摘要目的 探讨3种急性经口毒性替代法(固定剂量法、急性毒性分级法和上下法)在化学品急性毒性评价中的应用价值.方法 健康雌性SD大鼠,8～12周龄,体重160～200 g.分别选取10种化妆品原料和12种日化品原料共22种化学品作为受试物,参照经济合作与发展组织(OECD)3个急性经口毒性试验替代方法进行检测,依据全球化学品统一分类及标签制度(GHS)急性经口毒性分级原则获得各受试物毒性分级,分析各替代方法结果与传统试验方法之间的相关性和一致性.结果 与传统试验方法结果相比较,各替代方法判断化妆品原料急性毒性分级的一致率均为80%(8/10),固定剂量法、急性毒性分级法和上下法判断日化品原料的一致率分别为91.7%(11/12)、75.0%(9/12)和83.0%(10/12).各替代方法消耗动物数量均少于传统试验方法,差异有统计学意义(P<0.05),但所需实验时间长于传统试验方法,差异亦有统计学意义(P<0.05).结论 在化妆品和日化品原料急性经口毒性分析检测中,3种替代方法结果与传统试验方法具有较高的一致性和相关性,其中固定剂量法在日化品原料毒性检测中更具应用潜力.

abstractsObjective To evaluate three alternative methods for LD50 test-Fixed Dose Procedure (FDP),the Acute Toxic Class Method (ATC) and Up and Down Procedure (UDP).Methods Female SD rats (8～12 weeks of age,160~200 g) were used.Three alternative methods from OECD were applied to assess 22 chemicals (10 cosmetic raw materials and 12 raw materials of personal and home care products).The toxicity ranking for tested chemicals was established according to Globally Harmonized System(GSH).The results LD50 test were compared for the consistency and correlation between alternative methods and traditional test.Results For cosmetic raw materials,the concordance rate of the three alternative methods was 80%(8/10);for raw material of personal and home care products,the concordance rates of FDP,ATC and UDP was 91.7%(11/12),75.0%(9/12) and 83.0%(10/12),respectively.The number of animals required in three alternative methods was significantly lower than that in traditional test (P<0.05),but the time required in three alternative methods was significantly higher than that in traditional test (P<0.05 ).Conclusions High consistency and correlation were found between each alternative method and LD50 test.FDP may be more potential when applied to assess acute oral toxicity of cosmetic raw materials.