Chronic toxicity and oncogenicity studies of ingested 1, 3-dichloropropene in rats and mice.

Fischer 344 rats and B6C3F1 mice were administered 1, 3-dichloropropene (1,3-D) via their diets for up to 2 years, at dose levels of 0, 2.5, 12.5, or 25 mg 1,3-D/kg body wt/day for rats and 0, 2.5, 25, or 50 mg 1,3-D/kg body wt/day for mice. The test material was stabilized in the feed by microencapsulation in a starch/sucrose matrix (80/20%). Rats given 12.5 or 25 mg/kg/day, and mice given 25 or 50 mg/kg/day, had decreased body weights and body weight gains. There were no effects on survival or clinical pathology parameters for rats or mice. Histopathologic effects attributed to treatment in rats consisted of basal cell hyperplasia of the nonglandular mucosa of the stomach in males and females given 12.5 or 25 mg/kg/day for 12 and 24 months and an increased number of hepatocellular adenomas in males given 12.5 or 25 mg/kg/day and females given 25 mg/kg/day for 24 months. The increase in hepatocellular adenomas was statistically identified by pairwise comparison only in males given 25 mg/kg/day. An increased incidence of eosinophilic foci of altered cells in the liver was also noted in all treated groups of rats at 24 months. The latter observation, however, was considered of equivocal toxicological significance because of the common spontaneous occurrence of liver foci in aged Fischer 344 rats. The only histologic change attributed to treatment in mice was decreased size of hepatocytes in males given 50 mg/kg/day for 12 months. The decreased size of hepatocytes was consistent with decreased cytoplasmic glycogen content and corresponded to decreased liver weights. This effect was not present at 24 months. There was no oncogenic response observed in mice. The low-dose level of 2.5 mg/kg/day was interpreted as the no-observed-adverse-effect level (NOAEL) for systemic chronic toxicity of 1,3-D in the Fischer 344 rat. The no-observed-effect level (NOEL) for chronic systemic toxicity was 2.5 mg/kg/day in the B6C3F1 mouse.

Chronic dietary toxicity/oncogenicity studies on 2,4-dichlorophenoxyacetic acid in rodents.

Forms of 2,4-dichlorophenoxyacetic acid (collectively known as 2,4-D) are herbicides used to control a wide variety of broadleaf and woody plants. Doses in the 2-year chronic/oncogenicity rat study were 0, 5, 75, and 150 mg/kg/day. The chronic toxicity paralleled subchronic findings, and a NOEL of 5 mg/kg/day was established. A slight increase in astrocytomas observed (in males only) at 45 mg/kg/day in a previously conducted chronic rat study was not confirmed in the present study at the high dose of 150 mg/kg/ day. Doses in the 2-year mouse oncogenicity studies were 0, 5, 150, and 300 mg/kg/day for females and 0, 5, 62.5, and 125 mg/ kg/day for males. No oncogenic effect was noted in the study. In summary, the findings of these studies indicate low chronic toxicity of 2,4-D and the lack of oncogenic response to 2,4-D following chronic dietary exposure of 2,4-D in the rat and mouse.

Teratological evaluation of picloram potassium salt in rabbits.

The embryotoxic and teratogenic potential of orally administered picloram potassium salt was evaluated in New Zealand white rabbits. Artificially inseminated rabbits were given 0, 40, 200 or 400 mg picloram acid equivalent/kg body weight/day in the form of picloram potassium salt in aqueous solution on days 6 to 18 of gestation. The foetuses were removed for examination on day 29 of gestation. Transient weight loss was observed among rabbits given 200 or 400 mg/kg/day of the test material, though the total weight gain of the treated groups during gestation was comparable to that of controls. A few isolated, sporadic cases of foetal malformations were observed in the dosed groups, but there was no indication of a dose-related embryotoxic or teratogenic response to treatment.