Association of Di(2-ethylhexyl) Terephthalate and Its Metabolites with Nonalcoholic Fatty Liver Disease: An Epidemiology and Toxicology Study.

As an alternative plasticizer to conventional phthalates, di(2-ethylhexyl) terephthalate (DEHTP) has attracted considerable concerns, given its widespread detection in the environment and humans. However, the potential toxicity, especially liver toxicity, posed by DEHTP remains unclear. In this study, based on the 2017-2018 National Health and Nutrition Examination Survey, two metabolites of DEHTP, i.e., mono(2-ethyl-5-hydroxyhexyl) terephthalate (MEHHTP) and mono(2-ethyl-5-carboxypentyl) terephthalate (MECPTP), were found to be present in the urine samples of nearly all representative U.S. adults. Moreover, a positive linear correlation was observed between the concentrations of the two metabolites and the risk of nonalcoholic fatty liver disease (NAFLD) in the population. Results of weighted quantile sum and Bayesian kernel machine regression indicated that MEHHTP contributed a greater weight to the risk of NAFLD in comparison with 12 conventional phthalate metabolites. In vitro experiments with hepatocyte HepG2 revealed that MEHHTP exposure could increase lipogenic gene programs, thereby promoting a dose-dependent hepatic lipid accumulation. Activation of liver X receptor α may be an important regulator of MEHHTP-induced hepatic lipid disorders. These findings provide new insights into the liver lipid metabolism toxicity potential of DEHTP exposure in the population.

Characteristic and health risk of per- and polyfluoroalkyl substances from cosmetics via dermal exposure.

In this work, 45 cosmetic samples were collected from China, and 27 target per- and polyfluoroalkyl substances (PFAS) were analyzed by ultrahigh-performance liquid chromatography-high resolution mass spectrometry. PFAS were found in all samples, including the products marketed for pregnant women, and the total concentrations of PFAS measured in each sample were in the range of 4.05 - 94.9 ng/g. Short-chain perfluorinated carboxylic acids were the dominant compounds contributing to over 60% of the total content. Perfluorobutanoic acid, with high placental transfer efficiency, was the major PFAS in cosmetics for pregnant women. Three emerging PFAS, 2-perfluorohexyl ethanoic acid, 3-perfluoropentyl propanoic acid (5:3) and perfluoro-2-propoxypropanoic acid, were also identified in the cosmetic samples at quantifiable levels. Significantly, positive correlations between individual PFAS were observed, indicating that there may be a common source for PFAS in these samples. Statistical analyses suggested that using plastic containers and precursor substances may be potential sources of PFAS in terminal products, and product aging may increase PFAS levels. From the PFAS analysis of the cosmetics, the margin of safety (MoS) and hazard quotient (HQ) were calculated to assess human health risks through dermal exposure by using these products. Although the MoS and HQ values obtained were deemed acceptable, the cumulative effect caused by composite and long-term exposure to these contaminants needs to be given greater attention by health authorities.

The sources and bioaccumulation of per- and polyfluoroalkyl substances in animal-derived foods and the potential risk of dietary intake.

Per- and polyfluoroalkyl substances (PFAS) have attracted increasing attention due to their environmental persistence and potential toxicity. Diet is one of the main routes of human exposure to PFAS, particularly through the consumption of animal-derived foods (e.g., aquatic products, livestock and poultry, and products derived from them). This review summarizes the source, bioaccumulation, and distribution of PFAS in animal-derived foods and key influential factors. In most environmental media, perfluorooctanoic acid and perfluorooctane sulfonate are the dominant PFAS, with the levels of short-chain PFAS such as perfluorobutyric acid and perfluorohexane sulfonate surpassing them in some watersheds and coastal areas. The presence of PFAS in environmental media is mainly influenced by suspended particulate matter, microbial communities as well as temporal and spatial factors, such as season and location. Linear PFAS with long carbon chains (C ≥ 7) and sulfonic groups tend to accumulate in organisms and contribute significantly to the contamination of animal-derived foods. Furthermore, PFAS, due to their protein affinity, are prone to accumulate in the blood and protein-rich tissues such as the liver and kidney. Species differences in PFAS bioaccumulation are determined by diet, variances in protein content in the blood and tissues and species-specific activity of transport proteins. Carnivorous fish usually show higher PFAS accumulation than omnivorous fish. Poultry typically metabolize PFAS more rapidly than mammals. PFAS exposures in the processing of animal-derived foods are also attributable to the migration of PFAS from food contact materials, especially those in higher-fat content foods. The human health risk assessment of PFAS exposure from animal-derived foods suggests that frequent consumption of aquatic products potentially engender greater risks to women and minors than to adult males. The information and perspectives from this review would help to further identify the toxicity and migration mechanism of PFAS in animal-derived foods and provide information for food safety management.

Per- and Polyfluoroalkyl Substances in Personal Hygiene Products: The Implications for Human Exposure and Emission to the Environment.

Per- and polyfluoroalkyl substances (PFAS) have been related to reproductive toxicity in humans, but their occurrence in some specific personal hygiene products, i.e., sanitary pads, panty liners, tampons, paper diapers, menstrual cups, and bactericidal liquids, has not been extensively studied. This work investigated 31 representative PFAS in six categories of such personal hygiene products (n = 91). Perfluorinated carboxylic acids were the primary PFAS found in the samples, accounting for over 85% of the total concentrations of PFAS. Paper diapers contained the highest sum of PFAS concentrations (64.6 ng/g) followed by sanitary pads (52.3 ng/g) and menstrual cups (21.1 ng/g). The estimated exposure doses of perfluorooctanoic acid through dermal absorption from the use of menstrual cups and paper diapers for infants (adults) were 0.77 and 2.1 (1.2) ng/kg-bw/day, which contributed more than normal dust ingestion. The estimated emission of paper diapers and sanitary pads into the environment was 2.58 and 322 kg/year with an assumed leaching rate of 100%. The potential exposure of PFAS through the use of personal hygiene products observed in this work suggests a previously unreported exposure pathway of these chemicals to humans.

Electrospun fluorinated carbon nanotubes/silk fibroin composite nanofibers for the analysis of perfluoroalkyl and polyfluoroalkyl substances.

Assessment of the exposure risk of perfluoroalkyl and polyfluoroalkyl substances (PFASs) has been of public concern for many years. However, it is a challenging undertaking because of the trace levels of these contaminants in the environment and biological systems. In this work, fluorinated carbon nanotubes/silk fibroin (F-CNTs/SF) nanofibers were for the first time synthesized by electrospinning and evaluated as a new adsorbent in pipette tip-solid-phase extraction to enrich PFASs. The addition of F-CNTs increased the mechanical strength and toughness of the SF nanofibers, thus improving the durability of composite nanofibers. The proteophilicity of silk fibroin formed the basis of the good affinity of this material with PFASs. The adsorption behaviors of PFASs on the F-CNTs/SF were investigated by adsorption isotherm experiments to understand the mechanism of extraction. With analysis using ultrahigh performance liquid chromatography-Orbitrap high-resolution mass spectrometric, low limits of detection (0.006-0.090 µg L-1) and enrichment factors of 13-48 were obtained. Meanwhile, the developed method was successfully applied to the detection of wastewater and human placenta samples. This work provides a new idea for the design of novel adsorbents with proteins integrated in polymer nanostructures, a potential routine and practical monitoring technique for PFASs in environmental and biological samples.

Per- and polyfluoroalkyl substances exposure and its influence on the intestinal barrier: An overview on the advances.

Per- and polyfluoroalkyl substances (PFAS) are a class of artificially synthetic organic compounds that are hardly degraded in the natural environment. PFAS have been widely used for many decades, and the persistence and potential toxicity of PFAS are an emerging concern in the world. PFAS exposed via diet can be readily absorbed by the intestine and enter the circulatory system or accumulate directly at intestinal sites, which could interact with the intestine and cause the destruction of intestinal barrier. This review summarizes current relationships between PFAS exposure and intestinal barrier damage with a focus on more recent toxicological studies. Exposure to PFAS could cause inflammation in the gut, destruction of the gut epithelium and tight junction structure, reduction of the mucus layer, and induction of the toxicity of immune cells. PFAS accumulation could also induce microbial disorders and metabolic products changes. In addition, there are limited studies currently, and most available studies converge on the health risk of PFAS exposure for human intestinal disease. Therefore, more efforts are deserved to further understand potential associations between PFAS exposure and intestinal dysfunction and enable better assessment of exposomic toxicology and health risks for humans in the future.

Cucurbit(n)uril-functionalized magnetic composite for the dispersive solid-phase extraction of perfluoroalkyl and polyfluoroalkyl substances in environmental samples with determination by ultra-high performance liquid chromatography coupled to Orbitrap high-resolution mass spectrometry.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have raised serious public health concerns because of their potential adverse effects in humans as revealed by toxicological and epidemiological research. However, routine monitoring of PFASs is still challenging due to their trace levels in various environmental and biological matrices. In this study, magnetic composite materials based on iron (II, III) oxide (Fe3O4) with surface functionalization by cucurbit(n)uril (CB(n)) (Fe3O4@CB(n)) (n = 6, 7, 8), were prepared and evaluated as new adsorbents for the magnetic solid-phase extraction of nine PFASs in lake water, tap water and fish muscle samples. The Fe3O4@CB(n) was characterized to examine their surface morphologies, sizes magnetism and thermal stability. Featuring good aqueous solution dispersibility, the macrocyclic structure of Fe3O4@CB(n) was also endowed with strong host-guest interactions, allowing extraction and enrichment capability towards the PFASs in complex matrices. MSPE using Fe3O4@CB(7) combination with ultra-high performance liquid chromatography coupled to Orbitrap high-resolution mass spectrometry, gave satisfactory quantitative analytical performance with low limits of detection of 0.004-0.04 µg L-1 and limits of quantification of 0.005-0.1 µg L-1, linearities ranging from 0.01 to 10 µg L-1 with high coefficients of determination (R2 ≥ 0.993), and enrichment factors (15-76) for the nine target PFASs. The method proved to be effective for the enrichment and analysis of trace levels of PFASs in genuine environmental water and fish muscle samples, indicating that Fe3O4@CB(7) has promising applicability as an adsorbent for these contaminants.