Baroncelli S, Karrer D, Turillazzi P G
Toxicology and Behavior Unit, Istituto Superiore di Sanità, Rome, Italy.
J Toxicol Environ Health. 1995 Nov;46(3):355-67. doi: 10.1080/15287399509532041.
Pregnant Swiss mice were treated with 0, 5, 10, 20, and 30 mg/kg body weight of bis(tri-n-butyltin) oxide (TBTO) on d 6-15 of gestation. At birth litters were normalized to eight pups, and postnatal evaluation of pup growth rate and behavioral observations of dams were carried out. Litters were sacrificed on postnatal days (pnd) 7, 14, and 21, to perform hematological analysis, in connection with another study. Dam weight gain was impaired in all the treated groups (except at the lowest dose level) in the late phase of gestation. A high incidence of anticipated or delayed parturitions, without any correlation with fetal mass, was observed in the treated groups. All the treated dams showed a significant increase in resorptions, and a decrease in body weight gain between gestational day (gd) 6 and pnd 1. At birth, only the 20 and 30 mg/kg dose groups showed reduced litter size and reduced pup weight. Body weight gain reduction of pups persisted in wk 1 of life only in the 10 and 20 mg/kg dose groups. In addition, the maternal weight trend was affected during the lactation period in the higher dose groups. Postnatal death rate and growth rate of treated pups were affected by an altered maternal behavior; pups, apparently viable and with normal weight, were found often scattered throughout the cage with signs of wounds, and the percentage of dams that had not built a nest increased in the 10, 20, and 30 mg/kg dose groups. Total absence of parental care was noted in many litters, and many infanticidal events were reported. Our results seem to confirm low TBTO embryofetotoxicity, and strongly support the assumption that TBTO's toxicity to the mother is much stronger than its embryo-fetotoxic potential. Most of the reproductive parameters examined in this study were unaffected in the low-dose group, while some indices, such as gestation length and maternal weight gain between gd 6 and pnd 1, were markedly altered also at the 5 mg/kg dose level and appear to be sensitive parameters in assessing maternal toxicity.
妊娠瑞士小鼠在妊娠第6至15天接受0、5、10、20和30毫克/千克体重的双（三正丁基锡）氧化物（TBTO）处理。出生时将窝仔标准化为8只幼崽，并对幼崽生长速率进行产后评估，同时对母鼠进行行为观察。在产后第7、14和21天处死窝仔，以便结合另一项研究进行血液学分析。在妊娠后期，所有处理组（最低剂量组除外）的母鼠体重增加均受到损害。在处理组中观察到预期或延迟分娩的发生率很高，且与胎儿体重无任何关联。所有处理的母鼠在妊娠第6天至产后第1天之间的吸收显著增加，体重增加减少。出生时，只有20和30毫克/千克剂量组的窝仔数减少且幼崽体重减轻。仅在10和20毫克/千克剂量组中，幼崽体重增加减少在出生后第1周持续存在。此外，较高剂量组在哺乳期母鼠体重趋势受到影响。处理组幼崽的产后死亡率和生长速率受到母性行为改变的影响；经常发现明显存活且体重正常的幼崽散落在笼中并有伤口迹象，在10、20和30毫克/千克剂量组中未筑巢的母鼠百分比增加。在许多窝仔中发现完全没有亲代照料，并且报告了许多杀婴事件。我们的结果似乎证实了TBTO的低胚胎胎儿毒性，并有力地支持了以下假设，即TBTO对母体的毒性远强于其胚胎胎儿毒性潜力。本研究中检查的大多数生殖参数在低剂量组中未受影响，而一些指标，如妊娠长度和妊娠第6天至产后第1天之间的母鼠体重增加，在5毫克/千克剂量水平时也有明显改变，似乎是评估母体毒性的敏感参数。
