大鼠氯霉素4周经口连续染毒毒性的研究
Study on 4-week toxicity of chloramphenicol by continuous oral administration in rats
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摘要:
目的 研究氯霉素大鼠4周（28 d）经口染毒毒性，为其安全性评价提供毒理学相关参数。
方法 80只健康Wistar大鼠雌雄各半，随机分为1个对照组（5 g/L羧甲基纤维素钠溶液）和3个染毒组（高、中、低剂量组，氯霉素染毒剂量分别为60.0、30.0、7.5 mg/kg），每组20只，经口染毒，连续28 d。观察氯霉素对大鼠体重、血液指标及脏器系数的影响，并进行骨髓涂片及组织病理学检查。
结果 与对照组相比，高剂量组雄性大鼠第2周起体重增长受到抑制（P < 0.05），雌、雄大鼠平均红细胞容积、总蛋白、白蛋白降低（P < 0.05），雄性大鼠脑脏器系数与雌、雄大鼠肾脏脏器系数升高（P < 0.05）；中剂量组雌、雄大鼠平均红细胞容积、总蛋白、白蛋白降低（P < 0.05），雄性大鼠肾脏脏器系数升高（P < 0.05）；低剂量组大鼠各指标均未见明显改变。本试验条件下，大鼠氯霉素连续28 d经口染毒未观察到损害作用剂量为7.5 mg/kg，基准剂量为1.284 mg/kg，基准剂量下限为0.804 mg/kg，人类每日容许摄入量为8.04 μg/kg。
结论 氯霉素对雄性大鼠的毒性大于雌性大鼠。本研究为氯霉素每日摄入量安全限值的制定及风险评估提供了重要的数据参考。
Abstract:Objective To assess the 4-week (28-day) toxicity of chloramphenicol (CAP) by oral administration in rats and obtain safety evaluation parameters.
Methods Healthy Wistar rats (n=80, sex ratio=1:1) were randomly divided into one control group (5 g/L sodium carboxymethyl cellulose) and three exposure groups (high, medium, and low dose groups administered with 60, 30, and 7.5 mg/kg CAP, with 20 rats for each group, respectively), with 20 rats for each group. All rats were orally administered daily for 28 consecutive days. Body weight, hematological indicators, and organ coefficient were recorded, the bone marrow smear and pathological changes of organ tissues were examined.
Results Compared with the control group, in the high dose group, male rats' body weight growth were inhibited after two weeks (P < 0.05), both male and female rats showed reduced mean corpuscular volume, total protein, and albumin (P < 0.05), and male rats' brain organ coefficient and male and female rats' kidney organ coefficients were increased; in the medium dose group, both female and male rats' showed reduced mean corpuscular volume, total protein, and albumin (P < 0.05), and male rats' kidney organ coefficient was increased (P < 0.05); no obvious changes were observed in the low dose group. The no-observed-adverse-effect level (NOAEL) of CAP was 7.5 mg/kg, the benchmark dose was 1.284 mg/kg, and the benchmark dose lower confidence limit was 0.804 mg/kg under the current experiment conditions. The acceptable daily intake of CAP for human was 8.04 μg/kg.
Conclusion CAP poses greater toxicity to male rats than to female rats. The study provides important data for the formulation of daily safety limits and risk assessment of CAP.
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