Impact of Gestational Exposure to Individual and Combined Per- and Polyfluoroalkyl Substances on a Placental Structure and Efficiency: Findings from the Ma'anshan Birth Cohort.

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is inevitable among pregnant women. Nevertheless, there is a scarcity of research investigating the connections between prenatal PFAS exposure and the placental structure and efficiency. Based on 712 maternal-fetal dyads in the Ma'anshan Birth Cohort, we analyzed associations between individual and mixed PFAS exposure and placental measures. We repeatedly measured 12 PFAS in the maternal serum during pregnancy. Placental weight, scaling exponent, chorionic disc area, and disc eccentricity were used as the outcome variables. Upon adjusting for confounders and implementing corrections for multiple comparisons, we identified positive associations between branched perfluorohexane sulfonate (br-PFHxS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) with placental weight. Additionally, a positive association was observed between br-PFHxS and the scaling exponent, where a higher scaling exponent signified reduced placental efficiency. Based on neonatal sex stratification, female infants were found to be more susceptible to the adverse effects of PFAS exposure. Mixed exposure modeling revealed that mixed PFAS exposure was positively associated with placental weight and scaling exponent, particularly during the second and third trimesters. Furthermore, br-PFHxS and 6:2 Cl-PFESA played major roles in the placental measures. This study provides the first epidemiological evidence of the relationship between prenatal PFAS exposure and placental measures.

Association between Serum Per- and Polyfluoroalkyl Substance Levels and Risk of Central and Peripheral Precocious Puberty in Girls.

Concerns about the endocrine-disrupting effects of per- and polyfluoroalkyl substances (PFASs) have raised questions about their potential influence on precocious puberty in girls, which is an emerging concern in some populations. However, epidemiological evidence is lacking. In this study, 882 serum samples were collected from girls with central precocious puberty (CPP, n = 226), peripheral precocious puberty (PPP, n = 316), and healthy controls (n = 340) in 2021 in Shanghai, China. The serum levels of 25 legacy and emerging PFASs and 17 steroids were measured. Results showed that PFAS exposure was positively associated with estradiol levels. Eleven PFASs were significantly or marginally associated with the higher odds of the overall precocious puberty. Across subtypes, PFASs were more clearly associated with PPP, while the associations with CPP were consistent in direction but did not reach statistical significance. These findings were consistent with the assessment of PFAS mixtures using quantile-based g-computation (qgcomp) and Bayesian kernel machine regression, with perfluorobutane sulfonate and 6:2 polyfluorinated ether sulfonate showing the highest contribution to joint effects. Although changes in serum estradiol could arise from various factors, our results suggest that the PFAS exposure may contribute to the increase in estradiol secretion, thereby increasing the risk of precocious puberty, especially PPP. The potential effects of PFASs on precocious puberty warrant further investigation, given the associated complications of public health concern, including psychological distress and increased risk of multiple diseases.

Comprehensive Assessment of Exposure Pathways for Perfluoroalkyl Ether Carboxylic Acids (PFECAs) in Residents Near a Fluorochemical Industrial Park: The Unanticipated Role of Cereal Consumption.

With the replacement of perfluorooctanoic acid (PFOA) with perfluorinated ether carboxylic acids (PFECAs), residents living near fluorochemical industrial parks (FIPs) are exposed to various novel PFECAs. Despite expectations of low accumulation, short-chain PFECAs, such as perfluoro-2-methoxyacetic acid (PFMOAA), previously displayed a considerably high body burden, although the main exposure routes and health risks remain uncertain. Here, we explored the distribution of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in diverse environmental media surrounding a FIP in Shandong Province, China. PFECAs were found at elevated concentrations in all tested matrices, including vegetables, cereals, air, and dust. Among residents, 99.3% of the ∑36PFAS exposure, with a 43.9% contribution from PFECAs, was due to gastrointestinal uptake. Dermal and respiratory exposures were negligible at 0.1 and 0.6%, respectively. The estimated daily intake (EDI) of PFMOAA reached 114.0 ng/kg body weight (bw)/day, ranking first among all detected PFECAs. Cereals emerged as the dominant contributor to PFMOAA body burden, representing over 80% of the overall EDI. The median EDI of hexafluoropropylene oxide dimer acid (HFPO-DA) was 17.9 ng/kg bw/day, markedly higher than the USEPA reference doses (3.0 ng/kg bw/day). The absence of established threshold values for other PFECAs constrains a comprehensive risk assessment.

Unveiling Distribution of Per- and Polyfluoroalkyl Substances in Matched Placenta-Serum Tetrads: Novel Implications for Birth Outcome Mediated by Placental Vascular Disruption.

The placenta is pivotal for fetal development and maternal-fetal transfer of many substances, including per- and polyfluoroalkyl substances (PFASs). However, the intraplacental distribution of PFASs and their effects on placental vascular function remain unclear. In this study, 302 tetrads of matched subchorionic placenta (fetal-side), parabasal placenta (maternal-side), cord serum, and maternal serum samples were collected from Guangzhou, China. Eighteen emerging and legacy PFASs and five placental vascular biomarkers were measured. Results showed that higher levels of perfluorooctanoic (PFOA), perfluorooctane sulfonic acid (PFOS), and chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs) were detected in subchorionic placenta compared to parabasal placenta. There were significant associations of PFASs in the subchorionic placenta, but not in the serum, with placental vascular biomarkers (up to 32.5%) and lower birth size. Birth weight was negatively associated with PFOA (ß: -103.8, 95% CI: -186.3 and -21.32) and 6:2 Cl-PFESA (ß: -80.04, 95% CI: -139.5 and -20.61), primarily in subchorionic placenta. Mediation effects of altered placental angiopoietin-2 and vascular endothelial growth factor receptor-2 were evidenced on associations of adverse birth outcomes with intraplacental PFOS and 8:2 Cl-PFESA, explaining 9.5%-32.5% of the total effect. To the best of our knowledge, this study is the first to report on differential intraplacental distribution of PFASs and placental vascular effects mediating adverse birth outcomes and provides novel insights into the placental plate-specific measurement in PFAS-associated health risk assessment.

Nontargeted Identification and Temporal Trends of Per- and Polyfluoroalkyl Substances in a Fluorochemical Industrial Zone and Adjacent Taihu Lake.

Various per- and polyfluoroalkyl substances (PFASs) remain undiscovered and unexplored in the environment. The goals of this study were to discover new species of PFASs in effluent and surface waters from a fluorochemical industrial zone, and to assess their concentration, distribution, and temporal trends in the adjacent natural environment. In total, 83 emerging PFASs from 14 classes were identified, 22 of which were reported for the first time. Authentic standards were synthesized for 13 per- and polyfluoroalkyl ether carboxylic acids (PFECAs), thereby greatly expanding the scope of PFAS-targeted monitoring. The newly identified compounds accounted for 27%-95% of the total PFAS concentrations. Of note, a novel diether carboxylic acid, 2-[2-(trifluoromethoxy)hexafluoropropoxy]tetrafluoropropanoic acid (C7 HFPO-TA) was detected at an extremely high concentration in the fluorochemical zone effluent (447 000 ng/L) and at a median concentration in the fluorochemical zone surface water (670 ng/L), with detectable levels also found in the natural environment, that is, Wangyu River (23 ng/L) and Taihu Lake (5.6 ng/L). The distinct geographic distribution of C7 HFPO-TA suggests transport from the industrial point source to Taihu Lake via the Wangyu River. The concentration of C7 HFPO-TA in Taihu Lake, along with that of many other emerging PFASs, continued to grow in three sampling campaigns from 2016 to 2021. Considering the environmental persistence and toxicity of structurally similar PFECAs (e.g., HFPO-DA), studies on C7 HFPO-TA are urgently needed.

First Report on the Bioaccumulation and Trophic Transfer of Perfluoroalkyl Ether Carboxylic Acids in Estuarine Food Web.

As novel alternatives to legacy poly- and perfluoroalkyl substances (PFAS), perfluoroalkyl ether carboxylic acids (PFECAs) have been widely detected in the environment; however, there is limited information and knowledge regarding their bioaccumulation and trophic transfer behavior along the food chain. This research presents the first known published data on the bioaccumulation and trophic transfer characteristics of PFECAs in a source-impacted estuary. Elevated PFECA concentrations were observed in organisms (for instance, conch, with perfluoro-2-methoxyacetic acid (PFMOAA) concentration reaches up to 16 700 ng/g dry weight (dw)), indicating exposure risks to the consumers. Conch can be acted as a potential environmental bioindicator of PFMOAA. PFMOAA, hexafluoropropylene oxide trimer acid (HFPO-TrA) and PFOA were predominant detected in biotas. On the basis of trophic magnification factors (TMFs), PFECAs with ≥6 perfluorinated carbons (HFPO-TrA, hexafluoropropylene oxide tetramer acid (HFPO-TeA) and perfluoro (3, 5, 7, 9, 11-pentaoxadodecanoic) acid (PFO5DoA)) could be biomagnified along the food chain (TMF > 1), while PFMOAA with the least perfluorinated carbons undergone biodilution (TMF < 1). As seafood is an important dietary source of protein to human, there is a potential health risk related to the consuming polluted aquatic products.

Prenatal exposure to poly-/per-fluoroalkyl substances is associated with alteration of lipid profiles in cord-blood.

INTRODUCTION: Poly-/per-fluoroalkyl substances (PFAS) are widespread environmental pollutants that may induce metabolic perturbations in humans, including particularly alterations in lipid profiles. Prenatal exposure to PFAS can cause lasting effects on offspring metabolic health, however, the underlying mechanisms are still unknown. OBJECTIVES: The goal of the study was to investigate the impact of prenatal PFAS exposure on the lipid profiles in cord blood. METHODS: Herein, we combined determination of bile acids (BAs) and molecular lipids by liquid chromatography with ultra-high-resolution mass spectrometry, and separately quantified cord blood concentrations of sixteen PFAS in a cohort of Chinese infants (104 subjects) in a cross-sectional study. We then evaluated associations between PFAS concentration and lipidome using partial correlation network analysis, debiased sparse partial correlation, linear regression analysis and correlation analysis. RESULTS: PFAS levels showed significant associations with the lipid profiles; specifically, PFAS exposure was positively correlated with triacylgycerols (TG) and several bile acids. Importantly, exposure to perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) were associated with increased levels of TGs with saturated fatty acids while multiple classes of phospholipids were decreased. In addition, several free fatty acids showed significant positive correlations with PFOS. CONCLUSIONS: Our results indicated that prenatal exposure to PFAS mediated metabolic changes, which may explain the associations reported between PFAS exposure and metabolic health later in life.

Temporal Trends in Prenatal Exposure (1998-2018) to Emerging and Legacy Per- and Polyfluoroalkyl Substances (PFASs) in Cord Plasma from the Beijing Cord Blood Bank, China.

Due to developmental toxicity, prenatal exposure to per- and polyfluoroalkyl substances (PFASs) in animals may result in adverse effects on the fetus. However, little information is available on PFASs presence in the human cord plasma. Here, we measured the levels of 37 emerging and legacy PFASs in 650 cord plasma samples collected every 5 years spanning 1998 to 2018 by the Beijing Cord Blood Bank and evaluated changes in PFASs concentrations using generalized additive models. We observed an increase in the concentrations of 24 PFASs (Σ24PFASs) from 1998 to 2003 followed by a decrease every 5 years from 2003 to 2018. For legacy PFASs, similar trends were observed for PFOS, whereas PFOA levels did not decline until 2013. For emerging chemicals, 6:2 Cl-PFESA showed a similar trend as PFOS, and prenatal exposure to 6:2 Cl-PFESA could be traced back to 1998, with a median concentration of 0.411 ng/mL in plasma. Our data showed that prenatal exposure to legacy PFASs has gradually decreased in cord plasma from the Beijing Cord Blood Bank in recent years, and the discovery of the presence of emerging chemicals in 1998 suggested that further evaluation is needed to assess possible health risks to pregnant women and fetuses.

Novel Perfluoroalkyl Ether Carboxylic Acids (PFECAs) and Sulfonic Acids (PFESAs): Occurrence and Association with Serum Biochemical Parameters in Residents Living Near a Fluorochemical Plant in China.

Although perfluoroalkyl ether carboxylic (PFECAs) and sulfonic acids (PFESAs) have been widely detected in environmental matrices, their occurrence in humans and impact on human health remains insufficiently understood. Here, we report on 13 PFECAs and PFESAs in 977 sera samples collected from residents living near a fluorochemical plant in Shandong, China. The sum concentration of these emerging PFECAs accounted for 13% of the total PFASs in the serum of the participants, with the frequent detection of several PFECAs (>95%) (PFMOAA, PFO4DA, and PFO5DoDA at median concentrations of 12.91, 0.142, and 0.987 ng/mL, respectively) and PFESAs (98.7%) (Nafion byproduct 2 at a median concentration of 0.097 ng/mL). Serum PFMOAA, PFO5DoDA, and 6:2 Cl-PFESA levels were significantly higher in males than in females. Positive relationships were observed between age and PFMOAA, 6:2 Cl-PFESA, and H-PFMO2OSA levels, whereas HFPO-TA and PFO5DoDA serum concentrations in the 0-40-year age group were lower than that in the >40-year age group. Furthermore, multivariate linear regression models and sensitivity analyses showed positive associations among PFO5DoDA levels, elevated lipid parameters (cholesterol, low-density lipoprotein cholesterol, and triglycerides), liver function markers (albumin levels and alanine transaminase, aspartate aminotransferase, and glutamyl transpeptidase activities), and uric acid levels. Thus, our results suggest potential health risks from exposure to novel PFESAs and PFECAs (especially PFO5DoDA).

Hepatotoxic Effects of Hexafluoropropylene Oxide Trimer Acid (HFPO-TA), A Novel Perfluorooctanoic Acid (PFOA) Alternative, on Mice.

As an alternative to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer acid (HFPO-TA) has been increasingly used for fluoropolymer manufacture in recent years. Its growing detection in environmental matrices and wildlife raises considerable concern about its potential health risks. Here we investigated the effects of HFPO-TA on mouse liver following 28 days of exposure to 0.02, 0.1, or 0.5 mg/kg/d of HFPO-TA via oral gavage. Results showed that HFPO-TA concentrations increased to 1.14, 4.48, and 30.8 µg/mL in serum and 12.0, 32.2, and 100 µg/g in liver, respectively. Liver injury, including hepatomegaly, necrosis, and increase in alanine aminotransferase activity, was observed. Furthermore, total cholesterol and triglycerides decreased in the liver in a dose-dependent manner. Liver transcriptome analysis revealed that 281, 1001, and 2491 genes were differentially expressed (fold change ≥2 and FDR < 0.05) in the three treated groups, respectively, compared with the control group. KEGG enrichment analysis highlighted the PPAR and chemical carcinogenesis pathways in all three treatment groups. Protein levels of genes involved in carcinogenesis, such as AFP, p21, Sirt1 C-MYC, and PCNA, were significantly increased. Compared with previously published toxicological data of PFOA, HFPO-TA showed higher bioaccumulation potential and more serious hepatotoxicity. Taken together, HFPO-TA does not appear to be a safer alternative to PFOA.

Penetration of PFASs Across the Blood Cerebrospinal Fluid Barrier and Its Determinants in Humans.

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 ( RPFAS, PFASCSF/PFASserum) was positively correlated with the barrier permeability index RAlb (AlbuminCSF/Albuminserum), indicating that barrier integrity was the main determinant of PFAS penetration across the blood-CSF barrier. Positive associations between the RPFAS values of the main PFASs and serum C-reactive protein were observed, implying that inflammation facilitates the penetration of PFASs across the brain barrier.

Occurrence and Tissue Distribution of Novel Perfluoroether Carboxylic and Sulfonic Acids and Legacy Per/Polyfluoroalkyl Substances in Black-Spotted Frog (Pelophylax nigromaculatus).

Research on perfluoroalkyl substances (PFASs) continues to grow. However, very little is known about these substances in amphibians. Here we report for the first time on the occurrence, tissue distribution, and bioaccumulation of two novel PFASs, chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA) and hexafluoropropylene oxide trimer acid (HFPO-TA), in the black-spotted frog (Pelophylax nigromaculatus) from China. Frogs from cities with large-scale fluorochemical industries had significantly greater liver ∑PFAS levels (mean 54.28 ng/g in Changshu; 31.22 ng/g in Huantai) than those from cities without similar industry (9.91 ng/g in Zhoushan; 7.68 ng/g in Quzhou). Females had significantly lower liver PFAS levels than males, and older frogs tended to have lower PFAS levels than younger frogs. Skin, liver, and muscle contributed nearly 80% to the whole body burden of 6:2 Cl-PFESA in males, whereas the female ovary alone accounted for 58.4%. These results suggest substantial maternal transfer of 6:2 Cl-PFESA to eggs, raising concern regarding its developmental toxicity on frogs and other species. The bioaccumulation factor results (6:2 Cl-PFESA > PFOS; HFPO-TA > PFOA) suggest a stronger accumulative potential in the black-spotted frog for these alternative substances compared to their predecessors. Future studies on their toxicity and ecology risk are warranted.

Worldwide Distribution of Novel Perfluoroether Carboxylic and Sulfonic Acids in Surface Water.

Driven by increasingly stringent restrictions on long-chain per- and polyfluoroalkyl substances (PFASs), novel fluorinated compounds have emerged on the market. Here we report on the occurrences of several perfluoroalkyl ether carboxylic and sulfonic acids (PFECAs and PFESAs), including hexafluoropropylene oxide dimer and trimer acids (HFPO-DA and HFPO-TA), ammonium 4,8-dioxa-3 H-perfluorononanoate (ADONA), chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA), and its hydrogen-substituted analogue (6:2 H-PFESA) in surface waters from China ( n = 106), the United States ( n = 12), the United Kingdom ( n = 6), Sweden ( n = 10), Germany ( n = 14), The Netherlands ( n = 6), and Korea ( n = 6). Results showed that HFPO-DA, HFPO-TA, and 6:2 Cl-PFESA (median = 0.95, 0.21, and 0.31 ng/L, respectively) were frequently detected in all countries, indicating ubiquitous dispersal and distribution in global surface waters. The presence of 6:2 H-PFESA was widely detected in China (detection rate > 95%) but not in any other country. Only trace levels of ADONA (0.013-1.5 ng/L) were detected in the Rhine River flowing through Germany. The estimated total riverine mass discharges of HFPO-DA, HFPO-TA, and ΣPFESAs reached 2.6, 6.0, and 4.3 ton/year in five of the major river systems in China. Our results indicated that novel PFECAs and PFESAs might become global contaminants, and future investigations are warranted.

First Report on the Occurrence and Bioaccumulation of Hexafluoropropylene Oxide Trimer Acid: An Emerging Concern.

Here, we report on the occurrence of a novel perfluoroalkyl ether carboxylic acid, ammonium perfluoro-2-[(propoxy)propoxy]-1-propanoate (HFPO-TA), in surface water and common carp (Cyprinus carpio) collected from the Xiaoqing River and in residents residing near a fluoropolymer production plant in Huantai County, China. Compared with the levels upstream of the Xiaoqing River, HFPO-TA concentrations (5200-68500 ng/L) were approximately 120-1600-times higher downstream after receiving fluoropolymer plant effluent from a tributary. The riverine discharge of HFPO-TA was estimated to be 4.6 t/yr, accounting for 22% of total PFAS discharge. In the wild common carp collected downstream from the point source, HFPO-TA was detected in the blood (median: 1510 ng/mL), liver (587 ng/g ww), and muscle (118 ng/g ww). The log BCFblood of HFPO-TA (2.18) was significantly higher than that of PFOA (1.93). Detectable levels of HFPO-TA were also found in the sera of residents (median: 2.93 ng/mL). This is the first report on the environmental occurrence and bioaccumulation of this novel chemical. Our results indicate an emerging usage of HFPO-TA in the fluoropolymer manufacturing industry and raise concerns about the toxicity and potential health risks of HFPO-TA to aquatic organisms and humans.

Novel Chlorinated Polyfluorinated Ether Sulfonates and Legacy Per-/Polyfluoroalkyl Substances: Placental Transfer and Relationship with Serum Albumin and Glomerular Filtration Rate.

Per- and polyfluoroalkyl substances (PFASs) may cross the placental barrier and lead to fetal exposure. However, little is known about the factors that influence maternal-fetal transfer of these chemicals. PFAS concentrations were analyzed in 100 paired samples of human maternal sera collected in each trimester and cord sera at delivery; these samples were collected in Wuhan, China, 2014. Linear regression was used to estimate associations of transfer efficiencies with factors. Chlorinated polyfluorinated ether sulfonates (Cl-PFAESs, 6:2 and 8:2) were frequently detected (>99%) in maternal and cord sera. A significant decline in PFAS levels during the three trimesters was observed. A U-shape trend for transfer efficiency with increasing chain length was observed for both carboxylates and sulfonates. Higher transfer efficiencies of PFASs were associated with advancing maternal age, higher education, and lower glomerular filtration rate (GFR). Cord serum albumin was a positive factors for higher transfer efficiency (increased 1.1-4.1% per 1g/L albumin), whereas maternal serum albumin tended to reduce transfer efficiency (decreased 2.4-4.3% per 1g/L albumin). Our results suggest that exposure to Cl-PFAESs may be widespread in China. The transfer efficiencies among different PFASs were structure-dependent. Physiological factors (e.g., GFR and serum albumin) were observed for the first time to play critical roles in PFAS placental transfer.

Comparative hepatotoxicity of 6:2 fluorotelomer carboxylic acid and 6:2 fluorotelomer sulfonic acid, two fluorinated alternatives to long-chain perfluoroalkyl acids, on adult male mice.

Due to their structural similarities, 6:2 fluorotelomer sulfonic acid (6:2 FTSA) and 6:2 fluorotelomer carboxylic acid (6:2 FTCA) are often used as alternatives to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), respectively. With limited health risk data and 6:2 FTSA detection in water and sludge, the toxicity of these chemicals is of growing concern. Here, adult male mice were exposed with 5 mg/kg/day of 6:2 FTCA or 6:2 FTSA for 28 days to investigate their hepatotoxicological effects. In contrast to 6:2 FTCA, 6:2 FTSA was detected at high and very high levels in serum and liver, respectively, demonstrating bioaccumulation potential and slow elimination. Furthermore, 6:2 FTSA induced liver weight increase, inflammation, and necrosis, whereas 6:2 FTCA caused no obvious liver injury, with fewer significantly altered genes detected compared with that of 6:2 FTSA (39 vs. 412). Although PFOA and PFOS commonly activate peroxisome proliferator-activated receptor α (PPARα), 6:2 FTSA induced an increase in PPARγ and related proteins, but not in lipid metabolism-related genes such as PPARα. Our results showed that 6:2 FTCA and 6:2 FTSA exhibited weak and moderate hepatotoxicity, respectively, compared with that reported for legacies PFOA and PFOS.

Dietary exposure to di-isobutyl phthalate increases urinary 5-methyl-2'-deoxycytidine level and affects reproductive function in adult male mice.

Phthalates are a large family of ubiquitous environmental pollutants suspected of being endocrine disruptors. Epidemiological studies have associated phthalate metabolites with decreased reproductive parameters and linked phthalate exposure with the level of urinary 5-methyl-2'-deoxycytidine (5mdC, a product of methylated DNA). In this study, adult male mice were exposed to 450mg di-isobutyl phthalate (DiBP)/(kg·day) via dietary exposure for 28days. Mono-isobutyl phthalate (MiBP, the urinary metabolite) and reproductive function parameters were determined. The levels of 5mdC and 5-hydroxymethyl-2'-deoxycytidine (5hmdC) were measured in urine to evaluate if their contents were also altered by DiBP exposure in this animal model. Results showed that DiBP exposure led to a significant increase in the urinary 5mdC level and significant decreases in sperm concentration and motility in the epididymis, accompanied with reduced testosterone levels and down-regulation of the P450 cholesterol side-chain cleavage enzyme (P450scc) gene in the mice testes. Our findings indicated that exposure to DiBP increased the urinary 5mdC levels, which supported our recent epidemiological study about the associations of urinary 5mdC with phthalate exposure in the male human population. In addition, DiBP exposure impaired male reproductive function, possibly by disturbing testosterone levels; P450scc might be a major steroidogenic enzyme targeted by DiBP or other phthalates.

Nationwide distribution of perfluoroalkyl ether carboxylic acids in Chinese diets: An emerging concern.

With the phase-out of perfluorooctanoic acid (PFOA) and its replacement by perfluoroalkyl ether carboxylic acids (PFECAs), there is a potential for increased exposure to various new PFECAs among the general population in China. While there are existing studies on dietary exposure to legacy perfluoroalkyl and polyfluoroalkyl substances (PFASs), research on dietary exposure to PFECAs, especially among the general Chinese populace, remains scarce. In the present study, we investigated the distribution of PFECAs in dietary sources from 33 cities across five major regions in China, along with the associated dietary intake. Analysis indicated that aquatic animal samples contained higher concentrations of legacy PFASs compared to those from terrestrial animals and plants. In contrast, PFECAs were found in higher concentrations in plant and terrestrial animal samples. Notably, hexafluoropropylene oxide dimer (HFPO-DA) was identified as the dominant compound in vegetables, cereals, pork, and mutton across the five regions, suggesting widespread dietary exposure. PFECAs constituted the majority of PFAS intake (57 %), with the estimated daily intake (EDI) of HFPO-DA ranging from 2.33 to 3.96 ng/kg bw/day, which corresponds to 0.78-1.32 times the reference dose (RfD) (3.0 ng/kg bw/day) set by the United States Environmental Protection Agency. Given the ubiquity of HFPO-DA and many other PFECAs in the nationwide diet of China, there is an urgent need for further research into these chemicals to establish relevant safety benchmarks or consumption advisory values for the diet.

Associations between serum per- and polyfluoroalkyl substances and thyroid hormones in Chinese adults: A nationally representative cross-sectional study.

Disruption of thyroid homeostasis has been indicated in human studies on the effects of per- and polyfluoroalkyl substances (PFASs). However, limited research exists on this topic within the general Chinese population. Based on a substantial and representative sample of the Chinese adult population, our study provides insight into how PFASs specifically affect thyroid homeostasis. The study included 10 853 participants, aged 18 years and above, sampled from nationally representative data provided by the China National Human Biomonitoring (CNHBM). Weighted multiple linear regression and restricted cubic spline (RCS) models were used to explore the associations between eight individual PFAS concentrations and total thyroxine (T4), total triiodothyronine (T3), and the T4/T3 ratio. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (qgcomp) were employed to explore the joint and independent effects of PFASs on thyroid homeostasis. Both individual PFASs and PFAS mixtures exhibited a significant inverse association with serum T3 and T4 levels, and displayed a positive association with the T4/T3 ratio. Perfluoroundecanoic acid (PFUnDA) [-0.07 (95 % confidence interval (CI): -0.08, -0.05)] exhibited the largest change in T3 level. PFUnDA also exhibited a higher weight compared to other PFAS compounds in qgcomp models. Additionally, a critical exposure threshold for each PFAS was identified based on nonlinear dose-response associations; beyond these thresholds, the decreases in T3 and T4 levels plateaued. Specifically, for perfluoroheptane sulfonic acid (PFHpS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), an initial decline in hormone levels was observed, followed by a slight increase when concentrations surpassed 0.7 ng/mL and 2.5 ng/mL, respectively. Sex-specific effects were more pronounced in females, and significant associations were observed predominantly in younger age groups. These insights contribute to our understanding of how PFAS compounds impact thyroid health and emphasize the need for further research and environmental management measures to address these complexities.