The “European Human Biomonitoring Initiative” (HBM4EU) derives human biomonitoring guidance values (HBM-GVs) for the general population (HBM-GV_GenPop) and/or for occupationally exposed adults (HBM-GV_Worker) for several priority substances and substance groups as identified by policy makers, scientists and stakeholders at EU and national level, including bisphenol A (BPA).

Human exposure to BPA is widespread and of particular concern because of its known endocrine-disrupting properties. Unlike the conjugated forms of BPA circulating in the body, free BPA is known to interact with the nuclear estrogen receptors. Because free BPA is considered to be more toxicologically active than the conjugated forms (e.g. BPA-glucuronide (BPA-G) and BPA-sulfate (BPA-S)), its measurement in blood provides the superior surrogate of the biologically effective dose. However, considering the difficulty of implementing blood sampling in large HBM cohorts, as well as the current analytical capacities complying with the quality assurance (QA)/quality control (QC) schemes, total BPA in urine (i.e. the sum of free and conjugated forms of BPA measured after an hydrolysis of phase II metabolites) was retained as the relevant exposure biomarker for BPA.

HBM-GV_GenPop for total BPA in urine of 230 µg/L and 135 µg/L for adults and children, respectively, were developed on the basis of toxicological data. To derive these values, the concentrations of urinary total BPA consistent with a steady-state exposure to the temporary Tolerable Daily Intake (t-TDI) of 4 µg/kg bw/day set in 2015 by the European Food Safety Authority (EFSA) were estimated. The BPA human physiologically-based pharmacokinetic (PBPK) model developed by Karrer et al. (2018) was used, assuming an oral exposure to BPA at the t-TDI level averaged over 24 h. Dermal uptake of BPA is suspected to contribute substantially to the total BPA body burden, which in comparison with the oral route, is generating a higher ratio of free BPA to total BPA in blood. Therefore, an alternative approach for calculating the HBM-GV_GenPop according to the estimated relative contributions of both the oral and dermal routes to the global BPA exposure is also discussed.

Regarding BPA exposure at the workplace, the steady-state concentration of urinary total BPA was estimated after a dermal uptake of BPA that would generate the same concentration of free BPA in plasma (considered as the bioactive form) as would a 24 h-averaged intake to the European Chemicals Agency (ECHA)’s oral DNEL of 8 µg BPA/kg bw/day set for workers. The predicted concentration of urinary total BPA at steady-state is equivalent to, or exceeds the 95th percentile of total BPA in urine measured in different European HBM studies conducted in the general population. Thus, no HBM-GV_Worker was proposed, as the high background level of BPA coming from environmental exposure - mostly through food intake - is making the discrimination with the occupational exposure to BPA difficult.

“欧洲人类生物监测计划”（HBM4EU）推导了针对普通人群（HBM-GV _GenPop）和/或职业接触成年人（HBM-GV_工作人员）的几种优先物质和物质组的人类生物监测指导值（HBM-GV）。由欧盟和国家（包括双酚A（BPA））的政策制定者，科学家和利益相关者确定。

由于其已知的破坏内分泌的特性，人体对BPA的接触是广泛且特别令人关注的。与体内循环的BPA的结合形式不同，已知游离的BPA与核雌激素受体相互作用。因为游离的BPA被认为比缀合形式（例如BPA-葡糖醛酸（BPA-G）和BPA-硫酸盐（BPA-S））具有更高的毒理学活性，所以在血液中的游离BPA可以提供更好的生物有效剂量替代。但是，考虑到在大型HBM人群中实施血液采样的困难以及当前符合质量保证（QA）/质量控制（QC）计划的分析能力，尿液中的总BPA（即

HBM-GV _GenPop根据毒理学数据，成人和儿童的尿液中总BPA分别为230 µg / L和135 µg / L。为了得出这些值，尿液中总BPA的浓度与欧洲食品安全局（EFSA）于2015年设定的4 µg / kg bw /天的临时容许每日摄入量（t-TDI）的稳态摄入量相符估计的。Karrer等人开发的BPA人基于生理的药代动力学（PBPK）模型。使用（2018），假设在24小时内平均以t-TDI水平口服BPA。怀疑BPA的皮肤吸收对BPA的总体负担有重大贡献，与口服途径相比，血液中游离BPA与BPA的比率更高。因此，一种用于计算HBM-GV _GenPop的替代方法根据估计的口服和皮肤途径对全球双酚A暴露的相对贡献也进行了讨论。

关于工作场所中的双酚A暴露，估计皮肤吸收双酚A后尿液中总双酚A的稳态浓度与血浆中24小时平均摄入量相同，血浆中游离双酚A的浓度与生物活性形式相同。欧洲化学品管理局（ECHA）为工人设定的口服DNEL值为8 µg BPA / kg bw /天。在一般人群中进行的不同欧洲HBM研究中测得的稳态尿总BPA浓度等于或超过尿液中总BPA的95％。因此，没有提出HBM-GV_工人的提议，因为来自环境暴露的BPA的高背景水平（主要是通过食物摄入）使区分职业暴露于BPA变得困难。