SUBCHRONIC TOXICITY OF INGESTED 1,3-DICHLOROPROPENE IN RATS AND MICE

Male and female Fischer 344 rats and B6C3F1 mice (10/sex/dose group) w ere given 0, 5, 15, 50, or 100 mg/kg/day (rats) or 0, 15, 50, 100, or 175 (mice) mg/kg/day racemic 1,3-dichloropropene (1,3-D), respectively , via their diets for 13 weeks. Satellite groups of rats (recovery = 1 0 rats/sex/group) ingesting 0 or 100 mg/kg/day 1,3-D were provided con trol feed for an additional 4 weeks to examine recovery. The test mate rial was stabilized in the feed by microencapsulation in a starch/sucr ose matrix (80/20). The body weights of male and female rats ingesting greater than or equal to 5 and greater than or equal to 15 mg/kg/day, respectively, and of all treatment groups of mice were decreased rela tive to controls. The terminal body weights of high dose group rats an d mice were decreased approximately 13-16%. A number of changes in ser um biochemical parameters and decreases in organ weights accompanied t he depressed body weights of these animals. Histologically, the only t reatment-related change observed was a slight degree of basal cell hyp erplasia and hyperkeratosis in the nonglandular portion of the stomach s of a majority of male and female rats ingesting greater than or equa l to 15 mg/kg/day. After the 4-week recovery period, most treatment-re lated changes were noted to be reversible in nature. No treatment-rela ted histopathological changes were observed in the tissues of Created mice. Based upon relatively slight depressions in body weights at the lowest dosages tested, the no-observed-adverse-effect levels for male rats and both sexes of mice were determined to be 5 mg/kg/day and 15 m g/kg/day, respectively. A no-observed-effect level of 5 mg/kg/day was established for female rats. (C) 1996 Society of Toxicology