目的 通過考察烏梢蛇Zaocys dhumnades（Cantor）中鉛（Pb）和砷（As）的生物可給性，并探索靶器官毒性劑量（TTD）法在評估中藥中重金屬聯(lián)合暴露風(fēng)險(xiǎn)中的應(yīng)用，為限量標(biāo)準(zhǔn)的制定提供參考。方法 通過胃-腸兩步模擬消化（in vitro PBET）聯(lián)合電感耦合等離子體質(zhì)譜（ICP-MS）法對烏梢蛇中Pb和As的生物可給性進(jìn)行考察，根據(jù)其生物可給性計(jì)算其日暴露量。采用危害指數(shù)（HI）法對于Pb和As聯(lián)合暴露產(chǎn)生的健康風(fēng)險(xiǎn)進(jìn)行初步篩查；進(jìn)一步針對不同毒理學(xué)終點(diǎn)，采用TTD法對Pb和As的累積風(fēng)險(xiǎn)進(jìn)行更加精確的評估。結(jié)果 8批烏梢蛇中Pb和As的合格率為100%。HI法的初步評估結(jié)果表明，所有批次烏梢蛇中Pb和As的HI值均＜1。TTD法評估結(jié)果表明，作用終點(diǎn)心血管系統(tǒng)、神經(jīng)系統(tǒng)、腎臟、血液和睪丸，所有批次烏梢蛇的HI值均＜1，健康風(fēng)險(xiǎn)可接受。結(jié)論 基于生物可給性，探索烏梢蛇中Pb和As的累積風(fēng)險(xiǎn)評估方法，為中藥外源性有害殘留物風(fēng)險(xiǎn)評估的方法開發(fā)提供新的思路，為制定更加科學(xué)的限量標(biāo)準(zhǔn)提供技術(shù)支撐。

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

國家十三五“重大新藥創(chuàng)制”課題(2018ZX09735006);中國食品藥品檢定研究院中青年基金資助項(xiàng)目(2020A3)