Associations between both legacy and alternative per- and polyfluoroalkyl substances and glucose-homeostasis: The Isomers of C8 health project in China

Zhang, Yun Ting; Zeeshan, Mohammed; Song, Fan; Qian, Zheng min; Geiger, Sarah Dee; McMillin, Stephen Edward; Wang, Zhi Bin; Dong, Peng Xin; Ou, Yan Qiu; Xiong, Shi Min; Shen, Xu Bo; Zhou, Peien; Yang, Bo; Chu, Chu; Li, Qing Qing; Zeng, Xiao Wen; Feng, Wen Ru; Zhou, Yuan Zhong; Dong, Guang‐Hui

doi:10.1016/j.envint.2021.106913

Cited by 26 publications

(13 citation statements)

References 90 publications

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“…These alternatives are increasingly found in environmental and human samples at relatively high concentration due to the unrestricted use. For example, 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) concentrations were as high as 2.13 ng/mL in Shenyang population, China 8 , and have become one of the main PFAS in Chinese local surface waters 9 . And PFAS alternatives showed comparable or even greater toxicities in both epidemiological and toxicological studies 8 , 10 , 11 .…”

Section: Introductionmentioning

confidence: 99%

“…For example, 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) concentrations were as high as 2.13 ng/mL in Shenyang population, China 8 , and have become one of the main PFAS in Chinese local surface waters 9 . And PFAS alternatives showed comparable or even greater toxicities in both epidemiological and toxicological studies 8 , 10 , 11 . However, literature on immunotoxicity of PFAS alternatives is still scarce and inconsistent.…”

Section: Introductionmentioning

confidence: 99%

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Emerging and legacy PFAS and cytokine homeostasis in women of childbearing age

Nian

Zhou

Feng

et al. 2022

Sci Rep

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Per- and polyfluoroalkyl substances (PFAS) are widespread chemicals. Legacy PFAS have been phased out of production in most developed countries and emerging PFAS (short-chain PFAS and polyfluorinated compounds) are used as legacy PFAS alternatives. The effect of legacy and emerging PFAS on cytokine homeostasis in human remains poorly understood. This study aimed to evaluate the associations between legacy and emerging PFAS and cytokine profiles, and identify the main contributors to the disturbance of cytokine homeostasis. We quantified 21 PFAS in 198 Chinese women of childbearing age from 2015 to 2016. 13 cytokines were measured using the Meso Scale Discovery U-PLEX and V-PLEX platforms. The associations between PFAS exposure and cytokine levels were assessed using multiple linear regression (single-exposure), and Bayesian kernel machine regression (BKMR) models (PFAS mixture exposure). In single PFAS models, legacy and alternative PFAS were positively associated with Th1 and Treg cytokines, and negatively associated with Th2 and Th17 cytokines. For instance, each ln-unit increase in 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonate (PFOS) was associated with a decrease in IL-10 by − 0.228 (95% CI: − 0.336, − 0.120), − 0.153 (95% CI: − 0.277, − 0.030), and − 0.174 (95% CI: − 0.339, − 0.010), respectively. The BKMR model showed a significantly positive association of PFAS mixture with TGF-β and a negative association with IL-10. Overall, these results indicate that both legacy and emerging PFAS may affect the homeostasis of cytokines.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Emerging and legacy PFAS and cytokine homeostasis in women of childbearing age

Nian

Zhou

Feng

et al. 2022

Sci Rep

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“…Similarly, our previous study showed that 6:2 Cl-PFESA was more positively associated with glucose homeostasis, including fasting glucose, the homeostasis model assessment of insulin resistance (HOMA-IR), and the homeostasis model assessment of beta-cell function (HOMA-β) than PFOS. 6 Cell experiments demonstrated that 6:2 Cl-PFESA had a higher binding affinity to human serum albumin (HSA) than PFOS. 58 However, experimental studies on the eye disease toxicity of legacy PFASs and PFAS alternatives are still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…The Isomers of C8 Health Project is a cross-sectional investigation to evaluate human serum PFAS exposure and health outcomes, including diabetes, 6 visual impairment, 34 metabolic syndrome, 38 hyperuricemia, 39 and hypertension, 40 among others. This case−control study consists of 135 individuals diagnosed with eye diseases (cases) and 135 individuals from the general population with no reported symptoms of eye diseases (controls).…”

Section: Study Population and Designmentioning

confidence: 99%

“…11 Toxicological studies have shown that Cl-PFESAs induce developmental toxicity, 12 the disruption of thyroid hormone levels, 13 hepatotoxicity, 14 immunotoxicity, 15 reproductive toxicity, 16 and retinal disorders 17,18 in animals. Ample evidence exists linking Cl-PFESAs with various health conditions that affect blood lipids, 5 glucose homeostasis, 6 metabolic syndrome, 19 hepatitis B virus antibody levels, 20 function, 21 and neurodevelopment, 22 as well as adverse birth outcomes. 23 Nevertheless, no studies have explored the associations between Cl-PFESAs and eye diseases.…”

Section: Introductionmentioning

confidence: 99%

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Chlorinated Polyfluoroalkyl Ether Sulfonic Acids (Cl-PFESAs) Are Associated with Eye Diseases in Humans and Eye Toxicity in Zebrafish

Wu,

Liang,

Zhou

et al. 2024

Environ. Health

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Evidence from animal experiments has shown that chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs) can induce vision dysfunction in zebrafish. However, environmental epidemiological evidence supporting this hypothesis remains limited. In our case−control study, samples collected from 270 individuals (135 controls and 135 cases) from the Isomers of C8 Health Project data were analyzed for Cl-PFESAs. We also repeated our analysis on zebrafish to support our findings in humans and to decipher the mechanism underlying Cl-PFESA eye toxicity. The serum levels of per-and polyfluoroalkyl substances (PFASs) and alternatives were significantly higher in the cases than in the controls. Higher serum Cl-PFESA levels were associated with greater odds of eye diseases, and the trend showed a statistically significant dose-dependent relationship. The Shapley additive explanations (SHAP) value indicated that 8:2 Cl-PFESA was the dominant eye disease risk factor among the 13 studied PFASs. In zebrafish experiments, Cl-PFESAs induced eye toxicity in adult zebrafish by oxidative damage and cell apoptosis. Compared to the control group, there was significantly reduced thicknesses of the inner plexiform layer (IPL), outer plexiform layer (OPL), and retinal tissue in the zebrafish exposed to Cl-PFESAs. Our study provides human clinical and animal experimental data, showing that exposure to PFASs increases the odds of the development of eye toxicity.

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