Accumulation features and temporal trends (2002-2015) for legacy and emerging per- and polyfluoroalkyl substances (PFASs) in finless porpoises bycaught off Korean coasts.

Legacy and emerging per- and polyfluoroalkyl substances (PFASs) were measured in livers of finless porpoises (Neophocaena asiaeorientalis; n = 167) collected in Korean waters from 2002 to 2015 to investigate their occurrence, bioaccumulation feature, temporal trends, and ecotoxicological implications. Perfulorooctane sulfonate (PFOS), perfluoroundecanoate (PFUnDA), and perfluorotridecanoate (PFTrDA) were the predominant PFASs found in the porpoises. The concentration of 6:2 chlorinated polyfluoroalkyl ether sulfonate (F-53B), an alternative to PFOS, was comparable to that of PFTrDA. Perfluorooctane sulfonamide (FOSA), a precursor of PFOS, was also detected in all the porpoises examined. All PFASs, including F-53B, accumulated to higher concentrations in immature porpoises compared with mature specimens, implying substantial maternal transfer and limited metabolizing capacity for PFASs. A significant correlation was observed between PFOS and F-53B concentrations, indicating similar bioaccumulation processes. Based on prenatal exposure and toxicity, F-53B is an emerging contaminant in marine ecosystems. Significantly increasing trends were observed in the concentrations of sulfonates, carboxylates, and F-53B between 2002/2003 and 2010, whereas the FOSA concentration significantly decreased. During 2010-2015, decreasing trends were observed in the concentrations of FOSA and sulfonates, whereas concentrations of carboxylate and F-53B increased without statistical significance, likely due to a gap for the implementation of regulatory actions between sulfonates and carboxylates. Although PFOS and PFOA were found to pose little health risk to porpoises, the combined toxicological effects of other contaminants should be considered to protect populations and to mitigate PFAS contamination in marine ecosystems.

Target and non-target analyses of neutral per- and polyfluoroalkyl substances from fluorochemical industries using GC-MS/MS and GC-TOF: Insights on their environmental fate.

Novel and emerging per- and polyfluoroalkyl substances (PFAS) are a key issue of concern in global environmental studies. In this study, air, sediment, and wastewater samples were collected from areas in and/or surrounded by fluorochemical-related industrial facilities to characterize the contamination profiles of neutral and novel PFAS (n-PFAS) using a gas chromatograph-based target and non-target analyses. Fluorotelomer alcohols were predominant in the samples, accounting for 80 % of the n-PFAS, followed by fluorotelomer acrylates. Air samples collected proximate to the durable water repellent (DWR) facility had the highest concentration of n-PFAS, which was approximately two orders of magnitude higher than those found in others. Non-target analysis identified fluorotelomer iodides and fluorotelomer methacrylate in multiple matrices near DWR facilities, indicating significant contamination of n-PFAS. Levels of both C6- and C8-based PFAS reflected a shift in usage patterns from C8- to C6-based fluorochemicals. Matrix-dependent profiles of n-PFAS revealed that shorter-chain (e.g., C6) and longer-chain (>C8) PFAS were predominant in air and sediment, respectively, implying that air and sediment are mobile and secondary sources of PFAS. Untreated and treated industrial wastewater also contained n-PFAS and their transformation products. The findings shed light on our understanding of the multi-matrix distribution and transport of PFAS.

Identification of Mid-Polar and Polar AhR Agonists in Cetaceans from Korean Coastal Waters: Application of Effect-Directed Analysis with Full-Scan Screening.

Major aryl hydrocarbon receptor (AhR) agonists were identified in extracts of blubber, liver, and muscle from six long-beaked common dolphins (Delphinus capensis) and one fin whale (Balaenoptera physalus) collected from Korean coastal waters using effect-directed analysis. Results of the H4IIE-luc bioassay indicated that the polar fractions of blubber and liver extracts from the fin whale exhibited relatively high AhR-mediated potencies. Based on full-scan screening with high-resolution mass spectrometry, 37 AhR agonist candidates, spanning four use categories: pharmaceuticals, pesticides, cosmetics, and natural products, were selected. Among these, five polar AhR agonists were newly identified through toxicological confirmation. Concentrations of polar AhR agonists in cetaceans were tissue-specific, with extracts of blubber and liver containing greater concentrations than muscle extracts. Polar AhR agonists with great log KOA values (>5) were found to biomagnify in the marine food chain potentially. Polar AhR agonists contributed 8.9% of the observed AhR-mediated potencies in blubber and 49% in liver. Rutaecarpine and alantolactone contributed significantly to the total AhR-mediated potencies of blubber, whereas hydrocortisone was a major AhR contributor in the liver of the fin whale. This study is the first to identify the tissue-specific accumulation of polar AhR agonists in blubber and liver extracts of cetaceans.

Optimization of the QuEChERS method for multi-residue analysis of pharmaceuticals and pesticides in aquaculture products.

The aim of study was to optimize an QuEChERS extraction procedure for simultaneous determination of organic pollutants in aquaculture products. The QuEChERS extracts were measured using LC-HRMS. The target contaminants include 32 pesticides and 20 pharmaceuticals which have not been regulated for the products in Korea. The method was validated according to CODEX guideline (CAC/GL 71-2009). LOD and LOQ for all analytes ranged from 0.1 to 2 µg/kg and from 0.5 to 5 µg/kg, respectively. Intra-day (n = 5) and inter-day (n = 9) accuracy and precision were evaluated with the guideline. The validated method was applied to aquaculture products (n = 303). As a result, 14 pesticides and 8 pharmaceuticals were quantified. Fluxapyroxad, a fungicide frequently detected in domestic surface waters, was found with relatively higher concentration in 17 out of 23 species. It proves that a hydrophobic inland contaminant can be accumulated in the aquaculture products.

Within- and between-person variability of urinary phthalate metabolites and bisphenol analogues over seven days: Considerations of biomonitoring study design.

Urine was used as a part of a human biomonitoring study based on the excretion kinetics of less-persistent contaminants, such as phthalates and bisphenol A (BPA). Despite the advantages of being non-invasive and easy to collect, urine can show a large variability of concentrations of phthalate metabolites and BPA within a person depending on sampling time. Therefore, it is essential to assess the variability of urinary concentrations for comprehensive sampling design in the context of exposure and risk assessments. In this study, 18 phthalate metabolites and eight BPs were measured in all spot urine (n = 401) collected from 12 participants for seven consecutive days to evaluate within- and between-person variabilities. The intraclass correlation coefficients (ICCs) for all spot urines were poor for monomethyl phthalate (ICC: 0.002) and BPA (0.121) but were moderate for monoethyl phthalate (0.514) and monobenzyl phthalate (0.462). Based on the results of di (2-ethylhexyl) phthalate (DEHP) metabolites, the half-life and differences in metabolic capability seem to affect the ICCs. Urinary mono (2-ethylhexyl) phthalate (MEHP), a primary metabolite of DEHP, was suggested as a short-term exposure marker of DEHP in our study. Creatinine- and specific gravity-adjusted concentrations of phthalate metabolites and BPs resulted in increased ICCs, implying requirements for randomly collected spot urine. Most analytes in the first morning voids (FMVs) were correlated significantly with those in the daily composites, suggesting the feasibility of FMVs to estimate the daily exposure dose. This study facilitates a more comprehensive sampling design and data interpretation strategy for human biomonitoring studies.

Exposure to phthalates and bisphenol analogues among childbearing-aged women in Korea: Influencing factors and potential health risks.

Phthalates and bisphenol A (BPA), widely applied in industrial and consumer products, can affect hormones associated with the human reproductive system. Because the incidence of reproductive diseases is increasing, a comprehensive exposure assessment of phthalates and bisphenol analogues (BPs) is required for childbearing-aged women. Phthalate metabolites and BPs were measured in urine samples collected from 509 childbearing-aged women (20-48 years) in Korea to investigate their current exposure status, profiles, influencing factors, and potential health risks. DEHP metabolites and BPA were the dominant compounds found, indicating that they are highly consumed in daily life. Bisphenol S (BPS), as an alternative to BPA, was detected in most urine samples. Total concentrations of phthalate metabolites and BPs ranged from 3.42 to 3570 (GM: 45.6) ng/mL and from

Exposure to organophosphate esters, phthalates, and alternative plasticizers in association with uterine fibroids.

Exposure to endocrine disrupting chemicals is suggested to be responsible for the development or progression of uterine fibroids. However, little is known about risks related to emerging chemicals, such as organophosphate esters (OPEs) and alternative plasticizers (APs). A case-control study was conducted to investigate whether exposures to OPEs, APs, and phthalates, were associated with uterine fibroids in women of reproductive age. For this purpose, the cases (n = 32) and the matching controls (n = 79) were chosen based on the results of gynecologic ultrasonography among premenopausal adult women in Korea and measured for metabolites of several OPEs, APs, and major phthalates. Logistic regression models were employed to assess the associations between chemical exposure and disease status. Factor analysis was conducted for multiple chemical exposure assessments as a secondary analysis. Among OPE metabolites, diphenyl phosphate (DPHP), 2-ethylhexyl phenyl phosphate (EHPHP), and 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) were detected in >80% of the subjects. Among APs, metabolites of di-isononyl phthalate (DINP) and di(2-propylheptyl) phthalate (DPrHpP) were detected in >75% of the urine samples. The odds ratios (ORs) of uterine fibroids were significantly higher among the women with higher exposures to tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-butoxyethyl) phosphate (TBOEP), di(2-ethylhexyl) terephthalate (DEHTP), DPrHpP, and di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH). In addition, urinary concentrations of mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), a sum of five di(2-ethylhexyl) phthalate metabolites (∑5DEHP), and mono(4-methyl-7-hydroxyoctyl) phthalate (OH-MINP) were significantly higher in the cases. In factor analysis, a factor heavily loaded with DPrHpP and DEHP was significantly associated with uterine fibroids, supporting the observation from the single chemical regression model. We found for the first time that several metabolites of OPEs and APs are associated with increased risks of uterine fibroids among pre-menopausal women. Further epidemiological and mechanistic studies are warranted to validate the associations observed in the present study.

Associations of exposure to phthalates and environmental phenols with gynecological disorders.

Phthalates and environmental phenols might be associated with some benign diseases that have been found to be hormone-sensitive. Current knowledge on adverse effects of these chemicals among reproductive women is limited and often controversial. Therefore, the purpose of this study was to investigate the association between the urinary concentration of phthalates and environmental phenols and gynecological disorders from 512 women of reproductive age. The association between chemical concentration and disease in the control and case groups was statistically determined with the questionnaire survey data and measurements using the LC-MS/MS. The results have shown that DEHP metabolites, ethyl paraben and 3,4-DHB showed significant direct associations with leiomyoma and benign ovarian tumors (p < 0.05). We found statistically significant positive relationships between exposure to chemicals (some DEHP metabolites, DHB) and prevalence of gynecologic disorders (p < 0.05). Furthermore, the ORs for leiomyoma associated with these compounds in always user for personal care products (PCPs) was higher than those of sometimes user. High levels of urinary concentrations of these compounds such as DEHP metabolites and parabens and their metabolites showed significant associations with leiomyoma and benign ovarian tumors.

Association of urinary phthalate metabolites and phenolics with adipokines and insulin resistance related markers among women of reproductive age.

Chemicals such as phthalates and phenolics have been associated with metabolic markers in humans. However, most studies have only looked at a limited number of chemicals, and little is known about their potential effects on adipokines in humans. In the present study, the associations between dozens of urinary chemicals, including phthalate metabolites and phenolics, and markers related to insulin resistance as well as major adipokines, were assessed among the women of reproductive age (n = 459, between 20 and 48 years of age) recruited from major cities in Korea between 2015 and 2016. Adipokines such as adiponectin and leptin, and insulin resistance related markers such as glucose and insulin, were analyzed in serum. Associations between urinary chemicals and the adipokines or insulin resistance related markers were assessed in two steps. First, ordinary least squares (OLS) regression was used to assess the association of each urinary chemical with the adipokines or insulin resistance related markers (single-pollutant model). Second, several chemicals were selected using elastic net regression and were subsequently analyzed with OLS regression model (multi-pollutant model), considering simultaneous exposure to multiple chemicals. In both single- and multi-pollutant models, several urinary chemicals consistently showed significant associations with adipokines or the insulin resistance related markers. The sum of di-(2-ethylhexyl) phthalate metabolites (ΣDEHPm) and ethyl paraben (EtP) were associated with increased serum adiponectin levels. Urinary ΣDEHPm levels also showed positive associations with fasting glucose. Moreover, urinary mono-methyl phthalate (MMP), mono-isobutyl phthalate (MiBP), and bisphenol S (BPS) levels showed positive associations with the homeostasis model assessment for insulin resistance (HOMA-IR). Interestingly, urinary propyl paraben (PrP) levels showed a negative association with HOMA-IR, in both models. Our observations show that among many consumer chemicals, phthalates may affect serum adipokines, and thus glucose, and insulin resistance in adult females. Further confirmation is warranted in other populations.