Summit Toxicology, LLP, Falls Church, VA 22044, USA.
Regul Toxicol Pharmacol. 2011 Jul;60(2):189-99. doi: 10.1016/j.yrtph.2011.03.014. Epub 2011 Apr 3.
Measured concentrations of chemicals in blood or urine in biomonitoring studies provide an integrated reflection of exposures to chemicals via multiple routes and pathways. The potential significance of the measured concentrations of chemicals in the context of existing toxicology data and risk assessments can be assessed if chemical-specific quantitative screening criteria are available. This work presents the derivation of Biomonitoring Equivalents (BEs) for deltamethrin, a synthetic Type II pyrethroid. BEs are estimates of biomarker concentrations that are consistent with risk assessment-based exposure guidance values such as reference doses or acceptable daily intakes. BE values were derived for deltamethrin based on two biomarkers: deltamethrin in plasma and 3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (DBCA), a specific metabolite, in urine. BE values for deltamethrin in plasma were based on extrapolation from measured deltamethrin concentrations in plasma in rats under conditions consistent with the Point of Departure in the critical study underlying the USEPA RfD. BE values for DBCA in urine were derived based on pharmacokinetic data from a study in human volunteers on the urinary excretion of deltamethrin and metabolites. BE values for deltamethrin in plasma corresponding to the USEPA RfD for adults and children are 20 and 2μg/L, respectively. BE values for DBCA in urine corresponding to the adult and child-specific RfDs are 50 and 7μg/L, respectively. The urinary BE value corresponding to the ADI established by the European Commission and the Joint Meeting on Pesticide Residues is 60μg/L (as DBCA in urine). These values can be used to screen biomonitoring data in the context of current risk assessments for detlamethrin.
在生物监测研究中,血液或尿液中化学物质的测量浓度提供了通过多种途径和途径暴露于化学物质的综合反映。如果有化学物质特异性定量筛选标准,则可以评估现有毒理学数据和风险评估背景下测量的化学物质浓度的潜在意义。这项工作提出了拟除虫菊酯的生物监测等效物 (BE) 的推导,拟除虫菊酯是一种合成的 II 型拟除虫菊酯。BE 是与基于风险评估的暴露指导值(如参考剂量或可接受的每日摄入量)一致的生物标志物浓度的估计值。基于两种生物标志物:血浆中的拟除虫菊酯和尿液中的特定代谢物 3-(2,2-二溴乙烯基)-2,2-二甲基环丙烷羧酸 (DBCA),推导了拟除虫菊酯的 BE 值。基于在与 EPA RfD 基础关键研究中起点一致的条件下大鼠血浆中测量的拟除虫菊酯浓度外推得出了拟除虫菊酯在血浆中的 BE 值。基于在人类志愿者中进行的尿液中拟除虫菊酯及其代谢物排泄的药代动力学研究,推导了尿液中 DBCA 的 BE 值。对应于成人和儿童的 EPA RfD 的拟除虫菊酯在血浆中的 BE 值分别为 20 和 2μg/L。对应于成人和儿童特异性 RfD 的尿液中 DBCA 的 BE 值分别为 50 和 7μg/L。对应于欧盟委员会和农药残留联合会议建立的 ADI 的尿液中 DBCA 的 BE 值为 60μg/L(尿液中 DBCA)。这些值可用于在当前拟除虫菊酯风险评估背景下筛选生物监测数据。