ASSESSMENT OF THE DEVELOPMENTAL TOXICITY AND PLACENTAL-TRANSFER OF 1,2-DICHLOROETHANE IN RATS

This study evaluates the developmental toxicity and placental transfer of 1,2-dichloroethane (DCE) in rats. Sprague-Dawley rats were given 0 -2.4 mmol DCE kg(-1) day(-1) by gavage, or were exposed for 6 hr per d ay to 0-300 ppm DCE by inhalation, from Day 6 to 20 of gestation. Mate rnal toxicity was observed after inhalation exposure to 300 ppm DCE an d oral administration of 2.0 or 2.4 mmol DCE kg(-1). There was no evid ence of altered growth nor teratogenic effects after either inhalation or oral administration of DCE at any concentration tested. The time c ourse disposition of C-14 was examined over a 48-hr period in 12- and 18-day pregnant rats after a single oral dose of 1.6 mmol [C-14]DCE kg (-1). Peak concentrations of radiocarbon occurred between 2 and 4 hr p ostdose. Conceptus (Day 12) and fetal (Day 18) tissues accounted for 0 .06 and 0.4% of the administered dose, respectively. Up to 4 hr, level s of radiocarbon in placenta and fetus were slightly less than in mate rnal plasma of 18-day pregnant rats and were two to five times higher at later periods. At 2 hr, unchanged DCE accounted for most of radioac tivity (78-86%) recovered in maternal plasma, placenta, and fetus. Aci dic metabolites and radioactivity bound to macromolecules increased up to 24 hr (0.01 mu mol-eq DCE g(-1)) in either placental or fetal tiss ues. Thereafter, their levels declined more slowly than those in the m aternal plasma. Results from this developmental toxicity study in rats confirm embryonic exposure to radiocarbon associated with [C-14]DCE a nd/or its metabolites and has demonstrated the lack of observable tera togenic effects. (C) 1995 Society of Toxicology