Developmental Toxicity of 2,3,4,7,8-Pentachlorodibenzofuran in the Fischer 344 Flat

Developmental Toxicity of 2,3,4,7,8-Pentachlordibenzofuran inthe Fischer 344 Rat. COUTURE, L. A,, HARRIS, M. W., AND BIRNBAUM,L. S. (1989). Fundam Appl Toxicol 12, 358–366. Fischer344 rats were exposed acutely to 2,3,4,7,8-pentachlordibenzofuran(4-PeCDF) during the organogenic period to evaluate its potentialas an inducer of teratogenic and embryolethal effects. All damswere treated by gavage with a single dose of 0, 30, 100, or300 µg 4- PeCDF/kg body wt on gestation Day (gd) 8, 10,or 12. An additional treatment group was included on gd 12 andadministered 10µg 4-PeCDF/kg body wt po. All animals werekilled on gd 20 and maternal and fetal toxicities were assessed.Determination of embryotoxicity involved both soft tissue andskeletal examinations. 4-PeCDF induced a dose-related decreasein corrected maternal weight gain following treatment on gd8 and 10, as well as resulted in a concomitant Increase in theliver/body weight ratios, first evident at 30 µg/kg forall 3 days of exposure. The maternal thymus weight decreasedrelative to body weight compared with those of controls. Embryo-fetaltoxicity was evident from the high mortality (>80%) observedat 300 µg/kg for all 3 days of exposure. Mean fetal weight,a sensitive indicator of fetal toxicity, decreased comparedto that of controls at 30, 100, and 300 µg/kg followingtreatment on either gd 8, 10, or 12. 4- PeCDF induced cleftpalate in survivors at a dose of 300 µg/kg for all 3 daysof exposure. In conclusion, 4-PeCDF is maternally and fetallytoxic regardless of the gestation day of exposure, but inducedterata only at doses where overt maternal and fetal toxicitywere observed, in contrast to previously reported studies inthe mice where teratogenic effects were observed at nonfetotoxicdose levels. Thus, the mouse may be a more sensitive model forevaluating specific toxic responses induced prenatally followingexposure to the structurally related polyhalogenated aromatichydrocarbons which include the dioxins, furans, biphenyls, andnaphthalenes.