Karakoltzidis Achilleas, Karakitsios Spyros P, Gabriel Catherine, Sarigiannis Dimosthenis Α
Aristotle University of Thessaloniki, Department of Chemical Engineering, Environmental Engineering Laboratory, University Campus, Thessaloniki, 54124, Greece; HERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Balkan Center, Bldg. B, 10th km, Thermi Road, Thessaloniki, 57001, Greece.
Aristotle University of Thessaloniki, Department of Chemical Engineering, Environmental Engineering Laboratory, University Campus, Thessaloniki, 54124, Greece; HERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Balkan Center, Bldg. B, 10th km, Thermi Road, Thessaloniki, 57001, Greece; EnvE.X, K. Palama 11, Thessaloniki, Greece; National Hellenic Research Foundation, Athens, Greece.
Environ Res. 2025 Oct 1;282:121947. doi: 10.1016/j.envres.2025.121947. Epub 2025 May 29.
Per- and polyfluoroalkyl substances (PFASs) pose significant public health concerns due to their environmental persistence, bioaccumulation, and ubiquitous presence in human biomonitoring (HBM) data, despite regulatory restrictions. This study establishes a deterministic pharmacokinetic model for perfluorooctanoic acid (PFOA), enabling the estimation of PFOA concentrations in major human organs, even at low doses. The model integrates accumulation and recirculation mechanisms of PFOA in hepatic and renal tissues, leveraging publicly available HBM datasets (e.g., HBM4EU, NHANES, literature) to reconstruct bodyweight-normalized intake levels. Importantly, due to the extremely low urinary excretion concentrations of PFOA, most datasets were derived from blood-based measurements, particularly serum while confirming urine as unreliable biomarker of exposure. The analysis underscores the effectiveness of regulatory efforts in reducing PFOA exposures, as evidenced by declining time-trends in estimated exposure levels in recent studies. Risk characterization ratios were calculated based on recommended limits set by the European Food Safety Authority (EFSA), the United States, and Australia. While EFSA's tolerable weekly intake (TWI) indicated a high risk, other regulatory limits suggested less concern about risk at these intake levels. These findings highlight the need for continuous re-evaluation of exposures and targeted studies to identify key determinants of PFOA exposure, informing future regulatory measures. The study emphasizes the critical role of physiologically based pharmacokinetic (PBPK) modeling, HBM data, and exposure reconstruction in advancing chemical risk assessment. These tools form a science-based framework integral to the Chemical Strategy for Sustainability (CSS), enabling accurate predictions of internal exposure levels, empirical validation of models, and robust assessments of real-world exposure scenarios. The integration of these approaches supports the CSS goals of minimizing chemical risks while promoting innovation, ultimately contributing to a sustainable and protective regulatory landscape for human health and the environment.
全氟和多氟烷基物质（PFASs）因其在环境中的持久性、生物累积性以及在人类生物监测（HBM）数据中普遍存在，尽管受到监管限制，但仍引发了重大的公共卫生问题。本研究建立了全氟辛酸（PFOA）的确定性药代动力学模型，即使在低剂量下也能估算主要人体器官中的PFOA浓度。该模型整合了PFOA在肝脏和肾脏组织中的积累和再循环机制，利用公开可用的HBM数据集（如HBM4EU、美国国家健康与营养检查调查（NHANES）、文献）来重建体重标准化的摄入量水平。重要的是，由于PFOA的尿排泄浓度极低，大多数数据集来自基于血液的测量，尤其是血清，同时证实尿液作为暴露的生物标志物不可靠。分析强调了监管努力在减少PFOA暴露方面的有效性，最近研究中估计暴露水平的时间趋势下降证明了这一点。根据欧洲食品安全局（EFSA）、美国和澳大利亚设定的推荐限值计算风险特征比。虽然EFSA的每周可耐受摄入量（TWI）表明风险较高，但其他监管限值表明在这些摄入量水平下对风险的担忧较小。这些发现凸显了持续重新评估暴露情况和开展针对性研究以确定PFOA暴露关键决定因素的必要性，为未来监管措施提供信息。该研究强调了基于生理学的药代动力学（PBPK）建模、HBM数据和暴露重建在推进化学风险评估中的关键作用。这些工具构成了可持续化学战略（CSS）不可或缺的基于科学的框架，能够准确预测内部暴露水平、对模型进行实证验证以及对实际暴露场景进行有力评估。这些方法的整合支持了CSS的目标，即在促进创新的同时将化学风险降至最低，最终为人类健康和环境营造一个可持续且具有保护作用的监管环境。
