Developmental toxicity of 2,3,4,7,8-pentachlorodibenzofuran in the Fischer 344 rat

Fischer 344 rats were exposed acutely to 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF) during the organogenic period to evaluate its potential as an inducer of teratogenic and embryolethal effects. All dams were treated by gavage with a single dose of 0, 30, 100, or 300 micrograms 4-PeCDF/kg body wt on gestation Day (gd) 8, 10, or 12. An additional treatment group was included on gd 12 and administered 10 micrograms 4-PeCDF/kg body wt po. All animals were killed on gd 20 and maternal and fetal toxicities were assessed. Determination of embryotoxicity involved both soft tissue and skeletal examinations. 4-PeCDF induced a dose-related decrease in corrected maternal weight gain following treatment on gd 8 and 10, as well as resulted in a concomitant increase in the liver/body weight ratios, first evident at 30 micrograms/kg for all 3 days of exposure. The maternal thymus weight decreased relative to body weight compared with those of controls. Embryo-fetal toxicity was evident from the high mortality (greater than 80%) observed at 300 micrograms/kg for all 3 days of exposure. Mean fetal weight, a sensitive indicator of fetal toxicity, decreased compared to that of controls at 30, 100, and 300 micrograms/kg following treatment on either gd 8, 10, or 12.4-PeCDF induced cleft palate in survivors at a dose of 300 micrograms/kg for all 3 days of exposure. In conclusion, 4-PeCDF is maternally and fetally toxic regardless of the gestation day of exposure, but induced terata only at doses where overt maternal and fetal toxicity were observed, in contrast to previously reported studies in the mice where teratogenic effects were observed at nonfetotoxic dose levels. Thus, the mouse may be a more sensitive model for evaluating specific toxic responses induced prenatally following exposure to the structurally related polyhalogenated aromatic hydrocarbons which include the dioxins, furans, biphenyls, and naphthalenes.