University of Maryland University College, Adelphi, MD, USA; National Center of Environmental Assessment, US Environmental Protection Agency, Washing, D. C, USA.
Department of Environmental Toxicology, University of California, Davis, CA, USA.
Regul Toxicol Pharmacol. 2018 Aug;97:82-87. doi: 10.1016/j.yrtph.2018.06.008. Epub 2018 Jun 14.
Thiodiglycolic acid (TDGA) is a major metabolite of vinyl chloride monomer (VCM), and it has been suggested as an exposure biomarker for VCM. The validity of this biomarker when the level of VCM is less than 5 ppm, however, is questionable. The objective of this article is to evaluate the feasibility of using urinary TDGA as a biomarker of VCM exposure in a community health risk assessment setting where the concentration of VCM in air is typically very low (likely below 1 ppm). To achieve this objective, we examine the fraction of urinary TDGA associated with different levels of VCM exposures of three studies from different countries, using estimations of the TDGA metabolite predicted by a PBPK model. It is demonstrated that differences in background TDGA have considerable effect on the adequacy of TDGA as a biomarker of VCM. We conclude that, in a community health assessment setting, TDGA should not be used as an exposure biomarker for VCM without having a proper control group, and a PBPK model can be used first to determine whether or not the amount of TDGA in urine is of concern.
硫代二甘醇酸(TDGA)是氯乙烯单体(VCM)的主要代谢物,它被认为是 VCM 的暴露生物标志物。然而,当 VCM 水平低于 5ppm 时,这种生物标志物的有效性是值得怀疑的。本文的目的是评估在空气中 VCM 浓度通常非常低(可能低于 1ppm)的社区健康风险评估环境中,将尿中 TDGA 作为 VCM 暴露生物标志物的可行性。为了实现这一目标,我们使用 PBPK 模型预测的 TDGA 代谢物的估算值,检查了来自不同国家的三项研究中与不同 VCM 暴露水平相关的尿 TDGA 分数。结果表明,背景 TDGA 的差异对 TDGA 作为 VCM 生物标志物的充分性有很大影响。我们得出结论,在社区健康评估环境中,在没有适当对照组的情况下,不应将 TDGA 作为 VCM 的暴露生物标志物,并且可以首先使用 PBPK 模型来确定尿液中 TDGA 的量是否值得关注。