The objective of this study is to improve our ability to characterize the toxicity of drugs and chemicals to neonates relative to adults, and to explore the role of lactation in the induction of neonatal toxicity. Lactation is evaluated a a source of exposure to chemicals secreted into the milk and as the nutritional source for the newborn. A study was completed in which the toxicity of di(2-ethylhexyl) phthalate (DEHP) was examined in suckling and adult rats of different ages. Hepatic peroxisome proliferation, hypolipidemia, and histological testicular damage were determined as indices of toxicity. Administration of DEHP to lactating rats caused increases in hepatic peroxisomal enzyme activities in the dams and in the suckling pups indicating the transfer of DEHP or its metabolites through the milk. A gas chromatography method was developed to analyze DEHP and its metabolite, mono(2-ethylhexyl) phthalate (MEHP), in rat plasma and milk, and these methods will be used to determine the amount of DEHP and MEHP transferred through the milk of lactating rats. Another study was begun in which neontal rats were exposed to DEHP, and testicular morphology was examined after a 4 week recovery period. A study is underway to determine the extent of intestinal hydrolysis of DEHP in neonatal and adult rats and its role in the age-related differences in toxicity of DEHP.
