On the maternal transfer of 4-aminobiphenyl in rats

The potential for 4-aminobiphenyl (4-ABP) to be transferred from circulating blood into the milk of lactating Sprague-Dawley rats was determined. The distribution of 14C-labeled 4-ABP into milk was examined at time intervals of less than 1, 20, 60, 120, 240 and 480 min after i.v. dose administration. Elimination of radioactivity from blood and milk was determined to be biphasic. The levels of 4-ABP and/or metabolites were lower in milk than in blood at all time points examined. The levels of radioactivity detected in blood declined less rapidly than in milk. That is, the percent of the dose per ml of blood declined from 0.81-0.45, while the percent of the dose per ml of milk declined from 0.38-0.06 during the 8 h time period. The radioactivity present in milk was partially extractable with ethyl acetate with 43% of the radioactivity being extractable at the earliest time point while only 16% was extractable after 8 h. The level of radioactivity associated with the protein precipitate of the milk samples increased from 4-21% within 4 h after treatment. The potential of 4-ABP or its metabolites to exert a genotoxic effect on newborn pups via maternal transfer was also examined. Dams were treated on day 1 post partum and then daily with 4-ABP (10 mg/kg) in corn oil or corn oil alone for 2 weeks. Each experimental group had four liters of pups each containing 5 pups. Pups were sacrificed at 15 days of age, separated by sex and the levels of 4-ABP:DNA adducts in liver determined using 32P-postlabeling. DNA adduct profiles were similar between male and female pups with total adduct levels of 332 and 338 fmol of adducts/mg of DNA, respectively. These results indicate that the genotoxic effects of 4-ABP can be transmitted from exposed dams to the nursing offspring.