Department of Environmental and Occupational Health, The Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
Regul Toxicol Pharmacol. 2022 Jul;132:105171. doi: 10.1016/j.yrtph.2022.105171. Epub 2022 Apr 22.
1,3-butadiene is a known human carcinogen and a chemical to which humans are exposed occupationally and through environmental pollution. Inhalation risk assessment of 1,3-butadiene was completed several decades ago before data on molecular biomarkers of exposure and effect have been reported from both human studies of workers and experimental studies in mice. To improve risk assessment of 1,3-butadiene, the quantitative characterization of uncertainty in estimations of inter-individual variability in cancer-related effects is needed. For this, we ought to take advantage of the availability of the data on 1,3-butadiene hemoglobin adducts, well established biomarkers of the internal dose of the reactive epoxides, from several large-scale human studies and from a study in a Collaborative Cross mouse population. We found that in humans, toxicokinetic uncertainty factor for 99th percentile of the population ranged from 3.27 to 7.9, depending on the hemoglobin adduct. For mice, these values ranged from less than 2 to 7.51, depending on the dose and the adduct. Quantitative estimated from this study can be used to reduce uncertainties in the parameter estimates used in the models to derive the inhalation unit risk, as well as to address possible differences in variability in 1,3-butadiene metabolism that may be dose-related.
1,3-丁二烯是一种已知的人类致癌物，人类会因职业暴露和环境污染而接触到这种化学物质。在对 1,3-丁二烯进行吸入风险评估时，数据来自于工人的人类研究和实验研究中的老鼠，而这些数据分别是关于暴露和影响的分子生物标志物。为了改善 1,3-丁二烯的风险评估，需要对癌症相关影响的个体间变异性估计中的不确定性进行定量描述。为此，我们应该利用从几项大规模的人类研究和协作交叉小鼠群体研究中获得的 1,3-丁二烯血红蛋白加合物数据，这些数据是反应性环氧化物内剂量的可靠生物标志物。我们发现，在人类中，99%人群的毒代动力学不确定性因素范围为 3.27 至 7.9，具体取决于血红蛋白加合物。对于老鼠，这些值的范围从小于 2 到 7.51，具体取决于剂量和加合物。本研究中定量估计可以用于减少用于推导吸入单位风险的模型中参数估计的不确定性，以及解决可能与剂量相关的 1,3-丁二烯代谢变异性的差异。
