Liu Jiao-Jiao, Cui Xin-Xin, Tan Ya-Wen, Dong Peng-Xin, Ou Yan-Qiu, Li Qing-Qing, Chu Chu, Wu Lu-Yin, Liang Li-Xia, Qin Shuang-Jian, Zeeshan Mohammed, Zhou Yang, Hu Li-Wen, Liu Ru-Qing, Zeng Xiao-Wen, Dong Guang-Hui, Zhao Xiao-Miao
Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
Nursing College, Guangxi Medical University, Nanning 530021, China.
Environ Int. 2022 May;163:107179. doi: 10.1016/j.envint.2022.107179. Epub 2022 Mar 21.
Experimental evidence has shown that per- and polyfluoroalkyl substances (PFAS) alternatives and mixtures may exert hepatotoxic effects in animals. However, epidemiological evidence is limited. This research aimed to explore associations of PFAS and the alternatives with liver function in a general adult population. The study participants consisted of 1,303 adults from a community-based cross-sectional investigation in Guangzhou, China, from November 2018 to August 2019. We selected 13 PFAS with detection rates > 85% in serum samples and focused on perfluorooctane-sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their alternatives [6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 Cl-PFESA, and perfluorohexanoic acid (PFHxA)] as predictors of outcome. Six liver function biomarkers (ALB, ALT, AST, GGT, ALP, and DBIL) were chosen as outcomes. We applied regression models with restricted cubic spline function to explore correlations between single PFAS and liver function and inspected the combined effect of PFAS mixtures on liver by applying Bayesian kernel machine regression (BKMR). We discovered positive associations among PFAS and liver function biomarkers except for ALP. For example, compared with the 25th percentile of PFAS concentration, the level of ALT increased by 12.36% (95% CI: 7.91%, 16.98%) for ln-6:2 Cl-PFESA, 5.59% (95% CI: 2.35%, 8.92%) for ln-8:2 Cl-PFESA, 3.56% (95% CI: -0.39%, 7.68%) for ln-PFHxA, 13.91% (95% CI: 8.93%, 19.13%) for ln-PFOA, and 14.25% (95% CI: 9.91%, 18.77%) for ln-PFOS at their 75th percentile. In addition, higher exposed serum PFAS was found to be correlated with greater odds of abnormal liver function. Analysis from BKMR models also showed an adverse association between PFAS mixtures and liver function. The combined effect of the PFAS mixture appeared to be non-interactive, in which PFOS was the main contributor to the overall effect. Our findings provide evidence of associations between PFAS alternatives, PFAS mixtures, and liver function in the general adult population.
实验证据表明，全氟和多氟烷基物质（PFAS）的替代品及混合物可能对动物产生肝毒性作用。然而，流行病学证据有限。本研究旨在探讨PFAS及其替代品与一般成年人群肝功能之间的关联。研究参与者来自2018年11月至2019年8月在中国广州进行的一项基于社区的横断面调查中的1303名成年人。我们选择了血清样本中检出率>85%的13种PFAS，并重点关注全氟辛烷磺酸（PFOS）、全氟辛酸（PFOA）及其替代品[6:2氯化多氟醚磺酸盐（6:2 Cl-PFESA）、8:2 Cl-PFESA和全氟己酸（PFHxA）]作为结果的预测指标。选择六种肝功能生物标志物（ALB、ALT、AST、GGT、ALP和DBIL）作为结果。我们应用具有受限立方样条函数的回归模型来探索单一PFAS与肝功能之间的相关性，并通过应用贝叶斯核机器回归（BKMR）来检查PFAS混合物对肝脏的综合影响。我们发现除ALP外，PFAS与肝功能生物标志物之间存在正相关。例如，与PFAS浓度的第25百分位数相比，ln-6:2 Cl-PFESA使ALT水平升高12.36%（95%CI：7.91%，16.98%），ln-8:2 Cl-PFESA使ALT水平升高5.59%（95%CI：2.35%，8.92%），ln-PFHxA使ALT水平升高3.56%（95%CI：-0.39%，7.68%），ln-PFOA使ALT水平升高13.91%（95%CI：8.93%，19.13%），ln-PFOS在其第75百分位数时使ALT水平升高14.25%（95%CI：9.91%，18.77%）。此外，发现血清PFAS暴露水平较高与肝功能异常的几率更大相关。BKMR模型的分析也显示PFAS混合物与肝功能之间存在不良关联。PFAS混合物的综合效应似乎是非交互性的，其中PFOS是总体效应的主要贡献者。我们的研究结果为一般成年人群中PFAS替代品、PFAS混合物与肝功能之间的关联提供了证据。
