VOL.: 73 (1999) (p. 183)
CAS No.: 1897-45-6
Chem. Abstr. Name: 2,4,5,6-Tetrachloro-1,3-benzenedicarbonitrile
Exposure to chlorothalonil may occur during its production and during its application as a fungicide, bactericide and nematocide. It has been detected in some foods.
5.2 Human carcinogenicity data
No data were available to the Working Group.
5.3 Animal carcinogenicity data
Chlorothalonil was tested by oral administration in the diet in three experiments in mice and three experiments in rats. It produced renal tubular tumours (adenomas and carcinomas) in males of each species and in female rats. The incidences of forestomach papillomas and carcinomas were increased in males and females of each species.
5.4 Other relevant data
Chlorothalonil is metabolized in rats by conjugation to glutathione in the gastrointestinal tract and liver. After biliary excretion, uptake and metabolism of these conjugates in the kidney by the action of g -glutamyl transpeptidase and cysteine–conjugate b -lyase results in the production of di- and tri-thiols, which are thought to be responsible for the toxicity seen in the kidney. Sustained cytotoxicity and the resultant regenerative response in the kidney are found in conjunction with tumour formation after long-term exposure.
There may be less activity of g -glutamyl transpeptidase and cysteine–conjugate b -lyase in humans than in rats.
Forestomach tumours produced by chlorothalonil were associated with squamous hyperplasia and local irritation.
No data were available on reproductive or developmental effects.
No data were available on the genetic and related effects of chlorothalonil in humans or in rodents in vivo. In one study, 8-oxydeoxyguanosine products were observed in the livers of mice exposed in vivo. There is some evidence for genotoxicity in mammalian cells in vitro. Chlorothalonil was not mutagenic to bacteria.
There is inadequate evidence in humans for the carcinogenicity of chlorothalonil.
There is sufficient evidence in experimental animals for the carcinogenicity of chlorothalonil.
Chlorothalonil is possibly carcinogenic to humans (Group 2B).For definition of the italicized terms, see Preamble Evaluation.
Previous evaluations: Vol. 30 (1983); Suppl. 7 (1987) (p. 60)