Walden R, Schiller C M
Toxicol Appl Pharmacol. 1985 Mar 15;77(3):490-5. doi: 10.1016/0041-008x(85)90189-9.
Four (sub)strains of adult male rats were given single oral doses of various concentrations of TCDD to establish and compare the oral 30-day LD50 values. The strains of rats were Fischer (F/334N) supplied by Harlan Industries, Frederick Cancer Research Center, and Charles River Breeding Laboratories; and CD supplied by Charles River Breeding Laboratories. The Charles River/Fischer rats were most sensitive to TCDD (LD50 = 164, 95% confidence limits 104-217 micrograms/kg), the Frederick/Fischer and Charles River/CD rats were moderately sensitive to TCDD (LD50 = 303, 250-360; and 297, 240-360 micrograms/kg, respectively), and the Harlan/Fischer rats were most resistant to TCDD (LD50 = 340, 281-409 micrograms/kg). The mean times of death were from 24.5 +/- 1.0 to 28.3 +/- 0.5 days and the percentage body weight loss at death was 37.4 +/- 1.2 to 42.7 +/- 1.3%. One week after exposure of the Charles River/Fischer animal to 45 micrograms TCDD/kg (1/4 the established 30-day LD50 dose), the same serum profile was induced as previously observed in the Harlan/Fischer rat, which includes hypoglycemia, hypertriglyceridemia, and hypercholesterolemia. These results emphasize the importance of indicating the precise dose, strain of rat, and time after dosing before termination in reporting the effects of TCDD on a particular biological response.
给四组成年雄性大鼠分别口服不同浓度的2,3,7,8-四氯二苯并对二恶英(TCDD)单次剂量,以确定并比较经口30天半数致死剂量(LD50)值。这些大鼠品系包括由哈兰工业公司、弗雷德里克癌症研究中心和查尔斯河繁殖实验室提供的Fischer(F/334N)大鼠;以及由查尔斯河繁殖实验室提供的CD大鼠。查尔斯河/Fischer大鼠对TCDD最为敏感(LD50 = 164,95%置信区间为104 - 217微克/千克),弗雷德里克/Fischer和查尔斯河/CD大鼠对TCDD敏感性中等(LD50分别为303,250 - 360;以及297,240 - 360微克/千克),而哈兰/Fischer大鼠对TCDD最具抗性(LD50 = 340,281 - 409微克/千克)。平均死亡时间为24.5±1.0至28.3±0.5天,死亡时体重减轻百分比为37.4±1.2至42.7±1.3%。将查尔斯河/Fischer动物暴露于45微克TCDD/千克(既定30天LD50剂量的1/4)一周后,诱导出的血清特征与之前在哈兰/Fischer大鼠中观察到的相同,包括低血糖、高甘油三酯血症和高胆固醇血症。这些结果强调了在报告TCDD对特定生物学反应的影响时,指明精确剂量、大鼠品系以及给药至处死的时间的重要性。