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Amitrole

Publication Date: 9/93

TRADE OR OTHER NAMES

Amitrole is known as amino-triazole in Great Britain, France, New Zealand and the former USSR. Trade names include Amerol, Amino Triazole, Amitrol, Amizine, Amizol, Azolan, Azole, Cytrol, Diurol, and Weedazol (24, 25, 28).

REGULATORY STATUS

Amitrole is a Restricted Use Pesticide (RUP). RUPs may be purchased and used only by certified applicators. Products containing amitrole must bear the signal word "Caution" (25).

INTRODUCTION

Amitrole is a nonselective systemic triazole herbicide. It is used on non-cropland for control of annual grasses and perennial and annual broadleaf weeds, for poison ivy control, and for control of aquatic weeds in marshes and drainage ditches (25). All use of amitrole on food crops was canceled by the EPA in 1971 because it has caused cancer in experimental animals (31). It is available as soluble powders, soluble concentrates, suspension concentrates, water dispersible granules, liquid solutions, and wettable powders (25).

Amitrole was the chemical that gave rise to the Cranberry Crisis of 1959. This event involved the first enforcement of the Delaney Clause which prohibits any amount of any cancer causing substance to be in or on food. It also prompted growers to read and follow pesticide label directions more carefully. At the time, amitrole was registered for post harvest use on cranberries. This practice would leave no detectable levels on berries harvested the following year. However, misuse of this pesticide, either through over application the previous season or through pre-harvest application, led to residues on portions of the cranberry crops of 1957 and 1959. In 1959, just thirteen days before Thanksgiving, Arthur Flemming, then Secretary of Health, Education and Welfare, announced that the current crop of cranberries was contaminated with amitrole, a cancer causing weed killer. The actual levels detected on the berries were very low. 1587 metric tons of cranberries were seized by the Food and Drug Administration and, just three days before Thanksgiving, a plan was implemented to certify sufficient cranberries to meet holiday demands (6, 24).

TOXICOLOGICAL EFFECTS

ACUTE TOXICITY

Amitrole is a compound of very low acute toxicity to humans and other animals. Associated symptoms in humans include skin rash, vomiting, diarrhea, and nose bleeds. Poisoning of several species by amitrole is characterized by increased intestinal peristalsis (this may lead to diarrhea), fluid in the lungs, and hemorrhages of various organs. No toxic effects were observed in a woman who ingested 20 mg/kg. A single dose of 1,200 mg/kg reduced iodine uptake by the thyroid in healthy persons (6, 24, 30).

Amitrole is a mild skin and eye irritant (24, 28, 30).

The amount of amitrole that is lethal to one-half (50%) of experimental animals fed the material is referred to as its acute oral lethal dose fifty, or LD50. The oral and dermal LD50 for amitrole in rats is greater than 5,000 mg/kg. Studies have reported oral LD50s as high as 15,000 mg/kg in mice and 24,600 mg/kg in rats. In one study, the largest doses tested, 4,080 mg/kg orally and 2,500 mg/kg dermally, produced no toxic effects on rats. The dermal LD50 in rabbits is greater than 200 mg/kg (24, 25, 28).

CHRONIC TOXICITY

Amitrole has not been shown to be hazardous to workers, even after long term exposure (6). Amitrole has caused liver, thyroid and pituitary tumors in laboratory animals. Long term exposure to amitrole can cause reversible goiters (14, 30).

Reproductive Effects

In a 2-generation study in rats, the number of pups per litter and their weight at weaning were reduced for dams fed 5 or 25 mg/kg. Atrophy of the thymus and spleen also occurred at these high doses. Within a week after weaning, most of these pups died of a condition resembling runt disease. Similar effects have been observed in mice. Dietary doses of 1.25 or 5 mg/kg/day had no significant effect on reproduction (24).

Teratogenic Effects

Birth defects have occurred in the pups of pregnant rabbits, rats and mice exposed to amitrole, but only at doses high enough to also produce signs of toxicity in the mothers (31).

Mutagenic Effects

One laboratory assay has shown amitrole to be weak mutagen. All other assays have shown no mutagenic effects by amitrole (24, 31).

Carcinogenic Effects

Amitrole has induced thyroid and liver tumors in rats and mice. It has been classified as an human carcinogen by EPA because of the probable evidence for cancer induction in experimental animals in the absence of direct evidence for carcinogenic effects in humans (24, 29, 30, 31).

Organ Toxicity

Feeding of amitrole to rats at dietary levels of 3 or 6 kg/mg/day for 2 weeks caused enlargement of the thyroid and reduced uptake of radio iodine by the thyroid. A dietary level of 50 mg/kg/day produced significant enlargement of the thyroid after three days of feeding. Several studies have shown that amitrole inhibits the activity of various liver enzymes. Atrophy of the thymus and spleen occurred in pups of rat dams fed 5 or 25 mg/kg amitrol (24).

Fate in Humans and Animals

Amitrole is rapidly and completely absorbed into the body through the gastrointestinal tract when eaten. No metabolites are found in humans. Amitrole is excreted through the urine. The highest concentrations in all tissues generally occurs within one hour after exposure, and concentrations begin to decline after 2 to 6 hours (24).

When radio-labeled amitrole was administered to rats by stomach tube, 70 to 95.5% of the radioactivity was excreted in the urine during the first 24-hours. Radioactivity was detected in the rats' feces for 2 to 5 days after dosing. After six days, only 0.28 to 1.36% of the total dose remained in the rats' bodies, mainly in the liver (24).

ECOLOGICAL EFFECTS

Effects on Birds

Amitrole has a very low acute toxicity to upland game birds (29). The LD50 for amitrole in mallard ducks is 2,000 mg/kg (4).

Effects on Aquatic Organisms

Amitrole is slightly toxic to various species of freshwater fish and freshwater invertebrates (29).

Effects on Other Animals (Nontarget species)

Amitrole inhibits the growth of bacteria (7). It is non-toxic to bees (25).

ENVIRONMENTAL FATE

Breakdown of the Chemical in Soil and Groundwater

Because amitrole does not adsorb strongly to soil particles (Koc = 100 g/ml) and it is readily soluble in water, it has a moderate potential for groundwater contamination. Its soil half-life is 14 days (26). Microbial breakdown of amitrole takes 2-3 weeks in warm, moist soil (28). Some chemical degradation may occur in soils. Loss of amitrole from soils by volatilization or photodegradation is minor (27). Amitrole residues were not detected in crops planted into soil 1 to 50 days after treatment with amitrole (29).

Breakdown of the Chemical in Water

In aquatic environments, amitrole is not expected to breakdown by hydrolysis or photolysis, to volatilize, nor to bioaccumulate in aquatic organisms. The biodegradation half-life for amitrole in water is about 40 days. Degradation of amitrole in open waters may occur through oxidation by other chemicals. The main route of removal from waters may be through adsorption to sediment particles (27). Amitrole may persist in surface waters for longer than 200 days.

Breakdown of the Chemical in Vegetation

Amitrole is readily absorbed and rapidly translocated in the roots and leaves of higher plants (29). Plants are able to metabolize amitrole. This takes 1-4 weeks (7). Microbes break amitrole down to carbon dioxide (16).

PHYSICAL PROPERTIES AND GUIDELINES

Amitrole is a white, odorless crystalline powder with a bitter taste (24). Technical amitrole is an off-white powder (25). There is a slight fire hazard when amitrole is exposed to heat or flame. It may burn, but does not readily ignite (30).

Amitrole is mildly corrosive to iron, aluminum, copper and copper alloys. It forms chelates with these metals (22). If strongly heated, amitrole will emit very toxic fumes (16). The activity of amitrole is increased by ammonium thiocyanate (6).

Occupational Exposure Limits:

0.2 mg/m3 OSHA TWA
0.2 mg/m3 ACGIH TWA
0.2 mg/m3 NIOSH Recommended TWA
0.2 mg/m3 DFG MAK TWA (total dust) (30)

Physical Properties:

CAS #: 61-82-5
Chemical name: 3-amino-1,2,4-triazole
Specific gravity: 1.138 at 20 degrees C (28)
H20 solubility: 280 gm/liter at 25 degrees C (24)
Solubility in other solvents: Soluble in chloroform, ethanol and methanol. Slightly soluble in acetonitrile, ethyl acetate and methyl chloride. Insoluble in oils, kerosene, ether and acetone and nonpolar solvents (24, 25)
Melting point: 157 - 159 degrees C (318 degrees F) (24)
Flashpoint: aqueous and dry powder forms - nonflammable (2)
Vapor pressure: negligible, 4.4 x 10 to the minus 7th power mm (26)
Koc: 100 g/ml (26)
Chemical Class/Use: triazole herbicide

BASIC MANUFACTURER

Rhone Poulenc Ag Co.
PO Box 12014
2 T.W. Alexander Dr.
Research Triangle Park, NC 27709

Review by Basic Manufacturer:

Comments solicited: October, 1992
Comments received:

REFERENCES

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  3. Hazardous Materials Advisory Committee. 1974. EPA-SAB-74-001 Herbicide Report Chemical Analysis, Environmental Effects, Agriculture and Other Applied Uses. EPA: May.
  4. Tucker, Richard. 1970. Handbook of toxicity of pesticides to wildlife. USDI Fish & Wildlife Service.
  5. Worthing, C.R. (ed.). 1987. The pesticide manual: A world compendium. 8th Ed. The British Crop Protection Council. Croydon, England.
  6. Hayes, Wayland, Jr. 1982. Pesticides studied in man. Baltimore, MD: Williams & Wilkins.
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  10. Shepard, T.H. 1973. Catalog of teratogenic agents. Baltimore, MD: John Hopkins University Press.
  11. Schardein, James. 1985. Chemically induced birth defects. New York: Marcel Dekker.
  12. Suspected Carcinogens. A subfile of the registry of toxic effects of chemical substances. US Dept. of Health, Education and Welfare. 1976.
  13. Department of Transportation. 1984. Emergency Response Guidebook: Guidebook for hazardous materials incidents. Washington, DC: U.S. DOT.
  14. Hallenbeck, W.H. & K.M. Cunningham-Burns. 1985. Pesticides and human health. New York: Springer-Verlag.
  15. Lef'evre, M.J. 1980. First aid manual for chemical accidents. New York: Van Nostrand Reinhold.
  16. TOXNET. 1985. National library of medicine's toxicology data network. Hazardous Substances Databank. Public Health Service. National Institute of Healtyh. U.S. Department of Health and Human Services. Bethesda, MD: NLM.
  17. Sax, N.I. 1975. Dangerous properties of industrial materials. 4th Ed. New York: Van Nostrand Reinhold Co.
  18. Casarett, L.J. 1980. Casarett & Doull's Toxicology: the basic science of poisons. 2nd Ed. New York: Macmillan.
  19. Gosselin, R.E. 1984. Clinical toxicology of commercial products. 5th Ed. Baltimore, MD: Williams & Wilkins.
  20. National Fire Protection Association (NFPA). Fire Protection Guide. Hazardous Materials. 1978.
  21. Morgan, D.P. 1982. Recognition and management of pesticide poisonings. Iowa Pesticide Hazardous Assessment Project. 1982. Iowa City, IA.
  22. Windholz, M. (ed.) 1976. The Merck Index: an encyclopedia of chemicals and drugs. 9th Ed. Rahway, NJ: Merck.
  23. Sunshine, Irving. 1969. Handbook of analytical toxicology. Cleveland, OH: Chemical Rubber Co.
  24. Hayes, W.J. and E.R. Laws (ed.). 1990. Handbook of Pesticide Toxicology, Vol. 3, Classes of Pesticides. Academic Press, Inc., New York.
  25. Meister, R. T. (ed.). 1992. Farm Chemicals Handbook '92. Meister Publishing Company, Willoughby, Ohio.
  26. USDA SCS. 1990 (Nov.). SCS/ARS/CES Pesticide Properties Database: Version 2.0 (Summary). USDA - Soil Conservation Service, Syracuse, NY.
  27. Howard, P.H. (ed.). 1989. Handbook of Environmental Fate and Exposure Data for Organic Chemicals, Vol. III: Pesticides. Lewis Publishers, Chelsea, MI.
  28. WSSA Herbicide Handbook Committee. 1989. Herbicide Handbook of the Weed Science Society of America, 6th Ed. WSSA, Champaign, IL.
  29. US EPA. 1984 (March). Amitrole: Pesticide Registration Standard and Guidance Document. Office of Pesticides and Toxic Substances, US EPA, Washington, DC.
  30. Occupational Health Services, Inc. 1991 (Sept. 16). MSDS for Amitrole. OHS Inc., Secaucus, NJ.
  31. U.S. Environmental Protection Agency. 1992 (Oct. 8). Amitrole; Preliminary determination to terminate Special Review. Federal Register 57(196):46448-55.