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Profile Amitraz

Publication Date: 9/95

Amitraz is registered for use on pears, cattle, hogs, and cotton (4). It is not permitted on apples to prevent its residues in processed apples or meat producing animals which consume apple processing waste (3). Amitraz was a restricted use pesticide in 1985 because some studies showed it causes cancer in mice. But re-evaluation of the evidence has led to the current classification of Amitraz as an unrestricted or General Use Pesticide (GUP) (11). Amitraz is available in an emulsifiable concentrate, wettable powder, or a pour-on powder.
Amitraz is a triazapentadiene compound, a member of the amidine chemical family (2). It is an insecticide and acaricide used to control red spider mites, leaf miners, scale insects, and aphids. On cotton it is used to control bollworms, white fly, and leaf worms. On animals it is used to control ticks, mites, lice and other animal pests (5,6).The EPA classifies Amitraz as Class III - slightly toxic. However, products containing it bear the SIGNAL WORD: CAUTION (4, 11).

Amitraz is slightly toxic to mammals if ingested orally (7). The dose of Amitraz that is lethal to half of the test animals that ingest it is called the median lethal dose, or the LD50. The oral LD50 is 523- 800 mg/kg for amitraz in rats (1, 3, 4, 9). The oral LD50 is greater than 1,600 mg/kg for mice. Dermal exposure results in an LD50 of greater than 1,600 mg/kg for rats and greater than 200 mg/kg for rabbits (2, 4, 12).

The Lethal Concentration 50 or LC50 is the concentration of the chemical in air or water that kills half of the experimental animals exposed to it. The inhalation LC50 (6 hours) of amitraz for rats is 65 mg/l of air. Amitraz is not a skin irritant and does not sensitize skin (2).

Signs of acute amitraz poisoning in male and female rats treated with 440 mg/kg and 365 mg/kg respectively, include coolness to touch, reduced spontaneous activity, episodes of increased induced activity such as aggression in response to handling, and signs of general debilitation. Amitraz also may produce a slowly reversible emaciation in survivors (8).
In two-year feeding trials, rats who received 50 mg/kg/day in their diet and dogs who received 0.25 mg/kg/day of amitraz did not show any ill-effects (2).
Reproductive Effects
Doses of 200 mg/kg/day of amitraz for ten weeks decreased fertility in male and female rats. Female mice treated orally for 5 days with 50 mg/kg/day of amitraz and then mated showed a slight increase in loss of fetuses and a decrease in the number of living offspring. When male mice were given 50 mg/kg/day of amitraz orally for 5 days and then mated, the resulting embryos were significantly less likely to grow in the mother's uterus. Female mice who received 400 mg/kg/day of amitraz in their diet for up to 33 weeks, showed a significant increase in the time they were sexually receptive (8).

The highest dose of amitraz which has no observable effect on the death of unborn rats (fetotoxic NOEL) is 3 mg/kg/day. The highest dose of amitraz that does not cause an observable effect in the death of rat embryos (Embryotoxic NOEL) is 5 mg/kg/day (9). Rats who received 12 mg/kg/day of amitraz from day one of pregnancy until the young were weaned at 21 days old had a reduced number of young born and alive at day four (8). Rabbits who received 25 mg/kg/day of amitraz from days 6 to 18 of pregnancy had fewer and smaller litters (1). Although there have been reproductive effects observed in laboratory animals at some dose levels, likely human exposures are very much less than those which produced effects. These effects are unlikely in humans under normal circumstances.
Teratogenic Effects
In one study, rats treated with 12 mg/kg/day of amitraz from days 8 to 20 of pregnancy, the offspring were heavier but had less bone development than the offspring of untreated rats (8). However, an EPA study indicates that the highest dose at which amitraz has no observable effect on test rats' offspring (teratogenic NOEL) is 12 mg/kg/day (9). The teratogenic NOEL of rabbits is 25 mg/kg/day (1). These studies indicate that high doses of amitraz exposure during pregnancy produced adverse effects in laboratory animals. Likely human exposures are very much less than those which produced effects, and these effects are unlikely in humans under normal circumstances.
Mutagenic Effects
A variety of tests indicate that amitraz is not mutagenic and does not cause damage to DNA (8).
Carcinogenic Effects
Long term feeding studies show that amitraz is not carcinogenic in rats. However, it can cause tumors in female mice (8). Amitraz causes an increase in tumors of the lungs and lymph nodes in female mice, but not males, at 57 mg/kg/day over 20 months. A two-year study of female mice also showed an increase in tumors of the liver (hepatocellular tumors) at 57 mg/kg/day of amitraz (4, 5). Because amitraz causes cancer in female mice, but not male mice or male or female rats, it is unclassifiable as to human carcinogenicity (10).
Organ Toxicity
At high doses, amitraz can reduce the function of the hypothalamus, which helps regulate the metabolism by controlling hormone release in the body (4). A daily dose of 200 mg of amitraz per kilogram of body weight for ten weeks causes decreased growth and food consumption (8).
Fate in Humans and Animals
Available data suggest that amitraz, following absorption into the blood, is not readily absorbed into tissues, and is mostly excreted unchanged via the urine (2, 4, 8).
Effects on Birds
Amitraz is slightly toxic to birds. The dietary LC50 (8 day) is 7,000 mg/kg for mallard ducks and 1,800 mg/kg for Japanese quail (2, 7). The oral LD50 for bobwhite quail is 788 mg/kg (3). Amitraz may affect reproduction in birds. The avian reproduction NOEL is less than 40 ppm (4).
Effects on Aquatic Organisms
Amitraz is moderately toxic to fish (3, 4, 5). The LC50 (96-hour exposure) is 1.3 mg/l for bluegill sunfish and 3.2-4.2 mg/l for harlequin fish. For a 48-hour exposure of rainbow trout, a cold water species, the LC50 is 2.7-4.0 mg/l (2). Daphnia, a fresh water invertebrate, exhibited toxic effects at 35 ppb of amitraz in water (1).
Effects on Other Animals (Nontarget species)

Amitraz is relatively non-toxic to bees (5, 7). The LD50 is 12 micrograms per bee by ingestion and 3.6 mg/l by direct spraying (2).
Breakdown of Chemical in Soil
Amitraz is broken down rapidly in soil containing oxygen. The half- life in soil, the amount of time needed for the chemical to degrade to half its original concentration, is less than one day. Degradation occurs more rapidly in acidic soils than in alkaline or neutral soils (2).
Breakdown of Chemical in Vegetation
Reports indicate that amitraz may cause crop injury to young peppers and pears during high temperature conditions (5).
Amitraz is a straw colored crystalline solid and odorless. It is non-corrosive and stable to heat. UV light seems to have little effect on its stability. Slow decomposition occurs when amitraz is stored for prolonged periods under moist conditions (2).
Physical Properties:
CAS #: 33089-61-1
Chemical name: N,N'-[(methylimino) dimethylidyne]di-2,4-xylidine
Solubility in water at room temperature: ca. 1 mg/l (3)
Soluble in common organic solvents including acetone, toluene, and xylene (3)
Vapor pressure: 0.051 mPa at 20 degrees C (2)
Melting point: 86-87 degrees C (2)
Partition coefficient: (octanol/water) Kow = 316,000 (2)
Exposure Guidelines:
ADI: 0.003 mg/kg (human) (4).
NOEL: 0.25 mg/kg/day (dog); 3 mg/kg/day (rat) (10).
RfD: 0.0025 mg/kg/day (10).
NOR-AM Chemical Company
3509 Silverside Rd.
P.O. Box 7495
Wilmington, DE 19803
Telephone: 302-575-2000
Emergency : Day: 302-995-8632, Night: 302-656-5114
Review by Basic Manufacturer:
Comments solicited: October, 1994
Comments received: March, 1995

1. Meister, R.T., (ed.). 1994. Farm Chemicals Handbook '94. Meister Publishing Company. Willoughby, OH.
2. The Agrochemicals Handbook, Third Edition. 1994. Royal Society of Chemistry Information Systems. Unwin Brothers Ltd., Surrey, England.
3. Meister, R.T. (ed.). 1992. Farm Chemicals Handbook '92. Meister Publishing Company. Willoughby, OH.
4. U.S. Environmental Protection Agency. 1987. EPA Fact Sheet No. 147 Amitraz. U.S. EPA. Washington, DC.
5. Thomson, W. T. 1983. Agricultural Chemicals Book I Insecticides. Thomson Publications. Fresno, CA.
6. Budavari, Susan, (ed.). 1989. The Merck Index, Eleventh Edition. Merck and Company Inc. Rahway, NJ.
7. Briggs, Shirley. 1992. Basic Guide to Pesticides, Hemisphere Publishing. Washington, DC.
8. Hayes Jr., Wayland, and E.R. Laws, Jr., (eds.) 1991. Handbook of Pesticide Toxicology Volume 1. Academic Press, Inc., NY, NY.
9. Walker, M.M. and L.H. Keith. 1992. EPA Fact Sheet Database. Lewis Pubishers. Ann Arbor, MI.
10. U.S. Environmental Protection Agency. 1989. Toxchem No. 431 Documents 002372 ,002373, 0040344, and 0044586. U.S. EPA. Washington, DC.
11. Edwards, Dennis, U.S. EPA Product Manager. July 25, 1994. Phone conversation. U.S. EPA. Washington, DC.
12. National Institute for Occupational Safety and Health (NIOSH). 1993. Registry of Toxic Effects of Chemical Substances (RTECS). NIOSH. Cinncinati, OH.
13. U.S. Department of Health and Human Services Agency for Toxic Substances and Disease Registry. 1990. Draft Health Assessment Guidance Manual. U.S. Department of Health and Human Services. Atlanta, GA.

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