For definition of Groups, see Preamble Evaluation.
VOL.: 63 (1995) (p. 223)
Chem. Abstr. Name: 1,2,3-Trichloropropane
5.1 Exposure data
1,2,3-Trichloropropane, a chlorinated solvent, has been produced commercially for use as a paint and varnish remover and as a cleaning and degreasing agent. Currently, it is used primarily as a chemical intermediate. It has been detected in water, including drinking-water, and in soil as a result of its presence as an impurity in a commercial nematocide.
5.2 Human carcinogenicity data
No data were available to the Working Group.
5.3 Animal carcinogenicity data
1,2,3-Trichloropropane was tested for carcinogenicity by oral administration in one experiment in mice and in one experiment in rats. It produced tumours of the oral mucosa and of the uterus in female mice and increased the incidences of tumours of the forestomach, liver and Harderian gland in mice of each sex. In rats, increased incidences of tumours were observed in the preputial gland, kidney and pancreas of males, in the clitoral gland and mammary gland of females and in the oral cavity and forestomach of both males and females.
The metabolite, 1,3-dichloroacetone, initiated skin tumour development in mice when applied topically.
5.4 Other relevant data
No data are available on the toxicokinetics of 1,2,3-trichloropropane in humans. It is rapidly absorbed and excreted after oral administration to rats and mice. Its metabolic products bind covalently to rat hepatic protein and DNA. The reactive and mutagenic metabolite, 1,3-dichloroacetone, was formed by hepatic metabolism in rat and human microsomes in vitro.
1,2,3-Trichloropropane causes tissue necrosis in a number of organs in rats and mice; the liver and kidney are the main target organs in the rat. In addition, myocardial and nasal epithelial damage is observed; in mice, hepatic and bronchiolar necrosis are seen.
There are no data on the effects of 1,2,3-trichloropropane on human reproduction. Studies performed in rats provided no evidence of alteration of fertility or of embryotoxic effects. In a two-generation study in mice, there was evidence of impairment of the female reproductive system.
In single studies, DNA binding and induction of DNA breaks, but not of dominant lethal mutations, were reported in rodents treated in vivo.
Gene mutation, sister chromatid exchange and chromosomal aberrations, but not DNA damage, were induced in rodent cells in vitro (all single studies, except for sister chromatid exchange). 1,2,3-Trichloropropane was mutagenic to bacteria.
There is inadequate evidence in humans for the carcinogenicity of 1,2,3-trichloropropane.
There is sufficient evidence in experimental animals for the carcinogenicity of 1,2,3-trichloropropane.
1,2,3-Trichloropropane is probably carcinogenic to humans (Group 2A).
In making the overall evaluation, the Working Group took into account the following evidence:
(i) 1,2,3-Trichloropropane causes tumours at multiple sites and at high incidence in mice and rats.
(ii) The metabolism of 1,2,3-trichloropropane is qualitatively similar in human and rodent microsomes.
(iii) 1,2,3-Trichloropropane is mutagenic to bacteria and to cultured mammalian cells and binds to DNA of animals treated in vivo.
For definition of the italicized terms, see Preamble Evaluation.
See Also: Toxicological Abbreviations Trichloropropane, 1,2,3- (CICADS 56, 2003)