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The toxicity and carcinogenicity of chlorinated paraffins containing C12 with 60% Cl, and C23 with 43% Cl, were assessed in prechronic and 2-year gavage studies using F344/N rats and B6C3F1 mice of both sexes. Single administrations of chlorinated paraffins were nonlethal in rats and mice, but repeated-dose and 2-year studies demonstrated toxic responses that differed with the paraffins. The C23,Cl43% paraffin produced a granulomatous inflammation in the liver of female rats in 13-week studies, while the C12,Cl60% paraffin caused deaths of rats and mice in 16-day studies and marked liver enlargement in 13-week studies. In 2-year studies, the C23,Cl43% paraffin caused hepatic and lymphatic granulomatous inflammation and hyperplasia in both sexes of rats, and was associated with marginal increases in adrenal medullary pheochromocytomas in female rats and hepatocellular neoplasms in female mice and with clear increases in malignant lymphomas in male mice. The C12,Cl60% paraffin caused marked liver enlargement in rats and increased the severity of nephropathy in male rats and the incidence of nephropathy in female rats. C12,Cl60% also caused hepatocellular neoplasms in both sexes of rats and mice: kidney tubular cell adenomas and adenocarcinomas in male rats, thyroid follicular cell neoplasms in female rats and female mice, and a marginal increase in mononuclear cell leukemia in male rats. Thus, the short-chain, heavily chlorinated paraffin appears to have a greater potential for chronic toxicity and carcinogenicity than the longer-chain, lightly chlorinated paraffin. Both paraffins have been reported to be nonmutagenic in bacteria. (National Toxicology Program (1986) Technical Report, NIH Publications 86-2561 and 86-2564).

Thirteen-week toxicity studies of the flame retardant 2,2-bis(bromomethyl)-1,3-propanediol (BMP; dibromoneopentyl glycol; FR-1138; CAS No. 329690-0) were conducted in male and female F344/N rats and B6C3F1 mice. The chemical was administered by oral gavage in corn oil 5 days per week for 13 weeks to rats at doses of 0, 50, 100, 200, 400, and 800 mg/kg and to mice at doses of 0, 25, 50, 100, 200, and 400 mg/kg, or in the feed for 13 weeks at concentrations of 0, 1250, 2500, 5000, 10,000, and 20,000 ppm for rats and at 0, 625, 1250, 2500, 5000, and 10,000 ppm for mice. There was a dose-related decrease in body weight gain in rats and mice after chemical administration. Mortality attributed to toxicity of BMP was seen in the gavage study in 2/10 high-dose (800 mg/kg) male rats and 3/10 high-dose (400 mg/kg) male mice no dose-related mortality occurred in the feed study. Minimal degeneration in the renal papilla was seen in male rats at 800 mg/kg in the gavage study and at doses of 5000 ppm or more in the feed study. This was also present in one female rat at the 20,000 ppm dose. In male mice renal papillary necrosis occurred at 400 mg/kg after dosing by the gavage route and at 2500, 5000, and 10,000 ppm in the dosed-feed study. In female mice papillary necrosis occurred only at the 10,000 ppm dose in the feed study. Tubular cell regeneration of the renal cortex was also present in mice at the same dose levels at which the papillary necrosis was observed. Transitional cell hypeplasia of the urinary bladder was seen in male rats at 400 and 800 mg/kg and in both sexes of mice at 200 and 400 mg/kg. Hyperplasia of the urinary bladder was also seen when BMP was administered in the feed at doses of 20,000 ppm to male rats; at doses of 2500, 5000, and 10,000 ppm to male mice; and at doses of 5000 and 10,000 ppm to female mice. The kidney and urinary bladder are target organs when BMP is administered by gavage or the dosed-feed route; mice were more sensitive than rats for the development of kidney and bladder lesions. Male rats and mice were more sensitive than females for the development of renal papillary degeneration or necrosis.

Propantheline bromide, a drug used for the treatment of peptic ulcers, was studied in male and female Fischer 344/N rats and B6C3F1 mice for subchronic toxicity. The drug was administered in the feed for 13 weeks at 0, 220, 670, 2000, 6000, and 24,000 ppm in both species. Propantheline bromide caused a decrease in weight gain at 24,000 ppm in male and female rats and at 6000 and 24,000 ppm in male and female mice. All rats survived the treatment. The top dose of 24,000 ppm was fatal to mice. Clinical signs of toxicity (dilated pupils and decreased gastrointestinal emptying), similar to the atropine-like effects of propantheline bromide in man, were seen in male and female rats at 24,000 ppm. Hyperplasia of the transitional epithelium of the urinary bladder was seen in high-dose male rats at the end of 13 weeks.