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International Agency for Research on Cancer (IARC) - Summaries & Evaluations

AMITROLE

VOL.: 41 (1986) (p. 293)

5. Summary of Data Reported and Evaluation

5.1 Exposure data

Amitrole has been widely produced since the 1950s for use as a herbicide. Occupational exposures occur during production, formulation and application of this herbicide, and nonoccupational exposures may occur from residues in food.

5.2 Experimental data

Amitrole was tested in mice by oral administration, skin application and transplacental exposure, in rats by oral and subcutaneous administration, and in hamsters by oral administration. In mice, thyroid and liver tumours were produced after oral administration; no skin tumour was observed after topical application. The study by transplacental exposure yielded inconclusive results. In rats, amitrole induced thyroid and pituitary tumours after oral administration. No carcinogenic effect was observed in hamsters.

Dietary exposure of breeding pairs of rats to amitrole reduces growth and viability of offspring.

Amitrole does not induce DNA damage in bacteria but may have an effect in yeast. It is not mutagenic to Salmonella typhimurium or Escherichia coli. Amitrole induces aneuploidy in yeast, but not mutation in yeast or Aspergillus nidulans. However, conflicting results were obtained in assays for mitotic gene conversion and recombination. It is weakly mutagenic to Streptomyces coelicolor. It does not induce sex-linked recessive lethal mutations or nondisjunction in Drosophila melanogaster. Amitrole induced mutations at two loci in one mammalian cell line. Amitrole does not induce unscheduled DNA synthesis in hepatocytes of rats exposed in vivo. No aneuploidy or chromosomal aberration is found in cultured human lymphocytes. Micronuclei are not induced in mouse bone marrow. Cell transformation is induced in mammalian cells. A commercial preparation of amitrole induces chromosomal abnormalities in plants.

5.3 Human data

Two cytogenetic studies of occupational exposure to a number of herbicides, including amitrole, were available. A possible increase in the frequency of chromosomal aberrations was seen in one study, and an increased frequency of sister chromatid exchanges occurred in one group of workers in the other. The role of amitrole itself cannot be evaluated from these studies.

No data were available to evaluate the reproductive effects or prenatal toxicity of amitrole to humans.

In a small cohort study of Swedish railroad workers who had sprayed herbicides, there was a statistically significant excess of all cancers among those exposed to both amitrole and chlorophenoxy herbicides, but not among those exposed mainly to amitrole.

5.4 Evaluation

There is sufficient evidence for the carcinogenicity of amitrole to experimental animals.

There is inadequate evidence for the carcinogenicity of amitrole to humans.

For definition of the italicized terms, see Preamble Evaluation.

Previous evaluation: Vol. 7 (1974)

Subsequent evaluations: Suppl. 7 (1987); Vol. 79 (2001)

Last updated: 23 April 1998 


See Also:
        Amitrole (EHC 158, 1994)
        Amitrole (IARC Summary & Evaluation, Supplement 7, 1987)
        Amitrole (IARC Summary & Evaluation, Volume 7, 1974)
        Amitrole (ICSC)
        Amitrole (PDS)
        Amitrole (PIM 648)