and lungs occur later. Albuminuria, hematuria,

hypoglycemia,

and

hemoconcentration

may

be present. Ingestion or direct contact with mucous membranes causes corrosion equivalent to that from sulfuric acid. After absorption, pulmonary edema and injury to the

liver and kidney are the most prominent findings. B. Chronic poisoning does not occur. C. Laboratory Findings: 1. Hematocrit determination may reveal hemoconcentration. 2. Urine may show albumin and red blood cells.

115

116

Tri-ortho-cresyl

Treatment

of Acute

Phosphate

Poisoning:

A. Emergency Measures: Remove patient to fresh air and wash skin or mucous membranes with copious amounts of water. Showers and bubbler eye fountains must be available where dimethyl] sulfate is used. Washing should continue for at least 15 minutes. Treat skin corrosion the same as aburn. Observe exposed individuals for at least 24 hours for the development of symptoms. B. Antidote: None known. C. General Measures: 1. Inhalation of nebulized epinephrine, 1:100, may relieve bronchospasm and cough. 2. Do not give depressants such as morphine or barbiturates. D. Special Problems: Treat pulmonary edema (see p. 31). Prophylaxis: If the agent is spilled, the building must be evacuated the dimethyl sulfate decomposed by hosing with water or

and

spraying with 5% sodium hydroxide (caustic soda). Workers who enter contaminated areas must wear a positive- pressure air-line hose mask or self-contained breathing apparatus. Canister-type gas masks are not safe. Prognosis: The first 24 hours after poisoning is the most dangerous period. If pulmonary edema can be controlled, recovery is likely. Complete recovery from eye irritation may take up to one month.

TRI-ORTHO-CRESYL Tri+cresyl phosphate, isomeric

forms,

ortho-,

(CHgCgH4)3PO4, meta-,

and para-.

form is of toxicologic importance. appreciably

PHOSPHATE exists in three Only the ortho-

It is a liquid which fumes

at 100°C. a

Tri-ortho-cresyl

fireproofers,

phosphate

is used

in lubricants,

and as a plasticizer in plastic

coatings.

in

Fatty

foods stored in plastics containing free tri-ortho-cresyl phosphate will become contaminated. The fatal dose by ingestion is estimated to be 1 to 10 Gm. (15 to 150 gr.). Food contaminated to the extent of 0. 4% has caused serious poisoning. The m.a.c. has not been established. Up to ten deaths per year have been reported from ingestion or industrial exposure. Demyelinization of nerves is the most prominent finding. Degenerative changes are also found in the muscles and spinal cord. As a result of these changes, a flaccid paralysis

Tri-ortho-cresyl evelops which affects the more rms.

distal muscles

Phosphate

117

of the legs and

Tri-ortho-cresyl phosphate inhibits nonspecific cholinsterase but not acetylcholinesterase. The relationship beween this inhibition and the nerve demyelinization is unknown.

linical Findings: The principal manifestation of tri-ortho-cresyl phoshate poisoning is muscular paralysis. A. Acute Poisoning: (From ingestion, inhalation, or skin absorption.) Symptoms begin one to 30 days after exposure and include weakness of the distal muscles progressing to foot drop, wrist drop, and loss of plantar reflex. Laryngeal, ocular, and respiratory muscles are affected in severe poisoning. Death is from respiratory paralysis. B. Chronic Poisoning: The above symptoms may be produced by cumulative exposure over several months. C. Laboratory Findings: Noncontributory.

reatment: A. Acute Poisoning: 1. Emergency measures - Remove ingested poison by gastric lavage or emesis, followed by catharsis (see pp. 10 to 13). Give artificial respiration as needed. 2. Antidote - None known. 3. General measures - If respiratory depression or weakness of respiratory muscles occurs, give artificial respiration with oxygen. An iron lung or rocking bed may be necessary for several weeks before sufficient recovery occurs. B. Chronic Poisoning: Treat as for acute poisoning. rophylaxis: Food should never

ining unreacted

be stored

tri-ortho-cresyl

in plastic

containers

phosphate.

con-

Containers

I1d for food purposes are safe. Processes utilizing tri-ortho-cresyl phosphate at high mperatures must be totally enclosed to avoid contamination

workroom

air.

rognosis:

In paralysis from tri-ortho-cresyl phosphate, ay be gradual over

very May never

a period of one year.

occur.

recovery

Complete

re-

118

ACETALDEHYDE,

METALDEHYDE,

AND

PARALDEHYDE

ia a

vu

fo)

“So

| Ze

ICH2C

:

Metaldehyde

Cc SS

fe) | CN

Ho 8So

ane ue H3 ~ = @

Ces Acetaldehyde

Paraldehyde

Metaldehyde (B.p. 246°C.), a tasteless, water-insoluble solid; and paraldehyde (B.p. 124°C.), a water-soluble (1:8) liquid with burning taste and smell are polymers of acetaldehyde (B.p. 20°C.), a highly volatile, irritating, watermiscible liquid. In the presence of acids, paraldehyde decomposes readily and metaldehyde decomposes slowly to Paraldehyde is used as an hypnotic, metaldeacetaldehyde. hyde as a snail bait, and acetaldehyde as a reagent in chemical synthesis. The m.a.c. in air for acetaldehyde is 200 p.p.m. Levels for paraldehyde and metaldehyde have not been established. Deaths from acetaldehyde have not been reported in recent years, but about one death per year is reported for metaldehyde and one death per year for paraldehyde. Paraldehyde and metaldehyde presumably are decomposed slowly to acetaldehyde in the body. In the case of paraldehyde, the rate apparently does not exceed the rate of acetaldehyde oxidation, so that acetaldehyde does not accumu late. With metaldehyde, the rate of decomposition to acet-

aldehyde may exceed the rate of oxidation of acetaldehyde since fatalities have had symptoms poisoning.

Acetaldehyde,

a highly reactive

suggestive

chemical,

and depressing to all cells. Metaldehyde only after decomposition to acetaldehyde.

duces depression of the C.N.S.

of acetaldehyde

is irritating

apparently acts Paraldehyde pro-

without slowing of respi-

ration.

Pathologic findings in deaths from acetaldehyde poisonin; are pulmonary irritation and edema. After paraldehyde or metaldehyde poisoning, findings are not characteristic. Clinical Findings: The principal manifestations of poisoning with these agents are irritation and coma. A. Acute Poisoning: 1. Acetaldehyde - Exposure to the vapors causes severe

irritation of mucous

membranes,

reddening of the

Acetaldehyde, skin,

coughing,

gestion

causes

Metaldehyde,

pulmonary edema, nausea,

vomiting,

Paraldehyde

119

and narcosis.

In-

diarrhea,

and respiratory failure. 2. Paraldehyde - Ingestion ordinarily induces out depression

of respiration,

although

narcosis,

sleep with-

deaths

occa-

sionally occur from respiratory and circulatory failure after doses of 10 ml. or more. 3. Metaldehyde - Ingestion causes nausea, retching, severe

tion,

vomiting,

muscular

abdominal

rigidity,

pain,

temperature

convulsions,

coma,

eleva-

and

death from respiratory failure up to 48 hours after ingestion. B. Chronic Poisoning: 1. Acetaldehyde - Repeated exposure to the vapors causes dermatitis and conjunctivitis.

2. Paraldehyde ,

- Chronic medicinal use of paraldehyde

will produce mental deterioration and delirium tremens (see p. 110). 3. Metaldehyde - Amounts less than necessary to produce acute poisoning are without effect. Treatment: A. Acute Poisoning From Fume Exposure: 1. Emergency measures a. Remove from exposure. b. Give oxygen by inhalation. 2. Antidote - None known. 3. General measures - Treat pulmonary edema

(see p.

31). B. Acute Poisoning by Ingestion: 1. Emergency measures - Remove poison by gastric lavage or emesis followed by catharsis (see pp. 10 to

13). i) .

Antidote

- None

known.

3. General measures a. Treat coma (see p. 27). b. Treat hypoxia (see p. 17). C. Chronic Poisoning From Fume Exposure: Remove further exposure. D. Chronic Poisoning From Paraldehyde Ingestion: 1. Remove from further exposure. 2. Treat mental symptoms (see p. 111). Prophylaxis: Chronic use of paraldehyde should be avoided. m.a.c. for acetaldehyde must not be exceeded.

from

The

Prognosis: If patient survives for 48 hours after acute poisoning, recovery is likely. Complete recovery after chronic poisoning from paraldehyde is not likely.

120 ALDEHYDES, KETONES, ETHERS, AND (For treatment, see p. 119.)

ESTERS

Legend:

1 - Slight 2 - Noticeable

or

Cal

easily apparent 3 - Moderate

4 - Strong, ;

oak

==

a

5 s|

or

3

Be

2

intense effect

5

v

2

ho a

s °

| |

=

16

Pr Brey!

ioe

a

oe

4

SS

=

sy | 4

led

ALDEHYDES Acetaldehyde

4

ae

damage,

pulmonary edema,

Acrolein

Croton aldehyde

Formaldehyde Furfural

Metaldehyde

==

Noes

ft =

Not est.

Deis

Kidney damage. Cirrhosis edema,

ay

al

of

liver,

onvulsions,

pulmonary

coma.

KETONES

Acetone Butanone-2 Hexanone-2

|-Methyl-

pentanone-4 Cyclohexanone

Isophorone Ketene

500 250 100

3 2 |3 |

100

ne

iqaroarane

| 2 |Renal damage.

Not est.

Pulmonary

eying

edema,

as toxic as

phosgene (see p. 106).

Mesityl oxide Methyl propyl ketone

ETHERS Dioxane

Hemorrhagic

nephritis,

liver

necrosis,

Diethyl ether Isopropyl ether

400 2 [4] 300

ESTERS Amy! acetate

Butyl acetate

1 | Anesthetic effect from hydrolysis to alcohol,

200

ee

Ethyl acetate

400 ae

Ethyl formate

sees ditsamalliaet Hydrolyzes to formic acid (see

Congestion of liver and kidneys in high concentrations. p. 130).

Ethyl methaerylate Ethyl! silicate

400

100

4

heHydrolyzes to silicic acid, a powerful irritant. For treatment, see p. 118.

Methyl acetate a

aks

Methyl formate eae Methyl methacrylate

Propyl acetate

Basses.

Produces eye damage like methyl alcohol (see p. 107). ydrolyzes to formic acid (see p. 130). May produce eye damage like methyl alcohol (see p. 107). From burning resin (Plexiglas),

After effects are short-lasting.

Chapter 13

HYDROCARBONS

PETROLEUM DISTILLATES: KEROSENE, DISTILLATE, AND GASOLINE

SOLVENT

All the petroleum distillates are clear liquids. B.p.: Kerosene, 150 to 300°C. ; Solvent distillate, 100 to 150°C.; Gasoline, naphtha, petroleum ether, mineral spirits, paint thinner,

50 to 100°C.

Kerosene,

solvent

distillate

(Stoddard solvent),

and

gasoline are used as fuels and solvents.

Ingestion of more than 10 ml. (1/3 oz.) may be fatal,

al-

though reco Ss followed ingestion of 250 ml. (8 oz.). The m.a.c. inairis 500 p.p.m. The presence of benzene in gasoline increases the toxicit gréatly (see Diy 122). UpA0 ten fatalities per year have been reported from ingestion or inhalation of petroleum distillates. Petroleum distillates are irritants because they dissolve

fats.

They also depress the cells of the C.N.S. S. The effects

on liver, kidneys, and bone marrow nants such as benzene.

the pulmonary

may be from contami-

irritation. Aspiration during vomiting may

also be important. ~~ Pathologic findings in acute poisoning include pulmonary edema, bronchial pneumonia, and gastrointestinal irritation.

Degenerative

changes

in the liver and kidneys and hepeniants |

of the bone marrow may 1igh concentrations.

appear

after prolonged

inhalation

of/

Clinical Findings: The principal manifestations of poisoning with these agents are coma, and pulmonary irritation. A. Acute Poisoning: rom inhalation or ingestion.) Nausea, vomiting, cough, depression of the C.N.S. (dependent on the ingested amount), and pulmonary irritation progressing

to pulmonary

edema,

bloody sputum,

chial pneumonia with fever and cough. and emphysema toms of C.N.S.

may complicate recovery. depression are weakness,

121

and bron-

Pneumothorax The sympdizziness,

122

Benzene

peer and shallow

respiration,

unconsciousness,

and con-

vulsions. B, Chronic

Poisoning:

(From

inhalation.)

Dizziness,

weak-

ness, weight loss, anemia, nervousness, pains in the limbs, peripheral numbness, and paresthesias. CiLaboratory Findings: 1. The red blood cell count may be reduced. 2. The bone marrow may show hypoplasia. 3. The urine may show albumin and red cells. Treatment: A. Acute Poisoning: 1. Emergency measures - Remove ingested poison by gastric lavage with 2 to 4 L. of tap water or milk, using care to avoid aspiration. Do not use emesis. Follow by saline cathartic (see p. 13) emove patient to fresh air. nw

. Antidote

- None known.

3. General measures - Give artificial respiration with oxygen if respiration is depressed. 44 Special problems - Treat or prevent bronchial pneumonia by giving penicillin, one million units daily I.M., until temperature has been normal for three days.

B. Chronic

Poisoning:

Treat as for acute poisoning.

Prophylaxis: Kerosene, petroleum stored carefully.

solvent,

and gasoline should be

Prognosis:

Survival for 24 hours is ordinarily followed by complete recovery.

BENZENE

Liquid;

B.p.:

80°C.; Vapor pressure

at 20°C.:

74.6 mm.

Hg. The m.a.c. of benzene is 35 p.p.m. Up to ten deaths per year have been reported from benzene inhalation.

In large amounts, peated exposure

benzene depresses the C.N_S. ;

to small

In acute fatalities,

amounts

depresses the bonesnarrow.

the postmortem

findings include

Benzene

123

petechial hemorrhages;—nenceagulatedblood,» and congestion oF allorggns- Fe) Stee eS | eeeveberr In fatalities from chronic exposure, the findings include severe bone marrow aplasia, anemia; necrosis or fatty degeneration of the heart, liver, and adrenals; and hemorrhages.

Clinical Findings:

The principal manifestations of benzene poisoning are_ coma

and anemia.

A. Acute Poisoning:

(From inhalation or ingestion.)

Symp-

toms from mild exposure are dizziness, weakness, euphoria, headache, nausea, vomiting, tightness in the chest, and staggering. are exposure is more severe, symptoms progress to visual blurring, tremors; shallow, rapid respiration; paralysis, unconsciousness, and convulsions. Violent excitement or delirium may precede unconsciousness. Skin contact causes irritation, scaling, and cracking.

B. Chronic

Poisoning:

(From inhalation.)

Symptoms

include

headache, loss of appetite, drowsiness, nervousness, pallor, anemia, petechiae, and abnormal bleeding. The anemia may progress to complete aplasia of the bone marrow. Leukemia has been reported as a rare com-

plication of benzene-potsoning-———— C. Laboratory Findings: _ fs Vhe red blood | cell countmay b be diminished to 20% of

normal.

is

LHe Te

24 The white blood cell count may be diminished to 5 to 10% of normal. The differential count shows the greatest decrease in the polymorphonuclear leukocytes.

3. The thrombocytes may be reduced to 10 to 50% of normal. 4. The tourniquet test (Rumpel-Leede) is positive. 5. The bone marrow may appear normal, hypoplastic, hyperplastic.

or

Treatment:

A. Acute Poisoning: 1. Emergency measures - Remove patient from contaminated air and give artificial respiration with oxygen (see p. 24). Remove ingested benzene by gastric lavage with care to avoid aspiration, and catharsis (see pp. 11 to 13). Do not induce emesis.

2. Antidote - None known. 3. General a.

measures

Keep at complete normal.

b. DO NOT

drugs.

GIVE

}

bed rest until respiration

epinephrine

is

or ephedrine or related

They may induce fatal ventricular fibril-

124

Naphthalene

4. Special problems - Treat anemia by repeated blood transfusions. Treat as in acute poisoning. B. Chronic Poisoning:

Prophylaxis: Adequate ventilation must always be supplied in work Concentration in air rooms where benzene is being used.

A suitable analyzer is sold by

should be checked frequently. Harold Kruger

Instruments,

P.

Box

O.

San Gabriel,

164,

Where high vapor concentrations California. forced air masks should be used. A life-line responsible person outside the contaminated mandatory. If skin contact is unavoidable, neoprene

are unavoidable, attended by a enclosure is gloves must be

worn. Prognosis: In acute poisoning, death may occur up to three days Rapid progression of symptoms and lack of after poisoning. response

to removal

of benzene

indicate

a poor

outcome.

In chronic poisoning, a steady decrease in the cellular elements of the blood or bone marrow indicates a poor outIf the cellular elements remain at a constant low level come. Patients have reor rise gradually, recovery is likely. covered after as much as a year of almost complete absence of formation

of new blood elements.

NAPHTHALENE

Melting point: 80°C. ; B.p.: 80°C.: 9.8 mm. Hg. Naphthalene,

obtained from

218°C.;

Vapor pressure

coal tar,

at

is used as a moth-

sae repelient and synthetic intermediate. 1é fatal dose of ingested naphthalene is approximately a

).

in children rous most This chemical is dange

No upto the age of six, in whom absorption occurs rapidly. Approximately one death per m.a.c. has been established.

veer from naphthalene. besSean (epaniedise.. iiaarae oe aphthalene

causes

hemolysis

renal tubules by precipitated has been reported.

with subsequent blocking of

hemoglobin.

Hepatic

necrosis

Naphthalene

125

Clinical Findings: The principal manifestations from naphthalene poisoning are hemolysis, jaundice, and oliguria. A. Acute Poisoning: (From ingestion or inhalation. ) 1. Ingestion - Nausea, vomiting, diarrhea, oliguria, anemia, jaundice, and pain on urination progressing to oliguria or anuria. In more serious poisoning, excitement, coma, and convulsions may occur. 2. Inhalation - Headache, mental confusion, and visual disturbances have been reported from exposure to boiling naphthalene. B. Chronic Poisoning: 1. Repeated ingestion will cause the symptoms described for acute poisoning. 2. Local effects - Continued handling of naphthalene may produce a dermatitis characterized by itching, redness, scaling, weeping, and crusting of the skin. Eye contact causes corneal irritation and injury. C. Laboratory Findings:

1. RBC

may be 20 to 40% of normal.

WBC

may be in-

Hemolysis may be present (see p. 29). creased. 2. Urine may contain hemoglobin, albumin, and casts. Treatment: A. Acute Poisoning: 1. Emergency measures - Remove ingested naphthalene by gastric lavage or emesis and catharsis (see pp. 10 to 138). 2. Antidote - No antidote is known. 3. General measures a. Alkalinize urine - Give sodium bicarbonate, 5 Gm. (75 gr.) orally every four hours or as necessary to maintain alkaline urine. b. Give repeated small blood transfusions until hemo-

globin is 60 to 80% of normal. 4. Special problems - Treat anuria (see p. 29). B. Chronic Poisoning: Treat as for acute poisoning.

Prophylaxis: Store naphthalene safely. Exhaust ventilation is necessary during work with naphthalene. Periodic eye, blood, and urine

examinations

should

be made

in naphthalene

workers.

Prognosis: Rapid progression to coma and convulsions indicates poor prognosis. Anuria may persist for one to two weeks with eventual complete recovery. Local effects disappear in one to six months after discontinuing exposure.

126 TURPENTINE

Turpentine is a colorless liquid consisting of a mixture distilsaturated cyclic hydrocarbons obtained by the steam lation of pine secretions. varnishes, and polishes.

of

It is used as a solvent in paints, It evaporates readily at room tem-

perature and has a boiling range of 155 to 165°C. g. As little as 15 Gm. yj2 oz.) has caused fatal poisonin Approximately one fatality per The m.a.c. is 100 p.p.m. is inyear is reported from ingestion of turpentine, which tensely irritating to all tissues. The pathologic findings are intense congestion and edema The kidneys reveal in the lungs, brain, and gastric mucosa. degenerative

changes.

Clinical Findings: The principal manifestation of turpentine poisoning is irritation of mucous membranes. A. Acute Poisoning: 1. Ingestion - Abdominal burning, nausea, vomiting,

diarrhea, pain on urination, dark urine, unconsciousness, shallow respiration, pulmonary edema, bronchial pneumonia, and convulsions.

2. Inhalation - Irritation of eyes,

nose,

and throat;

dizziness; rapid, shallow breathing; rapid pulse, bronchial irritation, pulmonary edema, bronchial pneumonia, and unconsciousness or convulsions. B. Chronic poisoning has not been reported. C. Laboratory Findings:

1. The red blood cell count may be low.

2. The urine may contain hemoglobin, red blood cells, albumin, casts, and reducing sugar.

Treatment of Acute Poisoning: Remove A. Emergency Measures:

ingested poison by gastric Aspiration must be prevented (see lavage and catharsis. pp. 10 to 13). B. Antidote: None known. C. General Measures: 1. Give milk, 250 ml. (1 cup) or mineral oil, 30 ml. (1

oz.) as necessary to allay gastric irritation.

2. If respiration with oxygen.

is depressed,

give artificial respiration

3. Give fluids to 4 L. daily to maintain

maximum

urinary

output after danger from pulmonary edema has passed (after first 24 hours) and if renal function is unimpaired. D. Special Problems: 1. Treat pulmonary edema (see p. 31). 2. Treat anuria (see p. 29).

Turpentine

127

‘rophylaxis: Turpentine must be stored safely. Medications containig turpentine must be labeled, ‘‘For external use only.’’ The 1.a.c. must always be observed. A mask capable of aborbing organic vapors may be used for short periods if high oncentrations

must

be entered.

‘rognosis: If the patient lives for 24 hours, kely.

complete

HYDROCARBONS (For treatment, see p. ~egend: 1 - Slight effect 2 - Noticeable or

recovery

is

122.)

ey

ie eS)

&

2. g |

easily apparent

E

ohare

>

a)

a

3 - Moderate effect

a

go

J

3

by

&

s fis

4 - Strong,

or intense

effect

Acetylene A4mylene 3utadiene-1, 3utane umene “yclohexane “yclohexene JYecalin diphenyl

‘

ee:

H

26


> bo

ee

3%

CI

5 A

3

Not est. 500

3 2

2 1

2

Yaphtha solvent -entane -ropane

2 ta

tyrene

3

retraline “oluene

3 200

2

3 2 S 2 2

2 4

1 2

Chapter 14

CORROSIVES

OXALIC Formula: COOH—COOH; ciably when heated to 100°C.

ACID soluble in water;

fumes

appre-

Oxalic acid is used as a bleach and metal cleaner in industry and in household products. The fatal dose by ingestion is estimated to be 5 Gm. (75 gr.). Up to five deaths from oxalic acid occur yearly. Oxalic acid is a corrosive acid. Oxalates combine with serum calcium to form insoluble calcium oxalate. The reduction in available calcium leads to violent muscular stimulation with convulsions In deaths

following

and collapse. oxalic

acid poisoning,

calcium

oxalate

crystals are found in the renal tubules and in other tissues. The kidneys show cloudy swelling, hyaline degeneration, and sclerosis of the tubules. Corrosive changes may be found in the mouth, esophagus, and stomach. Cerebral edema also is a frequent finding. Clinical

Findings:

The principal manifestation

of oxalic acid poisoning is

anuria.

A. Acute Poisoning: (From ingestion.) Symptoms begin with local irritation and corrosion of the mouth, esophagus, and stomach, with pain and vomiting. These sym z toms are followed shortly by muscular tremors, convulsions, weak pulse, and collapse. Death may occur within minutes. After apparent recovery, acute renal

failure may occur from blocking of renal tubules by calcium

oxalate.

B. Chronic Poisoning: (From skin contact or inhalation.) Prolonged skin contact may cause cyanosis and gangrene by local corrosive affect. Prolonged inhalation of fumes produced by boiling oxalic acid solutions leads to oxalic acid poisoning with renal impairment.

C. Laboratory Findings: 1. Envelope-shaped calcium oxalate crystals, cells, and albumin are found in the urine. 128

red blood

Miscellaneous

Acids

129

2. Other clinical laboratory tests are noncontributory. Treatment:

A. Acute Poisoning: 1. Emergency measures - Remove lavage or emesis and catharsis. lactate,

10 Gm.

(2 tsp.),

oxalic acid by gastric Dissolve calcium in lavage, emesis, or

catharsis fluids. 2. Antidote - Precipitate oxalate by giving calcium in any form orally, such as milk, lime water, chalk, calcium gluconate, calcium chloride, or calcium lactate. Give calcium gluconate, 10%, 10 ml. I.V., and repeat if symptoms persist. 3. General measures - If renal function remains normal, give fluids to 4 L. daily to prevent precipitation of calcium oxalate in the renal tubules. B. Chronic Poisoning: Remove from further exposure.

Prophylaxis: Store and use oxalic acid safely. Avoid prolonged skin contact. Avoid fumes from boiling oxalic acid. Prognosis: If calcium likely.

antidotes

MISCELLANEOUS

can be given promptly,

ACIDS AND ACID-LIKE (See table on p. 130.)

recovery

is

CORROSIVES

The acid and acid-like corrosives listed in the table on p. 130 are used for cleaning metals and other products and in a variety of chemical reactions. Ingestion of 1 ml. of a corrosive acid has caused death. (See table on p. 130 for m.a.c.) Up to five deaths per year are reported from the ingestion of acids. Corrosive acids destroy tissues by direct chemical action. The tissue protein is converted to acid proteinate, which dissolves in the concentrated acid. Hemoglobin is converted to dark acid hematin and is precipitated. The intense stimu-

lation by acid causes reflex loss of vascular tone. The pathologic findings are those of corrosion and irritation. After ingestion, corrosive penetration of the esophagus and stomach are commonly found. The area of contact is stained brown or black except in the case of nitric and picric acids, which produce a yellow stain, Precipitated blood (coffee-grounds material) is frequently found in the stomach. The epithelium of the esophagus may desquamate in portions or as a whole. The eye shows swelling of the corneal lamella, with death of corneal cells.

130 ACID OR ACID-LIKE CORROSIVES (For treatment, see p. 131) Legend: 1 - Mild irritation and reddening. 2 - Strong irritation and erythema, blistering. 3 - Superficial destruction of skin or mucous membrane, 4 - Complete destruction of skin or mucous membrane,

n

A3o

& ov

2. io) &

Ay 4 3 ‘AiS) n > = form) A (usual

GCG, p.m.) (p. M.A’

Effect Pulmonar Corrosive Dose Fatal Estin:atedEffect

Acetic acid (glacial) Acetic anhydride Aluminum chloride

bo wo]

Aluminum sulfate Boron trifluoride Bromine

Calcium

Beet

aa

chloride

Chlorine

ae ee ee

Chlorosulfonic acid Copper sulfate Ferric chloride

ee a RE IRS 2 ee ae RE [ERR LSolidus) ina (oes a 280 Gandy 28

Hydrazoic acid Hydriodic acid

rEgae=

Formic acid

Hydrobromic acid

Hydrochloric acid Hydrofluorie acid Hydrogen bromate Hydrogen fodate Todine Maleic anhydride Nitric acid Nitrogen oxides

ae 2 S20: Ra DN egy ero eee era ee (RUE

pore

el, [oe

ea) ea a)

plague of Ot ee aa, | Piigdd = ye ak Pee Pagadianeed peal a a ee] ero (Geld « nn sides Wa i i |e ea Liquid Gas

Beas

Osmic acid Perchloric acid Picric acid Platinum salts

Eee

oe ee |

Ee :

wo

Sodium acid sulfate Stannic

chloride

Fuming

Sulfur dioxide Sulfur trioxide

Gas Gas

Sulfuric acid

acid Sulfurous Trichloroacetic Zine sulfate

Liquid

acid

equa Solid Solid

liquid

10

om 1 Gm, Pe 10 Gm,

|e] co |]

Acids

131

Clinical Findings: The principal manifestation of acid poisoning is corrosion. A. Acute Poisoning: ig Ingestion - Severe, burning pain in the mouth, pharynx, and abdomen followed by vomiting and diarrhea of dark precipitated blood. The blood pressure falls sharply. Brownish or yellowish stains may be found around or in the mouth. After initial recovery, onset of fever indicates mediastinitis or peritonitis from perforation of the esophagus or the stomach. If the patient recovers from the immediate damage, scar formation in the esophagus leads to progressively increasing difficulty in swallowing. . Inhalation

- Inhalation

of acid fumes

causes

coughing,

choking, and variable symptoms of headache, dizziness, and weakness followed after a six- to eight-hour latent period by pulmonary edema with tightness in the chest,

air hunger,

dizziness,

frothy

sputum,

and

cyanosis. The accompanying physical findings are moist rales, low blood pressure, and high pulse pressure. . Skin contact - Symptoms are severe pain and brownish or yellowish stains. Burns usually penetrate the full thickness of the skin, have sharply defined edges, and heal slowly with scar formation. Infections are common. . Eye contact - Conjunctival edema and corneal destruction occur from even dilute acids in the eyes. The symptoms are pain, tearing, and photophobia. B. Chronic Poisoning: (From inhalation.) Long exposure to acid fumes may cause erosion of the teeth followed by jaw necrosis. Bronchial irritation with chronic cough and frequent attacks of bronchial pneumonia are common. Gastrointestinal disturbances are also noted. C. Laboratory Findings: In acute poisoning, hemoconcen-

tration may be indicated by a rise in red blood cell count and hematocrit. Treatment:

A. Ingested Acid: ih Emergency measures a. Dilute the acid - Ingested acid must be diluted within seconds by drinking quantities of water, milk, or beaten eggs (at least 12). No time should be wasted searching for a chemical antidote since delay of a few minutes may allow lethal damage to the esophagus and stomach. If vomiting is persistent, administer fluids repeatedly. Ingested acid must be diluted approximately

less to tissues.

100 times

to render

it harm-

132

Acids

b. Gastric lavage - This may be done in the first hour after ingestion of corrosive without danger of perforation. Pass a Levine tube cautiously and lavage with 2 to 4 L. of lukewarm tap water, using not more than 250 ml. (1 cup) ata time. The Levine tube should be maintained in place until damage to the esophagus can be evaluated. c. Relieve pain - Give morphine sulfate, 5 to 10 mg. (4/12 to 1/6 gr.) every four hours as necessary. Avoid C.N.S. depression. d. Treat shock (see below). 2. Antidote - Chemical neutralization is not advised. 3. General measures a. Treat shock - Maintain normal blood pressure by transfusion and by the administration of 5% dextrose in saline (see p. 25). b. If symptoms are severe and perforation of the stomach or esophagus is suspected, give nothing by mouth and maintain suction on the Levine tube (see p- 11). Treat surgically. ce. Maintain nutrition by giving 400 Gm. of carbohydrate

I.V.

daily.

4. Special problems

- Prevent

esophageal

passing a mercury-filled bougie,

1 cm.

stricture

by

(1/2 inch) in

diameter, daily after danger from esophageal perforation has passed. Intervals between bouginage may eventually be lengthened to three or four months, but treatment must be continued throughout life.

B. Eye Contact: 1. Emergency measures - Dilute the acid. Flood affected area with quantities of water in a shower or by means of water bubbler eye fountain for at least 15 minutes. Eyelids must be held apart during the washing (see p. 14). 2. Antidote - Do not use chemical antidotes. The heat liberated in the chemical reaction may actually increase injury. 3. General measures - Eye burns require the immediate attention of an ophthalmologist. If an ophthalmologist is not immediately available, instill 1% atropine sulfate into the eye until the pupils are widely dilated. Then take the patient to an ophthalmologist. C. Skin Contact: 1. Emergency measures - Remove acid by flooding with water for at least 15 minutes. If the clothing is contaminated,

a stream

of water

must

be directed

under

the clothing while the clothes are being removed in order to remove the acid rapidly. 2. Antidote - Do not use chemical antidotes (see above). 3. General measures - Treat damaged areas by continuous

Alkalies

133

application of tyrothricin (0.05%), or polymyxin B sulfate (0.1%) wet dressings to prevent infection. Do not use occlusive dressings. D. Inhalation:

E. Chronic

Treat pulmonary

Poisoning:

Remove

edema

(See p.

31).

from further exposure.

°rophylaxis: Store acids and other corrosives

safely.

The m.a.c.

nust always be observed (see table on p. 130). Water bubbler ye fountains and showers must be available where skin or ~ye contact with acids is possible. Tight-fitting goggles, rubber aprons, and rubber gloves MUST be worn when handling acids. Employees must be irilled in the constant use of safety equipment.

>rognosis: Approximately 50% of those who ingest acid die from the mmediate effects. Damage to the esophagus and stomach ifter ingestion may progress for two to three weeks. Death rom peritonitis may occur as late as one month after insestion. Approximately 95% of those who ingest acid and re-

‘over from stricture.

the immediate

effects have

persistent

esophageal

Skin burns from acid are followed by extensive scarring. kin grafting is required if a good cosmetic effect is desired. Sorneal damage almost always results in blindness.

ALKALIES: POTASSIUM HYDROXIDE, SODIUM HYDROXIDE, POTASSIUM CARBONATE, AND SODIUM CARBONATE (See p. 135.) These agents are used in the manufacture

of soap,

chem-

cal

synthesis, and in cleaners. The fatal doses of alkalies are listed in the table on p. 135. Jp to 25 fatalities from sodium hydroxide or potassium hylroxide ingestion are reported yearly. The alkalies combine with: protein to form proteinates

ind with

fats to form

soaps,

thus producing

soft,

necrotic,

leeply penetrating areas on contact with tissues. The solulity of these products allows further penetration which may -ontinue for several days. Pathologic findings include gelatinous, necrotic areas at he sites of contact. Intense stimulation by alkalies causes reflex loss of vasular tone and cardiac inhibition.

Slinical Findings: The principal S corrosion.

manifestation

of poisoning

with the alkalies

134

Alkalies

A. Acute Poisoning: ill Ingestion - Ingestion of alkali is followed by severe The vomitus pain, vomiting, diarrhea, and collapse. If contains blood and desquamated mucosal lining. death does not occur in the first 24 hours, the patient

may improve

for two to four days and then have a

sudden

of severe

onset

abdominal

pain,

board-like

abdominal rigidity, and rapid fall of blood pressure indicating delayed gastric or esophageal perforation. Even though the patient recovers from the immediate damage, esophageal stricture will make swallowing difficult. 2. Eye contact with concentrated alkali causes conjunctival edema and corneal destruction. Extent of damage 3. Alkalies penetrate skin slowly. therefore

depends

on duration

of contact.

B. Chronic Poisoning: (From skin contact.) A chronic dermatitis may follow repeated contact with alkalies. C. Laboratory Findings: Red blood cell count and hematocrit are increased. Treatment:

A. Ingestion: dis Emergency measures a. Dilute the alkali - Give water or milk to drink immediately and allow vomiting to occur. At least 2 L.

of liquid must

be given if 30 Gm.

lye has been ingested.

(1 oz.) of

Fruit juice or vinegar may

then be given in order to neutralize the alkali. b. Gastric lavage - A Levine tube may be passed

safely within the first hour after poisoning. lavage with 2 to 4 L. administered

of water

using 240 ml.

Gastric

or vinegar is then

(8 oz.) portions

and re-

moving the liquid each time. 2. Antidote - At least 2 L. of fruit juice or vinegar shoulk be given for each 30 Gm. of alkali ingested. 3. General measures - Treat as on p. 132. B. Eye Contact: iF Emergency measures - Wash eye for 15 minutes with running water.

. Antidote - Irrigate eye for 30 to 60 minutes with normal saline solution. 3. General measures - Treat as on p. 132, paragraph

B

3. C. Skin Contact: Wash with running water until skin is free of alkali as indicated by disappearance of soapiness.

D. Chronic

Poisoning:

treat dermatitis

Remove

(see p.

36).

from further contact and

Ammonia,

Ammonium

Hydroxide

135

Prophylaxis: Store corrosive alkalies safely. Water bubbler eye fountains and showers must be available where skin or eye contact with alkalies is possible. Tight-fitting goggles, rubber aprons, and rubber gloves MUST be worn when handling alkalies in concentrated solutions. Employees must be drilled in the constant

use

of safety equipment.

Prognosis: Approximately 25% of those who ingest strong alkali die from the immediate effects. Damage to the esophagus and stomach after ingestion may progress for two to three weeks. Death from peritonitis may occur as late as one month after ingestion. Approximately 95% of those who ingest strong alkali and recover from esophageal stricture.

Corneal

damage

the immediate

is almost always

ALKALI

effects have

persistent

permanent.

CORROSIVES (Solids)

Legend: 1. Mild irritation and reddening. 2. Strong irritation and erythema,

3. 4.

blistering.

Estimated Fatal Dose

Corrosive Effect

Superficial destruction of skin or mucous membrane. Complete destruction of skin or mucous membrane. Calcium oxide Cement Potassium carbonate

Potassium

hydroxide

Sodium

carbonate

Sodium Sodium

hydroxide phosphate

Sodium

silicate

AMMONIA

AND

LK] WM] PP NOK w

AMMONIUM

HYDROXIDE

Ammonia (NHs3) is a gas at ordinary temperatures. Ammonium hydroxide (NH4OH) is a liquid containing 25 to 29% NH3; vapor pressure at 27°C.: 500 mm. Hg.

Ammonia is used in organic synthesis, as a refrigerant, and as a fertilizer. Ammonium hydroxide is used in organic synthesis and as a cleaner. The m.a.c. of ammonia is 100 p.p.m. The fatal dose of

ammonium

hydroxide by ingestion is about 30 ml.

(1 oz.) of a

136

Ammonia,

Ammonium

25% concentration.

Hydroxide

Up to five fatalities

from the ingestion of ammonium

per year

are reported

hydroxide or inhalation of

ammonia. Ammonia and ammonium hydroxide injure cells directly by alkaline caustic action and cause extremely painful irri-

tation of all mucous The pathologic

monary

edema,

ingestion,

membranes. findings in inhalation

pulmonary irritation,

the findings

are

the same

poisoning are pul-

and pneumonia. as

with

the other

After alkalies

(see p. 133).

Clinical Findings: The principal manifestation pounds is extreme irritation.

of poisoning with these

com-

A. Acute Poisoning: 1. Ingestion - Ingested ammonia

causes severe pain in the mouth, chest, and abdomen, with cough, vomiting, and shock-like collapse. Gastric or esophageal perforation may occur later with exacerbation of abdominal pain, fever, and abdominal rigidity. Lung

irritation and pulmonary 24 hours’ delay.

edema

may appear after 12 to

2. Ammonia fumes (1000 p. p.m.) cause irritation of the eyes and upper respiratory tract, with cough, vomiting, conjunctival injection, and redness of the mucous membranes of the lips, mouth, nose, and pharynx. Higher concentrations cause swelling of the lips and conjunctivae, temporary blindness, restlessness, tightness in the chest, frothy sputum indicating pulmonary

edema, cyanosis, and rapid, weak pulse. 3. Skin contact - If skin contact is prolonged more than a few minutes it causes severe burning pain and corrosive damage. 4. Eye contact with concentrated ammonia causes immediate severe pain followed by conjunctival edema and corneal clouding. Later, cataract formation and atrophy of the retina and iris may occur. B. Chronic poisoning has not been reported. C. Laboratory Findings: Noncontributory. Treatment

of Acute

A. Emergency

Poisoning:

Measures:

1. Remove ingested poison as described on p. 132. 2. Eye contamination - Wash eyes in a water bubbler eye fountain for at least 15 minutes. Follow this by repeated irrigation with normal saline solution. The patient should be taken to an opthalmologist for further treatment. 3. Inhalation - Remove patient from contaminated area an keep at bed rest.

Fluorine

and Derivatives

137

— Skin contamination - Wash skin for at least 15 minutes. B. Antidote: Fruit juice or vinegar may be given by mouth or used externally. C. General Measures: Treat as described on p. 132. D. Special Problems: 1. Treat 2. Treat

pulmonary edema (see p. 31). esophageal stricture (see p. 132).

-rophylaxis: Employees

working in areas where ammonia is used must e trained in escape methods and in the use of safety equipnent, including goggles, gas masks, showers, eye fountains, yater hoses, exits, and first aid equipment. Ammonia equipnent must be constantly inspected to prevent accidents. All alves should be carefully labelled to prevent accidental

pening. If a contaminated area must be entered, a full-face airine mask or self-contained oxygen mask must be worn. Proective clothing is also necessary if the concentration is bove

10, 000 p. p.m.

-rognosis: Patients who survive 48 hours after poisoning are likely 2 recover. Eye contact is frequently followed by permanent lindness. FLUORINE, HYDROGEN FLUORIDE, AND DERIVATIVES Both fluorine and hydrogen fluoride are gases at normal emperatures.

Fluorine is used in organic synthesis. Hydrogen fluoride s used in the petroleum industry and ir etching glass.

‘ryolite (sodium aluminum yrocesses.

Fluoride

fluoride) is used in many industrial

salts are

used

aries and in rodenticides. The m.a.c. in air for fluorine

in the prevention

is 0.1 p.p.m.

n air for hydrogen fluoride is 3 p.p.m.

of dental

The m.a.c.

The fatal dose of

sodium fluoride is 1 to 4 Gm. (15 to 60 gr.). Up to five atalities per year are reported from fluorine and its derivities.

Fluorine and fluorides act as direct cellular poisons by nterfering with calcium metabolism and enzyme mechanisms. “luorides form an insoluble precipitate with calcium and lower ylasma calcium. Hydrogen fluoride is directly corrosive to issues. Skin or mucous membrane contact with hydrogen fluoride yroduces deeply penetrating, necrotic ulcerations. Neutral fluorides in 1 to 2% concentrations will cause inAfter death, 1ammation and necrosis of mucous membranes.

138

Fluorine

and Derivatives

rigor mortis sets in rapidly. Postmortem findings are cerebral hyperemia and edema, pulmonary edema, and degenerative changes in the liver and kidneys. In fatalities from inhaling hydrogen fluoride or fluorine, pulmonary edema and bronchial pneumonia are the most prominent findings. In deaths following prolonged absorption of fluoride, the bone structure shows thickening with calcification in the ligamentous attachments. The bone marrow space is greatly reduced.

Clinical Findings: The principal manifestation of fluorine and fluoride poisoning is corrosion. A. Acute Poisoning: 1. Inhalation - Inhalation of hydrogen fluoride or fluorine causes coughing, choking, and chills lasting one to two hours after exposure. After an asymptomatic period of one to two days, fever, cough, tightness in the chest, rales, and cyanosis indicate pulmonary edema. These symptoms progress for one to two days and then regress slowly over a period of ten days to one month. 2. Ingestion - Ingestion of neutral fluorides such as sodium fluoride causes salivation, nausea, vomiting, diarrhea, and abdominal pain. Later, weakness, tremors, shallow respiration, and convulsions occur.

Death

is by respiratory paralysis.

occur

immediately,

jaundice

If death does not

and urine

suppression

may appear. 3. Contact - Skin or mucous membrane contact with hydrogen fluoride solution results in damage depending on the concentration.

Concentrations

above

60% result

immediately in severe, extremely painful burns. Such burns are deep and heal slowly. Concentrations less than 50% may cause slight immediate irritation or none at all. The acid penetrates readily, however, anda deep-seated ulceration results if contact continues for B.

more than a few minutes. Chronic Poisoning: (From inhalation or ingestion.) Intake of more than 6 mg. (1/10 gr.) of fluorine per day

results ness

in fluorosis.

of bones,

anemia,

Symptoms

are weight loss,

weakness,

general

discoloration of the teeth. C. Laboratory Findings: 1. In chronic exposure, x-ray evidence is indicative of fluorosis. 2.

In severe

fluorosis,

both

brittle-

ill health,

and

of osteosclerosis

red and white

blood

counts may be diminished. 3. Fluorine workers should have urine fluoride

cell

Fluorine determinations

at six-month

and Derivatives

139

intervals.

Treatment: A. Skin or Mucous Membrane Burns: 1. Emergency measures - Wash thoroughly under a stream of water for 15 to 30 minutes. Do not wait until symptoms appear before giving treatment. 2. Antidote - Coat the burn with a magnesium oxide— water paste containing 20% glycerin. Do not use oily ointments. Inject 10% calcium gluconate at the periphery of the burn to limit further destruction. 3. General measures - Open all blisters; if hydrogen fluoride has penetrated under the fingernails, remove nails with local anesthesia. Wash these areas for 15 to 30 minutes. Then apply magnesium oxide paste. B. Eye Burns: 1. Emergency measures - Wash eyes with running water for at least 15 minutes(see p. 14). 2. Antidote - Do not use chemical antidotes. 3. General measures a. Relieve pain by applying 1% butyn solution. b. Dilate pupil by instilling 1% atropine sulfate solution. Take patient to an ophthalmologist. C. Inhalation:

1. Emergency

measures

- Remove

patient to fresh air.

2. Antidote - Chemical antidotes are not advisable. 3. General measures - Keep at complete bed rest. 4. Special problems - Treat pulmonary edema (see p. D. Ingestion of Hydrogen Fluoride: Treat as for acid ingestion,

p.

131.

E. Ingestion of Neutral Fluorides: 1. Emergency measures - Give soluble form:

31).

milk,

lime

water,

calcium

calcium

gluconate

in any

solution,

or calcium lactate solution. The concentration of calcium should be 10 Gm. (1 heaping tsp.) in 250 ml. (1 cup) of water. Give calcium gluconate, 10 Gm. (1/3 oz.),

and sodium

sulfate,

30 Gm.

ml. (1 cup) water orally to precipitate fluoride from the intestine.

2. Antidote - Give calcium solution I.V.

slowly;

gluconate,

(1 o0z.),

in 250

and remove

10 ml.

repeat until symptoms

of 10% disappear.

3. General measures - Give milk and cream every four hours to relieve irritation of the esophagus and stomach. F. Fluorosis: Remove

from

further

exposure.

Prophylaxis: Hydrogen fluoride workers must be carefully instructed n the dangers of skin contact with hydrogen fluoride and in he necessity for immediate removal of even dilute solutions

140

Fluorine

and Derivatives

Showers and water bubbler eye founby prolonged washing. being used. tains must be available where hydrogen fluoride is enclosed Processes utilizing hydrogen fluoride must be totally rubber Workers should wear long rubber gauntlets, long aprons,

high rubber

boots,

and a wide

plastic

face

shield

Forced-air face masks while handling hydrogen fluoride. is should be worn if the air concentration of hydrogen fluoride Tools and benches sufficiently high to cause nasal irritation. must be decontaminated immediately by washing with ammonia or lye solutions after hydrogen fluoride is spilled. Prognosis:

After ingestion of neutral fluoride, survival for 48 hours After inhalation, survival for three is followed by recovery. Skin burns reto four days is usually followed by recovery. heal. to months two to one quire In fluorosis from chronic exposure, removal from exposure for a year or more may be necessary before osteosclerosis begins to reverse. Prognosis in burns of the esophagus or stomach from in-

gestion of hydrofluoric p. 133).

acid is the same

as in acid burns (see

Chapter 15

METALLIC

ANTIMONY Antimony

POISONS

AND

is used in alloys,

STIBINE

type metal,

foil,

ceramics, textiles, safety matches, ant paste, such as tartar emetic (antimony and potassium

Acid treatment

' colorless gas,

of metals

batteries,

and medicinals tartrate).

containing antimony releases

the

stibine (SbH3).

The m.a.c. in air for antimony is 0.5 mg./cu. m. The m.a.c. in air for stibine is 0.1p.p.m. The fatal dose of

antimony compounds by ingestion is 100 to 200 mg.

(14/2 to 3

gr.). Upto ten cases of antimony poisoning occur each year. Fatalities are rare. The mechanism of poisoning is similar to that of arsenic poisoning, presumably by inhibition of enzymes through combination with -SH groups. Antimony is strongly irritating to mucous membranes and to tissues. Stibine causes hemolysis and irritation of the

iC. Nos. Pathologic findings include fatty degeneration of the liver and parenchymatous The gastrointestinal

degeneration in the liver and other organs. tract shows marked congestion and edema.

Clinical Findings; The principal manifestations of antimony and stibine poisoning are gastrointestinal disturbances. A. Acute Poisoning: 1. Ingestion - The symptoms are nausea, vomiting, and severe diarrhea with mucus and later with blood. Hemorrhagic nephritis and hepatitis may also occur. 2.

Inhalation

(of stibine)

weakness,

jaundice,

B. Chronic

Poisoning:

Itching skin laryngitis, C. Laboratory 1. The red

- Headache,

anemia,

(From

fume

nausea,

vomiting,

and weak pulse. and dust exposure.

)

pustules, bleeding gums, conjunctivitis, headache, weight loss, and anemia. Findings: blood cell count is diminished. Eosinophils

may reach 25% of total white cells. 2. Urine shows

hemoglobin

141

and red cells.

142

Arsenic

and Arsine

Treatment: A. Acute Poisoning: 1. Emergency measures a. Remove ingested antimony compounds by gastric lavage, emesis, and catharsis (see pp. 10 to 13). b. Remove patient from further exposure to stibine. 2. Antidote - Give dimercaprol (see p. 46). 3. General measures - Treat as for arsenic poisoning (see p. 148). B. Chronic Poisoning: Remove from further exposure and give dimercaprol (see p. 46). Prophylaxis: Adequate fume and dust control is necessary the m.a.c. from being exceeded. Prognosis: Survival for 48 hours indicates

V ARSENIC Arsenic

is used

AND

that recovery

to prevent

is probable.

ARSINE

in ant poisons

insecticides,

weed

killers,

paint, wallpaper, ceramics, and glass. The action of acids on metals in the presence of arsenic forms arsine gas. Alloys such as ferrosilicon may release arsine upon contact with

water since the ferrosilicon may be contaminated with arsenic. The fatal dose of arsenic trioxide is about 120 mg. (2 gr.). The allowable food residue is limited by federal law to 0.65 mg. (1/100 gr.)/pound. Up to 20 deaths occur each year from arsenic or arsenic derivatives. Arsenic presumably causes

sulfhydryl (-SH) enzymes

toxicity by combining

olism, If death occurs

within a few hours,

shows

but other

inflammation

with

and interfering with cellular metabthe stomach

pathologic

changes

are

mucosa absent.

If death occurs more than a few hours after poisoning, pathologic examination shows inflammatory changes and partial desquamation

of the intestinal

mucosa.

gastrointestinal tract are distended, and found. In immediate deaths from_arsine vascular hemolysis is found. If death is days after arsenic in any form, the liver degenerative changes.

The

capillaries

of the

ecchymoses may be poisoning, intradelayed for several and kidneys show

Clinical Findings: The principal manifestations of arsenic and arsine poisoning are gastrointestinal disturbances. A. Acute Poisoning: 1. Ingestion - After ingestion of overwhelming amounts

of

Arsenic

and Arsine

143

arsenic (10 times the M.L.D.), initial symptoms are those of violent gastroenteritis: burning esophageal pain, vomiting, and copious watery or bloody diarrhea containing shreds of mucus. Later, the skin becomes cold and clammy, the blood pressure falls, and weakness is marked. Death is from circulatory failure. Convulsions and coma are the terminal signs. If death is not immediate, jaundice and oliguria or anuria appear after one to three days. Doses approaching the M.L.D. cause restlessness, nausea,

vomiting,

headache,

dizziness,

chills,

cramps,

irritability, and variable paralysis which may progress over several weeks.g 2. Inhalation of arsenic dusts may cause acute pulmonary edema, restlessness, dyspnea, cyanosis, cough with foamy sputum, and rales. 3. Exposure to arsine causes burning and stinging of the face and,

after three

to four hours,

tightness

of the

chest, nausea, dysphagia, hemoglobinuria, bronzing of the skin, and enlargement and tenderness of the liver and spleen.

B. Chronic Poisoning: (From ingestion or inhalation.) The following are affected variably. 1. C.N.S. - Polyneuritis, anesthesias, and paresthesias such as burning pains in the hands and feet. 2. Skin - Bronzing, alopecia, localized edema, and hyperkeratosis of the palms and soles of the feet. 3. Gastrointestinal tract - Cirrhosis of the liver, vomiting, abdominal cramps, salivation.

4. General effects - Anemia and weight loss. 5. Cardiovascular system and kidneys - Chronic tis,

cardiac

failure,

dependent

nausea,

nephri-

edema.

C. Laboratory Findings: 1. Acute poisoning a.

Urine

b.

casts. After arsine

may

show

inhalation,

globin. 2. Chronic poisoning a.

Arsenic

can

red blood

cells,

albumin,

the urine

and

contains

hemo-

-

be identified

in hair,

nails,

urine

sores. 2nd vomitus-by state or county toxicologic laboratories. b. Hepatic function may be impaired as shown by suitable tests (see p. 40). Treatment:

A. Acute Poisoning: 1. Emergency gastric

13).

measures

lavage,

- Remove

emesis,

ingested arsenic

and catharsis

(see pp.

by 10 to

144

Beryllium

2. Antidote - Give dimercaprol (see p. 46). 3. General measures a. Treat dehydration by giving 5% glucose in normal saline I. V. b. Treat pulmonary edema (see p. 31). c. Treat anuria (see p. 29). d. Treat liver damage (see p. 40). B. Chronic Poisoning: Remove from further exposure and give dimercaprol (see p. 46). Prophylaxis: Store arsenic safely. The m.a.c. of arsine in air must be observed at all times. Acid treatment of metals or dilution of acid sludge must be done with adequate fume control. Prognosis: In acute

arsenic

poisoning,

survival

for more

than one

week is usually followed by complete recovery. Complete recovery from chronic arsenic poisoning may require six months to one year.

BERYLLIUM Beryllium is used in alloys for electrical equipment. It is present in some fluorophors used in cathode ray tubes and fluorescent lights, but the use of these fluorophors in fluorescent lamps has been discontinued by most manufacturers. The fatal dose of beryllium is not known. Air contamination

in work

Since

1941,

rooms

must

be kept below

a detectable

470 cases

of berylliosis

have

in the United States.

been

amount.

reported

At least nine of these have ended fatally.

Beryllium

appears

to inhibit

enzymes.

The relation between

certain

magnesium-activated

this effect and the pathologic

changes induced by beryllium is not understood. Soluble beryllium salts are directly irritating to skin and mucous membranes and induce acute pneumonitis with pulmonary edema. At least part of the changes present in acute pneumonitis and chronic pulmonary granulomatosis develop as a result of hypersensitivity to the beryllium in the tissues.

At pathologic examination, granulomas consisting of monocytes, lymphocytes, and fibrous tissue are found at the site of beryllium localization. In deaths from acute pneumonitis, the lung alveoli are filled with mononuclear and plasma

cells.

Clinical Findings: The principal

dyspnea.

manifestation

of beryllium

poisoning is

Beryllium

145

A. Acute Poisoning: 1. Inhalation - Acute pneumonitis, with chest pain, bronchial spasm, fever, dyspnea, cyanosis, cough, bloodtinged sputum, and nasal discharge. Right heart

failure may occur as a result of increased pulmonary arterial

resistance.

Onset

of symptoms

occurs

two to

five weeks after an exposure of one to 20 days. 2. Skin contact - Cuts from beryllium-contaminated objects form deep ulcerations which are slow to heal. Acute dermatitis from contact with dust simulates first and second degree burns. 3. Eye contact - Dust contamination causes acute conjunctivitis with corneal maculae and diffuse erythema. B. Chronic Poisoning: 1. Inhalation - In chronic pulmonary granulomatosis (berylliosis),

weight

loss and marked

dyspnea

begin

three months to 11 years after first exposure. The disease may pursue a steady downhill course or may be marked by exacerbations and remissions. Right heart failure may occur as a result of increased pulmonary resistance. Fever is variable. 2. Skin contact - Eczematous dermatitis with a maculopapular, erythematous, vesicular rash appears ina large percentage of workers exposed to beryllium dusts. In such lium solutions

patients, patch tests with dilute berylshow positive reactions.

C. Laboratory Findings: D. X-ray Findings:

Noncontributory.

1. X-ray examination in acute pneumonitis reveals a diffuse increase in density of the lung fields. 2. In chronic pulmonary granulomatosis, x-ray examination reveals a ‘‘snowstorm’’ appearance of the lungs. Treatment:

A.Acute Pneumonitis: 1. Emergency measures a.

Complete

-

bed rest.

b. If cyanosis is present, give 40 to 60% oxygen mask (see p. 24). 2. Antidote - None known. 3. General measures a. Relieve bronchial spasm - Give epinephrine,

by

0. 2

mg. (0.2 ml. of 1:1000 solution) subcut. or aminophylline, 0.25 Gm. (33/4 gr.) I. V. every six hours. b.

Prevent

bronchial

pneumonia

- Give

penicillin,

one

million units I. M. daily. c. For right heart failure - Digitalize. d. Give cortisone or corticotropin (ACTH) to decrease the hypersensitivity reaction to beryllium.

These hormones will relieve symptoms lengths of time but are not curative.

for varying

146

Cadmium

B. Chronic Granuloma of Lungs (Berylliosis): Treat as in acute pneumonitis, with the exception that moderate activity is allowable. C. Skin Granuloma and Ulcers: Excise beryllium-contaminated areas of skin surgically. D. Beryllium Dermatitis or Conjunctivitis: 1. Remove from further exposure. Wash skin and eyes thoroughly (see p. 14). 2. Apply local anesthetic ointment to control pain.

Prophylaxis: Dusts and fumes from beryllium processes must be rigidly controlled. No beryllium is allowable in air. X-ray examinations of the chest are not useful in controlling exposure

or in case-finding.

X-ray

examination

of

the chest may become positive without any symptoms, or positive x-ray findings may only occur at the time of the onset of symptoms. Workers may be asymptomatic and have normal x-ray examinations of the chest during exposure to beryllium and develop symptoms and positive chest x-ray findings many years after discontinuing exposure. Prognosis: Recovery months.

from acute pneumonitis

Deaths

with chronic

have

been

pulmonary

(berylliosis) die. symptoms without

rare.

requires

two to six

Approximately

granulomatosis

2% of those

from beryllium

Adrenocortical hormones appear to improve affecting appreciably the outcome of the

disease.

/cADMIUM Cadmium is used for plating metals and in the manufacture of bearing alloys. Cadmium plating is soluble in acid foods such as fruit juice and vinegar. The fatal dose by ingestion is not known. Ingestion of as

little as 10 mg. (1/6 gr.) will cause marked symptoms. The m.a.c. in air is 0.1 mg. /cu. m. A yearly average of more than 100 nonfatal cases of cadmium poisoning by ingestion have occurred in the past ten years; at least two were fatal. An average of one fatality from inhalation of cadmium fumes occurs each year. The mechanism of poisoning is not known, but cadmium is damaging to all cells of the body. The pathologic findings in cases of fatal cadmium ingestion are severe gastrointestinal inflammation and liver and kidney damage. In fatal acute poisoning from the inhalafioof cadmium

lammation

fumes,

pathologic

of the pulmonary

examination

reveals

epithelium and pulmonary

in-

edema.

Cadmium

147

Pathologic examination in fatalities following long exposure cadmium fumes reveals emphysema.

to

Clinical Findings:

"The

principal manifestation of cadmium poisoning is

gastrointestinal irritation. A. Acute Poisoning: +. Ingestion - Nausea,

vomiting,

diarrhea,

headache,

muscular aches, salivation, and abdominal pain. . Inhalation of cadmium fumes causes metallic taste in the mouth, shortness of breath, pain in the chest,

cough with foamy or bloody sputum, weakness, and pains in the legs. Chest examination reveals bubbling rales. Urine formfation may be diminished later. Progression of the disease is indicated by onset of fever and by development of signs of lung consolidation. B. Chronic Poisoning: (From inhalation.) Loss of sense of smell, cough, dyspnea, weight loss, and yellow-stained teeth. The liver may be damaged. C. Laboratory Findings in Acute Poisoning: a Hematuria and albuminuria. 2. RBC and WBC are low. The erythrocyte sedimentation rate may be raised. . After ingestion or chronic inhalation, hepatic cell function may be impaired as shown by appropriate

tests (see p. 40). D. X-ray Findings: gAfter inhalation, shows a diffuse are those

increase

of bronchial

early chest x-ray

in lung dénsity; later findings

pneumonia.}

Treatment: A. Inhalation:

Ac Remove patient from further exposure. Ue Treat pulmonary edema (see p. 31). 3. Give dimercaprol (see p. 46). B. Ingestion: L Allay gastrointestinal irritation - Give milk or beaten eggs every four hours. Catharsis - Remove unabsorbed cadmium by catharsis with sodium sulfate, 30 Gm. (1 oz.) in 250 ml. (1 cup) of water.

3. Give dimercaprol (see p. 46) if symptoms 4. Treat liver damage (see p. 40).

persist.

Prophylaxis:

The m.a.c.

of cadmium

fumes

in air must always be ob-

served. Acid foods should never be stored cadmium-plated cooking utensils.

or prepared

in

148

Chromium

Prognosis: Symptoms from cadmium ingestion usually last no than 24 hours. In fume inhalation, mortality rate has approximately 15%. Survival for more than four days followed by recovery, but complete recovery may take months.

more been is six

CHROMIUM Chromium

is used

in chemical

electroplating,

leather

tanning,

The fatal dose

of a soluble

synthesis,

steel-making,

and as a radiator chromate

such

anti-rust.

as potassium

bichromate is approximately 5 Gm. (75 gr.). The m.a.c. in air for chromium (determined as chromic oxide) is 0.1 mg. / cu. m. One to five cases of chromium poisoning occur each year. Upto 20% of chromium workers develop dermatitis. Chromium is irritating and destructive to all cells of the body. In fatalities from acute poisoning, hemorrhagic nephritis

is found.

Clinical Findings: The principal manifestation of chromium poisoning is irritation or corrosion. A. Acute Poisoning: (From ingestion.) Dizziness, intense thirst, abdominal pain, vomiting, shock, and oliguria or anuria. Death is from uremia. B. Chronic Poisoning: (From inhalation or skin contact. ) Repeated skin contact leads to incapacitating eczematous dermatitis

with

edema,

and ulceration

which

heals

slowly.

Breathing chromium fumes over long periods causes painless ulceration, bleeding, and perforation of the nasal septum accompanied by a foul nasal discharge. Conjunctivitis, lacrimation, and acute hepatitis with jaundice have also been observed. Findings in acute hepatitis include nausea, vomiting, loss of appetite, and an enlarged, tender liver. The incidence of lung cancer is increased up to 15 times normal in workers exposed to dusty chromite, chromic oxide, and chromium ores.

C. Laboratory Findings: 1. Albuminuria and hematuria. 2. Hepatic cell function impairment appropriate tests (see p. 40).

may

be revealed

by

Treatment:

A. Acute Poisoning: 1. Emergency measures - Remove swallowed chromate by gastric lavage, emesis, and catharsis (see pp. 10 to) di3)))

Lead

149

2. Antidote - None known. 3. General measures - If oliguria or anuria is present, maintain careful fluid and electrolyte balance (see p. 29). B. Chronic Poisoning: ‘

1. Treat weeping dermatitis with 1% aluminum

acetate

wet dressings. Avoid further exposure to chromate. 2. Treat liver damage by giving high-carbohydrate, highprotein, high-vitamin diet (see p. 40).

Prophylaxis:

The m.a.c.

in air must always be observed.

Chromic

mist, fumes, and dust must be controlled. Chromate tions must not come in contact with the skin.

solu-

Prognosis: In acute poisoning, rapid progression to anuria indicates a poor outcome. Dermatitis and liver damage will respond to removal

from

further

exposure.

LEAD Lead is used in type metal, storage batteries, paint, solder, electric cable aki 2 pottery glaze, rubber, toys, asoline (tetraethyl lead rass alloys. The fatal emis of Spacrbed lead has been estimated to be 0.5 Gm. (74/2 aes Accumulation and toxicity occur if more

than 0.5 mg. (1/120 gr.) per day is absorbed. lead in air is i 105 mg./cu. m. The m.a.c.

The m.a.c. of of lead in food

is 2.56 mg. /Kg. Up to 100 cases

of poisoning,

with an average

of ten

fatalities are reported yearly. Most of these fatalities-are in children.

Most of these cases of lead poisoning have been

“discovered in a few hospitals, and it is possible that the incidence of lead poisoning may be at least ten times as high as these figures show. Lead is deposited and removed from bones in the same

way as i “toxicity

_ fo

body,

Lead deposited in the bones has no but when

lating in the blood stream edure

W.

increases

it

lead

is mobilized

becomes

toxic.

and circu-

Thus any pro-

bone formation will w ‘tend toforce the

:

iven in large doses.

The primary

effect of lead may be to cause spasm of the capillartes-and arterioles, In acute poisoning,

mation 6

pathologic

© pastrointestinal

findings include inflam-

mucosa

and re

tubular de-

generation.

Findings in chronic lead poisoning include diffuse

degeneration

of nerve

cells

and muscle

cells.

Cerebral

150 SYMPTOMS

AND SIGNS IN THE DIAGNOSIS OF LEAD POISONING*

Suggestive Evidence of Lead Absorption General 4

Patient

Suggestive Evidence of More Advanced or Definite Plumbism

Appearance: feels

restive,

moody, easily excited, ‘‘flustered.’’ Lead

Suggestive Evidence] of Incipient Intoxication Pallor, : lead line,

Anemia,

jaundice.

jeundice__em dice, emaciation,

lead line,

premature

aging.

line_o

Digestive System: Persistent metallic taste, slight loss of

appetite,

slight

constipation.

Nervous

Metallic taste, definite loss of

Metallic

taste,

appetite, coated tongue, slight

abdominal

abdominal colic, constipation.

constipation, the stool.

Slight headache, insomnia, slight dizziness, palpita-

Persistent

miting,

nausea

marked ——

colic, rigid bloodin blood In

System:

Patient is irritable and uncooperative.

tion,

increased

irritability, increased reflexes.

increased

headaches, insomnia,

twitching, visual

neuritis, iT

disturbances,

encephalitis nations,

coma),

Miscellaneous

|

increased dizziness (ataxia), confusion. Marked reflex changes, tremor, fibrillary

(halluci-

convulsions,

paralysis.

Changes:

None

Muscle

soreness,

General

weakness,

joint

easy fatigability, hypotension, Urine Examination: | Urine excretion

greater than 0.15 | mg./day of lead.

Blood Changes: Polycythemia or janemia, polychroma-| ftopniia increased platelets, percentage] of reticulocytes about]

doubled.

Trace

of albumin,

few granular casts.

Increase in albumin and casts. Hematoporphyrin present, Hematuria.

Increase in reticu|Decrease in hemolocytes. From 50 |globin. Decrease in to 100 stippled cells|total number of red per hundred thou|blood cells below 4 sand erythrocytes. |million. Increase in

Blood lead over 0.1 |all formsof basophilic

mg./100 ml.

cells.

Increase in

percentage of mononuclears, Anisocytosis and poikilocytosis. Nucleated

red cells

j /

present in the periph- / eral circulation. / Decreased platelets. ~ Blood lead over mg./100 ml. *Jones,

R.R.:

Industrial

Plumbism,

J.A.M.A.

104:195,

0.1

1935.

Lead

151

edema may also be present. There around capillaries and arterioles.

may be cellular infiltration

Clinical Findings:

150.)

(See table on p.

_The principal manifestations intestinal or 3

A. Acute

Poisoning:

(From

of lead poisoning are 5

gastro-

ingestion of soluble or rapidly

absorbed compounds of lead.) Metallic pai iti iarrhea, black st and coma.

taste, abdomi PML ollapse,

B. Chronic Poisoning: (From inhalation, ingestion, or skin absorption. ) 1. Early- Loss of appetite, weight loss, constipation, fatigue,

on

headache,

gums,

weakness,

metallic

taste,

lead line

and anemi

2. Wore advanced —Vague painsinarms, iegs_jomts.

and abdomen; sensory disturbances of extremities paralysis of extensor muscles of arms and legs with

-Removetead by gastric lavage with dilute magnesium sulfate or sodium-sulfate_solution or emesis and catharsis (see-pp:-10 to 13).

2. Antidotes

a

-

td) calcio

osage is 1.2 Gm./20 Kg.

p. 47). The The calculated dose is

diluted in 1 L. of 5% dextrose and given I.V. a period of at least two hours.

over

This dose is re-

peated daily for two to five days and if necessary for another two to five days after an interval of three to five days. b. If calcium edathamil is not available,.dimercaprol

{BAL®) may be given in doses of 3 to 4 mg. /Kg.

152

Manganese

and Potassium

Permanganate

twice daily for a total of ten days. A repeat course is given after one week if symptoms persist. Gat

er of the above antidotesis_available,

give

“calcium gluconate, 1 0%, 10 ml. I. V. every four-to six hours until severe symptoms subside. 3. General measures - Give a high-calcium, high—vita-

min Bdiet,and admitister atropine, 1 mg.(160gr subcut. or ieLa for abdominal PRS OTATORS two to

B. Chronic Poisoning: 1. Remove patient from further exposure to lead. 2. Antidote - Give edathamil calcium disodium, dimercaprol, or calcium gluconate as for acute poisoning 3. General measures as for acute poisoning. 4.

Special problems

-

a. Wristdrop and foot drop may be corrected by splinting until function returns. b.

Control convulsions

34).

in lead encephalopathy

(see p.

Prophylaxis: g paint should not be used=Angers Paint2 j ers hange clothing and he-before “eating. Precautions must be taken to keep lead in air below the m.a.c. Children must not be allowed to play with lead toys.

Prognosis:

~~ Until recently,

the death rates of patients with lead

encephalopathy was about 25%. About half of those who survived had permanent mental deterioration. The effect of edathamil calcium disodium on prognosis in lead encephalopathy has not been determined as yet.

Complete takes

recovery from other forms of lead poisoning

up to one year.

MANGANESE

Manganese

AND

POTASSIUM

PERMANGANATE

is used in the manufacture

of steel and dry

cell batteries. Potassium permanganate is used as an oxidizing agent. The m.a.c. in air is 6 mg./cu. m. of manganese. The fatal dose of potassium permanganate by ingestion is about 5

Gm.

(75 gr.). Up to ten cases of poisoning from the inhalation of manganese fumes or dust are reported yearly. Fatalities are rare. An average of one fatality from potassium permanganate occurs each year. The mechanism of manganese poisoning is not known.

Manganese

and Potassium

Permanganate

153

Inhalation of manganese fumes or dusts produces progressive deterioration in the C.N.S. Large oral doses of manganese compounds are without systemic effect in experimental animals. Potassium permanganate in high concentrations acts as a corrosive to mucous membranes. The effects of longcontinued ingestion of small amounts of manganese have not been investigated. The findings in one death suspected to be from ingesting manganese-contaminated drinking water were atrophy and disappearance of cells of the globus pallidus. Experimental animals show inflammatory changes in both gray and white

matter.

Concentrated

potassium

sive effects on any mucous

permanganate

causes

corro-

membrane.

Clinical Findings: The principal manifestations of poisoning with these compounds are C.N.S. disturbances. A. Acute Poisoning: Potassium permanganate causes acute corrosive damage to mucous membranes if applied in high concentrations or as crystals. The alkaline nature of potassium permanganate leads to extensive penetration and even perforation.

B. Chronic Poisoning: (From ingestion or inhalation.) 1. Ingestion - Drinking manganese-contaminated well water caused lethargy, edema, and symptoms of extrapyramidal tract lesions in one outbreak. Chronic poisoning from ingesting manganese in other forms has not been reported. 2. Inhalation of manganese dusts causes acute bronchitis, nasopharyngitis, ances,

dermatitis,

pneumonia, and liver

headache,

sleep disturb-

enlargement.

Later,

there are gradually progressive signs which simulate parkinsonian syndrome. These include weakness in the legs, increased muscle tone, hand tremor, slurred speech, muscular cramps, spastic gait, fixed facial expression, and mental deterioration.

C. Laboratory Findings: 1. Hepatic cell function may be impaired as shown appropriate tests (see p. 40).

2. Increased hemoglobin and RBC; decrease 3. C.S.F. may contain traces of globulin. Treatment: A. Acute Poisoning: 1. Emergency measures

by

in monocytes.

a. Dilute ingested potassium permanganate with tap water and remove by emesis or gastric lavage and catharsis (see pp. 10 to 13). b. Dilute potassium permanganate used as a douche with tap water.

154

Mercury

2. Antidote - None known. 3. General measures - Treat corrosive damage (see p. B28 4. Special problems - Perforations produced by potassium permanganate must be treated surgically. (From manganese. ) B. Chronic Poisoning: 1. Remove from further exposure. 2. Antidote - A course of dimercaprol should be tried (see p. 46). 3. General measures

-

10 ml.

a. Give calcium gluconate,

of 10% solution

I.V. daily. b. Give large doses of B vitamins, including Bj9c. Atropine or scopolamine, 1 mg. (60 gr.), to relieve tremor.

Prophylaxis: Workmen The m.a.c. must be observed at all times. Quarterly should change clothing and bathe on leaving work. physical examinations of all exposed workers will aid in the discovery of early changes. Batteries must not be buried near water supplies.

Prognosis: While liver and respiratory system damage from manganese are reported to respond to dimercaprol, this antidote If has no effect on the symptoms of C.N.S. deterioration. exposure is discontinued when C.N.S. symptoms first appear, recovery is likely.

MERCURY

20°C.

Air saturated with mercury at Mercury is a liquid. At 40°C., saturated air contains about 15 mg./cu. m.

contains 68 mg. /cu. m. Mercury or its salts are used in the manufacture of thermometers, fur felt, paints, explosives, electrical and The volatile diethyl and physical apparatus, and batteries.

dimethyl mercury compounds are used in treating seeds. Mercurous chloride (calomel) and organic mercurials are used medicinally.

salts is 1 Gm. (15 gr.)._InThe fatal dose of mercuric is not toxic since it is not absorbed.

gested metallic

mercury

to Mercurous chloride and organic mercurials are not likely

The m.a.c. in air is 0.1 mg. /cu. m. cause acute poisoning. Diethyl and dimethyl mercury are extremely poisonous and o level of exposure is safe. About 20 fatalities h year. salt ic L in Mercury

de

sses

cellular

enzymatic

mechanism

-

Mercury

combining with sulfhydryl groups;

for this reason,

155

soluble

psncurtsvesis ete toxindaall-relleeeTie biti conven mation? attai during renal excretion lead to specific damagé to renal glomeruli and tubules. ~~

y

In fatalities from mercurial poisoning, the pathologic findings are acute tubular and glomerular degeneration or hemorrhagic glomerular nephritis. The mucosa of the gastrointestinal tract shows inflammation, congestion, coagulation, and corrosion.

Clinical Findings: The principal manifestation of mercury anuria. A. Acute

salt poisoning is

Poisoning:

[Ingestion of mercuric salts causes metallic taste, thirst, severe abdominal pain, womitiamanninloody diarrhea.

Diarrhea

of mucus

shreds

and blood

may

continue for several weeks. One day to two weeks after ingestion, urine output diminishes or stops. Death is from mia. 2: ee concentration of mercury vapor will be foltowed-within-a-day or two b: fis, salivation, metallic taste, diarrhea, and renal concen / Inhaling volatile organic iexeuwsdala in high concentrations causes metallic taste, dizziness, clumsiness, slurred speech, vulsions. B. Chronic Poisoning:

diarrhea,

1. Ingestion of insoluble

or

and sometimes

fatal con-

oorly dissociated mercuric

salts, including mercurous, chloride and organic, mercurial compounds, over a prolonged period-causes stomatitis, Salivation, diarrhea, and renal damage.

In children,

repeated-administration.of.calomel

causes

a syndrome-known-as_erythredema. polyneuropathy (acrodynia-or—“‘pink-disease’’): Symptoms are photophobia, anorexia, restlessness, stomatitis, pains in the arms and the legs, pink palms, oliguria, and severe diarrhea. The symptoms may persist for weeks or months. 2. Inhalation or skin contact - Inhalation of mercury vapor,

dusts,

or organic

vapors,

or skin absorption

of mercury or mercury compounds over a long period causes mercurialism. Findings are extremely variable and include tremors, salivation, stomatitis,

“Ioosening of the teeth, biue tine on the gums, pain and numbness in the extremities, » nephritis, diarrhea, anxiety, headache, weight loss, anorexia, mental Sata UREP Guana

waren,»

pression, hallucinations, deterioration.

and evidences

of mental

156

Nickel

C. Laboratory Findings: 1. Urinary excretion of more than 0.1 mg. of mercury per day indicates the possibility of mercury poisoning. 2. Albuminuria and hematuria (may be absent in chronic poisoning).

Treatment:

A. Acute Poisoning: 1. Emergency measures

- Remove ingested poison by gastric lavage with tap water, emesis, and catharsis (see pp. 10 to 13). 2. Antidote - Give dimercaprol (see p. 46). 3. General measurés Treat anuria (see p. 29). B. Chronic Poisoning: ~ 1. Remove from further exposure. 2. Give dimercaprol (see p. 46). 3. General measures a. Treat oliguria (see p. 29).

b. Maintain nutrition by I. V.

or oral feedings.

Prophylaxis: The m.a.c. must be observed at all times; frequent air sampling is necessary. Floors in rooms where mercury is used must be im-

pervious and free from cracks. picked up immediately

sweeping compound. pounds,

by water

Spilled mercury pump

After handling mercury

the skin must

be thoroughly

should be

suction or by a wet

or mercury

com

cleaned.

Prognosis:

In acute and chronic poisoning, recovery is likely if dimercaprol treatment is given for at least one week. Recovery from mental deterioration caused by chronic mercury poisoning may never be complete. Improvement requires one to two years. :

NICKEL

CARBONYL,

NICKEL

Nickel carbonyl is formed by passing carbon monoxide over finely-divided metallic nickel. Nickel carbonyl is a liquid which boils at 45°C. It is important in the Mond proces for refining nickel. It is also used in petroleum refining. The m.a.c. in air of nickel carbonyl is 1 p.p.m. Up to five fatalities from nickel carbonyl inhalation occur each year. Inhaled nickel carbonyl decomposes to metallic nickel, which deposits on the epithelium of the lung. This finelydivided nickel is rapidly absorbed and damages the lung and brain. Postmortem examination in deaths caused by nickel

Phosphorus,

Phosphine,

Phosphides

157

carbonyl inhalation reveals edema and hyperemia of the lungs. Areas of necrosis and hemorrhage are found in the brain and lungs.

Clinical Findings: The principal manifestation of nickel carbonyl poisoning is dyspnea. A. Acute Poisoning: Inhalation of nickel carbonyl] is followed immediately by cough, dizziness, headache, and malaise. These symptoms are ordinarily relieved almost immediately by removal to fresh air. A delayed reaction, which begins after 12 to 36 hours, is characterized by progressive dyspnea, cough, cyanosis, fever, rapid pulse, nausea, and vomiting. Death from respiratory failure occurs between the fourth and twelfth days. B. Chronic Poisoning: Contact with nickel compounds causes dermatitis in a small percentage of workers. Workers exposed to nickel carbonyl show a high incidence of lung cancer. C. Laboratory Findings: Noncontributory. Treatment: A. Acute Poisoning: 1. Emergency measures

- Treat

cyanosis

and dyspnea

by giving 100% oxygen by mask (see p. 24).

If pul-

monary edema is present, treat as described on p. 31. 2. Antidote - Give dimercaprol (see p. 46). 3. General measures - After any exposure, keep patient at absolute bed rest for the first four days after poisoning, even if asymptomatic. Thereafter, keep at bed rest until cyanosis is relieved. B. Chronic Poisoning: Remove from further exposure. Prophylaxis: The m.a.c. for nickel carbonyl must always be observed. No person with chronic pulmonary disease should work where Contaminated atmosnickel carbonyl exposure can occur. pheres can only be entered by using an air-line face-mask. Prognosis: Survival for more than 14 days is followed by recovery. Cyanosis and dyspnea are indices of the severity of poisoning.

PHOSPHORUS, Phosphorus

exists

PHOSPHINE, in two forms:

absorbed,

and nonpoisonous

poisonous

form

which

air. Red phosphorus phosphorus.

PHOSPHIDES a red,

granular,

form; and a yellow,

waxy,

will burn on contact with water

is sometimes

contaminated

non-

highly or moist

with yellow

158

Phosphorus,

Phosphine,

Phosphides

Phosphorus is used in rodent and insect poisons, fireworks, and fertilizer manufacture. The action of water or acids on metals will liberate phosphine if phosphorus is present as a contaminant. Phosphine may also be present in acetylene. Phosphides, especially zinc phosphide, are used as rat poisons. These release phosphine on contact with water. The fatal dose of yellow phosphorus is approximately 50 mg. (3/4 gr.). The m.a.c. in air of yellow phosphorus is 0.1

mg./cu.

m.

The m.a.c.

in air of phosphine is 0.05 p.p.m.

Up to five fatalities from yellow phosphorus, phosphine, or phosphides are reported each year. Phosphorus causes tissue destruction, with disturbance in carbohydrate,

fat,

and protein

metabolism

in the liver.

Deposition of glycogen in the liver is inhibited; deposition of fat is increased. Chronic absorption of phosphorus leads to (1) increased bone formation under the epiphysial cartilage, and (2) impairment of blood circulation in bone by bone formation in haversian and marrow canals. These changes lead to necrosis and sequestration of bone; they occur most frequently in the mandible. The pathologic findings in yellow phosphorus poisoning are icterus, fatty degeneration and necrosis of the liver and kidneys, and hemorrhages, congestion, and erosion of the gastrointestinal tract. Pathologic findings from phosphine inhalation are pulmonary hyperemia and edema. Zinc phosphide ingestion causes both fatty degeneration and necrosis of the liver and pulmonary hyperemia and edema. Clinical Findings: The principal manifestations of poisoning with these compounds are icterus and collapse. A. Acute Poisoning: 1. Ingestion of yellow phosphorus is followed within one to two hours by nausea, vomiting, diarrhea, anda

garlic odor of breath and excreta. Death in coma may occur in the first 24 to 48 hours, or symptoms may improve for one or two days and then return, with nausea, vomiting, diarrhea, liver tenderness and enlargement, icterus, prostration, fall of blood pressure, oliguria, and multiple petechial hemorrhages. Onset of Cheyne-Stokes respiration followed by convulsions, coma, and death may occur up to three weeks after poisoning. Phosphide ingestion causes icterus, liver tenderness and enlargement, and pulmonary edema with dyspnea and cyanosis. Death may occur up to a week after poisoning. 2. Skin contact - Phosphorus on the skin causes second to third degree burns surrounded by blisters. These burns heal slowly.

Phosphorus,

Phosphine,

Phosphides

159

3. Inhalation of phosphorus is followed, after one to three days, by the symptoms of acute phosphorus poisoning. Phosphine or phosphide inhalation causes fall of blood pressure, dyspnea, pulmonary edema, collapse, vomDeath usually occurs iting, convulsions, and coma. in the first four days, but may be delayed one to two weeks. (From ingestion or inhalation of B. Chronic Poisoning: The first yellow phosphorus, phosphine, or phosphides.) symptom is toothache, followed by swelling of the jaw and then necrosis of the mandible (phossy jaw). Other findings are weakness, weight loss, loss of appetite, anemia, and spontaneous fractures. C. Laboratory Findings: 1. Impairment of liver function is shown by appropriate tests (see p. 29). 2. Blood N.P.N. and urea are increased in acute poisoning.

3. Hematuria

and albuminuria

may be present.

Treatment: A. Acute Poisoning: 1. Emergency measures a. Remove poison by gastric lavage with 5 to 10 L.

of

tap water.

b. If a gastric tube is not immediately available, repeat the administration of 1 L. of water followed by the stimulation of vomiting at least three times. c.

Give 120 ml. (4 oz.) of mineral oil, followed by 30 Gm. (1 oz.) of sodium sulfate dissolved in 250 ml. Repeat after two hours. (1 cup) of water.

d. Remove phosphorus contamination from the skin or eyes by copious irrigation with tap water for at least 15 minutes. 2. Antidote - None known. 3. General measures a.

Treat

pulmonary

edema

(see p.

31).

b. Give 1 to 4. L. of 5% glucose in water or 10% invert

sugar in water 1.V. daily until high-carbohydrate, high-protein diet can be given by mouth, B. Chronic Poisoning: Remove from further exposure and treat jaw necrosis by surgical excision of sequestered bone.

Prophylaxis: The m.a.c. of phosphorus, phosphine, and phosphides in Special clothing, to the air must be observed at all times. be changed daily, should be provided phosphorus workers. Workers must bathe on leaving work and must be educated in Safety showers and eye the hazards of phosphorus exposure.

160

Metal

Fumes

fountains must be provided where used. Dental examination pending on exposure.

yellow phosphorus

should be made

is being

frequently,

de-

Prognosis: In poisoning from ingestion of phosphorus, fatality rate is about 50%. In phosphine inhalation, survival for four days is ordinarily followed by recovery.

ZINC F Zinc fumes

TAL FUME FEVER

are produced in welding,

smelting zinc alloys or galvanized iron.

metal cutting,

and

Zine fumes are

most often responsible for metal fume fever, but other metal fumes will also cause the disease. Soluble zinc salts, such as zinc chloride, are used in smoke generators. The m.a.c. in air for zinc oxide fumes is 15 p.p.m. Up to ten fatalities in a single year have resulted from the inhalation of zinc chloride fumes. No fatalities from breathing zinc oxide fumes have been reported in recent years. Fumes from zinc or soluble zinc salts irritate the lungs. Other physiologic changes are not known. The pathologic findings in fatalities from zinc chloride or zinc fume inhalation are pulmonary edema and damage to the respiratory tract.

Clinical Findings: The principal manifestations of zinc fume or other metal fume poisoning are muscular aches and fever. A. Acute Poisoning: (From inhalation.) Inhalation of zinc

‘yausea,_ a, vomiting, muscular aches, and weakness. hie ‘ haling fumes of soluble

zinc salts such as zinc chloride

may cause pulmonary edema_with cyanosis and-dyspnea.

B. Chronic poisoning does not occur. C. Laboratory Findings:

Noncontributory.

Treatment of Acute Poisoning: A,-Freat pulmonary-edema (see p. 31). B. Treat metal fume fever by bed rest and give acetylsalicylic acid to-relieve symptoms of fever and pain. Prophylaxis:

Zinc chloride smoke generators should not be operated in such a way that workers will be exposed. Fumes from melting

zinc must

be controlled by proper

Prognosis: In zinc fume fever,

recovery occurs

air exhaust.

in 24 to 48 hours.

Miscellaneous

In pulmonary edema from zinc chloride fumes,

Metals

161

the fatality

rate has been 10 to 40%.

MISCELLANEOUS M.A.C.

Not est.|Shortness

Not est.|

dermatitis

and vesiculation.

Metal

fume

edema,

0.1

Silver

Not

est.

est.

may

pneumonia.

headache,

vomit-

Remove from exposure. Remove from exposure. Remove

from

exposure. Remove

from

exposure.

Skin implants gangrene,

cause

necro-

subcutaneous

emphysema. Garlic breath,

gastroin-

testinal upset,

nervousness.

Argyria with brownish to black discoloration of face and hands. Garlic odor of breath, metallic taste,

Not

sneezing,

damage

bronchial

Dizziness, 100 fiken® fing, coma.

with

ae ore

0,1

Selenium

Vanadium

fever,

Renal

ee eer Not est.|

lung

hyperemia

sis,

Tellurium

of breath,

densities,

nausea. occur.

Hydrogen selenide Iron carbonyl Magnesium

Treatment

Effects

(p. p.m.) Cobalt

METALS

nausea,

loss

of

appetite. Rhinorrhea, sneezing, sore chest, wheezing, dyspnea, weakness, bronchitis, pneumonitis.

Remove implant sur-

gically. Remove from exposure. Remove from exposure. Give dimercaprol (BAL®) Give ascorbic acid, 1 Gm.

per day.

Chapter 16

CYANIDES, SULFIDES, AND CARBON MONOXIDE HYDROGEN

CYANIDE AND DERIVATIVES: CYANOGEN CHLORIDE, CYANIDES, AND NITROPRUSSIDES

CRYLONITRILE,

CYANAMIDE,

Hydrogen cyanide is used as a fumigant

and in chemical _

_synthesis. Acrylonitrile is used in the productionof synthetic rubber. Cyanamide is used as a fertilizer and as a source of

hydrogen cyanide. Cyanogen Chloride is used in chemical synthesis.

Cyanide salts are used in metal cleaning,

ing, refining,

and in therecovery of gold from ores.

_

harden-

Nitro-

prussides are used in chemical synthesis. Hydrogen cyanide (HCN) is a liquid which boils at 26.5°C. Acrylonitrile (CH9=CHCN) is a liquid which boils at

TRA The m.a.c. of hydrogen cyanide is 10 p.p.m. The m.a.c. for acrylonitrile is 20 p.p.m. The fatal dose of hydrogen cyanide is 50 mg. (3/4 gr.); of potassium cyanide, 200 mg. (3 gr.). The fatal dose of calcium cyanamide is estimated to be 50 Gm. (11/2 oz.). Up to 50 deaths per year have been reported from hydrogen cyanide or derivatives. Cyanide apparently poisons by inhibiting the cytochrome oxidase system for oxygen utilization in cells. Other enzyme

systems are also inhibited, Cyanide causes

but to a lesser degree.

first a marked

affecting chemoreceptors

in

increase

in respiration by

the carotid body and respiratory

center and then paralyzes all cells. Pathologic findings in fatal cases of cyanide poisoning are not characteristic. The odor of bitter almonds may be

noticeable at autopsy. Ingestion of potassium or sodium cyanide causes congestion and corrosion of the gastric mucosa. Clinical Findings: The principal manifestation

of poisoning with these compounds is respiratory stimulation. A. Acute Poisoning: 1. Cyanide, cyanamide, cyanogen chloride, nitroprusside - Ingesting or inhaling large amounts of these compounds (10 times the M.L.D. of cyanide) causes immediate

unconsciousness,

162

convulsions,

and death

Hydrogen Cyanide and Derivatives

163

within one to 15 minutes. Ingesting, inhaling, or absorbing through the skin an amount of cyanide near the M.L.D. causes dizziness, rapid respiration, headache, drowsiness, rapid pulse, and unconsciousness. Death in convulsions occurs within four hours with all cyanide derivatives except sodium nitroprusside, whi which 2.

may cause death aalaieas12hoursafteringestion)

Acrylonitrile - Inhaling acrylonitrile causes nausea, vomiting, diarrhea, weakness, headache, and jaundice. Skin contact with acrylonitrile causes blistering but is not likely to cause general symptoms. B. Chronic Poisoning: Inhaling small amounts of cyanogen chloride over several months causes dizziness, weakness, congestion of lungs, hoarseness, conjunctivitis, loss of appetite, weight loss, and mental deterioration. Similar symptoms have also been reported from inhaling cyanide in low concentrations for one year or more. C. Laboratory Findings: Noncontributory. Treatment:

A. Inhaled Cyanide: | De Emergency 1measures a.

Remove

-

to uncontaminated

atmosphere.

b. ;Give amyl nitrite inhalation, one ampul (0.2 ml. min.), every “five minutes. if the systolic blood pressure g. c.; Remove clothing and wash and water. d. Give artificial respiration

Stop administration goes below 80 mm.

exposed

skin with soap

if respiration fails.

2. Antidotea.

Sodi nitrite - As soon as possible give 10 ml. of 3% sodium nitrite solution I. V. at the rate of 2.5 to 5 ml. per minute. Stop administration if the sys-

tolic blood pressure b. Sodium

ml.

thiosulfate...

goes below Follow

80 mm.

sodium

Hg.

nitrite with 50

of 25% sodium thiosulfate solution 1.V.

ata

rate of 2.5 to 5 ml. per minute. c. Be prepared to repeat sodium nitrite and sodium thiosulfate if symptoms reappear. B. Ingested Cyanide: 1.; Emergency measures a. Amyl nitrite inhalation, one ampul (0.2 ml., 3

|

min.),

every five minutes.

-b. Gastric lavage (see p. 11). c. Catharsis (see p. 13). d. Give artificial respiration if respiration fails. 2. Antidote - Treat as for inhaled cyanide (see above).

164

Sulfides,

Mercaptans,

Carbon Disulfide

Prophylaxis: The m.a.c.

of cyanide in work rooms must be observed at all times. Emergency treatment kits containing 0.2 ml. (3 min.) ampuls of amyl nitrite, 10 ml. ampuls of 3% sodium nitrite, and 25 ml. ampuls of 25% sodium thiosulfate with suitable syringes and needles should be immediately available where cyanide is being used. Prognosis: In acute cyanide poisoning, usually followed by recovery.

HYDROGEN

survival for four hours

SULFIDE, OTHER SULFIDES, CARBON DISULFIDE

Hydrogen

is

MERCAPTANS,

sulfide is released spontaneously by the decom-

position of sulfur compounds

fineries, tanneries, mines, sulfide is used as a solvent,

and is found in petroleum

re-

and rayon factories. Carbon diespecially in the rayon industry.

Mercaptans are released in the course of petroleum refining. Hydrogen sulfide (HS) is a gas. Carbon disulfide (CS) is a liquid which boils at 46°C. It ignites at a temperature

slightly above that of boiling water (117°C.). Ethyl mercaptan (C)H5SH) and methyl mercaptan (CH3SH) are gases. The m.a.c. in air for both hydrogen sulfide and carbon disulfide is 20 p.p.m. Tolerances for other sulfide compounds have not been established. Up to ten fatalities per year are reported from

poisoning by sulfides.

Hydrogen sulfide causes both anoxic effects and damage to the cells of the C.N.S. by direct action. Carbon disulfide damages chiefly the C.N.S., the peripheral nerves, and the hemopoietic system. There are no characteristic pathologic findings in sudden fatalities from hydrogen sulfide poisoning; if death is delayed 24 to 48 hours, pulmonary edema and congestion of the lungs are found. Ingestion of carbon disulfide causes congestion and edema of the gastrointestinal tract. The characteristic unpleasant (rotten egg) odor is noticeable at autopsy. In deaths from carbon disulfide, degenerative changes may be found in the brain and spinal cord.

Clinical Findings: The principal manifestation of poisoning with these compounds is irritation. A. Acute Poisoning: 1. Hydrogen sulfide - The effects of exposure to hydrogen sulfide are dependent on the concentration. One p.p.m produces a barely detectable odor. Fifty p.p.m. creates

an unpleasant

odor,

but after a short

time

the

Sulfides,

Mercaptans,

Carbon Disulfide

165

smell diminishes. Above 50 p.p.m. symptoms are gradually progressive, with painful conjunctivitis, appearance of a halo around lights, headache, anosmia, nausea, rawness in the throat, cough, dizziness, drowsiness, and pulmonary edema. Concentrations above 500 p.p.m. cause immediate loss of consciousness, depressed respiration, and death in 30 to 60 minutes. . Carbon

disulfide

-

a. Vapor exposure to carbon disulfide at levels from 100 to 1000 p.p.m. causes symptoms progressing from restlessness, irritation of the mucous membranes,

blurred

vision,

nausea,

vomiting,

and

headache to unconsciousness and paralysis of respiration. If consciousness returns, blurred vision, irritability, and even psychotic behavior are observed.

b. Skin contact with carbon disulfide causes reddening and burning and later cracking and peeling. If the liquid remains in contact for several minutes, a second degree burn may result. c. Ingestion of carbon disulfide causes vomiting, headache, cyanosis, respiratory depression, fall of blood

pressure,

loss of consciousness,

tremors,

convulsions, and death. . Ethyl and methyl mercaptan in high concentrations cause cyanosis, convulsions, coma, and fever. Since dangerous concentrations are 10, 000 times those detectable by smell, exposure is unlikely. B. Chronic Poisoning: 1, Hydrogen sulfide - Prolonged exposure causes persistent low blood pressure, nausea, loss of appetite, weight loss, impaired gait and balance, conjunctivitis, and chronic cough.

. Carbon

disulfide - Continued exposure

or skin absorption

first causes

bizarre

by inhalation sensations

in

the extremities and then sensory loss and muscular weakness. Later symptoms are irritability, memory loss, blurred vision, loss of appetite, insomnia, mental depression, partial blindness, dizziness, weakness, and parkinsonian tremor. Examination may reyeal vascularization of the retina, dilatation of retinal arterioles, and blanching of the optic disc. The corneal and pupillary reflexes may be diminished or lost.

-. Laboratory Findings: 13 Differential count may reveal a decrease in the polymorphonuclear leukocytes and an increase in lymphocytes. . Hematuria and albuminuria may be present.

166

Carbon

Monoxide

3. Hepatic cell function may be impaired as shown by appropriate tests (see p. 40). Treatment: A. Acute Poisoning: 1. Emergency measures a. Remove from exposure. b. Give artificial respiration with oxygen if respiration is affected (see p. 24). c. Remove swallowed poison by gastric lavage, emesis and catharsis (see pp. 10 to 13). 2. Antidote - None known. 3. General measures a. Treat pulmonary edema (see p. 31). b. Keep patient at bed rest for three to four days. B. Chronic Poisoning: Remove from further exposure.

Prophylaxis: The m.a.c. must be observed at all times. The odor of carbon disulfide or hydrogen sulfide should not be relied upon Loss of the sense of smell occurs to give adequate warning. rapidly. Workers should alternate between jobs requiring exposure to carbon disulfide and jobs in uncontaminated air.

Air-line face-masks must be worn when entering highly conSafety harness and a lifeline attended by a taminated areas. responsible

person

are necessary.

Prognosis: In hydrogen sulfide poisoning, if the patient survives the first four hours, recovery is assured. In carbon disulfide poisoping, gradual improvement takes place over

several months

but complete

CARBON

recovery may never

for

occur.

MONOXIDE

Carbon monoxide is produced by the incomplete: combustion of carbon or carbonaceous materials. Any flame or

combustion device is likely to emit carbon monoxide. The exhaust from incomplete combustion of natural gas or petroleum fuels may contain as much as 5% carbon monoxide. An unvented natural gas heater may emit as much as one cubic foot of carbon monoxide per minute, enough to make the air in a small room highly dangerous within a few minutes. The exhaust from internal combustion engines contains from 3 to 7% carbon monoxide. At 20 m.p.h. an automobile produces about 200 cu. ft. of carbon monoxide per hour.

The m.a.c.

of carbon monoxide is 100 p.p.m.

A concentration above 4000

p.p.m.

(0.01%).

(0.4%) is rapidly fatal.

Carbon

More

Monoxide

than 2000 fatalities from carbon monoxide

167

occur

each year. Carbon monoxide combines with hemoglobin to form carboxyhemoglobin, which is incapable of carrying oxygen, and tissue anoxia results. jOne part of carbon monoxide in 300 parts of oxygen or 1500 parts of air will cause approximately 50% saturation of hemoglobin with carboxyhemoglobin.\ Pathologic examination in fatal cases of carbon monoxide poisoning reveals microscopic hemorrhages and necrotic areas throughout the body. There are also intense congestion

and edema of the brain, Tiver, “kidneys,

and spleen. The

tissues may be bright red. Microscopic examination reveals ‘damage to nerve cells, especially in the cerebral cortex and medulla} Clinical

Findings: rincipal manifestations

soning are dyspnea an cute Poisoning: (From inhalation.) The absorption of carbon monoxide and the resulting symptoms are closely dependent on the concentration of carbon monoxide in the inspired air, the time of exposure, and the state of activity of the person exposed.

1. A concentration of 100 p.p.m.

(0.01%) will not pro-

duce symptoms during an eight-hour exposure. 2. Exposure to 500 p.p.m. (0.05%) for one hour during

light work

may causeno symptoms or only slight head-

ache and shortness

of breath.

The blood will contain

approximately 20% carboxyhemoglobin. A longer ex- / posure to the same concentration, or greater activity,

will raise theblood-saturation to 40 to 50% with symptoms ofheadache, nausea, ‘irritability,

increased res-

piration, chest pain, confusion, impaired judgment, and fainting on increased e» exertion. _ The lips and skin may be bright 1red.{- > 3. Concentrations

over

1000 p.p.m. (0.1%)

cause un-

Sonscinianessyeupiratory failure, and death ifexposure

is continued for more

than one hour.

The blood

will contain 60°t6 90% carboxyhemoglobin., If recovery

occurs,

symptoms

regress

gradually.

a high igh blood saturation persists for several hours,

If

—

tremors, mental deterioration, and psychotic behavior may persist or reappear after a symptom-free interval

| of one to two weeks. These symptoms of C.N.S. damage} may be permanent. B4Chronic Poisoning: Chronic poisoning in the sense of ‘accumulation of carbon monoxide in the body does not soccur.

However,

repeated anoxia

from

carbon

monoxide

*absorption will cause gradually increasing C.N.S. damage twith loss of sensation in the fingers, poor memory, *positive Romberg’s sign, and mental deterioration.

ee

168

Carbon

Monoxide

C. Laboratory Findings: 1. White blood cell count may be normal or elevated to 18, 000 or higher.

2.) Blood containing more than 40% carboxyhemoglobin ‘| will retain a bright red color after diluting one drop with 5 ml. of 1% ammonium hydroxide and adding 10

mg.

(1/6 gr.) of sodium hydrosulfite.

becomes brown ay treated in this way 3. Albuminura may be present.

Normal blood

or brown-black.

Treatment: A. Emergency Measures: 1., Remove from exposure.

.bGive 100% oxygen by mask for one hour. reduce

the

blood

carboxyhemoglobin

This will

below the danger-

3.\If respiration is depressed, give artificial respiration ees 100% oxygen until respiration is normal. may of washed red cells, up to 2L., 4.,A transfusion help lower blood carboxyhemoglobin if given within the first 30 minutes B. Antidote: Give oxygen as under Emergency Measures. Cy oe ua Measures: Maintain body warmth.

2 Msn 3 .| Give 50 ml.

ad pressure pe (see p. 25). of 50% glucose I.V.

to reduce

cerebral

edema... 4

Prophylaxis: Air concentration must be kept below the m.a.c. at all times by proper ventilation. All combustion devices must be These devices include flame water vented to the outside air. heaters, stoves, gas refrigerators, and internal combustion engines.

Prognosis: Complete recovery is not sends if symptoms of mental deterioration_persist for two weeks

Chapter 17

PNEUMOCONIOSES

SILICOSIS Dust containing silica is produced during rock cutting, drilling, crushing, grinding, mining, abrasive manufacture, pottery making, and processing of diatomaceous earth. Many substances containing silica are capable of causing silicosis. Particles less than 5yu in diameter appear to be the most important in causing silicosis. Concentrations of dust should be kept below five million particles per cubic foot of air if more than 50% of dust is silica. If only 5% of the dust is silica, the number of dust particles allowable is 50 million per cubic foot of air. More than 1000 new cases of silicosis occur each year. However, the number of deaths directly resulting from silicosis is not known. Silica particles smaller than 5y in diameter are taken up from alveoli by phagocytic cells which then travel along the lymph channels toward the lymph nodes. Some of these phagocytes do not reach the lymph nodes but collect in nodules along the lymph channels. These nodules then gradually increase in size through proliferation of fibrous tissue to form the silicotic nodule. Pathologic examination reveals nodular fibrosis of the lungs. Progression of tuberculosis is greatly increased in silicosis, but apparently susceptibility is not increased.

Clinical Findings:

“The

principal manifestation of silicosis is dyspnea.

A. Acute pneumoconiosis does not occur from silica. B. Chronic Pneumoconiosis: Breathing silica dust in concentrations greater than the m.a.c. for six months to 25 years causes progressive dry cough, shortness of breath on exertion, and decreased chest expansion. As the disease progresses, the cough becomes productive of stringy mucus, vital capacity decreases further, and shortness of breath becomes more severe. If the patient gets tuberculosis, the course is rapidly downhill with increased cough, dyspnea, and weight loss.

C. X-ray Findings:

K-ray examination of the chest reveals 169

170

Silicosis

first a diffuse granular appearance. As the disease progresses, the fibrosis becomes linear, and later defiIf tuberculosis is superimposed on the nitely nodular. original disease, large nodules, cavities, and pneumonic

changes are found. X-ray alone should not be relied upon to make the diagnosis of silicosis since other pneumoconioses

may

give a similar

D. Laboratory Findings: duction as the disease

x-ray appearance.

Vital capacity shows progresses.

gradual re-

Treatment: A. Exposure to silica dust must be reduced to a safe amount. Complete change of occupation is not advisable. B. Antidote: None known. C. General Measures: 1. Activity should be restricted to an amount which does not produce dyspnea. However, exercise to tolerance is important for rehabilitation. 2. Inhalation of aluminum dust has not proved effective in controlled experiments. 3. One to two months of positive-pressure breathing therapy, as administered by suitable equipment (see pp. 357 and 381) three or more times daily for periods

of 20 to 30 minutes, may increase vital capacity and pulmonary ventilation capacity by 5 to 50%. 4. Administration rine,

1:1000;

1:100,

of bronchodilators isoproterenol,

by aerosol may

positive-pressure

improve

breathing

such as epineph-

1:100;

or phenylephrine,

effectiveness

of

therapy.

Prophylaxis:

~~~ Frequent quantitative dust counts and analyses must be made

in work

must

be kept within safe limits.

requiring exposure

to dust.

Particle

Workers

exposed

counts to dust

should have yearly chest examinations. Air-line

face-masks

and protective

suits must

be worn

where dust cannot be controlled, such as in sandblasting. Wet processes to control dusts must be used wherever feasible.

Dust- producing

operations

should be segregated.

Prognosis: After developing

silicosis, a worker may live and work longer in his regular job, at which he is satisfied, than he would after changing to a new job where he is not exposed to silica but where he does not have the security of familiar surroundings and work. However, exposure to silica must be reduced to a safe amount. An x-ray appearance identical with that seen in silicosis may be produced by dusts which do not cause progressive disease. Workers should not be frightened with the diagnosis

Other

Non-metallic

Dusts

171

of silicosis unless the history indicates a sufficient exposure to silica. Silicosis may appear and progress more than five years after discontinuing exposure. Removal from exposure does not stop progression of the disease. If a person with silicosis avoids tuberculosis, acute pulmonary infections, and excessive exertion, he will live approximately a normal life span. Severe attacks of purulent bronchial pneumonia are frequent

in silicotics,

and emphysema

EFFECTS MAC

OF

EXPOSURE

is likely to progress

TO NONMETALLIC

DUSTS

Clinical Findings

(par-

gradually.

Prognosis

ticles/cu.ft.) Asbestos

5 million

Interstitial pulmonary fibrosis, asbestos bodies in sputum.

Barite (barium sulfate Alundum| (Al203)

Not est.

Mica

Not est.

Tale

50 million

Coal dust

Sugar cane dust

|Interstitial

Nodulation of lungs lung fibrosis|

with emphysema,

Not est.

Bauxite Glass fiber Cotton dust

None

Not est. Not est. Not est.

Not est.

Progressive (see silicosis)

Ground glass

severe dyspnea, and pneumothorax. Similar to silicosis (see p. 169).

Fibrosis

| Nonprogressive

of |Progressive

lungs

Pleural

cal-|

Progressive

cification,

fibrosis, Fine fibro-

Similar to silicosis | Progressive (see p. 169). Similar to silicosis Like silico-| Progressive _|(see p. 169). sis Skin irritation, no lung | No change No disease involvement, Progressive dyspnea, Emphysema| Nonprogressive emphysema, weakness. in early stages Asymptomatic silica present

unless in dust

or unless tuberculosis develops. Cough, dyspnea, hemoptysis, chills and fever, weakness, weight loss.

Nodulation

Nonprogressive

Miliary mottling

Nonprogressive

Section IV

Household Chemicals Chapter 18

COSMETICS POTASSIUM

BROMATE

Potassium bromate (KBrOg) is used as a neutralizer in cold waves. On contact with acids, such as gastric hydrochloric

acid,

it releases

hydrogen

bromate,

an irritating

acid.

The fatal dose of potassium bromate is estimated to be 4 Gm. (60 gr.), or 120 ml. (4 oz.) of a 3% solution. The usual neutralizer contains 15 Gm. (1/2 oz.), which is diluted in 500 ml. (1 pint) of water to make a 3% solution. About 10 fatalities from potassium bromate have been reported.

Potassium bromate and hydrogen bromate are extremely irritating and injurious to tissues, especially those of the C.N.S. and kidneys. The pathologic findings include kidney damage and hemolysis. Clinical

Findings:

The principal manifestations of potassium bromate poisoning are vomiting and collapse. A. Acute Poisoning: (From ingestion.) Vomiting, diarrhea, abdominal pain, oliguria or anuria, lethargy, coma, convulsions, low blood pressure, and fast pulse. B. Chronic poisoning has not been reported. C. Laboratory Findings: 1, Hematuria and albuminuria. 2. Elevated N.P.N. during oliguria or anuria. Treatment: A. Emergency Measures: emesis, and catharsis

Remove poison by gastric lavage, (see pp. 10 to 13). The gastric lavage or emetic should consist of 30 to 50 Gm. (1 heaping tbsp.) sodium bicarbonate to each quart of water.

B. Antidote: Give sodium thiosulfate, 1 to 5 Gm. (15 to 75 gr.) 1I.V. as a 10% solution. C. General Measures: Relieve gastric irritation by giving milk or cream every hour. D. Special Problems:

Treat anuria (see p. 29), 172

Cosmetics

173

Prophylaxis:

Nonpoisonous -

cold wave neutralizers are available and

should be used. If poisonous be stored and used safely.

neutralizers

are used they must

Prognosis:

Complete recovery is possible even when anuria one week. About 10% of those poisoned have died, MISCELLANEOUS Cosmetic Substance Cold wave lotion

lasts

COSMETICS Treatment

Thioglycollic acid, thioglycerol.

Sensitivity

INeither of these chemcals is poisonous by ingestion in the quantiies in which they are present in cold waves. epeated use of cold wave

preparations

may

cause sensitivity derma itis characterized by

dermatitis will disappear on discontinuing the use of cold wave preparations.

edema, burning of the skin, itching, anda

papular rash; these thio compounds are presumably responsible. Corn

cures

Deodorants

Salicylates, salicylic acid,

See p. 183.

See p.

Aluminum chloride or other

[Irritation of the gastric mucosa, but no corro-

|Give milk |and stimu-

aluminum

Depilatories}

dye

sulfide

and

Not

likely to cause

other aromatic

|ous poisoning

gestion of usual house-

com-

133, Discontinue use, ).

seri-

amino pounds.

bleach

164.

|Naphthylamine, |Sensitivity dermatitis phenylenedior irritation of eyes amines, tolylene4may occur (see p. 96 diamines,

Face powder Freckle remover

late vom-

Thallium Barium sulfide Sodium

Eyelash

salts

183.

after in-

hold preparations.

hey palnave ie Por

to

a dermatitis.

Mercurials,

See p.

154.

Hydrogen peroxide, 6 to 30%.

Concentrated solutions |(20 to 30%) of hydrogen peroxide are strong irritants to the skin or mucous membranes.

Discontinue

use, See p. 154. See p. 183. Dilute concentrated

hydrogen peroxide by giving water,

174 MISCELLANEOUS

COSMETICS

(Cont’d.)

Cosmetic Substance

Hair

dyes,

Treatment

Naphthylamines,

|Any of these compounds

[See p. 93.

may cause liver damage permanent | phenylenediamines, tolylene- and skin sensitization if used excessively (see diamines, and

Hair dyes, temporary

other aromatic amino com-

p.

pounds.

poisoning after ingestio of usual household

Silver, mercury, lead, arsenic, pyrogallol, bismuth, and other metals.

96).

cause

Not likely to

serious

acute

preparations. Metal poisoning may occur following the ingestion of these metallic hair dyes.

Remove poison (see p. 10). Give dimercaprol if symptoms

occur,

See p.

Hair lacquer (wave set) Hair straighteners Hair

tonic

Vegetable gums. Synthetic gum.

|Sensitivity dermatitis may occur. Not poison-| ous after ingestion.

See p.

Sodium hydroxide (up to 15%). Alcohol, arsenic, lead, silver,

pyrogallol.

Lip dye

Eosin

Perfume

Alcohol 50%).

The small quantity of active ingredient present in hair tonic makes poisoning unlikely.

Cheilitis, facial dermatitis, or stomatitis.

(up to

See p.

107.

46).

Discontinue use. 133.

Remove ingested poison (see Po-1-O--)} pedi symptoms develop, dimercaprol may be necessary (see p. 46). Discontinue use. See p. 107.

Chapter 19 FOOD

POISONING

BOTULISM The

botulinus

toxin is a heat-labile

protein which

can be

lestroyed by boiling for at least 15 minutes. Botulism is caused by the exotoxin produced by the anSuch growth freerobic growth of Clostridium botulinum. ently occurs in under-processed, nonacid canned foods. The foods most often responsible are meats, fish, and vegeOlives and fruits are occasionally responsible. ables. The fatal dose of a contaminated food may be less than )ml.

Up to 10 fatalities

(1 tsp.).

Botulinus

toxin causes

occur

paralysis

per year.

of muscles

by blocking

Other he transfer of nerve impulses at the motor end-plate. -ells appear to be affected also. Pathologic findings are congestion and hemorrhages in Degenerative 111 the organs and especially in the C.N.S.

shanges

occur

in the liver and kidneys.

Clinical Findings:

"The

principal manifestations

of botulism are vomiting

and muscular paralysis. (From ingestion.) Symptoms begin A. Acute Poisoning: with nausea, vomiting, and sometimes diarrhea and abAfter a 12 to 24 hour delay, muscle dominal distress. involvement

is indicated

by double

vision,

difficulty

in

swallowing, weakness, and paralysis of the respiratory muscles. B. Chronic poisoning does not occur, Noncontributory. C. Laboratory Findings: Treatment: Immediately upon suspecting food A. bmergency Measures: poisoning, remove the toxin by gastric lavage, emesis, and catharsis (see pp. 10 to 13). Give up to 50 ml. of botulinus antitoxin I. V. B. Antidote: Serum sensitivity must be tested by injecting 0.1 ml. of a 1:10 dilution of antitoxin in saline intradermally; wait one hour before giving a large dose.

C. General Measures:

Treat respiratory depression by 175

176

Bacterial Food Poisoning artificial

respiration.

In respiratory

paralysis,

maintain

respiration by use of body respirator, rocking bed, or other mechanical aid (see p. 353). Artificial respiration may be life-saving in cases of botulism not amenable to treatment by other means; it should be continued until all vital signs have definitely ceased. Prophylaxis:

—— Process

canned foods according to the methods approved

by the Department

of Agriculture

as described

Canning of Fruits and Vegetables’’ A1.77:8;

and

‘‘Home

Canning

(ten cents),

of Meat’’

in ‘‘Home

Catalog No.

(ten cents),

Catalog

No. Al.77:6. The pamphlets are obtainable from the Superintendent of Documents, Government Printing Office, Washington 25,

Boil

D.C.

or pressure

cook

suspected

canned

foods for 15

minutes before serving. If poisoning occurs in any member of a family or group, treat every person who may have eaten the suspected food. Do not wait for symptoms

suspected

to develop.

Label,

food in such a way that others

Prognosis: Approximately

60% of those poisoned

BACTERIAL

FOOD

seal,

and store

will not be poisoned.

will die.

POISONING

Bacterial food poisoning may be caused by the enterotoxins elaborated during the growth of salmonellae, staphylococci, or clostridia in foods stored at room temperature. Th toxins produced by these organisms are proteins, easily

destroyed by heat. The foods most often responsible for this type of poisoning are ham, tongue, sausage, dried meat, fish products, milk and milk products (including cream and cream filled bakery goods), and eggs. Bacterial food poisoning is ordinarily self-limited; symptoms arise presumably from the local effects of the toxins.

The fatality rate is approximately

1%.

Clinical

Findings:

~The

principal manifestations of bacterial food poisoning

are vomiting and diarrhea. A. Acute Poisoning: Nausea, vomiting, diarrhea, and weakness beginning within three to six hours after ingestion. These symptoms ordinarily progress for 12 to 24 hours

and then regress.

Abdominal

severe.

fever,

Malaise,

and shock occur B. Chronic

pain and tenesmus

muscular

cramps,

rarely.

poisoning

has not been

reported.

may be

dehydration,

Chemical

Food Poisoning

177

C. Laboratory Findings: 1. Blood count may reveal hemoconcentration. 2. Urinalysis may reveal a trace of albumin. Treatment:

A. Emergency

Measures:

Remove

intestinal tract by gastric to 11). If diarrhea is not be given (see p. 13). B. Antidote: None known. C. General Measures: 1. Bed rest. 2. Nothing by mouth until hours. Then give oral hours before beginning 3. If vomiting

.

the toxin from

the gastro-

lavage or emesis (see pp. 10 present, a saline cathartic may

vomiting has subsided for four fluids as tolerated for 12 to 24 regular diet.

and diarrhea

are

severe,

balance by giving 5% dextrose

maintain

fluid

in saline I. V.

4. Codeine, 30 mg. (1/2 gr.) orally or subcut., or camphorated tincture of opium (paregoric), 4 to 12 ml. (1 to 3 tsp.), after each bowel movement. 5. Atropine, 1 mg. (1/60 gr.) subcut. if gastrointestinal hyperactivity persists. 6. Bismuth subcarbonate, 1 Gm. (15 gr.), after each bowel movement may suffice in mild cases.

Prophylaxis: If foods

containing

meats,

milk

or milk

products,

eggs are not eaten immediately after being cooked, should be stored under refrigeration. Prognosis: If the patient lives for 48 hours,

CHEMICAL

FOOD

recovery is likely.

POISONING

Storage of foods such as fruit juice or sauerkraut fainers

lined with

cadmium,

zinc,

or

they

or antimony

in con-

will lead to

acute gastric irritation manifested by nausea, vomiting, and jiarrhea. The disease usually lasts 24 to 48 hours. If necessary, atropine, 0.5 mg. (7/120 gr.), and bismuth subcarbonate, 5 Gm. (1 tsp.), may be given to relieve abdominal distress. If symptoms are persistent and indicate metal poisoning, specific treatment may be necessary. (See cadmium, 9. 146; antimony, p. 141.) Food poisoning may also occur when meat preservatives which contain sodium nitrite are ised excessively or erroneously in place of salt (see p. 253).

Chapter 20 MISCELLANEOUS HOUSEHOLD CHEMICALS

BLEACHING SOLUTIONS (CLOROX®, PUREX®, SANI-CLOR®) Bleaching solutions are 3 to 6% solutions of sodium hypoThey are corrosive to the same extent that chlorite in water. similar concentrations of sodium hydroxide are corrosive. Upon contact with acid gastric juice or acid solutions they release hypochlorous acid, which is extremely irritating to skin and mucous membranes but apparently is rapidly inactivated Buffering the by blood serum and has low systemic toxicity. acid by the administration of sodium bicarbonate offers the Do not use acid best means of reducing the irritative effect. antidotes in the treatment of sodium hypochlorite poisoning. The fatal dose for children is estimated to be about 15 to

30 cc.

(1/2 to 1 oz.).

Clinical Findings:

“The

principal manifestation of poisoning with bleaching

solutions is severe irritation. A. Acute Poisoning: (From ingestion or inhalation.) Inhaling hypochlorous acid fumes causes severe pulmonary irritation with coughing and choking followed by pulmonary edema. Ingestion causes irritation and corrosion of mucous membranes. Edema of the pharynx and larynx may be severe. Perforation of the esophagus or stomach has occurred but is rare. Prolonged skin contact with bleaching solution causes irritation. B. Chronic poisoning does not occur.

C. Laboratory

Findings:

Noncontributory.

Treatment:

A. Emergency Measures: 1. Remove bleaching solution from the skin by flooding with water. 2. Remove swallowed or emesis,

bleaching

using a solution

178

solution by gastric lavage of sodium

bicarbonate,

Bleaching Solutions

179

30 to 50 Gm. per liter (1 heaping tbsp. per quart). After emesis or lavage, give a cathartic consisting of sodium sulfate, 30 Gm. (1 oz.), and sodium bicarbonate, 10 Gm. (1 heaping tsp.), in 250 ml. (1 cup) of DO NOT USE ACID ANTIDOTES. water. Use sodium bicarbonate as described under B. Antidote: emergency measures. Treat as for sodium hydroxide poiC. General Measures: soning (see p. 133). rophylaxis: Bleaching rognosis:

Recovery ours.

solutions

should be stored and used safely.

is likely if treatment is started within a few

MISCELLANEOUS

HOUSEHOLD

Poisonous

Common Name ‘anned heat

Ingredient Methy!1 alcohol,

(Sterno®)

denatured ethyl

‘arbide

alcohol Calcium

carbide

CHEMICALS

Remarks

See p.

reatment

107.

ee p.

[Releases acetylene on contact with

107.

Remove by giving large

water.

*hlorinated lime

‘leaning solvents, (inflammable)

Irritating but not Calcium hypocorrosive. chlorite (10% available chlorine) |Also called Stoddard Petroleum hydrosolvent or French carbons Toxicit, dry cleaner. is about the Same as that

“leaning solvents, (noninflammable,

‘‘safe’’) Sloth dyes

Carbon tetrachloride, tri|chloroethylene

Aniline dyes

of kerosene

(see p. 121). “Safe’’ only because it is noninflammable.

May produce irritation

gastric

or methe-

moglobinemia.

|See p.

|Remove gastric

100.

by

lavage or emesis,

180 MISCELLANEOUS Common Name Cloth-mark-

HOUSEHOLD

Poisonous Ingredient Aniline

(Cont’d.)

Remarks Produces

Treatment

methemo-

See p. 92.

globinemia by skin absorption or in-

ing ink

Crayons

CHEMICALS

p-Nitroaniline

gestion. Produces

methemo-

|See p.

92.

See: pi“

83%.

See p.

142.

See p. See p.

154. 141.

globinemia if inDishwashing machine compounds Drain cleaners (Drano® Fireworks

Sodium phosphate and sodium silicate

Arsenic

gested (see p. 43). |Irritating and corrosive to mucous membranes,

z

:

Mercury Antimony Lead

Thiocyanate

:

:

See p.

151.

See ps

252:

Fluorescent

lamps Fuel tablets Furniture polish

Germicidal detergents Indelible pencils

Metaldehyde Rretecgeted

See p. 118. *niaae irritation

Turpentine

Petroleum carbons Cationic

hydro-

[sc aed | deter-

Triphenylmethane

See p.

240.

See p. 118. Force fluids. See p.

126.

See p.

121.

See p.

240.

|Extremely injurious |Eye conto tissues, Puncture]tamination wounds or eye-con|is treated

tamination from pencil scrapings

by washing

causes

for at least

pain,

and necrosis.

edema,

with water 15 minutes

followed by the repeated instil-

lation of 1% fluorescein solution which will remove the

indelible dye by forming a soluble

salt

(see p. 14). Treat punc-

ture wounds

by surgical Ink eradicator

Sodium chlorite

hypo-

See p. 178.

debridement, See p. 178.

181 MISCELLANEOUS

HOUSEHOLD

CHEMICALS

(Cont’d.)

Poisonous

Treatment

Ingredient

Methoxyphenamine (Orthoxine®) Methylhexaneamine Forthane®

1

200 200

Naphazoline

3

10

(Privine®) Phenylpropanolamine Propadrine® Phenylpropylmethylamine| (Vonedrine®) Propylhexadrine (Benzedrex®)

*Estimated

112 | Orally.

peroneal

Methoxamine

for children

would be at least

or subcut.

Orally. Orally.

Y~ | Intranasally.

200

3

Intranasally.

200

3

Intranasally or orally.

200

3

Intranasally

up to two years

10 times

I.M.

as high,

of age.

or orally.

Adult

M.L.D.

Epinephrine Prognosis: If patient survives

and Related Drugs

223

24 hours he will probably recover.

EPHEDRINE,

EPINEPHRINE,

AMPHETAMINE,

PRIVINE, AND RELATED DRUGS (See table on p. 222.) i.

—OH

H—C—

OH

H

H

H

Rabin

C—N

|

CH,

OHS

H

t2/

[aber

CHEE

CH,

Ephedrine

Epinephrine

H

loss

|

Vie

H

Naphazoline (Privine®)

Amphetamine

Epinephrine, ephedrine, and related agents are widely sold on prescription and in proprietary mixtures for the treatment

of nasal

One

congestion,

to 10% of users

asthma,

and hay fever.

of epinephrine

or substitutes

have

re-

See p. 222 for estimated fatal actions from overdosage. Fatalities are rare. doses. Epinephrine and substitutes stimulate muscle and gland They cells innervated by the sympathetic nervous system. also produce variable stimulatory effects on the C.N.S. The pathologic findings are not characteristic.

Clinical Findings: The principal manifestation of poisoning with these drugs is convulsions. (From injection, ingestion, inhalation, A. Acute Poisoning: Nausea, vomiting, or application to mucous membrane.) chills,

cyanosis,

nervousness,

irritability,

fever,

224

Epinephrine

and Related Drugs

tachycardia, dilated pupils, blurred vision, opisthotonos, spasms, convulsions, gasping respiration, coma, and respiratory failure. The blood pressure is raised

markedly initially, but may be below normal later. B. Chronic Poisoning: Prolonged nasal use of epinephrine or substitutes leads to chronic nasal congestion. Prolonged oral use of amphetamine or ephedrine or similar drugs in large doses by emotionally unstable individuals may lead to personality changes with a psychic craving to continue the use of the drug. C. Laboratory Findings: Noncontributory. Treatment: A. Acute Poisoning: 1, Emergency measures a. Delay absorption of ingested drug by giving tap water, milk, or universal antidote and then remove by gastric lavage or emesis followed by catharsis (see pp. 10 to 13). b. If respirations are shallow or if cyanosis is present, give artificial respiration (see p. 19). c. Maintain blood pressure in cardiovascular collapse (see p. 25). 2. Antidote - None known. 3. General measures - Control convulsions by ether inhalation (see p. 34). B. Chronic Poisoning: Discontinue use. Prophylaxis: Parents should be warned of the dangers of incautious administration of potent nose drops to infants. Nasal inhalers and amphetamine preparations should be stored safely. Prognosis:

If the patient survives likely.

the first six hours,

recovery

is

225 PHYSOSTIGMINE, PILOCARPINE, NEOSTIGMINE, METHACHOLINE AND RELATED DRUGS

CHy

|

—Oo—cC

fe) Zegy Ne

| N’

a

H

Cr

3

N'

Se

ie

CHg3

CHg Physostigmine (Eserine)

CH

oh

H

H

H

basil

|

fs vefprmie: |ems ef ot H

HC

H

S

H5C

(e

a

N

O

heute

Pilocarpine

(Alkaloid) H3C Bala

+

mn

H3C

Gat

mae

CH,

4

oO

CH,

Methacholine

(Mecholy]®)

H3C Ce

° Na

CH,

—O—C—N

H3C

CH,

Neostigmine

(Prostigmin®)

Physostigmine,

pilocarpine,

neostigmine,

and metha-

choline are used for the treatment of myasthenia gravis, for atonic conditions of the gastrointestinal tract and urinary bladder,

and for certain

cardiac

irregularities.

226 PHYSOSTIGMINE

AND

RELATED

DRUGS

Drug

Method of

Benzpyrinium

Bethanechol

Administration Orall

(Stigmonene®

(Urecholine®

Methacholine

3

(Mecholyl®

Neostigmine (Prostigmin®)

60 10

Pilocarpine

GON

Physostigmine

| 6

*Estimated

By

injection

Vg

By injection

1 V6

Orally By injection

|

Orall

| ¥i0 | Orally

for adult.

More than 20 fatalities from these compounds have been reported in the literature. Physostigmine, benzpyrinium, and neostigmine inhibit the esterase responsible for hydrolyzing the parasympathetic effector, acetylcholine. Pilocarpine, bethanechol, and methacholine act at the same point as does acetylcholine. As a result of these actions, these drugs stimulate muscles and glands innervated by the parasympathetic nervous system. The pathologic findings are congestion of the brain, lungs, and gastrointestinal tract. Pulmonary edema may occur.

Clinical

Findings:

~The

principal manifestation of poisoning with these drugs

is respiratory

difficulty.

A. Acute Poisoning: (From ingestion, injection, or application to mucous membranes.) Tremor, marked peristalsis with involuntary defecation and urination, pinpoint pupils, vomiting, cold extremities, bronchial con-

striction with difficult breathing and wheezing, twitching of muscles, fainting, slow pulse, convulsions, and death from asphyxia or cardiac slowing. B. Chronic Poisoning: Repeated small doses may reproduce the syndrome described above under Acute Poisoning. C. Laboratory Findings: Noncontributory. Treatment: A. Acute Poisoning: 1. Emergency measures - Give artificial until antidote can be given.

2. Antidote - Give atropine,

2 mg.

respiration

(1/30 gr.) I. V. slowly.

Repeat this dose I. M. every two to four hours as neces sary to relieve respiratory difficulty. B. Chronic Poisoning: Treat as described under Acute Poisoning. Prophylaxis: When using physostigmine

and related

drugs,

atropine

Ergot and Derivatives should be readily available for immediate Prognosis: If atropine

can be given,

ERGOT,

recovery

ERGOTAMINE,

c

use.

is immediate.

ERGONOVINE

H

CH,

Seat) ate finacs ake

HN

Be Cc—c¢

227

CH,OH s

CHo

AYECc RDH A

ax

tc

3

Ergonovine

CHg

Ergotamine

Ergot is a fungus which grows on rye. The derivatives, including ergotamine and dihydroergotamine, are used in the treatment of headaches; ergonovine and methylergonovine are used as uterine stimulants. Ergot is used in various pro-

prietary mixtures as an abortifacient. Rye flour is sometimes contaminated by the ergot fungus. The fatal dose of ergot may be as low as 1 Gm. (15 gr.).

228

Ergot and Derivatives

Fatalities from ergotamine or other purified derivatives have not been reported; presumably the fatal dose is high in relation to therapeutic

dose.

Ergot and its alkaloids stimulate smooth muscles of the arterioles, intestines, and uterus. The pathologic findings include congestion and inflammatory changes in the gastrointestinal tract and kidneys. Gangrene of the fingers and toes may be present. Clinical Findings: The principal manifestations of poisoning with these drugs are convulsions and gangrene. A. Acute Poisoning: (From ingestion, injection, or application to mucous membranes.) Vomiting, diarrhea, dizziness, rise or fall of blood pressure, weak pulse,

dyspnea,

convulsions,

loss of consciousness.

The dose

necessary to produce abortion may cause fatal poisoning. B. Chronic Poisoning: (From ingestion, injection, or application to mucous membranes.) Ergotism includes two types of manifestations which may occur together or separately: 1. Those resulting from contraction of blood vessels and reduced circulation include numbness and coldness of the extremities, tingling, pain in the chest, and gangrene of the fingers and toes. 2. Those resulting from nervous system disturbances include vomiting, diarrhea, headache, tremors, contractions

C. Laboratory

of the facial

Findings:

muscles,

and convulsions.

Noncontributory.

Treatment: A. Acute Poisoning: 1. Emergency measures - Delay absorption of ingested poison by giving tap water, milk, or universal antidote and then remove by gastric lavage or emesis followed

by catharsis

(see pp.

10 to 18).

2. Antidote - None known. 3. General measures - Treat convulsions (see p. 34). B. Chronic Poisoning: Discontinue the use of ergot preparations. Gangrene will require surgical amputation. Prophylaxis: Do not give over 3 mg. (1/20 gr.) of purified ergot derivatives (including ergotamine) daily; higher doses are likely to result in peripheral vascular disturbances. Ergot preparations are contraindicated in pregnancy prior to term, in obliterative vascular disease, infections, and kidney or liver disease.

Ergot and Derivatives

229

Prognosis: In acute poisoning from ergot, death may occur up to one week after poisoning. Complete recovery usually occurs in chronic poisoning if the use of ergot derivatives is discontinued prior to the appearance of gangrene.

Chapter 25

ANTISEPTICS

BORIC

ACID,

Boric

SODIUM

acid (H3BO3)

BORATE, is a white

SODIUM

PERBORATE

compound

which is soluble

to the extent of 5% in water at 68°F. (20°C.). Sodium borate or borax (Na, B,0 .10H,O) is a white compound which is

soluble to the extent of 14% in water at 131°F. (55°C.). Sodium perborate (NaBO..4H,O) is a white compound which is slightly soluble in cold water and decomposes in hot water. Boric ative,

and

acid is used as an antiseptic, to make

talcum

powder

flow

as a food preservfreely.

Sodium

(borax) is used as an antiseptic and cleaning agent. perborate is used as a mouth wash and dentifrice. The

fatal

dose

of boric

acid,

sodium

borate,

borate

Sodium

or sodium

perborate for an adult is estimated to be 5 to 15 Gm. (75 gr. to Y2 oz. ). The fatal dose for an infant is proportional to weight. Up to five fatalities occur per year. Boric acid and borates are toxic to all cells. The effect on an organ is dependent on the concentration reached in that

organ.

Because

the highest concentrations

are reached

during

excretion, the kidneys are more seriously damaged than other organs. The renal excretion of toxic doses requires one week. The pathologic findings are gastroenteritis, fatty degener-

ation of the liver and kidneys, of all organs.

cerebral

Clinical Findings: The principal manifestations pounds

are

A. Acute

skin excoriations,

Poisoning:

absorption from development of:

(From mucous

edema,

of poisoning

fever,

and congestion

with these

com-

and anuria.

ingestion,

skin absorption,

membranes.)

or

Progressive

1. Vomiting and diarrhea of mucus and blood. 2. Erythroderma, followed by desquamation, excoriations, blistering, bullae, and sloughing of epidermis. 3. Lethargy. 4.

Twitching

of facial muscles

by convulsions. 5. Hyperpyrexia, jaundice,

230

and extremities,

and anuria.

followed

Boric

Acid

231

6. Cyanosis, fall of blood pressure, collapse, coma, and death. B. Chronic Poisoning: (From ingestion, skin absorption, or absorption from body cavities or mucous membranes. ) 1. Prolonged absorption causes anorexia, with weight loss and mild diarrhea. 2. Local use of sodium perborate in high concentrations in the mouth may cause chemical burns, low resistance to trauma, and retraction of gums. C. Laboratory Findings: 1. Urine shows albumin, epithelial casts, and red blood cells.

2. The presence of boric acid or borates can be shown by applying a drop of urine acidified with hydrochloric acid to turmeric paper. A brownish-red color is produced. 3. Blood N. P.N. and urea may be increased. 4. Hepatic cell function may be impaired as revealed by the appropriate tests (see p. 40). Treatment: A. Acute Poisoning: 1. Emergency measures a. Remove boric acid from skin or mucous membranes by washing. b. Delay absorption of ingested boric acid by giving tap water,

milk,

or

universal

antidote

and

then

re-

move by gastric lavage or emesis followed by catharsis (see pp. 10 to 13). 2. Antidote - None known. 3. General measures a. Maintain urine output by giving liquids orally; if patient is vomiting, give 5% dextrose, 10 to 40 ml. /

Kg. I.V. daily.

7

b. Control convulsions by cautious administration of c.

ether (see p. 34). Remove boric acid or borates

from the circulation

by peritoneal dialysis or with an artificial kidney if available (see p. 31). 4. Special problems - Treat anuria (see p. 29). B. Chronic Poisoning: Discontinue use of boric acid or borate products.

Prophylaxis: Parents should be warned of the dangers of applying powdered boric acid to infants. Boric acid solution should not be used as an antiseptic on baby bottles or nipples. Prognosis: More than 50% of infants who have symptoms poisoning will die.

of boric

acid

232

IODINE, IODOFORM, IODOCHLORHYDROXYQUIN (VIOFORM®), IODIDES Iodine is a brown, flaky compound which is soluble in alcohol and insoluble (0.03%) in water. It is precipitated by starch. The solubility of iodine is greatly increased in the presence of iodide. lIodoform consists of a slightly yellowish powder or crystalline material with a penetrating odor. Itis

insoluble in water but soluble in alcohol.

lodochlorhydroxy-

quin is a brownish-yellow powder with a slight odor. It is insoluble in water and alcohol. Sodium and potassium iodides are white crystals, insoluble in water. Iodine is used as an antiseptic and for the treatment of thyroid diseases. lodoform (triiodomethane) and iodochlorhydroxyquin (Vioform®) are used as antiseptics. The fatal dose of iodine and iodoform is estimated to be 2 Gm. (30 gr.); as many as ten fatalities occur yearly. Most are suicidal deaths, but some occur accidentally in children or through errors in drinking from the wrong medicine bottle. Fatalities have not been reported from iodochlorhydroxyquin poisoning. Iodine has a direct action on cells by precipitating proteins. The affected cells may be killed. The effects of iodine are thus similar to those produced by acid corrosives (see p. 131). Iodoform in large doses depresses the C.N.S. The pathologic findings are excoriation and corrosion of mucous membranes of the mouth, esophagus, and stomach. The kidneys show glomerular and tubular necrosis. Clinical

The

Findings:

principal manifestations

agents are vomiting,

collapse,

of poisoning with these

and coma.

A. Acute Poisoning: 1. Ingestion of iodine causes severe vomiting, frequent liquid stools, abdominal pain, thirst, metallic taste, fever, anuria, delirium, stupor, and death in uremia. 2. Application of iodine to the skin may cause weeping, crusting, blistering, and fever. Individual susceptibility to such reactions shows great variation in that some will react after momentary contact with weak solutions

contact

whereas

others

will not react

after repeated

with strong solutions.

3. Application

of iodoform

to skin or mucous

membranes

may cause veSiculation and oozing with intense itching, burning pain, tenderness, and irritability. 4. Injection of iodine

compounds

may

cause

sudden

fatal

collapse (anaphylaxis) as a result of hypersensitivity. Symptoms are dyspnea, cyanosis, fall of blood pressure, unconsciousness, and convulsions. 5. Ingestion of iodoform

causes

nausea,

vomiting,

Iodine

diarrhea,

respiratory

coma,

distress,

233

and circulatory

collapse.

B. Chronic Poisoning: 1. Prolonged ingestion of iodine or iodine compounds leads to iodism, with skin erythema, conjunctivitis, stomatitis, acne, rhinorrhea, urticaria, anorexia, weight loss, sleeplessness, and nervous symptoms. For this 2. Iodine or iodine compounds are sensitizers. reason, repeated contact may be followed by sensitivity dermatitis

(see p.

36).

Urine may C. Laboratory Findings: casts, and red blood cells.

epithelial

show albumin,

Treatment: A. Acute Poisoning:

1. Emergency measures

-

a.

Remove swallowed iodine by gastric lavage or emesis with starch solution made by adding 15 Gm. (1 heaping tbsp.) of cornstarch or flour to 500 ml. (1 pint) of water. Follow by catharsis with 30 Gm. (1 oz.) of sodium sulfate and 15 Gm. of starch in 250 ml. (1 cup) of water. b. Give milk orally to relieve gastric irritation. c. Treat anaphylaxis by giving epinephrine, 0.3 to

1 ml.

of 1:1000 solution I.M.

or 1.V.

repeatedly to

maintain pulse and blood pressure. Give positive pressure artificial respiration. Give diphenhy-

dramine (Benadryl®),

50 mg.

(3/4 gr.) I.V.

slowly.

Give hydrocortisone, 4 to 10 mg. (1/15 to 1/6 gr.) I.V. per hour until symptoms abate. . Antidote - No antidote is known. 3. General measures - If urine output is reduced, regulate fluid and electrolyte intake (see p. 29). 4. Special problems a. Treat skin eruptions by applying mild astringent wet dressings (see p. 36). b. Treat esophageal stricture (see p. 132). B. Chronic Poisoning: 1. Discontinue use of iodine or iodides. 2. High sodium chloride intake will speed recovery. 3. Give cortisone, 25 to 100 mg. every six hours orally until symptoms abate. i]

Prophylaxis:

Patients should be tested for sensitivity to iodine or A suitable test for drugs to iodine compounds prior to use. be used on the skin is to place a drop of the solution on the

skin and leave the area uncovered for 30 minutes. action

contraindicates

Any re-

the further use of the drug in question.

If injection of the drug is contemplated,

a drop of the solution

234

Potassium

Permanganate

may be placed in the conjunctival ritation noted after 30 minutes.

sac,

and the presence

of ir-

Prognosis: If the patient survives 48 hours after the ingestion of iodine he is likely to recover, although stricture of the esophagus may complicate recovery. In sensitivity reactions following the injection of iodine compounds, survival is likely if the patient lives for one hour.

POTASSIUM

PERMANGANATE

Potassium permanganate (KMnO,) is a water-soluble, violet, crystalline compound used as a disinfectant and oxidizing agent. It has an undeserved reputation as an abortifacient when used in the vagina. The fatal dose is estimated to be 10 Gm. (150 gr.). The incidence of poisoning from potassium permanganate is rising. At least five fatalities occur every year. Potassium permanganate acts by destroying cells of the mucous membranes by alkaline caustic action (see p. 133). Pathologic findings are necrosis, hemorrhage, and corrosion of the mucous membranes with which potassium permanganate has come in contact. The liver and kidneys show degenerative changes. Clinical

Findings: The principal manifestation of poisoning with potassium permanganate is corrosion. A. Acute Poisoning: 1. Ingestion of solid or concentrated potassium perman-

ganate causes brown discoloration and edema of the mucous membranes of the mouth and pharynx; cough, laryngeal edema, and stridor; necrosis of oral and pharyngeal mucosa; slow pulse; and shock with fall of blood

pressure.

If death

is not immediate,

jaun-

dice and oliguria or anuria may appear. 2. Application of solid or concentrated potassium permanganate solution to the mucous membranes of the vagina or urethra causes severe burning, hemorPerforation of the rhages, and vascular collapse. vaginal wall may occur, resulting in peritonitis with Examination reveals a fever and abdominal pain. chemical burn which is stained brown. B. Chronic Poisoning: (From ingestion or application to

skin or mucous membranes.) Repeated use may lead to corrosive damage as described for acute poisoning. Repeated use of concentrations greater than 1:1000 on the skin may lead to a chemical burn.

Phenol

Derivatives

235

Treatment: A. Acute Poisoning: 1. Emergency measures a. Remove poison from mucous membranes by washing repeatedly with tap water. Delay absorption of ingested poison by giving water, milk, or universal antidote and then remove by gastric lavage or emesis followed by catharsis (see pp. 10 to 13). b. Treat shock (see p. 25). 2. Antidote - None known. 3. General measures a. Give demulcent drinks such as milk to lessen gastric irritation. b. Treat perforations surgically. 4. Special problems - Treat anuria (see p. 29). B. Chronic Poisoning: Discontinue use of potassium permanganate and treat chemical burns. Prophylaxis:

"Patients

should be warned of the dangers of using crystals

of potassium permanganate or solutions than 1:5000 on mucous membranes.

Prognosis: Death may occur up to a month by potassium permanganate.

more

concentrated

from the time of poisoning

PHENOL AND DERIVATIVES (See table on p. 237; formulas on p.

236.)

Pure phenol (carbolic acid) is a white solid which liquifies (liquified phenol) upon the addition of 5% water. Upon the ad-

dition of more

water,

ally separates

into two layers,

the solution

becomes

the upper

milky and eventu-

containing approxi-

mately 5% phenol and the lower, 95% phenol. When 20 parts of water have been added, the entire solution again becomes clear. Creosotes (wood tar or coal tar) are mixtures of phenolic compounds and other compounds obtained by the destructive distillation of wood or coal. A large number of phenol derivatives are used as antiseptics, disinfectants, caustics, germicides, surface anesthetics, and preservatives. The fatal doses are listed in the table on p. 237.

236 OH

OH

|

OH

|

|

‘Non

|

OH Phenol

Resorcinol

(Solid)

(Solid)

Hydroquinone (Solid)

OH

re

| OP roe

“ae

HAC 33 pe H3C

OH

ou

Carvacrol

Pyrogallol

(Solid)

(Liquid) OH

OH

OH

|

|

a=

—CH3

Or

Sj

ou

=) ] cl

| CH,(CHy)4CHg 0-Cresol (Solid)

Hexylresorcinol (Solid)

Pentachlorophenol (Solid)

OH OH

B-Naphthol

a~-Naphthol (Solid)

OH

|

(Solid)

a

73

coe SCH ”

ENS

H3C

H3C

Pl

OH Thymol (Solid)

Menthol (Solid)

237 PHENOL

AND

PHENOL

eae

DERIVATIVES Fatal

Carvacrol Coal tar

Dose

gr. or 30 30

2

Creosote (wood tar)

75

Guaiacol Hexachlorophene Hexylresorcinol

2 2 5

Hydroquinone

30 30 75

audales eoasee

30

Menthol

30

Pentachlorophenol Phenol

2 2

Resorcinol Saponated solution of cresols

Thymol

30 30

[aca eaQ2Ut » Eres)

30 150

Panne aah a

[SERGIO

Deaths from poisoning with phenol and derivatives as high as 50 to 100 per year. Phenol thus poisons

denatures all cells

and precipitates directly.

may be

cellular proteins

In small

amounts,

and

it has a

salicylate-like stimulating effect on the respiratory center. This causes respiratory alkalosis followed by acidosis which results partly from uncomplicated renal loss of base during the stage of alkalosis, partty from the acidic nature of the phenolic radical, and partly from derangements in carbohydrate metabolism. Pathologic findings in deaths from phenol or related compounds

are necrosis

of mucous

membranes,

cerebral

and degenerative changes in the liver and kidney. necrosis may also be present.

edema,

Bladder

Clinical Findings: The principal manifestations of poisoning with these agents are vomiting, collapse, and coma. A. Acute Poisoning: (From ingestion or application to skin or mucous membranes of phenolic compounds.) Local findings are painless blanching or erythema. Corrosion may occur. General findings are nausea, vomiting, diarrhea, cyanosis, hyperactivity, stupor, blood pressure fall, hyperpnea, abdominal pain, convulsions, coma, and pulmonary edema followed by pneumonia. If death from respiratory failure is not immediate, jaundice and oliguria or anuria may occur. B. Chronic Poisoning: (From ingestion or absorption from

238

Phenol

Derivatives

skin or mucous membranes.) Repeated use may cause symptoms described for acute poisoning. C. Laboratory Findings in Acute or Chronic Poisoning: alts Test urine with a few drops of ferric chloride. Violet or blue color indicates the presence of a phenolic compound. 2.

Urine

3. Blood

shows

red blood

carbon

cells,

albumin,

dioxide combining power

and

casts.

may be below

20 mEq. /L. 4. Hepatic cell function may be impaired as revealed appropriate tests (see p. 40). 5. The N.P.N. is raised.

by

Treatment: A. Acute Poisoning: 1 Emergency measures a. Ingested - Delay absorption of ingested poison by giving tap water, milk, or universal antidote and then remove by repeated gastric lavage or emesis with tap water followed by 50 ml. (2 oz.) castor oil, which dissolves phenol and retards its absorption

and hastens

its removal.

Follow

castor oil by a

saline cathartic (see p. 13). b. Surface - Remove poison by washing skin or mucous membranes with large amounts of water for at least 15 minutes. Follow by repeated application of castor oil or 10% ethyl alcohol. 2. Antidote - None known. 3. General measures a. If blood carbon dioxide combining power is below 25 mEq./L. and urine output is adequate, give 1 L. lactated Ringer’s solution I. V. every six hours until fluids can be given by mouth. Then give 120 ml. (4 oz.) of saturated sodium bicarbonate solution

(1 tsp. in one-half glass of water) every hour until carbon dioxide combining power is above 25 mKq. / L.

or until urine is alkaline.

b. Control convulsions by cautious usé of ether or I. V. barbiturates (see p. 34). 4. Special problems a. Treat liver damage (see p. 40). b. Treat anuria (see p. 29). B. Chronic Poisoning: Discontinue further use of phenol and treat as for acute poisoning. Prophylaxis: Phenol and derivatives must be stored safely. Phenolic ointments of any concentration should not be used over large areas of the body.

Formaldehyde

239

Prognosis:

If patient survives for 48 hours,

recovery is likely.

FORMALDEHYDE Formaldehyde able as a 40%

(HCHO)

solution

is a gas which is ordinarily avail-

(formalin)

for use

as a disinfectant,

antiseptic, deodorant, tissue fixative, or embalming fluid. The polymerized form, trioxymethylene (paraformaldehyde) can be decomposed by heat to formaldehyde for fumigating purposes. The fatal dose of formalin is 60 to 90 ml. (2 to 3 oz.); up to five fatalities from formaldehyde poisoning occur

every year. Formaldehyde reacts chemically with most substances in cells and for this reason depresses all cellular functions and leads to death of the cells. The pathologic findings from the ingestion of formaldehyde are necrosis and shrinking of the mucous membranes. Degenerative changes may be found in the liver, kidneys, heart, and brain. Clinical Findings: The principal manifestations of formaldehyde poisoning are collapse and anuria. A. Acute Poisoning: Ingestion causes immediate and severe abdominal pain followed by collapse, loss of consciousness, and anuria. There may be vomiting and diarrhea. Death is from circulatory failure. B. Chronic poisoning does not occur. C. Laboratory Findings: The urine may show albumin, casts, or red blood cells.

Treatment of Acute Poisoning: A. Emergency Measures: 1. Delay absorption of ingested formaldehyde

by giving tap water, milk, or universal antidote and then remove by gastric lavage or emesis with tap water or, prefer-

ably,

with 1% ammonium

carbonate

solution.

Follow

this by catharsis with 30 Gm. (1 oz.) sodium sulfate in 250 ml. (1 cup) of 1% ammonium carbonate solution. 2.

Treat

shock

(see p.

25).

If pulse

and blood pressure

are severely depressed, give levarterenol (Levophed®) (see p. 31). B. Antidote: Use ammonium carbonate as described above. C. Special Problems: Treat anuria (see p. 29). Prophylaxis:

Store formaldehyde

safely.

240

Cationic

Detergents

Prognosis:

If the patient survives recover.

for 48 hours,

CATIONIC Cationic

detergents

he probably will

DETERGENTS

are a group of organic compounds

Au characterized

by the general formula,

Ry |

ee:

R3

5

RRS

|

Raq where R,_4 represent alkyl or aryl substituents and xX” represents a halogen. Cationic detergents are characterized by

the fact that the hydrophobic

part of the molecule

Nt R3

|

R is positive rather than negative, as in ordinary soaps. Thus these detergents release an anion (Cl~ or Br ) upon solution in water rather than a cation (K*, Na‘), as in the case of ordinary soap. Cationic detergents such as benzethonium chloride

(Phemerol®),

benzalkonium chloride (Zephiran®),

methyl-

benzathonium chloride (Diaperene®), and cetylpyridinium chloride (Ceepryn® chloride) are used to destroy bacteria skin,

surgical

instruments,

cooking

equipment,

sick

on

room

supplies, and diapers. The fatal dose by ingestion is estimated to be 1 to 3 Gm. (15 to 45 gr.). At least three fatalities have occurred from accidental ingestion.

Concentrated solutions of cationic detergents are readily absorbed and interfere with many cellular functions. They are rapidly inactivated by tissues and by ordinary soaps. The pathologic findings are not characteristic.

Clinical Findings:

~The

principal manifestations of poisoning with these

agents are vomiting, collapse, and coma. A. Acute Poisoning: (From ingestion.) Nausea, vomiting, collapse, convulsions, coma, and death within one to

four hours. B. Chronic poisoning has not been reported. C. Laboratory Findings: Noncontributory.

Zinc Stearate

241

Treatment: A. Emergency Measures: Remove unabsorbed detergent by gastric lavage or emesis with tap water followed by catharsis (see pp. 10 to 13).

B. Antidote:

Ordinary

soap is an effective antidote for un-

absorbed cationic detergent. No antidote is known for the systemic effects following absorption. C. General Measures: Treat convulsions (see p. 34).

Prophylaxis: Cationic detergent solutions should be stored in distinctive bottles (never in soft drink bottles) in a safe place. Prognosis: If the patient

survives

for 48 hours,

he probably

will re-

cover.

ZINC Zinc

stearate

STEARATE

is a white,

water-insoluble

powder

which

will readily absorb oils and odors, It is used as a powder to allay skin irritation, as an astringent, and as a mild local antiseptic.

The amount necessary to cause death in infants apparently is small since at least 30 deaths have occurred from the inhalation

of zinc

stearate.

In the lungs,

zinc

stearate

acts

as

a chemical irritant, causing a progressive chemical pneumonitis. The pathologic findings are pneumonia, pulmonary edema, and pulmonary granulomatosis.

Clinical Findings: The principal manifestations of zinc stearate poisoning are fever and respiratory difficulty. A. Acute Poisoning: (From inhalation.) Fever, cough, difficult breathing, cyanosis, and evidence of bronchial pneumonia. B. Chronic Poisoning: Repeated inhalation of zinc stearate leads to the findings described for acute poisoning. C. X-ray Findings: Examination of the chest reveals diffuse bronchial pneumonia. D. Laboratory Findings: Noncontributory. Treatment:

A. Acute

Poisoning:

1. Discontinue use of zinc stearate. 2. Antidote - None known. 3. General measures a. Prevent extension of bronchial

pneumonia

- Give

242

Potassium,

Sodium

penicillin, spectrum

Chlorate

one million units I. M.

daily,

or a broad-

antibiotic.

b. Treat cyanosis with oxygen (see p. 24). B. Chronic

Poisoning:

Treat

as for acute

poisoning.

Prophylaxis: Zinc stearate cation to the skin.

should not be used in powders

Prognosis: Cases of zinc stearate

pneumonitis

have

for appli-

been almost

uni-

formly fatal.

POTASSIUM

AND

SODIUM

CHLORATE

Sodium chlorate (NaClO4) and potassium chlorate (KC10,4) are frequent ingredients in mouthwashes and gargles. They are water-soluble and act as mild oxidizing agents. The fatal dose is about 15 Gm. (1/2 oz.) for adults and 2 Gm. (30 gr.) for children, but no fatalities have been reported in recent years. Chlorate ion is irritating to mucous membranes in concentrated solution; after absorption, it produces methemoglobinemia by virtue of its oxidizing properties. However, the chlorate is not reduced in the process but acts catalyst, so that a small amount of chlorate can produce

as a a

large amount of methemoglobin. Pathologic findings in deaths from chlorate are gastrointestinal congestion and corrosion, kidney injury, liver damage, and chocolate color of the blood. Clinical

Findings:

The principal manifestations of poisoning with these agents are vomiting and cyanosis. A. Acute Poisoning: (From ingestion.) Nausea, vomiting, diarrhea, abdominal pain, hemolysis, cyanosis, anuria, confusion,

and convulsions.

B. Chronic Poisoning: (From ingestion.) Continued use in doses less than necessary to produce the symptoms described for acute poisoning may lead to loss of appetite and weight loss. C. Laboratory Findings: 1. Methemoglobinemia, anemia of the hemolytic type, or elevation 2.

Urine

of serum

contains

hemoglobin

potassium.

red blood

cells,

albumin,

casts,

and

products.

Treatment:

A. Acute Poisoning: 1. Emergency measures

- Delay absorption of ingested

Chloramine-T

243

poison by giving water, milk, or universal antidote and then remove by gastric lavage or emesis followed by catharsis (see pp. 10 to 13). 2. Antidote - If methemoglobinemia is severe, give methylene blue (see p. 44). 3. General measures a. Give milk or sweetened drinks to relieve gastric irritation. b. Keep

patient warm

and quiet until cyanosis

dis-

appears. c. Force fluids to 2 to 4 L.

daily to remove chlorate if urine output is adequate. 4. Special problems - Treat anuria (see p. 29). B. Chronic Poisoning: Discontinue use of drug and treat as for acute poisoning.

:

Prophylaxis: Chlorates be replaced

should never be taken internally. They should in mouthwashes and gargles by less harmful drugs.

Prognosis: Death may

symptoms

occur up to one week after poisoning,

are mild or absent after the first 12 hours,

but if

recovery

is to be expected.

CHLORAMINE-T Chloramine-T is a water-soluble compound containing about 12% of available chlorine which is released slowly on contact with water. In solid form it is used as a water purifier and in solution as a mouthwash and for irrigating wounds. The fatal dose may be as low as 0.5 Gm. (71/2 gr.), although much larger doses have been ingested without adverse effects. At least six fatal cases of chloramine-T poisoning have occurred. It has been postulated that poisoning may occur through the conversion of chloramine-T to a cyanide derivative under certain circumstances. The pathologic findings are not characteristic. Clinical

Findings:

The principal manifestations of poisoning with chloramine-T are cyanosis and respiratory failure. A. Acute Poisoning: Cyanosis, collapse, frothing at the mouth, and respiratory failure within a few minutes after ingestion. B. Chronic poisoning has not been reported. C. Laboratory Findings: Noncontributory.

244

Silver Nitrate

Treatment of Acute Poisoning: A. Emergency Measures: Delay absorption of ingested chloramine-T by giving water, milk, or universal antidote and then remove by gastric lavage or emesis followed by catharsis (see pp. 10 to 13). B. Antidote: Give antidotes as suggested for cyanide poisoning (see p.

162).

Prophylaxis: Users of chloramine-T should be warned the compound. It should be stored safely.

Prognosis: If the patient lives for 24 hours,

SILVER

against ingesting

recovery

is likely.

NITRATE, SILVER PROTEHINATES, AND SILVER PICRATE

Silver nitrate is a water-soluble salt which precipitates with chloride to form insoluble silver chloride. It is used as a local styptic and antiseptic. The colloidal silver proteinates are

used as antiseptics

Silver picrate (Picragol®) and in suppositories

on skin and mucous

membranes.

is used as a 1% powder

as an antiseptic

on mucous

in kaolin,

membranes.

The fatal dose of silver nitrate may be as low as 2 Gm. (30 gr.), although recovery has occurred following ingestion of larger doses. No fatalities have been reported in recent years. The silver proteinates and silver picrate have not produced fatal poisoning. Silver nitrate causes a local corrosive effect but is not

likely to produce

systemic

effects because

silver ion is pre-

cipitated by proteins and chloride. Pathologic findings are local corrosive damage to the gastrointestinal tract, and there may be degenerative changes in the kidneys and liver. Re-

peated use of silver in any form will eventually cause argyria. Excessive use of silver picrate may cause renal damage. Clinical Findings: The principal manifestations of poisoning with these agents are blackening of mucous membranes, vomiting, and collapse.

A. Acute Poisoning: (From ingestion of silver nitrate. ) Pain and burning in the mouth, blackening of skin and mucous

membranes,

vomiting

shock,

of black

and death

throat,

material,

and abdomen; diarrhea,

in convulsions

salivation,

anuria,

collapse,

or coma.

B. Chronic Poisoning: (From application of silver compounds to skin or mucous membranes.) Repeated application or ingestion of silver nitrate or silver proteinates

Silver

Nitrate

245

causes argyria, a permanent bluish-black discoloration of the skin and of the conjunctivae and other mucous membranes. The discoloration first appears in areas most exposed to light, usually the conjunctivae. If silver is not immediately discontinued, the discoloration will spread over the entire body. C. Laboratory Findings: Noncontributory. Treatment: A. Acute Poisoning: 1. Emergency measures a. Dilute ingested silver nitrate by giving water containing 10 Gm. (2 tsp.) of sodium chloride per liter repeatedly to precipitate silver ion as silver chloride. Then remove by gastric lavage or emesis (see pp. 10 to 11) followed by catharsis with sodium sulfate, 30 Gm. (1 oz.) in 250 ml. (1 cup) water containing 10 Gm. (2 tsp.) sodium chloride to remove silver from the intestines. b. Treat shock (see p. 25). 2. Antidote - Give sodium chloride as described under

emergency measures. 3. General measures a. Give milk or sweetened b.

drinks to relieve gastric irritation. Give meperidine (Demerol®), 100 mg. (2 era): or codeine, 60 mg. (1 gr.) to relieve pain.

B. Chronic Poisoning: No method the pigmentation of argyria.

is known

which will bleach

Prophylaxis:

Silver nitrate sticks should be stored safely. proteinates should not be used repeatedly mucous membrane or skin diseases.

Silver

for the treatment

of

Prognosis:

If treatment with sodium

chloride can be started shortly

after the ingestion of silver nitrate, recovery is likely. The pigmentation of argyria is permanent.

246 MISCELLANEOUS

ANTISEPTICS

Drug

Acetomeroctol

Occasional

See p.

urticaria

154.

(Merbak®) Ammoniated mercury Merbromin (Mercurochrome®) Mercocresol (Mercresin®) Nitromersol

progressing to weeping dermatitis.

anemia,

Rarely,

leukopenia,

liver damage.

and

Repeated

(Metaphen®) Phenyl mercuric bromide Phenyl mercuric chloride Phenyl mercuric iodide Phenyl mercuric nitrate (Merphenyl nitrate®) Thimerasol Merthiolate®

Asterol® dihydrochloride

ingestion may

symptoms mercury

cause

of chronic poisoning

(see p. 154).

Intensive skin application may cause hallucinations, muscular tremors, con-

|Discontinue

use.

Discontinue

use,

Discontinue

use.

vulsions.

Butamben

picrate

(Butesin® picrate)

Exfoliative with

erythema, Dichlorophene

dermatitis

itching,

Stomatitis,

burning,

scaling. glossitis,

cheilitis from

sensiti-

zation.

Hydrogen 30%

Mandelic Mercuric

Mercury

peroxide

acid chloride

protoiodide

Congestion, irritation of mucous membranes, distension of abdomen from release of gas. Gastric irritation, nausea, renal irritation, acidosis.

(Seep. «(See 154 Repeated ingestion may

Remove by | gastric lavage.

Discontinue

use.

ps 18, 104.

See p.

cause symptoms of chronic mercury poisoning (see p. 154). Methenamine

Skin

rash, kidney and bladder irritation, hematuria, nausea, vomiting.

Discontinue

use.

Nitrofurazone (Furacin®) Pyridium Selenium sulfide (Selsun®) Undecylenic acid

Weeping, crusting dermatitis.

Discontinue

use.

Methemoglobinemia,. See p. 161.

Discontinue See p. 161.

use.

Exudative

Discontinue

use.

dermatitis.

Chapter 26

CARDIAC

DIGITALIS

AND

DRUGS

DIGITALIS

PREPARATIONS

Ss

ay

O

ad

CH,

| OH

—O= (Digitoxose), Digitoxin

Digitalis and cardiac glycosides are used for the treatment of heart failure. Other digitalis preparations include deslanoside

(Cedilanid-D®),

digilanid,

toside C (Cedilanid®),

digoxin,

gitalin (Gitaligin®),

The fatal dose of digitalis is approximately

(30 to 45 gr.).

lana-

and Urginin®. 2 to 3 Gm.

The fatal dose of digitoxin is 3 to 5 mg. (1/20

For other digitalis-like preparations, the fatal to /12 gr.). dose is 20 to 50 times the maintenance dose of the preparation. Up to five fatalities occur every year. Digitalis and the cardiac glycosides increase the force of contraction of the myocardium. In excessive doses they increase the irritability of the ventricular muscle, resulting first in extrasystoles, then ventricular tachycardia, and Digitalis and digitaliseventually ventricular fibrillation. like preparations also stimulate the C.N.S.

247

248

Digitalis

Clinical Findings: The principal manifestations of digitalis poisoning are vomiting and irregular pulse. A. Acute Poisoning: (From injection or ingestion.) Headache, nausea, vomiting, diarrhea, yellow vision, slow or irregular pulse, fall of blood pressure, cardiac irregularities, and death, usually from ventricular fibrillation. B. Chronic Poisoning: (From injection or ingestion.) The above symptoms will come on gradually if overdoses are The occurrence of nausea and vomiting tend to taken. limit dosage. C. Laboratory Findings: Ls The Ecg. may show heart block, ventricular extrasystoles, ventricular tachycardia, depressed ST segment, and lengthened P-Q interval or complete heart

block. 2. Eosinophilia may be present. Treatment:

A. Acute Poisoning: is Emergency measures a. Delay absorption of ingested drug by giving tap water, milk, or universal antidote and then remove by gastric lavage or emesis followed by catharsis (see pp. 10 to 138). b. Do not give epinephrine or other stimulants. These may induce ventricular fibrillation. . Antidote - None known. . General measures a. If kidney function is normal,

give potassium chloride, 2 Gm. (30 gr.) dissolved in water orally every hour until Ecg. shows improvement. . If kidney function is impaired, serum potassium must be determined prior to the administration of potassium chloride.

B. Chronic Poisoning: Discontinue drug temporarily and then regulate dosage according to needs of patient. Prophylaxis: Store digitalis safely. first sign of intoxication. Prognosis: Recovery

Reduce

dosage of digitalis at the

is likely if the patient survives

24 hours.

249 QUINIDINE

CHOH

CH3;0—

i

—

CH»

SS

ib

“cH=cx,

5

Quinidine

Quinidine is a cinchona bark. It larities. The fatal dose gr.) as a result of each year. Quinidine

white water-soluble alkaloid obtained from is used for the treatment of cardiac irregu-

of quinidine may be as low as 0.2 Gm. (3 hypersensitivity. Up to five fatalities occur

depresses

the

metabolic

activities

of all cells,

Doses within but its effect on the heart is most pronounced. the therapeutic range may cause slowing of conduction, prolonged refractory period, and even heart block. Larger doses

may cause ventricular fibrillation. The pathologic findings in acute fatalities are not characteristic. In some cases petechial hemorrhages may be seen throughout the body. Clinical Findings: The principal manifestations of quinidine poisoning are fall of blood pressure and nausea. A. Acute Poisoning: (From ingestion.) Overdoses and sometimes doses within the therapeutic range cause tinnitus, headache, nausea, diarrhea, dizziness, severe fall of blood pressure with disappearance of pulse, nystagmus, bradycardia, and respiratory failure. B. Chronic Poisoning: (From ingestion.) Thrombocytopenic purpura may develop after a short course of quinidine. After recovery, single doses of 0.05 to 0.1 Gm. (1 to 1/2 gr.) will cause return of the purpuric manifestations.

Drug

fever,

phylactoid reactions ministration.

urticaria,

may

exfoliation,

also result from

and ana-

quinidine ad-

C. Laboratory Findings: 1. In purpura from quinidine, are diminished in number.

2. Ecg.

the blood thrombocytes

findings may include widening of QRS

lengthened

ventricular

Q-T

interval,

beats,

appearance

complex,

of premature

and lengthening of P-R interval.

250

Procaineamide

Hydrochloride

Treatment:

A. Acute

Poisoning:

1. Emergency measures a. Delay absorption of ingested quinidine by giving water, milk, or universal antidote and then remove by gastric lavage or emesis followed by

catharsis (see pp. 10 to 13). b. Raise blood pressure by I. V.

saline or blood trans-

fusions. If the blood pressure fall is severe, add epinephrine or levarterenol (Levophed®) to 1 L. of saline and give I.V. (see p. 26). 2. Antidote - None known. B. Chronic Poisoning: Treat thrombocytopenic purpura by repeated small transfusions. Do not repeat administration of quinidine in such patients.

Prophylaxis: Store quinidine safely. Begin administration of quinidine gradually. Dosage should begin by a test dose of 0.1 Gm. (iy/2 gr.). If no reaction occurs a second dose of 0.1 Gm. can be given after two hours. Maximum dosage should not exceed single doses of 0.2 Gm. at intervals of not less than one hour. Dosage is reduced upon the appearance of therapeutic response or signs of toxicity as described above. Do not give quinidine in the presence of complete heart block. Prognosis:

If patient survives probably will recover.

for 24 hours

PROCAINEAMIDE

l

after acute

HYDROCHLORIDE

i

ae

Zo —N—CH, CH un

oF

HN

Procaineamide

(Pronesty]®)

CHy CH

poisoning,

he

Procaineamide Procaineamide

regularities.

Hydrochloride

is used for the treatment

As little as 200 mg.

(2 ml.

of cardiac

251 ir-

of 10% solution

I. V.) has caused death as a result either of hypersensitivity or rapid injection. At least four fatalities have been reported from procaineamide poisoning. The rapid administration

of procaineamide

causes

ir-

regularities of ventricular contraction, including tachycardia or fibrillation. Agranulocytosis from procaineamide is apparently a hypersensitivity reaction. The pathologic finding in death from agranulocytosis is a lack of myeloid elements in the bone marrow. In sudden deaths following I. V. procaineamide administration, the pathologic findings are not characteristic. Clinical Findings: The principal manifestations of procaineamide poisoning are irregular pulse and fall of blood pressure. A. Acute Poisoning: (From I1.V. injection.) Rapid I.V. administration

of procaineamide

may

cause

the pulse to be-

come suddenly irregular or disappear entirely with collapse and fall of blood pressure and ALMOST IMMEDIATE ONSET OF CONVULSIONS AND DEATH. B. Chronic Poisoning: (From ingestion.) Continued use of procaineamide has led to fever, chills, pruritus, urticaria, malaise, and agranulocytosis.

C. Laboratory Findings: 1. In acute poisoning, the Ecg. reveals abnormalities ventricular beat with ventricular extrasystoles. 2.

In chronic

minished

poisoning,

the blood

count

may

reveal

of

di-

or absent granulocytes.

Treatment: A. Acute Poisoning: 1. Emergency measures - Treat cardiac arrest following I. V. injection of procaineamide (see p. 32). 2. Antidote - None known. 3. Do not give epinephrine or similar drugs. These may induce irregularities of ventricular contraction. B. Chronic Poisoning: 1. Discontinue the use of the drug at the first sign of symptoms.

2. Antidote - None known. 3. General measures - Treat agranulocytosis

(see p.

45).

Prophylaxis: Do not give procaineamide I. V. at a rate greater than 0.2 Gm. per minute. A complete blood count should be taken repeatedly when a patient develops an infectious illness during the administration of procaineamide.

252

Thiocyanates

Prognosis:

If ventricular irregularity during the administration of procaineamide does not progress to ventricular fibrillation, the patient will recover. At least 90% of patients with agranu-

locytosis from procaineamide

are likely to recover.

THIOCYANATES Sodium and potassium thiocyanate (NaSCN or KSCN) were formerly used for the treatment of hypertension but have been largely replaced.

The fatal serum level of thiocyanate is 20 mg. /100 ml. More than 20 fatalities have been reported from thiocyanate poisoning. Thiocyanate depresses the metabolic activities of all cells but effects are most noticeable on the brain and heart. The time required to reduce the blood level of thiocyanate by 50% is approximately one week in the presence of normal kidney function. In the presence of impaired kidney function, the excretion is even slower, and the possibility of toxic reactions is increased. The pathologic findings include myocardial damage, focal brain damage, thyroid enlargement, and thrombophlebitis. Clinical Findings:

~The

principal manifestation of thiocyanate poisoning is

psychotic behavior. A. Acute Poisoning: (From ingestion.) Disorientation, weakness, low blood pressure, confusion, psychotic havior,

muscular

spasms,

convulsions,

be-

and death.

B. Chronic Poisoning: (From ingestion.) Prolonged use may cause dermatitis, hives, and abnormal bleeding. The thyroid may be enlarged. C. Laboratory Findings: The blood thiocyanate level should never exceed 10 mg. per 100 ml. Treatment: A. Acute Poisoning:

1. Emergency measures - Remove ingested thiocyanate poison by gastric lavage or emesis followed by catharsis (see pp. 10 to 13). 2. Antidote - None known. 3. General measures a. Give 2 to 4L. of fluid orally or I. V. daily in the presence of normal kidney function to maintain adequate urine output. b. Remove thiocyanate by peritoneal lavage or by hemc dialysis (see p. 31) if necessary. B. Chronic Poisoning: Discontinue the use of thiocyanate.

Nitrates

253

Prophylaxis: Thiocyanate

should not be given therapeutically without careful control of blood thiocyanate levels. Prognosis: The patient may

show temporary improvement on disHowever, after continuing the administration of thiocyanate. several days of improvement, the patient may go downhill and die as late as two weeks after discontinuing the medication.

GLYCERYL

TRINITRATE,

Glyceryl trinitrate,

ethyl nitrite,

CpH5,ONO,

NITRITES,

C3H5(NO3)3,

NITRATES

a liquid (nitroglycerin);

a gas; sodium nitrite,

NaNO»,

a

solid; and other organic nitrates are used medically to dilate In some in-coronary vessels and to reduce blood pressure. stances, nitrates such as bismuth subnitrate or nitrate from

well water may be converted to nitrite by the action of intestinal bacteria. The nitrites then may cause nitrite poiNitrites are also used to preserve the color of meat soning. in pickling or salting processes. Fatal doses have been recorded as follows: Ethyl nitrite, in a three-year-old child, 4 Gm. (60 gr.); glyceryl trinitrate, The allow2 Gm. (30 gr.); sodium nitrite, 2 Gm. (30 gr.). able residue of nitrite in food is 0.01%. More than 10 p.p.m. of nitrate in well water may induce methemoglobinemia in infants. Up to ten fatalities per year have occurred from glyceryl trinitrate and other nitrites. The nitrites dilate blood vessels throughout the body by a direct relaxing effect on smooth muscles. Nitrites also will cause methemoglobinemia. The pathologic findings are chocolate-colored blood as a result of conversion of hemoglobin to methemoglobin and congestion of all organs.

Clinical Findings: The principal manifestations of poisoning with these drugs are fall of blood pressure and cyanosis. A. Acute Poisoning: (From ingestion, injection, inhalation, or absorption from skin or mucous membranes.) Headache, flushing of the skin, vomiting, dizziness, collapse, marked

fall of blood

pressure,

cyanosis,

coma,

and re-

spiratory paralysis. B. Chronic Poisoning: Repeated administration may lead to the above findings. Nitroglycerin workers show marked tolerance to repeated exposure. Since this tolerance disappears rapidly, a short absence from exposure may lead to severe poisoning from amounts that were previously safe.

254

Anticoagulants

C. Laboratory Findings:

Methemoglobinemia

may be present.

Treatment: A. Acute Poisoning: 1. Emergency measures a. Delay absorption of ingested nitrites or nitrates by giving water, milk, or universal antidote and then remove by gastric lavage or emesis followed by catharsis (see pp. 10 to 13). b. Maintain blood pressure by the injection of epinephrine,

1 ml.

of 1:1000

solution

subcut.,

or lev-

arterenol (Levophed®) (see p. 31). c. Remove

poison from the skin by scrubbing with

soap and water.

2. Antidote - None known. 3. General measures - Treat severe methemoglobinemia with dyspnea by methylene blue injection (see p. 44). B. Chronic Poisoning: Depending on the severity of the symptoms, treat as for acute poisoning. Prophylaxis: Use water free of nitrates for preparing infant formulas. Curing salts containing nitrites must be used in quantities no greater than allowable by the U. S. Department of Agriculture Such salts should not be used in other foods or as table salt. Prognosis:

If the blood pressure likely.

can be maintained,

recovery

is

ANTICOAGULANTS: BISHYDROXYCOUMARIN, ETHYL BISCOUMACETATE, HEPARIN, PHENINDIONE (See formulas

on p. 255.)

The various anticoagulant drugs are used to inhibit the clotting mechanism. Fatalities have been recorded after the following daily doses: bishydroxycoumarin (Dicumarol®), 100 mg. (11/2 gr.)s ethyl biscoumacetate (Tromexan®), 0.6 Gm. (10 gr. ); phen-

indione (Danilone®),

200 mg.

(3 gr.).

Up to 100 fatalities per

year occur from poisoning with anticoagulants. The coumarin and indanedione anticoagulants inhibit prothrombin formation in the liver and increase capillary fragility. This effect is increased by repeated dosage. Heparin acts, by several as yet incompletely understood mechanisms, to prevent the conversion of prothrombin to thrombin and the

action of thrombin on fibrinogen. Numerous gross and microscopic at autopsy.

hemorrhages

are found

Anticoagulants

“

255

i

Geuse 0 of Bishydroxycoumarin

(Dicumarol®)

Sure Phenindione Examples

of Anticoagulants

Clinical Findings: The principal manifestation of poisoning with the anticoagulants is bleeding. (From ingestion.) Hemoptysis, hemaA. Acute Poisoning: turia, bloody stools, hemorrhages in organs, widespread bruising, and bleeding into joint spaces. Repeated use leads (From ingestion.) B. Chronic Poisoning: In addition to hemorto findings as in acute poisoning. rhagic effects, phenindione may cause jaundice, enlarge-

ment of liver, and skin rash. C. Laboratory Findings: 1. The prothrombin concentration is lowered after coumarin and indanedione anticoagulants. 2. The clotting time is prolonged after heparin. or microscopic hematuria may be present. w . Gross 4. WBC may be increased after phenindione administration.

5. RBC

may be reduced.

Treatment: A. Acute Poisoning From Coumarin or Indanedione Anticoagulants: 1. Emergency measures a. Discontinue drug at the first sign of bleeding. b. Give repeated transfusions of fresh citrated blood. 2. Antidote - No specific antidote is known.

256

Hydralazine

3. General measures a. Give vitamin K, 100 mg. I.M. every four hours, phytonadione (Mephyton®), 50 to 100 mg. slowly T-We

or

b. Absolute bed rest must be maintained to avoid inducing further hemorrhages. B. Acute Poisoning From Heparin: 1. Emergency measures a. Discontinue administration of the drug. b. Limit absorption of subcut. or I.M. administered drug by tourniquet and ice pack (see p. 14). c. Give repeated fresh blood transfusions until bleeding stops.

2. Antidote - None known. C. Chronic Poisoning: Treat as for acute poisoning.

Prophylaxis: The use of coumarin anticoagulants must be controlled by repeated reliable prothrombin determinations. Heparin dosage is controlled by clotting time determinations. These

drugs should be used only under daily supervision by a physician. Prognosis:

Death may occur up to two weeks after discontinuing drug. However, adequate therapy with vitamin K will bring the prothrombin back to normal in 24 to 48 hours.

HYDRALAZINE

Hydralazine

(Apresoline®)

Hydralazine (Apresoline®) is a synthetic drug used for the treatment of hypertension. Only one death following hydralazine medication has been reported, but the incidence of serious reactions following continued administration is between 10 and 20%. Pathologic findings in reactions to hydralazine include rheumatic nodules and collagenous necrosis of the skin.

Hydralazine Clinical

257

Findings:

The principal manifestations of hydralazine poisoning are fall of blood pressure and joint swelling. A. Acute Poisoning: (From ingestion or I.V. or 1.M. injection.) Headache, severe hypotension, coronary in-

sufficiency, and anuria. B. Chronic Poisoning: (From ingestion.)

Fever, headache, dermatitis, lymph gland enlargement, and splenomegaly, progressing to severe arthralgia simulating rheumatoid Joint inarthritis or disseminated lupus erythematosus. volvement may vary from vague generalized stiffness and aching to severe pain, swelling, and redness of one to Pericarditis and pleural effusion may several joints. appear. Activation of peptic ulcer has also been reported. Cc. Laboratory Findings:

1. Urine may show albumin or red blood cells. 2. C.B.C. may show microcytic or normocytic anemia, leukopenia, or lupus erythematosus cells. 3. Serum proteins may show increase in globulin fraction. Treatment:

A. Acute Poisoning: 1. Emergency measures a. Cautious reduction of dosage is indicated in severe Overdoses should be rehypotensive reactions. moved by gastric lavage or emesis followed by catharsis (see pp. 10 to 13). b. Treat shock (see p. 25). 2. Antidote - None known. 3. Special problems - Treat anuria (see p. 285 B. Chronic Poisoning: 1. Emergency measures - Discontinue use. 2. Antidote - None known. 3. General measures a. Give acetylsalicylic acid, 1 to 3 Gm. (15 to 45 pr.) daily, until symptoms regress. b. Give cortisone, 50 to 150 mg. daily, if necessary.

Prophylaxis: Patients must be warned to discontinue lazine upon the appearance of any reaction. Prognosis: If the patient lives for 24 hours

the use of hydra-

after a severe

hypotensive

reaction, survival is likely. Complete recovery from rheumatoid reactions has always occurred.

258 OTHER

CARDIOVASCULAR Clinical

DRUGS

Findings

Hexamethonium salts

Prolonged fall of BP and failure of renal function.

Khellin

Nausea,

Rauwolfia

Tetraethyl ammonium Veratrum

vomiting,

Treatment

Treat low BP (see p. 25).

diarrhea, |Discontinue

dermatitis, dizziness, and sleepiness or wakefulness.

|use.

Anginal pain, nasal stuffiness. Severe fall of BP.

Discontinue use. Treat low BP (see p. 25). Atropine, 1

salts Vomiting,

BP, 343).

stupor,

bradycardia

fall of

(see p.

mg. (1/60 gr.) subcut.

Chapter 27

CHEMOTHERAPEUTIC

DRUGS

SULFONAMIDES

(See table on p. 262.)

NHo

OS

|

HN

NH»

0

——

~~

Oo=s=0

N

N. vy

|

ISON |

ee

N

N tet

|

CH, Sulfadiazine

Sulfamerazine

NO9

NH»

CHg P-Nitrosulfathiazole

Sulfisoxazole

259

CH3

260

Sulfonamides

NHo NH,

| O=SsS=O

~~ 4

! HN——

pale. = =

eH.

aN —— eae O

oS
p

—CH;

HO —

—OH

I

l

COCH)CH2CH3

Filicie Acid Some

Aspidinol

of the active principles

from

aspidium

Aspidium (Filix mas, male fern) or the oleoresin is used in the treatment of worm infestations. The fatal dose of oleoresin of aspidium may be as small as 4 Gm. (60 gr.) in children. In recent years, however, fatalities from aspidium have been rare. Aspidium is irritating to all cells with which it comes in contact.

The pathologic findings are congestion and degenerative changes in the gastrointestinal tract, liver, kidneys, and lungs. Clinical Findings: The principal manifestations of poisoning with these drugs are vomiting and respiratory failure. A. Acute Poisoning: (From ingestion.) Progressive vomiting,

diarrhea,

blurred

vision,

abdominal excitement,

pain,

headache,

tremors,

colored

collapse,

or

convul-

sions, and death in respiratory failure. If death is not immediate, jaundice and blindness may persist for weeks. B. Chronic Poisoning: Repeated small doses may cause the above findings.

C. Laboratory Findings: 1. Urine

may

show

albumin,

red blood

cells,

and casts.

2. Hepatic cell function may be impaired as revealed by the appropriate

tests (see p. 40).

Treatment: A. Acute Poisoning: 1. Emergency measures a. Remove swallowed poison by gastric lavage or emesis followed by catharsis (see pp. 10 to 13). Avoid castor oil or other oily cathartics. b. Control cardiovascular collapse (see p. 25). 2. Antidote - None known. 3. General measures - Control convulsions (see p. 34). B. Chronic Poisoning: Treat as for acute poisoning.

272

Bismuth

Compounds

Prophylaxis:

Potentially lethal drugs such as aspidium should never be used in the treatment

of nonfatal worm

Prognosis: Death may occur

up to one week

BISMUTH

infestations.

after poisoning.

COMPOUNDS

oO

.0)

Il

Il

CH,— C — OBiO

CHg— C—ONa

| 5 ie wfree

+' HN—

| : LR ‘ioe

i] CHj;— C—ONa

+ * 3HN—CH,—

CH,— C—O

Il C—ONa

(dior de!

Bismuth Sodium

Triglycollamate

(Bistrimate®)

ll NH—

C—

= CH,OH

COO-

-— QF Bi

e

Bi,O3

| HO —As—

O—B>O

ll

bee

3

oO

Glycobiarsol

Bismuth Subsalicylate

(Milibis®) oO Il ay

Bi(Ss—CH,—C—ONa), ’

es

Aes

Bismuth Sodium Thioglycollate

—(BiO),CO, 2

Bismuth

3

/2H,O

1

4BiNO, (OH), + BiO(OH) .

Subcarbonate

.

Bismuth

7

Subnitrate

(Thio-bismol®)

Bismuth subsalicylate (soluble in oil), bismuth sodium triglycollamate, and bismuth sodium thioglycollate (soluble in

water) are given by injection in the treatment of infectious diseases.

Bismuth

subcarbonate,

bismuth

glycobiarsol are insoluble compounds intestinal diseases. Fatal poisoning from

subnitrate,

and

used in the treatment of

injectable bismuth

compounds

is rar

Bismuth

Compounds

273

and none have been reported in recent years. Injection of as little as 0.5 Gm. (71/2 gr.) of a water-soluble bismuth compound has caused anuria from which the patient recovered. Absorbed bismuth produces effects similar to those of arsenic absorption (see p. 142). Insoluble, nonabsorbable bismuth compounds do not cause bismuth poisoning. However, bismuth subnitrate may cause serious nitrite poisoning by conversion of the nitrate to nitrite through the action of bacteria in the intestine. The fatal dose of bismuth subnitrate may be as low as 5 Gm. (75 gr.) in infants (see p. 253). Pathologic findings in bismuth poisoning include liver damage, kidney damage, congestion of the intestines, and blue line of the gums. Clinical Findings: The principal manifestation of bismuth poisoning is anuria. A. Acute Poisoning: (From injection.) Headache, depression gastroenteritis, liver damage, anuria, and shock. B. Chronic Poisoning: (From injection or ingestion.) Stomatitis, blue line on the gums, skin eruptions resembling pityriasis rosea, anorexia, weight loss, renal damage, jaundice,

diarrhea,

and

exfoliative

dermatitis.

C. Laboratory Findings: (Acute or chronic poisoning.) 1. Albuminuria or hematuria. 2. In jaundice, liver function may be impaired as revealed by appropriate tests (see p. 40). 3. N.P.N. may be elevated. Treatment: A. Acute Poisoning: 1. Emergency measures - None are of use in slowing the absorption of injected bismuth. 2. Antidote - Give dimercaprol (BAL®) (see p. 46). 3. General measures -

a. Give atropine, gastrointestinal

1 mg.

(4/60 gr.) subcut.

to relieve

discomfort.

b. Give meperidine (Demerol®), 100 mg. or codeine, 60 mg. (1 gr.), to relieve discomfort.

c. Give fluids to 2 to 4L.

(it/2 gr.), abdominal

daily if kidney function is

not impaired. 4. Special problems

- Treat anuria (see p. 29). B. Chronic Poisoning: 1. Discontinue medication at the first sign of toxicity.

2. Antidote - Give dimercaprol (BAL®) (see p. 40). 3. General measures

- Maintain good oral hygiene and

adequate nutrition. 4. Special problems - Treat liver damage

anuria (see p. 29).

(see p. 40) and

,

274

Bismuth

Compounds

Prophylaxis: Weekly urinalyses should be made during bismuth therapy and the medication discontinued if albuminuria or hematuria Bismuth medication can be resumed when albumiappears. nuria and hematuria disappear.

Prognosis: Recovery given.

is likely if dimercaprol

(BAL®) therapy can be

275 CHEMOTHERAPY: Drug

MISCELLANEOUS Clinical Findings and Contraindications

Dp-Aminosalicylic acid (PAS)

Reduce

acidosis,

discontinue

hypopotassemia,

nausea,

tosis, chloride

hydro(Camo-

quin® hydro-

Treatment

Fever, pruritus, erythematous macular or bullous eruptions, vomiting,

jaundice,

Amodiaquin

AGENTS

laryngeal

leukocy-

edema. Reduce dosage or

Nausea, vomiting, diarrhea, salivation, clumsiness, con-

vulsions.

discontinue drug.

chloride) _

Arsthinol (Balarsen®)|See Arsenic, Carbarsone

or

drug.

anorexia,

diarrhea,

dosage

Nausea,

p. 142.

See p.. 142.

vomiting.

Reduce dosage or discontinue

drug; give

Chlorguanide

hydro-

chloride (Guanatol® hydrochloride, Paludrine® hydrochloride) Chloroquine phosphate (Aralen® phosphate) Diiodohydroxyquinoline (Diodoquin®) Gentian violet

Isoniazid (Nydrazid®)

Oxophenarsine hydrochloride (Mapharsen®) Pamaquine naphthoate,

Pentaquine phosphate,

Primaquine

Nausea,

hematuria,

albuminuria,

dimercaprol (see p. 46). Reduce

anorexia,

dosage

anuria.

or

discontinue drug. Diarrhea,

nausea,

headache,

dizziness,

blurred

vision.

Reduce dosage or discontinue

Iodism

drug.

—Theduee dosage or discontinue drug. Nausea, vomiting, kidney Reduce dosirritation. age or discontinue drug. Dizziness, headache, paresReduce thesias, twitching, deafness, dosage or polyneuritis, toxic hepatitis, discontinue paralysis. Sense Severe fall of blood pressure. |See p. 142. For other findings, see Arsenic

(see p. 232).

p.

Hemolytic

142.

anemia,

hypotension,

postural

“reais

methemoglobin-

emia, hemolytic anemia, gastric distress, weakness.

dosage

or

discontinue drug.

diphos-

phate

Pelletierine

tannate

|Dizziness,

visual disturbances,

|Reduce

headaches, weakness, vomiting and diarrhea, muscular

dosage or discontinue

cramps

|drug.

ing,

progressing

convulsions,

to twitch-

and pene)

276 CHEMOTHERAPY: Sa

Drug Phenarsone

sul-

hydro-

chloride (Atabrine® hydrochloride) Stibamine

AGENTS

Clinical Findings and Contraindications

foxylate (Aldarsone®) Quinacrine

MISCELLANEOUS

glucoside

(Neostam®) Stibophen (Fuadin®)

Stilbamidine isethionate

Thiosemicarbazone

Severe

fall of blood pressure.

For other findings, paeeenie p. 142. Hepatitis,

|psychosis,

|Vomiting,

aplastic

Treatment |See p.

142.

see anemia,

yellow skin.

diarrhea,

(Cont'd.)

fall in

blood pressure, respiratory |depression, sensitivity reactions, liver damage. Contraindicated in liver, kidney, or pulmonary disease. Liver or kidney damage from old solutions. Do not use in presence of liver or kidney damage. |Liver damage, skin eruptions, anemia, leukopenia

Reduce

dosage or discontinue drug. Reduce

dosage or discontinue drug.

Use only fresh solutions,

|Reduce dosage or discontinue drug.

Chapter 25

STIMULANTS

CAFFEINE,

THEOPHYLLINE,

THEOBROMINE

i

fe)

BKC

CH

By

seh os ot

HN

CH

een

x

|

Ncn

3

Nosy

nZ

oF

ie

|

|

CH,

CH,

Caffeine

Theobromine

H3C

i ‘y &

|

NH Sex N

Zz of

CH, Theophylline

Caffeine,

treatment

theophylline,

of shock,

and theobromine

asthma,

are

and heart disease

Fatalities have resulted from 0.1 Gm.

used

for the

and as diuretics.

(11/2 gr.) of

aminophylline (theophylline ethylenediamine) I.V. or 1 Gm. (15 gr.) of aminophylline by rectal suppository. Almost all deaths have followed the I. V. administration of aminophylline. Deaths

have

not been

reported

after caffeine

or theobromine.

Injection of aminophylline in hypersensitive subjects causes immediate vasomotor collapse and death. Rapid I. V. injection of aminophylline apparently causes cardiac inhibition. In large doses, aminophylline and theobromine depress the C.N.S., whereas caffeine stimulates the C.N.S. The pathologic findings are not characteristic.

277

278

Strychnine

Clinical Findings: The principal manifestations

of poisoning with these drugs are collapse and blood pressure fall. A. Acute Poisoning: I.V. administration of aminophylline is sometimes followed by sudden collapse and death within one to two minutes. Repeated rectal administration of aminophylline to infants may cause severe vomiting, collapse,

and death.

Doses

of caffeine

up to 10 Gm.

(150 gr.) orally have caused vomiting and convulsions; complete recovery occurred in six hours. B. Chronic poisoning has not been reported. C. Laboratory Findings: Noncontributory. Treatment:

A. Emergency Measures: 1. Give oxygen by pressure mask (see p. 24). 2. Maintain blood pressure (see p. 25). 3. Remove rectally administered aminophylline by enema B. Antidote: None known. C. General Measures: Control convulsions (see p. 34).

Prophylaxis: Test the sensitivity of the patient to 1. V. aminophylline by giving 0.1 ml. I. V. and waiting one minute. Rate of injection should not exceed 0.1 Gm. per minute. Prognosis: ~~ Toxic reactions

to I.V.

injections

of aminophylline

have

been almost uniformly fatal. Patients with convulsions without treatment.

from

caffeine have

STRYCHNINE

H

CH

iies, limpidus infamatus Tityus bahiensis

Central

U.S.

to

Prionurus crassicauda uscorpius italicus Androctonus

australis

Buthus occitonus B. quinquestriatus

B. carolinianus Buthacus arenicola Parabuthus sp.

46

America

South America

ug

47 34 N.

Africa

oes

|

eae he

No. 317)

and

34 34 None 34 31

326 DIAGNOSIS

AND TREATMENT OF POISONING OTHER INSECTS AND ARACHNIDS

Name

Ticks: Dermacentor sp. Ixodidae sp.

Range

Bee,

Wasp,

Yellow

Jacket

Treatment

Clinical Findings

California

Worldwide

| Respiratory failure may occur. Severe pain and swelling, persisting for 1 to 2 weeks. Multiple stings may cause severe fall of BP, difficult breath-

cautiously.

tion, edema of the face and lips, and

cus

(wasp)

itching. | Numbness,

diarrhea,

of 1:1000

dramine, 50 mg. subcut. or I. V.

action may cause severe collapse, bronchial constric-

California

Epinephrine, 0.2 to 0.5 ml.

Give diphenhy-

A sensitivity re-

californi

surgical excision. Apply moist heat.

subcut.

ing, collapse, and hemoglobinuria.

Epyris

TO

Remove the N.W. U.S. | Ataxia, weakness, tick by applyparalysis coming on British ing kerosene 12 to 24 hours after Columbia, S. Africa, | attachment of the tick. or ether or by

Australia, Europe. Ornithodorus sp.

DUE

itching,

wheezing,

prostration, sweating, drowsiness,

Give cortisone or corticotropin for severe collapse. Apply ice pack to stings.

with recovery in 30 minutes. See above under

Millipedes

bee,

wasp,

and

yellow jacket. Vesicular dermatitis with intense itching and burning lasting for one to 24 hours,

| Relieve itching by cold applications.

Chapter 35

FISH

SHELLFISH

Mussels, clams, and oysters growing on the open ocean become poisonous during the warm months (May to September) from feeding on certain dinoflagellates, including Gonyaulax ecatenella. One mussel, clam, or oyster may contain a fatal dose of poison. More than ten deaths have been reported in

U. S. literature from this type of poisoning. The poisonous principle contained in the shellfish is a nitrogenous compound which produces a curare-like muscular

paralysis.

The pathologic

findings in deaths from shellfish

poisoning are not characteristic.

Clinical Findings: The principal manifestation respiratory paralysis.

of shellfish poisoning is

After ingestion of poisonous shellfish, the following are observed to occur: numbness and tingling of lips, tongue, face, and extremities; and nausea and vomiting progressing to respiratory paralysis. Convulsions may or may not occur. Laboratory findings are not characteristic.

Treatment:

A. Emergency Measures: 1. Remove ingested shellfish by gastric lavage or emesis followed by catharsis (see pp. 10 to 13). 2. If respiratory depression is present, give artificial

respiration with oxygen (see p. 24). B. Antidote:

None

known.

Prophylaxis: Do not eat shellfish during the summer September).

months

(May to

Prognosis:

The fatality rate is 1 to 10%. {2 hours,

recovery is likely.

327

If the patient survives for

328 FISH POISONING (See pp. 330 to 333.)

The flesh of a number

of fish found in tropical waters ma)

be poisonous at certain times of the year. They apparently become poisonous by feeding on certain marine organisms. Some fish, such as puffers (family Tetraodon), trigger fish, and parrot fish are poisonous during most of the year. Other: such as the moray eel, surgeon fish, moon fish, porcupine fish, file fish, and goat fish, are poisonous only a part of the year in some localities. Still other fish, including barracuda pompano, mackerel, butterfly fish, snapper, sea bass, perch and wrasse, are only sporadically poisonous in certain localities and in other places are always safe to eat (see pp. 330 to 333). More than 300 species have been reported to cause outbreaks of fish poisoning. Of these, the puffer family appears to have the most potent toxin since the mortality rate may be as high as 50%. In other types of fish poisoning the mortality

rate ranges from less than 1% to as high as 10% depending on the physical condition of the individual, the amount of fish eaten, and the potency of the toxin. The incidence of poisoning may be as high as 5 to 50% of the population in tropical countries where fish forms a large part of the diet. Fifty to 100 cases are reported yearly in

Hawaii,

with a mortality rate of less than 1%.

The poison present in the flesh or viscera of the fish apparently exerts its primary effect on the peripheral nervous system. The physiologic effects produced by the poison are not understood. The pathologic findings are not characteristi

Clinical Findings: The principal manifestations of fish poisoning are vomiting and muscular paralysis. Symptoms of acute poisoning begin 30 minutes to four hours after ingestion and include numbness and tingling of the face and lips which spreads to fingers and toes. This is followed by nausea, vomiting, diarrhea, malaise, dizziness, abdominal pain, these symptoms

and muscular weakness. In severe poisoning progress to foaming at the mouth, muscular paralysis, dyspnea, or convulsions. Death may occur from convulsions or respiratory arrest within one to 24 hours. If the patient recovers from the immediate symptoms, muscular weakness and paresthesias of the face, lips, and mouth may persist for weeks. These paresthesias characteristicall consist of reversed temperature sensations. Thus cold food or other cold objects cause a searing pain or an ‘‘electrical shock’’ sensation, and hot things feel cold. Laboratory findings are not contributory.

Poisonous

Fish

329

Treatment:

A. Emergency 1. Remove followed 2. Maintain 3. Treat

Measures: the ingested fish by gastric lavage or emesis by catharsis (see pp. 10 to 13). adequate airway (see p. 17).

respiratory failure (see p.

19).

None known. B. Antidote: C. General Measures:

ile Treat convulsions

2. Calcium gluconate,

(see p.

34).

10 ml.

be helpful as a nonspecific

of 10% solution I.V.

may

cellular protectant.

Prophylaxis: Adequate

since some

prophylactic measures have not been developed tropical fish which are considered edible may

The most common poisonous fish sometimes be poisonous. The following fish found in are shown on pp. 330 to 333. tropical waters should never be eaten: Puffers (see Fig. 13), trunk or box fish, trigger fish (see Fig. 9), thorn fish, file fish (see Fig. 12), and porcupine fish (see Fig. 10).

Prognosis: The prognosis in any particular outbreak of fish is difficult to predict since mortality may vary from However, the lower rate than 1% to more than 50%. expected when the fish is known to be a common type fish.

VENOMOUS

Name Sting-ray (Urobatis halleri and others)

poisoning less may be of edible

FISH

Clinical Findings

Treatment

Penetration of the skin by the barb |1. Cleanse wound by in the tail of the sting-ray causes in-irrigation and remove

tense local pain,

swelling,

nausea,

vomiting, abdominal pain, dizziness, weakness, generalized cramps, sweating, fallof BP. Re-

covery occurs in 24 to 48 hours.

{foreign material. 2. Soak wound in hot water for 30 to 60 minl|utes.

3.

Surgical debride-

ment and closure wound.

Scorpion fish (Scorpaena guttata)

Jelly-fish or Portuguese

Man-of-war (Physalia Palagica)

1 Spines of the gill-covers may penetrate skin and cause severe local pain and swelling, with extension of pain and swelling to involve the entire extremity.

Contact with these jelly-fish causes urticarial wheals, numbness and pain of the extremities, severe chest and abdominal pain, abdomi-

nal rigidity,

and dysphagia.

of

1, Treat as for stingray. 2, Infiltrate wound

with 1% procaine if pain is severe. Inject 10 ml. of 10% calcium gluconate I.V. to relieve muscular cramps.

inlaid eB tenis aes5 RS = doders

330

POISONOUS

Fig. 9 - Triggerfish (Balisioides niger). (Never safe to eat.) at any time.

FISH*

Likely to be dangerously

Fig. 10 - Porcupine fish (Diodon hystrix). Frequently tropical localities. (Never safe to eat. )

Fig.

11 - Parrot fish (Scarus microrhinus). Likely poisonous at any time. (Never safe to eat.)

*Halstead, Armed

Bruce

Forces

W.;

Med.

Poisonous

poisonous

1954,

in some

to be dangerously

fishes and ichthyosarcotoxism.

J. 5:2:157-175,

poisonous

U. S.

Poisonous

Fig. 12 - Filefish (Alutera scripta). localities. (Never safe to eat.)

Fig.

13 - Puffer (Arothron hispidus). at any time. (Never safe to eat.)

Fig.

14 - Moray eel (Gymnothorax

some

tropical

Frequently

poisonous

331

in some

Likely to be dangerously

javanicus).

Fish

poisonous

Frequently poisonous

in

localities.

Fig. 15 - Barracuda (Sphyraena barracuda). few tropical localities.

Sporadically poisonous

in a

332

Poisonous

Fish

Fig. 16 - Surgeonfish (Ctenochaetus some tropical localities

Fig.

17 - Pompano localities

(Caranx

strigosus).

sexfasciatus).

Frequently

Sporadically

poisonous

poisonous

in

in a few

be

Fig. 18 - Sea bass, or grouper (Cephalopholis ous in a few tropical localities.

argus).

Sporadically poison-

-

Fig. 19 - Wrasse localities

Poisonous

(Coris gaimardi).

Sporadically

* Bass: oness)

Fig. 20 - Red snapper (Lutjanus few tropical localities.

vaigiensis).

Fig. 21 - Surmullet, or goatfish (Parupeneus poisonous in some tropical localities.

poisonous

Fish

333

in a few

wan

Sporadically

trifasciatus).

poisonous

in a

Frequently

Chapter 36

PLANTS

AKEE The unopened unripe fruit and the cotyledons of the tropical akee (Blighia sapida) are poisonous. In Cuba and Jamaica up to 50 cases of poisoning, with some deaths, occur yearly. Approximately 85% of these cases of poisoning are in children.

Poisoning

has

not been

reported

from

Florida,

where the akee is also grown. One unripe fruit contains a lethal dose of the poison which is soluble in boiling water. The toxic effects produced by akee are as yet poorly under stood. The pathologic findings in the brain are congestion and hemorrhages in the subarachnoid space and parenchyma. The lungs show congestion and serous exudate. The liver and kidneys reveal marked fatty degeneration; less marked degenerative changes are seen in the heart and brain. Clinical Findings: The principal manifestations of akee poisoning are vomiting and circulatory collapse. A. Symptoms and Signs: (From ingestion.) Nausea, vomiting, and abdominal discomfort usually begin within two hours after ingestion. The patient recovers from this

attack and is symptom-free for two to six hours. Vomiting or retching may then return, followed shortly by convulsions, coma, hypothermia, and fall of blood pressure. In fatal cases, death occurs within 24 hours after ingesting the fruit. B. Laboratory Findings: 1. The blood chloride is increased. 2. RBC and WBC are decreased. 3. Hepatic cell function may be impaired as revealed by appropriate tests (see p. 40). Treatment:

A. Emergency Measures: Remove the poison by gastric lavage or emesis followed by catharsis (see pp. 10 to 13). B. Antidote: None known. Alcohol was at one time thought to be a useful antidote, not effective.

but experiments

334

indicate

that it is

Castor and Jequirity Beans C. General

335

Measures:

1. Control convulsions (see p. 34). 2. Give carbohydrates as 5% glucose I. V. dissolved

or as sugar

in fruit juice orally to protect the liver (see

p. 40). 3. Treat uremia

(see p. 29).

Prophylaxis: Only fully-opened fruit should be picked. Fallen, unripe fruit should be burned to prevent children from eating it. If fruit is cooked,

used for further

the water

should

be discarded

and not

cooking.

Prognosis: Recovery is rare after the onset of convulsions or coma. Patients having only the primary attack of vomiting recover completely in a few days.

CASTOR

BEAN,

JEQUIRITY

BEAN

The castor bean plant (Ricinus communis) is grown for commercial and ornamental purposes. The residue or pomace after castor oil extraction of castor beans gives rise to dust which may cause sensitivity reactions or poisoning. Jequirity (rosary bean, Abrus precatorius) is grown as an ornamental vine in tropical climates. The beans are 6 mm. (1/4 inch) long, bright orange with one black end. They are used as rosary beads and as decorations for costumes. Ingestion of only one castor or jequirity bean has caused fatal poisoning when the beans were thoroughly chewed. If the beans are swallowed whole, poisoning is unlikely because the hard seed coat prevents rapid absorption. Ricin, a toxic albumin found in castor beans, and abrin, a Similar albumin found in jequirity beans, cause agglutination

and hemolysis of red cells at extreme dilutions (1:1, 000, 000). They are also injurious to all other cells. The pathologic findings in fatal cases of castor bean or jequirity bean poisoning include hemorrhages and edema of the gastrointestinal tract, hemolysis, and degenerative changes in the kidneys.

Clinical Findings: The principal manifestations beans

are vomiting,

diarrhea,

A. Acute Poisoning: to three days, pain,

(From ingestion.)

nausea,

drowsiness,

culatory collapse, to death in uremia

of poisoning with these

and circulatory

vomiting,

disorientation,

collapse.

After a delay of one

diarrhea, cyanosis,

abdominal stupor,

cir-

and oliguria may begin and progress up to 12 days after poisoning.

336

Fava

Beans

B. Chronic Poisoning: (From inhalation of dust from castor bean pomace.) Dermatitis and inflammation of the nose, throat, and eyes. Instances of asthma have also been reported from exposure to the dust. C. Laboratory Findings: 1.

The

urine

may

show

albumin,

and hemoglobin. 2. The blood may show increase

casts,

red blood

cells,

in urea and N.P.N.

Treatment: A. Acute Poisoning: 1. Emergency measures a. Remove ingested beans by gastric lavage or emesis followed by catharsis (see pp. 10 to 13). b. Maintain circulation by blood transfusions (see p. 25). 2. Antidote - None known. 3. General measures - Alkalinize urine by giving 5 to 15 Gm. (75 gr. to 1/2 oz.) of sodium bicarbonate daily to prevent precipitation of hemoglobin or hemoglobin products

in the kidneys.

4. Special problems - Treat anuria (See p. 29). B. Chronic Poisoning: Remove from exposure. Prophylaxis: Children should not be allowed access to castor beans or jequirity beans. Dust from handling castor bean pomace should be controlled by proper air exhaust. Prognosis: The fatality rate is approximately

5%.

Death

may occur

up to 14 days after poisoning.

FAVA

BEANS

Fava beans (Vicia faba) or horse beans are grown commercially for use as a food. Severe reactions occur occasionally to ingestion of fava beans or to inhalation of the pollen of growing plants. At least eight cases of favism have been reported in the United States.

States,

Deaths

have not been reported

in the United

but have occurred in Italy.

Fava beans induce agglutination and hemolysis in certain individuals, apparently as a result of hypersensitivity although prior contact is not always discoverable. The pathologic findings are hemolysis and hemoglobin precipitation in the kidneys.

Hemlock

337

Clinical Findings: The principal manifestations of favism are jaundice and oliguria. A. Symptoms and Signs: (From ingestion of beans or inhalation of pollen.) Fever, malaise, urine, Oliguria, pallor, enlargement

jaundice, dark of spleen and liver beginning one to two days after ingesting the beans o~ one to eight hours after inhaling the pollen from the plant. B. Laboratory Findings: 1. Anemia and increased serum bilirubin (see p. 40). 2. N.P.N. may be increased if oliguria occurs. 3. Hemoglobinuria. Treatment: A. Antidote:

None

known.

B. General Measures: 1. Give blood transfusions

until anemia

2. Alkalinize urine with 2 Gm. carbonate

is corrected.

(1/2 tsp.) of sodium bi-

every four hours.

3. In the presence of normal kidney function, maintain urine output by giving 2 to 4 L. of fluid daily orally or :Ea a 4. Give cortisone, 100 to 400 mg. daily; or hydrocortisone, 4 to

10 mg.

units

per

subcut.

hour

or I.M.

C. Special Problems:

I.V.;

or corticotropin,

in divided

up to 50

doses.

Treat anuria (see p. 29).

?rophylaxis: In order to prevent the development of sensitivity, fava 2eans should not be served as food to children under the age of one year. ?rognosis: Recovery

is likely with adequate

HEMLOCK (See formula on p.

treatment.

338.)

The poisonous plants of the parsley family include poison 1emlock (Conium maculatum), water hemlock (Cicuta macuata and other Cicuta species), and dog parsley (Aethusia ynapium). Up to ten cases of poisoning occur yearly. Fatalities are 7 at intervals of several years. A piece of plant 1 rae (1/2 inch) in diameter may produce fatal poisoning.

Cicuta species contain cicutoxin, which is a C.N.S. timulant like picrotoxin. Conium maculatum and Aethusia cynapium contain a ‘umber of piperidine derivatives, including coniine, which

338

Hemlock

—— CH,CH,CH, N

|

H

Coniine (a-n-Propylpiperidine)

cause peripheral muscular paralysis similar to that from curare. The pathologic findings in Cicuta poisoning are similar to those from picrotoxin (see p. 281). The pathologic findings in Conium poisoning are inflammation of the gastrointestinal tract with congestion of the abdominal organs. Clinical Findings: The principal manifestations of hemlock poisoning are convulsions and respiratory failure. A. Symptoms and Signs: (From ingestion. ) 1. Cicuta species (e.g., water hemlock) cause abdominal pain, nausea, vomiting, diarrhea, convulsions,

cyanosis, and respiratory failure. 2. Conium (poison hemlock) and Aethusia (dog parsley) cause gradually increasing muscular weakness followed by paralysis with respiratory failure. B. Laboratory Findings: The urine may reveal temporary albuminuria. Treatment:

A. Emergency Measures: 1. Remove poison by gastric lavage or emesis followed by catharsis (see pp. 10 to 13). 2. Treat respiratory failure by artificial respiration with oxygen (see p. 24). B. Antidote: None known. C. General Measures: Control convulsions (see p. 34).

Prophylaxis: Children

or adults

should

never

eat unidentified

wild

plants.

Prognosis: With early and adequate

less than 10%.

therapy the death rate should be

339 MUSHROOMS Poisonous mushrooms may grow wherever nonpoisonous mushrooms grow. The most dangerous species are the fly agaric (Amanita muscaria) and the destroying angel (Amanita phalloides). Poisoning occurs occasionally from the false morel (Gyromitra esculenta) and other species. (See table on p. 340.) schol of part of one mushroom of a dangerous species may be sufficient to cause death Over 100 fatalities occur each year from eating poisonous mushrooms. Amanita muscaria contains the alkaloid muscarine, which stimulates smooth muscles and those organs which receive augmentor fibers from the parasympathetic nervous system. Amanita phalloides contains a principle which damages cells throughout the body. Liver, kidneys, brain and heart are especially affected. Other mushrooms of the Amanita family

as well as of the genus

Galerina

(Galerina

venenata)

may

cause similar poisoning. The pathologic findings in fatalities from mushroom poisoning are fatty degeneration in the liver, kidneys, heart, and skeletal muscles. Clinical Findings: h inci vomiting, respiratory

j tions ushroom difficulty, and jaundice.

poisoni

1. Amanita muscaria causes excitement, delirium, salivation, wheezing, vomiting, diarrhea, slow pulse, and muscular tremors, all beginning one to two hours after ingestion. 2. Amanita phalloides, other Amanita species, and Galerina venenata cause, after a latent interval of 12 to 24 hours, severe nausea, vomiting, diarrhea, bloody vomitus and stools, painful tenderness and enlargement of the liver, oliguria or anuria, jaundice, pulmonary

edema,

depression,

headache,

mental

and signs of cerebral

confusion

and

injury with coma

or

convulsions.

3. Ingestion of other poisonous mushrooms may cause any or all of the following: vomiting, diarrhea, double vision, muscular pains, cyanosis from methemoglobinemia, jaundice, convulsions, and coma. B. Laboratory Findings: 1. Increase in N.P.N. 2. Liver function may be impaired as revealed by appropriate tests (see p. 40). 3.

The

urine

casts.

may

show

red blood

cells,

albumin,

or

340 POISONOUS Common

Name

Scientific

MUSHROOMS Effects

Name

Destroying angel

|Amanita phalloides

Fly agaric

Amanita

muscaria

Liver and kidney damage. Parasympathetic

Galerina

venenata

Liver,

stimulation. kidney,

brain

damage.

False morel

Gyromitra

Vomiting, diarrhea, convulsions, coma. Vomiting, diarrhea.

esculenta

Clitocybe illudens Hebeloma forme

crustulini-

Parasympathetic stimulation, diarrhea.

vomiting,

Inocybe sp. Lactarius vellereus Paneolus campanulatus

Russula

Vomiting,

diarrhea.

foetens

Treatment:

A. Amanita muscaria: 1. Emergency measures - Remove ingested mushrooms by gastric lavage or emesis followed by catharsis (see pp. 10 to 13).

2. Antidote - Give atropine,

2 mg. (1/30 gr.) subcut.,

and repeat every 30 minutes until symptoms are relieved. B. Amanita phalloides or Other Poisonous Mushrooms: 1. Emergency measures - Remove ingested mushroom by gastric lavage or emesis followed by catharsis (see pp. 10 to 13); repeat at least three times the first day and daily thereafter until symptoms begin to subside.

2. Antidote - Give atropine,

2 mg.

(1/30 gr.) subcut.

every hour and then as necessary to maintain complete atropinization. 3. General measures a. Large quantities of carbohydrate appear to help protect the liver from further damage. Give 4 to

5 L. of 5% dextrose,

10% fructose,

or 10% invert

sugar I. V.

every 24 hours if the urine output is

adequate.

Of this fluid,

a quantity equal to that

lost as vomitus or stool should contain 0.9% sodium chloride. b. As soon as fluids can be given by mouth, give oral

fruit juices fortified by glucose, c.

L.\, up to 4 t0)5 ls. daily. Control pain by morphine sulfate,

120 Gm. 10 mg.

(4 oz.)/ (6 gr.)

Poison Ivy and Sumac

341

subcut. every six hours as necessary. Use codeine for younger children. 4. Special problems - Treat anuria (see p. 29).

Prophylaxis: Wild mushrooms should never identification is possible.

be eaten unless

positive

Prognosis: Approximately 50% of those individuals poisoned by Amanita phalloides Or other mushrooms which damage the liver and other internal organs will die. In the absence of injury to internal organs and with adequate atropinization, fatal.

POISON

mushroom

poisoning is not likely to be

IVY (POISON OAK) AND

POISON

SUMAC

Poison ivy or poison oak (Rhus toxicodendron, Rhus radicans, Rhus diversiloba) and poison sumac Rhus vernix) are all related plants which grow widely in the United States. Fatalities are rare, but at least 50% of those who handle Rhus will have a severe dermatitis and up to 10% will have temporarily disabling generalized effects. Rhus toxicodendron and related species contain the poisonous principle urushiol, an extremely irritating oily resin whict is apparently a potent sensitizer since repeated contact appears to increase the severity of the reaction. Renal irritation occurs after severe exposure. In deaths from poison ivy and related plants, the pathologic findings include renal and myocardial damage. Clinical

Findings:

The principal manifestations of poisoning with these plants are vesiculation and generalized edema. A. Acute Poisoning: (From contact, ingestion, or inhalation of smoke.

)

1. Local effects beginning

12 hours to seven days after

contact include itching swelling, papulation, vesiculation, oozing, and crusting. 2. General effects - Generalized edema, pharyngeal or laryngeal edema, oliguria, weakness, malaise, and fever.

B. Chronic

Poisoning:

Repeated exposure

increases the

severity of symptoms. Attempts to produce immunity by repeated exposure may lead to severe poisoning. C. Laboratory Findings: 1. Urine

may

show

albumin,

2. Blood examination

red blood cells,

and casts.

may reveal a high N.P.N.

342

Poison Ivy and Sumac

Treatment:

A. Emergency Measures: 1. Remove skin contamination by thorough washing with strong laundry soap and water.

2. Apply 2% ferric chloride in 50% aqueous alcohol liberally to exposed areas

to precipitate

the resin.

3. Wash again with strong laundry soap and water. 4. Launder or expose clothing to air and sunlight for 48 hours. 5. Remove ingested poison by gastric lavage or emesis followed by saline catharsis (see pp. 10 to 13). B. Antidote: None known.

C. General Measures: 1. Treat exudative stage by exposure to air or with mild wet dressings such as aluminum acetate, 1%, or potassium

permanganate,

1:10, 000,

if the irritation

is

severe. 2. Cortisone or hydrocortisone appear to be effective in relieving discomfort in 25 to 50% of cases when applied topically in a dosage of 5 to 25 mg. per Gm. of ointment. 3. In severe generalized reactions to poison ivy, systemic administration of cortisone or corticotropin will relieve symptoms but will not shorten the course of the disease. Dosage of cortisone is 25 to 100 mg. orally every six hours. Dosage of corticotropin is 5

to 10 4. Give three 5. Give lieve 6. Give 7. Give D. Special

units every six hours. diphenhydramine or other antihistamine, 50 mg. to four times daily. phenobarbital, 100 mg., three times daily to reanxiety. starch or oatmeal baths to allay itching. 2 to 4L. fluids daily if urinary output is normal. Problems: Treat anuria (see p. 29).

Prophylaxis: Teach children to recognize and avoid the plants. Wear heavy clothing and leather gloves if contact with Rhus is unavoidable. The use of silicone base cream appears to give some protection. Clean skin thoroughly with strong soap and water after contact. Desensitization of hypersensitive

attempted with commercially

individuals available antigens.

Prognosis: Recovery is usually complete

may be

in two to three weeks.

343 VERATRUM

AND

ZYGADENUS

Hellebore (Veratrum alba, viride, or californicum) is widely distributed in the northern temperate zone; the death camas (Zygadenus venenosus) grows in the Northwest United States. Both are members of the lily family. Veratrum derivatives are used in the treatment of hypertension. A number of cases of poisoning have been reported recently,

but fatalities

are

rare.

The

fatal

dose

of the fresh

plant may be as small as 1 Gm. (15 gr.). Veratrum and Zygadenus contain nitrogenous compounds which slow the heart rate and lower blood pressure by a vagus reflex which originates in receptors in the heart and lungs. Larger doses raise the blood pressure by a direct effect on the vasomotor center in the brain. The pathologic findings are not characteristic. Clinical Findings: The principal manifestations of poisoning with these plants are vomiting and fall of blood pressure.

A. Acute Poisoning: (From ingestion.) Nausea, severe vomiting, diarrhea, muscular weakness, visual disturbances, slow pulse (down to thirty or below), and low blood pressure (50 mm. Hg systolic or less). With excessive amounts, the blood pressure may rise to 200 mm. Hg or higher accompanied by a rapid thready pulse. B. Chronic Poisoning: Repeated ingestion of small doses may produce tolerance to blood pressure lowering effect but apparently not to the blood pressure raising effect. C. Laboratory Findings: Noncontributory. Treatment: A. Acute Poisoning: 1. Emergency measures - Remove ingested poison by gastric lavage or emesis followed by catharsis (see pp. 10 to 13). 2. Antidote - None known.

3. General measures a. Atropine will block the reflex fall of blood pressure and the bradycardia. Give 2 mg. (2/30 gr.) subcut. ; repeat every hour until symptoms are controlled. b. If hypertension is present, give sympathetic blocking agents such as phentolamine hydrochloride

(Regitine®), 50 to 100 mg. (3/4 to 14/2 gr.) orally, or hydralazine, 10 to 20 mg. (4/6 to 1/3 gr.) I. M. B. Chronic

Poisoning:

Discontinue the use of veratrum

drugs.

Prophylaxis: Children should be warned to avoid eating strange plants. Drugs containing veratrum must be stored safely.

Prognosis: If atropine

can be given,

recovery

is likely.

“(ez~