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The ingestion of fruits containing perfluoroalkyl acids (PFAAs) presents potential hazards to human health. This study aimed to fill knowledge gaps concerning the tissue-specific distribution patterns and bioaccumulation behavior of PFAAs and their isomers, alternatives, and precursors (collectively as per-/polyfluoroalkyl substances, PFASs) within citrus trees growing in contaminated fields. It also assessed the potential contribution of precursor degradation to human exposure risk of PFASs. High concentrations of total target PFASs (∑PFASs target , 92.45-7496.16 ng/g dw) and precursors measured through the total oxidizable precursor (TOP) assay (130.80-13979.21 ng/g dw) were found in citrus tree tissues, and short-chain PFASs constituted the primary components. The total PFASs concentrations followed the order of leaves > fruits > branches, bark > wood, and peel > pulp > seeds. The average contamination burden of peel (∑PFASs target : 57.75%; precursors: 71.15%) was highest among fruit tissues. Bioaccumulation factors (BAFs) and translocation potentials of short-chain, branched, or carboxylate-based PFASs exceeded those of their relatively hydrophobic counterparts, while ether-based PFASs showed lower BAFs than similar PFAAs in above-ground tissues of citrus trees. In the risk assessment of residents consuming contaminated citruses, precursor degradation contributed approximately 36.07% to total PFASs exposure, and therefore should not be ignored., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Experimental studies suggested per- and polyfluoroalkyl substances (PFASs) may disrupt estrogens in animals, however, the epidemiological evidence on the associations of PFASs with estrogens is sparse. We investigated the associations of legacy PFASs and their alternatives, including F-53B, the perfluorooctane sulfonate (PFOS) replacement that is specifically and commonly used in China, with estrogen concentrations in newborns. We quantified six PFASs and three estrogens in the cord sera of 942 newborns from a birth cohort in Wuhan, China, between 2013 and 2014. After adjusting for confounders and correcting for multiple comparisons, we observed that both legacy PFASs and their alternatives were associated with higher serum levels of estradiol (E2). Some of the PFASs were associated with increasing levels of estrone (E1) and estriol (E3). Analysis of PFASs in mixture using weighted quantile sum regressions showed that F-53B contributed 20.1% and 48.5% to the associations between PFASs and E1 and E2, respectively. This study provided epidemiological data on the associations between common PFAS exposures and estrogens in newborns. Additional toxicology studies are needed to fully understand the effects of PFASs on estrogens and the mechanisms., (Copyright © 2020. Published by Elsevier B.V.)

Given that per- and polyfluoroalkyl substances (PFASs) exhibit different distribution in the serum and semen of adult men, improving our understanding of the predictors of PFAS concentrations in paired serum and semen samples from an individual is essential. Here, we investigated and compared the effects of emerging and legacy PFAS concentrations in serum and semen on reproductive hormone levels in serum within a Chinese adult male population. We explored the relationships among perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorooctane sulfonate (PFOS), and chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) in serum and semen with reproductive hormones in serum among 651 adult men from Nanjing, China. Significant relationships among all analyzed serum and semen PFASs and decreased total testosterone (total T) were found. Serum and semen PFOA levels were associated with significant decreases in free T. Furthermore, the levels of sex hormone-binding globulin (SHBG) were significantly decreased in association with PFNA, PFOS, and 6:2 Cl-PFESA exposure. Negative relationships between the total T/luteinizing hormone (LH) ratio and semen concentrations of selected PFASs were also observed. After adjustment of PFAS concentrations (in both semen and serum), stronger associations of PFASs with total T, free T, estradiol (E2), SHBG, and total T/LH were observed in semen than in serum. We found that 84.8% of the associations between serum PFOA with total T were mediated by semen PFOA. Thus, elevated PFAS exposure may have negative effects on male reproductive health, and semen PFAS may be a better exposure indicator for the male reproductive system than serum PFAS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Per- and polyfluoroalkyl substances (PFASs) have been ubiquitously detected in the environment and marine animals. However, little is known about these substances and their associations with health parameters in wild terrestrial mammals. In this study, we determined PFAS levels and distribution in the blood of captive Siberian tigers in Harbin, China, and evaluated potential exposure pathways by daily intake. In addition, for the first time, we explored the associations between serum PFAS concentrations and clinical parameters. Results showed that perfluorooctanoate (PFOA) was the dominant PFAS compound in blood (accounting for 64%), followed by perfluorooctanesulfonate (PFOS). In addition, 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) concentrations were also detected in blood and dietary food. Furthermore, significant positive age relationships were observed for levels of perfluoroheptanoate (PFHpA), PFOA, PFOS, and 6:2 Cl-PFESA in the blood of female tigers. Results showed that PFOA and PFOS in dietary food accounted for over 70% of total daily intake of PFASs, indicating that meat consumption is a predominant exposure pathway in tigers. We also found positive associations between higher exposure to PFASs (including PFOA, PFOS, and 6:2 Cl-PFESA) and elevated serum levels of alanine transaminase (ALT), a marker of liver damage. Thus, comprehensive health assessments of PFAS burdens in wildlife are needed., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Exposure to per-/polyfluoroalkyl substances (PFASs) can disrupt endocrine hormones in humans. Prior studies have focused on the harmful effects of the two traditional per-/polyfluoroalkyl substances (PFASs), perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Other PFASs, used as the replacements of PFOS and PFOA, are widely and increasingly detected in humans. Whether these replacements influence glucocorticoids and progestogens in newborns remains unknown., Objective: To investigate the associations between exposures of PFOS, PFOA and their replacements and glucocorticoids and progestogens in newborns., Methods: We measured the concentrations of 13 PFASs, 3 glucocorticoids (11-deoxycortisol, cortisol and cortisone) and 2 progestogens [progesterone, 17-hydroxyprogesterone (17OHP)] in the cord sera of 374 neonates in a birth cohort from Wuhan, China, between 2013 and 2014. We evaluated the associations of each PFAS with glucocorticoids and progestogens using multiple linear regression models, and multiple comparisons were additionally corrected via false discovery rates (FDR)., Results: Out of the 13 PFASs, 9 were detected in over 95% of cord sera. The Chinese specific PFOS replacement - 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA, trade name F-53B) was positively associated with 13.13% change in cortisol in girls (95% CI = 4.47%, 22.52%, for each IQR increase in 6:2 Cl-PFESA). Seven PFASs had positive associations with the precursor of cortisol, namely 11-deoxycortisol (percent change ranged from 6.41% to 11.24%, for each IQR increase in PFASs). Perfluorobutane sulfonate (PFBS) in cord sera was positively associated with progesterone in the linear model, whereas PFOS and perfluorohexane sulfonate (PFHxS) levels were associated with progesterone in the quartile models. No PFASs were related to 17OHP or cortisone., Conclusions: In this study, PFOS, PFOA and/or their replacements were positively associated with progesterone, cortisol and 11-deoxycortisol in newborns. These results suggested that not only PFOS and PFOA, but also other PFASs have potential impacts on glucocorticoids and progestogens in newborns., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Laboratory studies indicate that exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) can induce neurobehavioral effects in animals. However, the penetration of PFASs across the brain barrier and its determining factors are yet to be clarified in humans. We studied PFAS levels in 223 matched-pair serum and cerebrospinal fluid (CSF) samples from hospital in-patients using UPLC/MS/MS. Among the 21 target analytes, PFOA, PFOS, and 6:2 Cl-PFESA were dominant in serum, with mean concentrations of 7.4, 6.8, and 6.2 ng/mL, respectively, contributing 79% to the total PFAS burden in serum. In CSF, PFOA, PFOS, and 6:2 Cl-PFESA were again the dominant PFASs, with mean concentrations of 0.078, 0.028, and 0.051 ng/mL contributing 36%, 13%, and 24%, respectively, to the total PFAS burden in CSF. Furthermore, PFAS penetration ( R PFAS , PFAS CSF /PFAS serum ) was positively correlated with the barrier permeability index R Alb (Albumin CSF /Albumin serum ), indicating that barrier integrity was the main determinant of PFAS penetration across the blood-CSF barrier. Positive associations between the R PFAS values of the main PFASs and serum C-reactive protein were observed, implying that inflammation facilitates the penetration of PFASs across the brain barrier.

The compound 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), an alternative to perfluorooctanesulfonate (PFOS) in the metal-plating industry, has been widely detected in various environmental matrices. However, its hepatotoxicity has yet to be clarified. Here, male mice were exposed to 0.04, 0.2, or 1 mg/kg/day of 6:2 Cl-PFESA for 56 days. Results demonstrated that relative liver weight increased significantly in the 0.2 and 1 mg/kg/day 6:2 Cl-PFESA groups, whereas liver lipid accumulation increased in all 6:2 Cl-PFESA groups. Serum enzyme activities of alanine transaminase and alkaline phosphatase were increased. Serum triglycerides and low-density lipoprotein cholesterol both increased, whereas serum total cholesterol and high-density lipoprotein cholesterol decreased following 6:2 Cl-PFESA exposure. A total of 264 differentially expressed proteins (127 up-regulated and 137 down-regulated), mainly involved in lipid metabolism, xenobiotic metabolism, and ribosome biogenesis, were identified by quantitative proteomics. Bioinformatics analysis highlighted the de-regulation of PPAR and PXR, which may contribute to the hepatotoxicity of 6:2 Cl-PFESA. Additionally, 6:2 Cl-PFESA induced both cell apoptosis and proliferation in the mouse liver. Compared to the overt toxicity of PFOS, 6:2 Cl-PFESA exhibited more-serious hepatotoxicity. Thus, caution should be exercised in the application of 6:2 Cl-PFESA as a replacement alternative to PFOS in industrial areas.

As an alternative to perfluorooctanesulfonate (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (commercial name: F-53B) has been used as a mist suppressant in Chinese electroplating industries for over 30 years. It has been found in the environment and fish, and one acute assay indicated F-53B was moderately toxic. However, the toxicological information on this compound was incomplete and insufficient for assessment of their environment impact. The object of this study was to examine the developmental toxicity of F-53B using zebrafish embryos. Zebrafish embryos were incubated in 6-well plates with various concentrations of F-53B (1.5, 3, 6, and 12mg/L) from 6 to 132h post fertilization (hpf). Results showed that F-53B exposure induced developmental toxicity, including delayed hatching, increased occurrence of malformations, and reduced survival. Malformations, including pericardial and yolk sac edemas, abnormal spines, bent tails, and uninflated swim bladders, appeared at 84 hpf, and increased with time course and dose. A decrease in survival percentages was noted in the 6 and 12mg/L F-53B-treated groups at 132 hpf. Continuous exposure to 3mg/L F-53B resulted in high accumulation levels in zebrafish embryos, suggesting an inability for embryos to eliminate this compound and a high cumulative risk to fish. We also examined the cardiac function of embryos at specific developmental stages following exposure to different concentrations, and found that F-53B induced cardiac toxicity and reduced heart rate. Even under low F-53B concentration, o-dianisidine staining results showed significant decrease of relative erythrocyte number at 72 hpf before the appearance of observed effects of F-53B on the heart. To elucidate the underlying molecular changes, genes involved in normal cardiac development were analyzed using real-time qPCR in the whole-body of zebrafish embryos. F-53B inhibited the mRNA expression of β-catenin (ctnnb2) and wnt3a. The mRNA levels of β-catenin targeted genes (nkx2.5 and sox9b), which play critical roles in cardiogenesis, were also reduced after exposure. Thus, exposure to F-53B impaired the development of zebrafish embryos and disrupted cardiac development, which might be mediated by effects on the Wnt signaling pathway and decrease of erythrocyte numbers., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Perfluorooctane sulfonate (PFOS) is a commonly used and widely distributed perfluorinated compound proven to cause adverse health outcomes. However, how PFOS affects liver cell proliferation is not well understood. In this experiment, we exposed a human liver cell line (HL-7702) to 50 μM PFOS for 48 h and 96 h. We identified 52 differentially expressed proteins using a quantitative proteomic approach. Among them, 27 were associated with cell proliferation, including hepatoma-derived growth factor (Hdgf) and proliferation biomarkers Mk167 (Ki67) and Top2α. Results from MTT, cell counting, and cell cycle analysis showed low-dose PFOS (<200 μM) stimulated HL-7702 cell viability at 48 h and 96 h, reduced the G0/G1 percentage, and increased the S+G2/M percentage. Moreover, levels of Cyclin D1, Cyclin E2, Cyclin A2, Cyclin B1 and their partner Cdks were elevated, and the expression of regulating proteins like c-Myc, p53, p21 waf/cip1 and Myt1, as well as the phosphorylation levels of p-Wee1(S642), p-Chk1(S345) and p-Chk2(T68), were disturbed. We hypothesized that low-dose PFOS stimulated HL-7702 proliferation by driving cells into G1 through elevating cyclins/cdks expression, and by promoting cell cycle progression through altering other regulating proteins. This research will shed light on the mechanisms behind PFOS-mediated human hepatotoxicity., (Copyright © 2015 Elsevier B.V. All rights reserved.)