应用毒物代谢动力学模型推导生物接触限值的探讨

The study on application of toxicokinetics to derive biological exposure limits

目的 应用毒物代谢动力学基本原理 ,探讨将作业场所空气中有害物质容许接触限值(PEL)转换为机体生物材料中生物接触限值 (BEL)的方法。方法 以毒物代谢动力学单室模型结合常规轮班工时制特点 ,推导等效于PEL的血、尿BEL数学模型。结果 设定我国最高容许浓度为时间加权平均浓度 ,以德国生物耐受量 (BAT)和美国生物接触指数 (BEIs)现行的标准为例 ,应用数学模型计算的血中丙酮和铅BEL值与其PEL有较好的联系性。以此提出我国血中丙酮BEL建议值 (2 5mg/L) ,并验证我国血铅BEL(0 .4mg/L)的合理性。同时以德国、美国和我国现行作业场所 6种挥发性有机溶剂PEL为例 ,计算尿中BEL ,依据计算值提出了我国 6种化学物尿中BEL特异性指标的建议值 :苯———t,t 粘糠酸 2 0mg/L、二硫化碳——— 2 硫代噻唑烷 4 羧酸 3mg/L、乙苯———扁桃酸 2 0 0mg/L、五氯酚———总五氯酚 1.2mg/L、苯酚———苯酚 6 0mg/L、二甲苯———甲基马尿酸 10 0 0mg/L。结论 毒物代谢动力学模型能定量拟合BEL ,是研究和制定BEL方法中的一种有效手段 。

Objective To study theoretical approach to extrapolate from ambient permissible exposure limits(PEL) to biological exposure limits(BEL) in the biological media by application of the fundamental concepts of toxicokinetics. Methods A single compartment toxicokinetic model coupled with usual work schedule is used to assess the relationship of PEL to BEL.Mathematical models to establish BEL in blood and urine bioequivalent to external airborne exposure limits are derived. Results Suppose maximum allowable concentration(MAC) in China be the time weighted average concentration,the current standards of German Biologischer Arbeitsstoff Toleranz Wert(BAT) and American Biological Exposure Indices(BEIs) are used as a specific examples involving acetone and lead in blood,the calculated BEL are associated with the PEL of Germany and USA,China's proposal BEL(25 mg/L) of acetone in blood and BEL(0.4 mg/L) of lead in blood proved to be available.The extrapolation from PEL of six volatile organic compounds to BEL in urine is approximately equal to BEL published in Germany and USA,the BEL in urine derived from China's MAC for six chemicals are presented:benzene (t,t muconic acid:20 mg/L),carbon disulfide (TTCA:3 mg/L),ethylbenzene(mandelic acid:200 mg/L),pentachlorophenol(total pentachlorophenol:1.2 mg/L),phenol(phenol:60 mg/L) and xylenes(methylhippuric acid:1 000 mg/L). Conclusion Toxicokinetic model may simulate quantitatively BEL,which is one of efficient methods for the research and establishment of BEL.It is necessary that toxicokinetic information be taken into account when establishing the BEL for a variety of industrial chemicals.