Couture L A, Harris M W, Birnbaum L S
Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Fundam Appl Toxicol. 1989 Feb;12(2):358-66. doi: 10.1016/0272-0590(89)90052-3.
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.
在器官形成期，将Fischer 344大鼠急性暴露于2,3,4,7,8 - 五氯二苯并呋喃（4 - PeCDF），以评估其致畸和胚胎致死效应诱导剂的潜力。所有母鼠在妊娠第8、10或12天通过灌胃给予0、30、100或300微克4 - PeCDF/千克体重的单剂量。在妊娠第12天还包括一个额外的治疗组，给予10微克4 - PeCDF/千克体重口服。所有动物在妊娠第20天处死，并评估母体和胎儿毒性。胚胎毒性的测定涉及软组织和骨骼检查。4 - PeCDF在妊娠第8天和第10天治疗后导致校正后的母体体重增加呈剂量相关下降，同时肝/体重比增加，在所有3天暴露中，30微克/千克时首次明显。与对照组相比，母体胸腺重量相对于体重下降。在所有3天暴露中，300微克/千克时观察到的高死亡率（大于80%）表明胚胎 - 胎儿毒性明显。平均胎儿体重是胎儿毒性的敏感指标，在妊娠第8、10或12天治疗后，30、100和300微克/千克时与对照组相比下降。在所有3天暴露中，300微克/千克剂量下，4 - PeCDF在存活者中诱导腭裂。总之，无论暴露的妊娠天数如何，4 - PeCDF对母体和胎儿均有毒性，但仅在观察到明显母体和胎儿毒性的剂量下诱导畸形，这与先前在小鼠中的报道研究相反，在小鼠中，在非胎儿毒性剂量水平观察到致畸效应。因此，小鼠可能是评估暴露于结构相关的多卤代芳烃（包括二恶英、呋喃、联苯和萘）后产前诱导的特定毒性反应的更敏感模型。
