Breslin W J, Kirk H D, Johnson K A
Mammalian and Environmental Toxicology Research Laboratory, Dow Chemical Company, Midland, Michigan 48674.
Fundam Appl Toxicol. 1988 May;10(4):736-43. doi: 10.1016/0272-0590(88)90200-x.
Diglycidyl ether of bisphenol A (DGEBPA) was tested for its potential to cause embryo/fetal toxicity and teratogenicity in pregnant rabbits. DGEBPA was applied daily to the clipped skin of New Zealand White rabbits for approximately 6 hr/day at dose levels of 0 (polyethylene glycol 400, vehicle control), 30, 100, or 300 mg/kg body weight/day on Days 6 through 18 of gestation. Fetuses were examined for external, visceral, and skeletal alterations on Day 28 of gestation. Maternal toxicity was observed among pregnant rabbits in the 300 mg/kg/day dose group as evidenced by moderate to severe erythema, fissures, hemorrhage, and slight edema at the exposure site. Similar, but less severe skin lesions were observed in pregnant rabbits in the 100 mg/kg/day exposure group. A slight erythema at the site of application was observed in dams in the 30 mg/kg/day dose group. The erythema in rabbits from the low dose group was indistinguishable from the erythema caused by the occlusive bandages/jackets used to hold the test material in place and, thus, was not considered toxicologically significant. No evidence of embryo/fetal toxicity or teratogenicity was observed at any dose level. Thus, the embryo/fetal no-observed-effect level for dermally applied DGEBPA was 300 mg/kg body weight/day, the maximum tolerated dose.
对双酚A二缩水甘油醚（DGEBPA）在孕兔中引起胚胎/胎儿毒性和致畸性的可能性进行了测试。在妊娠第6天至18天，将DGEBPA每天涂于新西兰白兔剃毛的皮肤上，每天约6小时，剂量水平为0（聚乙二醇400，溶剂对照）、30、100或300毫克/千克体重/天。在妊娠第28天检查胎儿的外部、内脏和骨骼变化。在300毫克/千克/天剂量组的孕兔中观察到母体毒性，表现为暴露部位出现中度至重度红斑、皲裂、出血和轻微水肿。在100毫克/千克/天暴露组的孕兔中观察到类似但较轻的皮肤损伤。在30毫克/千克/天剂量组的母兔中，在涂抹部位观察到轻微红斑。低剂量组兔子的红斑与用于固定测试材料的封闭绷带/夹克引起的红斑无法区分，因此，在毒理学上不被认为具有显著性。在任何剂量水平下均未观察到胚胎/胎儿毒性或致畸性的证据。因此，经皮应用DGEBPA的胚胎/胎儿未观察到影响水平为300毫克/千克体重/天，即最大耐受剂量。
