Characterization of population variability of 1,3-butadiene derived protein adducts in humans and mice.
Characterization of population variability of 1,3-butadiene derived protein adducts in humans and mice.
复制标题
1，3-丁二烯衍生蛋白加合物在人类和小鼠中的群体变异性特征。
DOI：
10.1016/j.yrtph.2022.105171
复制
发表时间：
2022-07
影响因子：
3.4
通讯作者：
Wright, Fred A.
中科院分区：
文献类型：
--
作者：
Boysen, Gunnar;Rusyn, Ivan;Chiu, Weihsueh A.;Wright, Fred A.
1，3-丁二烯是一种已知的人类致癌物，也是一种人类因职业和环境污染而暴露于其中的化学品。1，3-丁二烯的吸入风险评估是在几十年前完成的，当时还没有关于暴露和影响的分子生物标志物的数据，这些数据来自工人的人体研究和小鼠实验研究。为了改善1，3-丁二烯的风险评估，需要对癌症相关效应的个体间变异性估计的不确定性进行定量表征。为此，我们应该利用关于1，3-丁二烯血红蛋白加合物的数据的可用性，这些加合物是反应性环氧化物内部剂量的公认生物标志物，来自几项大规模人体研究和一项协作交叉小鼠群体的研究。我们发现，在人体中，第99百分位数人群的毒代动力学不确定因子范围为3.27至7.9，取决于血红蛋白加合物。对于小鼠，这些值的范围从小于2到7.51，取决于剂量和加合物。本研究的定量估计值可用于降低模型中用于推导吸入单位风险的参数估计值的不确定性，以及解决可能与剂量相关的1，3-丁二烯代谢变异性的可能差异。
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.
登录
查看更多内容
影响因子：
2.5
作者：
Churchill, Gary A.;Gatti, Daniel M.;Munger, Steven C.;Svenson, Karen L.
通讯作者：
Svenson, Karen L.
影响因子：
5.1
作者：
Boysen, Gunnar;Georgieva, Nadia I.;Swenberg, James A.
通讯作者：
Swenberg, James A.
新的啮齿动物种群模型可能会为人类健康风险评估和确定对环境暴露的遗传敏感性的识别。
影响因子：
10.4
作者：
Harrill AH;McAllister KA
通讯作者：
McAllister KA
DOI：
10.1007/s00335-018-9734-y
发表时间：
2018-03
期刊：
Mammalian genome : official journal of the International Mammalian Genome Society
影响因子：
--
作者：
Venkatratnam A;House JS;Konganti K;McKenney C;Threadgill DW;Chiu WA;Aylor DL;Wright FA;Rusyn I
通讯作者：
Rusyn I
影响因子：
2.7
作者：
Krueger, Caitlin C. Jokipii;Madugundu, Guru;Tretyakova, Natalia
通讯作者：
Tretyakova, Natalia