For definition of Groups, see Preamble Evaluation.
VOL.: 48 (1990) (p. 123)
Chem. Abstr. Name: Benzenamine, 4-chloro-2-methyl-
Chem. Abstr. Name: Benzenamine, 4-chloro-2-methyl-, hydrochloride
para-Chloro-ortho-toluidine and its hydrochloride have been produced since the 1920s and have been used as chemical intermediates in the manufacture of azo dyes for textiles and pigments and, since the 1960s, in the manufacture of chlordimeform, an insecticide. Occupational exposure can occur during production and use of para-chloro-ortho-toluidine; however, no data on levels were available. para-Chloro-ortho-toluidine has been detected as a metabolite of chlordimeform in plants and in humans.
para-Chloro-ortho-toluidine hydrochloride was tested for carcinogenicity by administration in the diet in two strains of mice and in two strains ofrats. It produced haemangiomas and haemangiosarcomas in one strain of mice and haemangiosarcomas in the other. In one study in rats, an increase in the incidence of adrenal phaeochromocytomas was seen in male animals given the high dose.
A mortality study of workers in the manufacture of organic dyes with mixed exposures, including potential exposure to para-chloro-ortho-toluidine, showed a small, nonsignificant excess of cancers at all sites. Following two reported cases of bladder cancer among workers exposed before 1970 in the production and processing of para-chloro-ortho-toluidine, who were probably exposed to higher levels than in the previous study, a large excess of bladder carcinoma was found on further follow-up.
para-Chloro-ortho-toluidine caused bladder irritation and haematuria in men exposed occupationally. It formed DNA adducts in rats and mice and bound to haemoglobin in rats treated in vivo.
In a single study, para-chloro-ortho-toluidine did not induce heritable translocations in mice in vivo; in another study, it induced somatic specific locus mutations in mice in vivo. In single studies in rodent cells in culture, it caused DNA strand breaks, sister chromatid exchange and chromosomal aberrations. It was mutagenic to bacteria in one study in the presence of an exogenous metabolic system.
There is sufficient evidence for the carcinogenicity of para-chloro-ortho-toluidine hydrochloride in experimental animals.
There is limited evidence for the carcinogenicity of para-chloro-ortho-toluidine in humans.
In formulating the overall evaluation, the Working Group took note of the fact that any salt of para-chloro-ortho-toluidine with a strong acid can be expected to behave chemically in a manner similar to the hydrochloride salt in solution and in vivo.
para-Chloro-ortho-toluidine and its strong acid salts are probably carcinogenic to humans (Group 2A).
For definition of the italicized terms, see Preamble Evaluation.
Previous evaluations: Vol.: 16 (1978) (p. 277); Vol.: 30 (1983) (p. 65); Suppl. 7 (1987) (p. 60)
Subsequent evaluation: Vol. 77 (2000)
Last updated 01/20/98
See Also: Toxicological Abbreviations