The NTP has issued the final version of its technical report on the toxicology of o-chloropyridine, a chemical intermediate in drug and agrochemical manufacturing, following 2 weeks’ dermal exposure or 3 months’ oral administration to rats and mice.

In the dermal studies, o-chloropyridine was applied to the skin of rodents (5/sex/species/group) at doses equivalent to 0, 6.25, 12.5, 25, 50 or 100 mg/kg bw/day, 5 days/week (12 exposure days) in a 16-day period. There were no deaths, nor any effect on mean group body weights. Liver weights of male rats in the two highest-dose groups were significantly greater than the controls; no gross or microscopic lesions (in any tested animals) were considered to be treatment-related.

o-Chloropyridine was supplied to rodents (10/sex/species/group) in drinking water for 14 weeks, at concentrations of 0, 10, 30, 100, 300 or 1000 ppm. All tested animals survived to the end of the study. Body weights of both rats and mice in the high-dose groups were significantly reduced compared to controls. There were treatment-related changes to organ weights and lesions in male and female rats and mice, with the kidney, spleen, bone marrow and liver identified as the primary target tissues. The lowest-observed-effect level (LOEL) was established at 10 ppm (1 mg/kg bw/day) on the basis of increased absolute and relative kidney weights in male rats, although there were no concomitant histopathological changes. The same LOEL was established in female rats, on the basis of effects in the spleen and

bone marrow. Male mice in all treatment groups had significantly higher absolute and relative liver weights; the LOEL was 10 ppm (1.5 mg/kg bw/day). This effect was also observed in female mice at higher concentrations (LOEL 300 ppm; about 38 mg/kg bw/day). o-Chloropyridine did not increase the frequency of micronucleated erythrocytes in blood samples taken from tested animals at the end of the exposure period.

US National Toxicology Program (2017). Technical report on the toxicity studies of o-chloropyridine (CAS No. 109-09-1) administered dermally and in drinking water to F344/N rats and B6C3F1/N mice. NTP TOX-83. February 2017. https://ntp.niehs.nih.gov/ntp/htdocs/st_rpts/tox83_508.pdf

 

The above items were taken from the April 2017 issue of Toxicology and Regulatory News which is sent automatically to members of bibra (click here)

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