PRENATAL OR POSTNATAL EXPOSURE TO BIS(TRI-NORMAL-BUTYLTIN)OXIDE IN THE RAT - POSTNATAL EVALUATION OF TERATOLOGY AND BEHAVIOR
PRENATAL OR POSTNATAL EXPOSURE TO BIS(TRI-NORMAL-BUTYLTIN)OXIDE IN THE RAT - POSTNATAL EVALUATION OF TERATOLOGY AND BEHAVIOR
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DOI：
10.1016/0041-008x(89)90060-4
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发表时间：
1989-01-01
影响因子：
3.8
通讯作者：
REITER, LW
中科院分区：
文献类型：
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作者：
CROFTON, KM;DEAN, KF;REITER, LW
本文介绍了一系列筛选试验的结果，以确定大鼠发育暴露于TBTO的潜在致畸性和神经毒性。对于产前暴露，怀孕的Long Evans大鼠在妊娠第6天至第20天（GD 6-20）插管0-16 mg/kg/天氧化三丁基锡TBTO。对于出生后暴露，大鼠幼仔在出生后第5天（PND 5）插管0-60 mg/kg TBTO。在产前暴露后，允许母鼠产仔，并使用产后畸形筛查对幼崽进行评估。两种暴露的产后评估包括运动活动（PND 13-64）、声惊吓反应（PND 22-78）、生长和脑重量。妊娠大鼠的最大耐受剂量（MTD）为5 mg/kg/d，为未妊娠大鼠MTD的三分之一。在所需剂量下，活产数量减少，生长和生存能力下降。10毫克/公斤/天。12 mg/kg/d组腭裂发生率为3%。出生后暴露于60mg /kg和所有产前剂量后均有死亡。10毫克/公斤/天。所有产后剂量均显著降低断奶前体重，所有产前剂量均低于2.5 mg/kg/天。只有高剂量组（10 mg/kg/天和60 mg/kg）的体重下降持续到断奶后。行为评估显示运动活动发展（仅产前暴露）和声惊吓反应（仅产后暴露）的短暂改变。只有在产生明显的母体毒性和/或产后死亡的剂量下，才观察到持续的行为效应。TBTO对大鼠的致畸和神经毒性潜力的证明与相关的母鼠毒性和/或幼鼠死亡率相混淆。
The results of a series of screening tests to determine the potential teratogenicity and neurotoxicity of development exposure to TBTO in rats are presented in this paper. For prenatal exposure, pregnant Long Evans rats were intubated with 0-16 mg/kg/day bis(tri-n-butyltin)oxide TBTO from Days 6 to 20 of gestation (GD 6-20). For postnatal exposure, rat pups were intubated with 0-60 mg/kg TBTO on Postnatal Day 5 (PND 5). Following prenatal exposure, dams were allowed to litter and pups were evaluated using a postnatal teratology screen. Postnatal evaluation for both exposures included motor activity (PND 13-64), the acoustic startle response (PND 22-78), growth, and brain weight. The maximally tolerated dose (MTD) in pregnant rats was 5 mg/kg/day, which is one-third the MTD in nonpregnant rats. There were decreased numbers of live births, and decreased growth and viability at dosages .gtoreq.10 mg/kg/day. Cleft palate was found in 3% of the 12 mg/kg/day group. There was mortality following postnatal exposure to 60 mg/kg and all prenatal dosages .gtoreq. 10 mg/kg/day. Preweaning body weight was significantly decreased for all postnatal dosages, and all prenatal dosages > 2.5 mg/kg/day. Body weight reductions persisted to the postweaning period only in the high dose groups (10 mg/kg/day and 60 mg/kg). Behavioral evaluation demonstrated transient alterations in motor activity development (prenatal exposure only) and the acoustic startle response (postnatal exposure only). Persistent behavioral effects were observed only at dosages that produced overt maternal toxicity and/or postnatal mortality. The demonstration of the teratogenic and neurotoxic potential of TBTO in rats is confounded by associated maternal toxicity and/or pup mortality.