目的 通过考察乌梢蛇Zaocys dhumnades（Cantor）中铅（Pb）和砷（As）的生物可给性，并探索靶器官毒性剂量（TTD）法在评估中药中重金属联合暴露风险中的应用，为限量标准的制定提供参考。方法 通过胃-肠两步模拟消化（in vitro PBET）联合电感耦合等离子体质谱（ICP-MS）法对乌梢蛇中Pb和As的生物可给性进行考察，根据其生物可给性计算其日暴露量。采用危害指数（HI）法对于Pb和As联合暴露产生的健康风险进行初步筛查；进一步针对不同毒理学终点，采用TTD法对Pb和As的累积风险进行更加精确的评估。结果 8批乌梢蛇中Pb和As的合格率为100%。HI法的初步评估结果表明，所有批次乌梢蛇中Pb和As的HI值均＜1。TTD法评估结果表明，作用终点心血管系统、神经系统、肾脏、血液和睾丸，所有批次乌梢蛇的HI值均＜1，健康风险可接受。结论 基于生物可给性，探索乌梢蛇中Pb和As的累积风险评估方法，为中药外源性有害残留物风险评估的方法开发提供新的思路，为制定更加科学的限量标准提供技术支撑。

Objective Investigating bioaccessibility of lead (Pb) and arsenic (As) in Zaocys dhumnades(Cantor) and exploring the application of target-organ toxicity dose modification of hazard index (TTD) method in assessing the risk of combined exposure to heavy metals in traditional Chinese medicines (TCMs), in order to provide reference for the formulation of limit standards.Method The bioaccessibility of Pb and As in Zaocys dhumnades(Cantor) was investigated by in vitro PBET digestion method combined with inductively coupled plasma mass spectrometry (ICP-MS), and the exposure doses were calculated based on bioaccessible contents. The health risk caused by combined exposure to Pb and As was preliminary screened by Hazard Index (HI) method. Moreover, a more accurate TTD method was used.Results The qualified rates of Pb and As in 8 batches of Zaocw dhumnades (Cantor) were 100%. The HI results indicated that the HI values of Pb and As in all batches of Zaocw dhumnades (Cantor) were less than one. The results of TTD method showed that for the end points of cardiovascular system, blood, nervous system, kidney and testis, the HI values of all batches of Zaocw dhumnades (Cantor) were less than one, and the health risk was acceptable.Conclusion The cumulative risk assessment of Pb and As in TCMs is proposed based on their bioaccessibility in this study, which offers novel ideas for the development of risk assessment methods of exogenous harmful residues in TCMs, and provides technical support for formulating scientific limit standards.

R965.3

国家十三五“重大新药创制”课题(2018ZX09735006);中国食品药品检定研究院中青年基金资助项目(2020A3)