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首页> 外文期刊>The Journal of toxicological sciences >Susceptibility of newborn rats to hepatotoxicity of 1,3-dibromopropane and 1,1,2,2-tetrabromoethane, compared with young rats.
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Susceptibility of newborn rats to hepatotoxicity of 1,3-dibromopropane and 1,1,2,2-tetrabromoethane, compared with young rats.

机译：与新生大鼠相比，新生大鼠对1,3-二溴丙烷和1,1,2,2-四溴乙烷的肝毒性的敏感性。

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Newborn rat studies were conducted with oral administration of 1,3-dibromopropane (DBP) and 1,1,2,2-tetrabromoethane (TBE) from postnatal Days 4 to 21 to allow comparison of NOAELs and unequivocally toxic levels with those from 28-day young rat studies starting at 5-6 weeks of age. The unequivocally toxic level was estimated by our specified criteria, requiring simultaneous change of organ weights, histopathology, some biochemical parameters and body weights, because in this study only hypertrophy of hepatocytes was observed as a major histopathological change. DBP caused centrilobular hypertrophy of hepatocytes with alteration in biochemical parameters, as well as lowering of body weights, regardless of sex, in both newborn and young rats. NOAELs and unequivocally toxic levels were considered to be 50 and 150 mg/kg/day in newborn rats and 10 and 250 mg/kg/day in young rats, respectively. In the newborn rat study of TBE, some hepatic effects observed at the top dose of 50 mg/kg were not considered adverse because of the lack of histopathological changes. Significant lowering of body weight was noted at 200 mg/kg in the dose-finding study but histopathological data were not available. In the young rat study, there was no definite toxicity at 6 mg/kg and hypertrophic changes in liver and thyroids without body weight change occurred at 200 mg/kg. There were no clear sex differences in both the newborn and young rat studies. NOAELs were considered to be 50 and 6 mg/kg/day in newborn and young rats, respectively, but unequivocally toxic levels for both rats could not be estimated. Abnormalities of external and sexual development and reflex ontogeny in the newborn were not observed with either chemical. Based on these results, it can be concluded that the target organ of DBP and TBE is the liver in both newborn and young rats, and that while the doses at which toxic signs began to appear are higher in newborn rats, those causing clear toxicity may be paradoxically lower in the newborn case.
机译：从出生后的第4天到第21天，通过口服1,3-二溴丙烷（DBP）和1,1,2,2-四溴乙烷（TBE）进行新生大鼠研究，以比较NOAEL和明确的毒性水平与28-从5-6周龄开始的全天幼鼠研究。明确的毒性水平是根据我们指定的标准估算的，需要同时改变器官重量，组织病理学，一些生化参数和体重，因为在这项研究中，仅肝细胞肥大被视为主要的组织病理学变化。 DBP在新生大鼠和幼年大鼠中均引起肝细胞小叶肥大，其生化参数发生改变，并且体重降低，无论性别如何。在新生大鼠中，NOAEL和明确的毒性水平分别为50和150 mg / kg /天，在年轻大鼠中，分别为10和250 mg / kg /天。在TBE新生大鼠研究中，由于缺乏组织病理学改变，在最高剂量50 mg / kg时观察到的某些肝功能不被视为不良反应。在剂量寻找研究中发现体重显着降低至200 mg / kg，但尚无组织病理学数据。在年轻的大鼠研究中，在6 mg / kg时没有确定的毒性，在200 mg / kg时肝脏和甲状腺的肥大性变化没有体重变化。在新生鼠和幼鼠研究中均没有明显的性别差异。新生鼠和幼鼠的NOAELs分别被认为是50和6 mg / kg / day，但是无法估计两只大鼠的明确毒性水平。两种化学药品均未观察到新生儿的外部和性发育异常以及反射个体发育。根据这些结果，可以得出结论，新生鼠和幼鼠的DBP和TBE的靶器官都是肝脏，尽管新生鼠开始出现中毒症状的剂量较高，但引起明显毒性的剂量可能在新生儿病例中反而降低。

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