The approximate oral toxicity in rats of selected household products

TOXICOLOGY

The

AND APPLIED

PHARMACOLOGY

Approximate

3, 689-695

(1961)

Oral Toxicity in Rats Household Products

HAROLD C. HODGE AND WILLIAM Departments

of Pharmacology of Medicine

and Radiation and Dentistry, .Received

April

Biology, Rochester,

of

Selected

L. DOWNS University of Rochester New York

School

11, 1961

The Federal Hazardous Substances Labeling Act “to regulate the interstate distribution and sale of hazardous substances intended or suitable for household use” became law on July 12, 1960. The legislative history of the Act shows that the primary intent of the lawmakers was to reduce the incidence of accidental ingestion, particularly by small children, of hazardous products that might be found in the household. The means provided by the Act for safeguarding the public is to require appropriate cautionary labeling of such substances as may cause “substantial personal injury or substantial illness” in their ‘Lcustomary or reasonably foreseeable handling or use, including reasonably foreseeable ingestion by children.” Many hazardous substances, including drugs, “economic poisons,” certain fuels, foods, and cosmetics are exempted from the provision of this Act since they are subject to other federal laws. Information on deaths due to accidental poisoning by solids and liquids is compiled annually by the National Office of Vital Statistics. These data for 19.58 (U. S. Department of Health, Education, and Welfare, 19.58) are summarized by several categories of products (1) for all ages and (2) for children under 5 years of age in Table 1. The under-five age group accounts for nearly one-third of the poisoning deaths (see also American Medical Association, 1960). In this group, as for all ages, medicines account for over onethird of the deaths. The two next most important specific categories in the under-five age group, petroleum products and lead compounds, cause relatively few deaths outside that group. Hazardous substances covered for the first time by the New Act are not listed as such in publications of the Bureau of Vital Statistics, and mostly would be classed in the “all others” category of Table 1. Almost all the products newly covered must thus 689

690

HAROLD

C.

HODGE

AND

WILLIAM

L.

DOWNS

account for no more than 16% of accidental fatal poisonings among small children (the actual incidence presumably is lower since undetermined sources are included). With the exception of the caustic poisons (covered by the new law and formerly by the Federal Caustic Poison Act), most deaths by poisoning are ascribed to substances (Table 1) not covered by the new act. ACCIDENTAL

FATAL

POISONINGS

TABLE

1

BY

AND

SOLID

LIQUID

SUBSTANCES

All ages Category Medicines Alcohol Noxious food Petroleum products Industrial solvents Caustic poisons Lead compounds Economic poisons (mercury, arsenic, and antimony compounds and fluorides) All others

from

U. S. Department

Age group

under

5

Total

7n

Total

549 322 5 83

38.5 22.5 0.3 5.8

150 6 3 75

35.6 1.4 0.7 17.8

41 57 70

2.9 4.0 4.9

8 24 61

1.9 5.7 14.5

50 252

3.5 17.6

27 68

6.3 16.1

1429 a Data

(1958)~

of Health,

100.0 Education,

%

422 and

Welfare

100.0

(1958).

To obtain orientation as to what household products might be considered hazardous from the standpoint of acute oral toxicity, and faced with a paucity of published information (Deichmann and Gerarde, 1958; Dreisbach, 1959; Gleason et al., 1957; Gosselin, 1957, 19.59; Thienes, 1940), a survey of household product toxicity was undertaken using minimal numbers of rats and seeking preliminary or “screening” data. Common household products were selected, e.g., foods and condiments, cosmetics, cleaning and polishing agents, common solvents, a drug, and tobacco. Several substances commonly responsible for accidental poisonings (e.g., kerosine, aspirin) were included; products which carry poison labels because of their caustic nature were not. The products were purchased in a supermarket or a neighborhood store; no effort was made to find the composition of the products except from information on the labels.

ORAL

TOXICITY:

HOUSEHOLD

691

PRODUCTS

METHODS

Adult female albino rats of the Rochester (ex-Wistar, 1923) strain, which had fasted 24 hours, were given by stomach tube doses of the products ranging from 0.5 to 50 g/kg. The materials were administered either without dilution (liquids and pastes) or mixed in weighed proportions with amounts of water as small as possible. Groups, usually of two rats each, were tested at doses progressing by roughly a factor of 2. The lethal range is defined as the range between (1) the highest dose tolerated by all treated rats and (2) the lowest dose that killed all treated rats. Rats were observed for periods of at least 2 weeks; survivors were then sacrificed and gross autopsy examinations performed. RESULTS

Lethal ranges of the products are given in Table 2. TABLE LETHAL

RANGES

OF SELECTED~

Product Cleaner, window (solution) Cloves (ground) Floor wax, liquid Floor wax, paste Ginger (ground) Horseradish (grated, prepared) Mustard (dry) Nutmeg (ground) Pepper, black (ground) Pepper, cayenne (ground) Polish, furniture (liquid) Polish, metal (powdered) Polish, shoe (liquid) Sugar (granulated) a b C d

HOUSEHOLD OF SINGLE

Toxicity ratingc 1 1

2 PRODUCTS IN RATS; ORAL DOSES

Estimated lethal range (g/k)

1 1 1 1 1 1 1

Estimated lethal range on volume basisb (ml/W

AND VOLUME

Concentration k/l00 g mixture) U”

20-35 35s>50

1 1 1

WEIGHTS

>12.5 35>50 >17 >12.5 >12.5 >12.5

-

1

25->36 -

1

23->32

74->

105

>jo 20-50 >29.1 31.1->44.5 >37.6 >24.4 >22.6 >27.4 zo->so

31

U U 33 67 33 2S 25 25

27%>39.6

u 50

>jo 25.3->35.2

u 50

Not necessarily representative of all products in each class. Volume of product administered on basis premix volume per kilogram. Gleason et al. (1957). U = Undiluted liquid; numbers are grams of product per 100 g mixture.

692

HAROLD

C.

HODCE

AND

TABLE

2 (Continued)

Toxicity ratingC

Product

1 1

Vanilla (extract) Whiskey (86 proof, blended) Alchohol, rubbing (70% isopropyl alcohol) Bleach, liquid (S.25% sodium hypocblorite) Cleanser, all purpose (liquid) Cleanser (powdered) Cream of tartar Detergent, all purpose (household, granulated) Detergent, light duty, household (liquid) Gasoline Kerosine Nail polish (liquid) Nail polish remover Paint (house, white) Sage (ground) Soap (toilet bar) Wintergreen (essence) Aspirin (acetylsalicylic acid) Baking soda (sodium bicarbonate) Bleach (powdered) Carbon tetrachloride Disinfectant (alkly aryl quaternary ammonium compound) Permanent wave neutralizer (powdered) Permanent wave solution Table salt (sodium chloride) Tobacco (cigarette butts) Turpentine C To ingest these would be required.

doses

of the

WILLIAM

DOWNS

Estimated lethal range on volume basis” (ml/kg)

Estimated lethal range k/kg) -

Concentration k/l00 g mixture)

20-35

cl

20-50

U

2

-

s-10

U

2 2

-

Z-IO 10-3s

U U

2 2

7-25 10-22

7.2-25.8 12.3-27.1

so so

2

4-9

11.2-25.2

so

s-10 IO-35

U

10-3s

U u U U

2 2

-

2 2

-

2 2

2

10-3s s-10 S-25 >S

2 2

6-> -

16

>31.6 7.1->18.9 8-10

3

l-3F

1.4-4.1

3 3

3-4 3-6

2.9-3.9 8.5-l 7.0

u

11 33

U 10 so so

3

-

l-3

U

3

-

0.5-2

U

3

0.8-Z -

1.1-2.7

17 U

3-6 3-4

2.4-4.8 22.7-30.3

3 3 3 3

nominal

L.

-

S-grain

tablets,

1-2

2-3

2 tablets/kg

so 10

U to 7 tablets/kg

ORAL

TOXICITY:

HOUSEHOLD

PRODUCTS

693

All the materials tested fall in toxicity classes 1, 2, and 3, as defined in Clinical Toxicology of Commercial Products (Gleason et aZ., 1957). In class I (“practically non-toxic” materials: lethal dose-15 g/kg or more), 16 products were listed, including soap, sugar, polishing and cleaning agents, a number of condiments, and whiskey. In class 2 (“slightly toxic” materials: lethal dose--5-15 g/kg), 15 products were listed including gasoline and kerosine, some cosmetics, a paint, soap, househould detergents, a liquid bleach, rubbing alcohol, essence of wintergreen, and cream of tartar. In class 3 (“moderately toxic” materials: lethal dose-OS-5 g/kg), 10 products were listed, including a dry bleach, carbon tetrachloride, turpentine, table salt, baking soda, aspirin, a permanent wave solution, a permanent wave neutralizer, and ground-up cigarette butts. Although only one product in a given class was tested, the category in which it is listed may not be entirely inappropriate for the class, because a tenfold range of toxic doses is spanned in class 3, a threefold range in class 2, and class 1 has no defined span. DISCUSSION

Some materials, for example, carbon tetrachloride and aspirin, on the basis of extensive clinical experience are usually given toxicity ratings for man higher than moderately toxic (class 3). On the other hand, experience would indicate that the reverse almost certainly holds true for table salt and baking soda, which are less hazardous to man than their toxicity to rats would indicate. The question as to what degree of toxicity should constitute a basis for requiring a signal word (e.g., DANGER) under the Hazardous Substances Labeling Act deserves extended study and discussion. In Clinical Toxicology of Commercial Products (Gleason et al., 1957) a scale of toxicity ratings and descriptive terms has been employed. In toxicity class 6 are listed “supertoxic” substances with probable lethal doses in the adult human of less than 5 mg/kg. In toxicity class 5, “extremely toxic” substances are listed for which the probable lethal doses are less than 50 “g/kg. In toxicity class 5, “extremely toxic” substances are listed for which the probable lethal doses are less than 50 mg/kg. Products in these two categories are defined as “highly toxic” in the Act and the labels must bear the signal word “DANGER.” At the other end of the toxicity “practically non-toxic,” and class 2, “slightly toxic,” scale are class 1, substances. To endanger life, substances in these two classes must be consumed by a 70-kg individual in quantities greater than 1 pint (5 g/kg,

694

HAROLD

C.

HODGE

AND

WILLIAM

L.

DOWNS

approximately) and are thus sufficiently innocuous that ordinarily no warning word is needed. There remain two toxicity classes: class 3, “moderately toxic” substances (lethal dose-500 mg/kg to 5 g/kg) and class 4, “very toxic” substances (lethal dose-50 to 500 mg/kg). For substances in these two classes, and considering for the moment the toxicity and not other possible dangers, the hazardous nature (and the decision on labeling) should be determined only in part by the acute oral toxicity. Thus, kerosine (Clinical Toxicology of Commercial Products toxicity rating: class 3), which from the crude screening data on rats in Table 1 is placed in class 2, frequently causes fatal poisonings in children. Gerarde (1959) demonstrated that the hazard from kerosine is not reflected by the oral LDBo. Kerosine, a material of low toxicity when taken into the stomach, is dangerously toxic when aspirated, e.g., by choking or during vomiting. In the rabbit, the oral LDsO is 28 g/kg; in the rat intratracheally, the LDr,” is 0.2 g/kg; the ratio is 140: 1. None of the substances in Table 2 is more toxic than class 3. It is ridiculous to consider putting a toxic warning on baking soda or table salt, both of which are found in class 3. On the other hand, the hazards from aspirin and carbon tetrachloride (also class 3 in Table 2) are well established; these substances have been given toxicity ratings of 4 in Clinical Toxicology of Commercial Products (pp. 28, 35). The hazards of ingesting light, fluffy products may be limited by the large volumes required to furnish toxic doses (weight per kilogram body weight). In Table 2, column 4 lists the estimated lethal ranges on a volume basis. For a number of products, the largest doses were the limit of the capacity of the animal’s stomach and even these doses were not uniformly fatal. Gosselin examined toxicity ratings on about 5000 products: in toxicity class 4 were found disinfectants (such as those used for garbage cans), some dry cleaner solvents, degreasers, some depilatories, some drain cleaners, naphthalene moth repellants, rust removers, radiator cleaners, leather dyes, indelible inks, fire extinguisher liquid, and many agricultural chemicals. Some of these undoubtedly warrant a signal word on the label and many do carry cautionary labeling, e.g., those agricultural chemicals regulated by other federal laws. It is conceivable that a commercial package of one of these materials would not need a warning label, if, for example, the quantity was minuscule compared to a hazardous dose. A workable basis of operation would be established, in our opinion, if (1) all substances lethal in amounts of 500 mg/kg or less orally were

ORAL

TOXICITY:

HOUSEHOLD

695

PRODUCTS

labeled in an appropriate way except when experts agreed that no substantial hazard was involved; and (2) all substances of lesser acute oral toxicity were unlabeled unless experts concluded that a hazard was clearly demonstrated. SUMMARY The acute, “screening,” oral toxicities of about 40 common household products purchased in neighborhood stores were determined in adult albino female rats. All products fell in toxicity classes 1, 2, or 3 as defined in Gleason et al. (1957), i.e., had lethal doses greater than 500mg/kg. From the standpoint of acute oral toxicity, appropriate labeling is suggested for substances lethal in amounts of SOOmg/kg or less unless experience has demonstrated a negligible hazard; substances of lesser toxicity would remain unlabeled unless hazard was demonstrated. REFERENCES AMERICAN

problem,

MEDICAL

ASSOCIATION.

(1960).

Hidden

hazards:

the

unlabeled

poison

21 pp.

W. B., and GERARDE, H. W. (1958). Signs, Symptoms and Treatment Acute Intoxications, 2nd ed. C. C Thomas, Springfield, Illinois. DREISBACH, R. H. (1959). Handbook of Poisoning: Diagnosis and Treatment, 2nd ed. Lange Medical Publications, Los Altos, California. GERARDE, H. W. (1959) Toxicological studies on hydrocarbons. V. Kerosine. Toxicol. Appt. Pharmacol. 1, 462-474. GLEASON, M. N., GOSSELIN, R. E., and HODGE, H. C. (1957). Clinical Toxicology of Commercial Products. Williams & Wilkins, Baltimore, Maryland. GOSSELIN, R. E. (1957). How toxic is it? J. Am. Med. Assoc. 163, 1333-1337. GOSSELIN, R. E. (1959). Toxicity ratings and the manufacturer. Ckem. Specialties Mfrs. Assoc. Proc. 46th Ann. Meeting, 5 pp. THIENES, C. H. (1940). Clinical Toxicology. Lea & Febiger, Philadelphia, Pennsylvania. U. S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE. (1958). Vital Statistics of the United States, Vcl. II, p, 176. U.S. Government Printing Office, Washington. D. C. DEICHMANN,

of Certain