Bioassay of Chlorothalonil for Possible Carcinogenicity
(CAS No. 1897-45-6)
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Chemical Formula: C8Cl4N2
Chlorothalonil is a broad-spectrum fungicide which has been in use in the United States since 1963. It is registered for foliar and root applications on vegetables, fruits, green house plants, and turf, and as a seed treatment for cotton. Chlorothalonil is also used in formulating paints and stains for mildew resistance.
A bioassay of technical-grade chlorothalonil for possible carcinogenicity was conducted by administering the test chemical in the diet to Osborne-Mendel rats and B6C3F1 mice.
Groups of 50 rats of each sex were administered chlorothalonil at one of two doses for 80 weeks, then observed for 30-31 weeks. Time-weighted average doses for both males and females were 5,063 or 10,126 ppm. Matched controls consisted of groups of 10 untreated rats of each sex; pooled controls consisted of the matched-control groups combined with 55 untreated male or female rats from similar bioassays of five other test chemicals. All surviving rats were killed at 110-111 weeks.
Groups of 50 mice of each sex were administered chlorothalonil at one of two doses for 80 weeks, then observed for 11-12 weeks. Time-weighted average doses for males were 2,688 or 5,375 ppm, and for females, 3,000 or 6,000 ppm. Matched controls consisted of groups of 10 untreated mice of each sex; pooled controls consisted of the matched-control groups combined with 50 untreated male or female mice from similar bioassays of five other test chemicals. All surviving mice were killed at 91-92 weeks.
Clinical signs that appeared with increasing frequency in dosed rats included hematuria and, from week 72 until termination of the study, bright-yellow urine. Since the dosed female mice did not have depression in mean body weights or decreased survival compared with the controls, they may have been able to tolerate a higher dose.
In rats, adenomas and carcinomas of the renal tubular epithelium occurred with a significant dose-related trend in both the males (P=0.030) and the females (P=0.007). These neoplasms also occurred at a higher incidence in the high-dose males (P=0.035) and the high-dose females (P=0.016) than in the corresponding controls (males: pooled controls 0/62, low-dose 3/46, high-dose 4/49; females: pooled controls 0/62, low-dose 1/48, high-dose 5/50). These tumors included both adenomas and carcinomas which are considered to be histogenically related. Thus these findings are interpreted as sufficient evidence for the carcinogenicity of chlorothalonil.
In mice, no tumors were found to occur at a greater incidence among dosed animals than among controls.
It is concluded that under the conditions of this bioassay, technical-grade chlorothalonil was carcinogenic to Osborne-Mendel rats, producing tumors of the kidney. Chlorothalonil was not carcinogenic for B6C3F1 mice.
Report Date: 1978