EXPERIMENTAL-DESIGN CONSIDERATIONS - A DETERMINANT OF ACUTE NEONATAL TOXICITY

EXPERIMENTAL-DESIGN CONSIDERATIONS - A DETERMINANT OF ACUTE NEONATAL TOXICITY
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DOI:
10.1002/tera.1420310203
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发表时间:
1985-01-01
期刊:
TERATOLOGY
影响因子:
--
通讯作者:
MACTUTUS, CF
MACTUTUS, CF
中科院分区:
其他
文献类型:
--
作者:
BOOZE, RM;MACTUTUS, CF

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直接比较了通过分窝(代表单窝中的所有剂量组)和巢式(随机分配至单窝的所有幼仔接受相同剂量)设计给予三乙基铅(TEL)的大鼠幼仔。选择嵌套设计以在每窝内的幼仔中产生统一的行为模式,而选择分窝设计以促进幼仔竞争和差异化的母性护理。在产后第5天,幼仔接受12、13、14或15 mg/kg TEL给药,每种设计由12窝幼仔代表。尽管两种设计的LD 50值无显著差异,但在分窝设计中,12 mg/kg剂量组的死亡率显著高于嵌套设计组。分窝给药动物的断奶前存活时间也缩短。在断奶前期间,相对于巢式设计动物,在分窝组中观察到显著的生长降低(7-16%)。新生儿毒性并非独立于实验设计考虑因素,窝仔竞争和/或幼犬诱导的母体护理因素值得进一步研究。
Rat pups dosed with triethyl lead (TEL) via both split-litter (representing all dosage groups within a single litter) and nested (all pups randomly assigned to a single litter receive the same dose) designs were directly compared. The nested design was chosen to produce a uniform behavioral pattern across pups within each litter, whereas the split-litter design was chosen to promote pup competition and differential maternal care. On postpartum day 5, pups were administered either 12, 13, 14 or 15 mg/kg TEL, with each design represented by 12 litters. Although the LD50 values for the 2 designs were not significantly different, there were significantly more deaths in the 12 mg/kg dosage group within the split-litter design than in the nested design group. Preweaning survival times for split-litter dosed animals were also decreased. Significant growth reduction (7-16%) was observed in the split-litter group, relative to the nested design animals during the preweaning period. Neonatal toxicity is not independent from experimental design considerations, and the factors of littermate competition and/or pup-induced maternal care deserve further study.