Studies were conducted to characterize the toxicity of drugs and chemicals to neonates relative to adults, and to evaluate the role of lactation in the induction of neonatal toxicity. The effects of chemicals on the quality and quantity of milk produced were determined, and the chemical species excreted into the milk were identified and quantitated. A study was completed in which the concentrations of di-(2-ethylhexyl) phthalate (DEHP) and its monoester metabolite, mono-2-ethylhexyl phthalate (MEHP), were determined in the milk and plasma of lactating rats after oral doses of DEHP to the dams. High levels of DEHP and lower, but significant, levels of MEHP were present in the milk of DEHP- treated dams. Increases in peroxisomal enzyme activities were observed in the pups suckling the DEHP-treated dams. Milk composition and mammary gland nucleic acid content (DNA and RNA) were also affected by DEHP treatment. In another study, neonatal male rats were treated for one week with DEHP and the fertility and testicular parameters in the rats was assessed in mating trials after different periods of recovery. The concentrations of the H2-receptor antagonist, cimetidine, in the milk and plasma of lactating rats was determined and the effect of maternal dosing with cimetidine during lactation on the activity of a microsomal monooxygenase in the pups was evaluated.
