Abstract  Spatial trends of concentrations of perfluorinated chemicals (PFCs) were investigated in harbour seal liver tissue from seven locations in Denmark, ranging from the Wadden Sea in the southern North Sea to the Western Baltic. All samples were collected during the phocine distemper epizootic in 2002 which provided access to a large number of comparable samples over a short time period. PFOS was dominating (mean: 92% of ∑PFC) among the PFCs in the samples, followed by considerably lower concentrations of PFHxS (1.8%), PFDA (1.7%), PFNA (1.6%) PFUnA (1.5%), PFOA (0.9%) and PFOSA (0.5%). The concentrations of all the investigated compounds showed significant differences among the seven locations. PFOS showed the highest concentrations in the Wadden Sea, where high burdens have also been recorded in German seals. Most compounds showed a trend towards higher concentrations at one or both extremes of the geographic range. Two different patterns of relative PFC concentrations were detected; one in the inner Danish waters where PFOSA and PFUnA were more prevalent and another in the Wadden Sea and Limfjord where PFOA, PFHxS and PFNA were found in greater proportions. These patterns probably represent Baltic and North Sea contamination sources.

Abstract  Perfluorooctanesulfonate (PFOS) at 1.6-39 ng/g ww and 4.8-200 pg/mL, respectively, perfluorooctanoate (PFOA) at 0.06-0.28 ng/g ww and<0.05-1.8 pg/mL, and perfluorodecanoate (PFDA) at 0.13-0.57 ng/g ww and 0.05-1.8 pg/mL, were detected in all specimens of European Beaver's (Castor fiber) liver as well as in whole blood of Cod (Gadus morhua), Velvet Scoter (Melanitta fusca), Eider Duck (Sommateria mollisima), Long-tailed Duck (Clangula hyemalis), Razorbill (Alca torda), Red-throated Diver (Gavia stellata) sampled in Poland. At smaller concentrations and at less frequency was perfluorononanoate (PFNA) at 0.05-1.4 ng/g ww and<0.2-2 pg/mL, perfluorohexanoate (PFHxA) at 0.03-0.23 ng/g ww and<0.05-0.69 pg/mL, while perfluorohexanesulfonate (PFHxS) at 0.05-4.3 pg/mL and perfluorooctanesulfonamidoacetate (PFOSA) at 0.1-13 pg/mL were also found in Cod as well as in molluscivorous diving-ducks and fish-eating birds but not in Beaver, while perfluoroheptanoate (PFHpA) at<0.05-0.74 pg/mL was found only in Cod.

Abstract  Perfluoroalkylated compounds (PFCs) are used in fire-fighting foams, treatment of clothes, carpets and leather products, and as lubricants, pesticides, in paints and medicine. Recent developments in chemical analysis have revealed that fluorinated compounds have become ubiquitously spread and are regarded as a potential threats to the environment. Due to the carbon-fluorine bond, which has a very high bond strength, these chemicals are extremely persistent towards degradation and some PFCs have a potential for bioaccumulation in organisms. Of particular concern has been the developmental toxicity of PFOS and PFOA, which has been manifested in rodent studies as high mortality of prenatally exposed newborn rats and mice within 24 h after delivery. The nervous system appears to be one of the most sensitive targets of environmental contaminants. The serious developmental effects of PFCs have lead to the upcoming of studies that have investigated neurotoxic effects of these substances. In this review the major findings of the neurotoxicity of the main PFCs and their suggested mechanisms of action are presented. The neurotoxic effects are discussed in light of other toxic effects of PFCs to indicate the significance of PFCs as neurotoxicants. The main findings are that PFCs may induce neurobehavioral effects, particularly in developmentally exposed animals. The effects are, however, subtle and inconclusive and are often induced at concentrations where other toxic effects also are expected. Mechanistic studies have shown that PFCs may affect the thyroid system, influence the calcium homeostasis, protein kinase C, synaptic plasticity and cellular differentiation. Compared to other environmental toxicants the human blood levels of PFCs are high and of particular concern is that susceptible groups may be exposed to a cocktail of substances that in combination reach harmful concentrations.

Abstract  We have evaluated the effect of the perfluorinated fatty acids pentadecafluoro-n-octanoic acid (PFOA) and nonadecafluoro-n-decanoic acid (NDFDA) on the ability of a human B-lymphoblastoid cell line to bind the lipid-binding, membrane-impermeant, fluorescent dye merocyanine 540 (MC540). Subtoxic concentrations of perfluorinated fatty acids (0.9 mM PFOA; 0.5 mM NDFDA) greatly diminish binding of MC540 by normal plasma membranes, as determined by fluorescence flow cytometry. When perfluorinated fatty acids are added to cells at toxic or lethal concentrations (1.2 mM PFOA; 0.75 mM NDFDA), MC540 binding increases dramatically, with entrance of dye to internal membrane domains. Neither perfluorinated fatty acid molecule reduces the ability of surface immunoglobulin to migrate laterally and cap on cells. Our data suggest that perfluorinated fatty acids either interact directly with lipid binding sites for MC540, and thereby inhibit dye intercalation, or alter membrane lipid architecture and lipid packing to diminish MC540 binding. Both possibilities support a direct, physical, membrane-altering mechanism for perfluorinated fatty acid toxicity on mammalian cells.

Abstract  A single ip injection of perfluoro-n-decanoic acid (PFDA) to male Wistar rats resulted in an initially rapid, then gradual decrease in food consumption and a parallel loss of body weight. Body temperatures and resting heart rates were significantly depressed by PFDA treatment. As early as 12 h following a single dose of PFDA, serum thyroxine (T4) levels were significantly reduced and remained depressed throughout the 8 day study. Serum triiodothyronine (T3) was reduced by 35% 12 h following PFDA treatment and remained at that level throughout the study. These preliminary data suggest that an action on the thyroid axis may be an early primary response to PFDA and that some of the observed subsequent effects may in part be secondary to the change in thyroid hormone levels.

Abstract  Perfluorinated compounds (PFCs) are negatively charged and have low pK(a) values in water; therefore, a laboratory-scale electro-microfiltration (EMF) unit that applies a direct-current electrical field across its membrane can greatly enhance their removal from aqueous systems. We examined the effects of an aqueous inorganic matrix (pH: 4, 7, or 10; ionic strength: 0.4-4.8 mM; ionic composition: Na(2)SO(4), NaCl, NH(4)Cl or CaCl(2)) and an organic matrix such as dissolved organic matter (DOM) on the ability of EMF to remove perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Decreased removal of PFOX (X = A or S) was observed when the proton concentration and the ionic strength increased. When the applied electrical field strength was less than the critical electrical field strength (E(critical, HA)), PFOX removal was lower in the presence of DOM. We hypothesize that these matrices affect PFOX rejection by altering membrane zeta potential during filtration in the presence of an electrical field. In addition, EMF was found to remove three other PFCs effectively (perfluorodecanoic acid, perfluorohexane sulfonate, and perfluorohexanoic acid), and was also able to remove 70% PFOX and 80% DOC from real industrial wastewaters.

Abstract  Perfluoroalkyl acids (PFAAs) are globally found in various media, including food and especially fishery products. In the present study, the dietary exposure to 15 perfluoroalkyl acids was assessed for 3 French adult populations, namely high seafood consumers, high freshwater fish consumers, and pregnant women. Purified food extracts were analysed by LC-MS/MS and PFBA, PFPA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnA, PFTrDA, PFTeDA, PFBS, PFHxS, PFHpS, PFOS and PFDS were monitored and quantified according to the isotope dilution principle. Under lower bound (LB) hypothesis (i.e. contamination values<LOD considered as 0), high freshwater fish consumers appear as the most exposed to PFOS (7.5ng.kg(-1) bw.d(-1)), PFUnA (1.3ng.kg(-1) bw.d(-1)), PFDA (0.4ng.kg(-1) bw.d(-1)) and PFHpS (0.03ng.kg(-1) bw.d(-1)) while high seafood consumers appear as the most exposed to PFOA (1.2ng.kg(-1) bw.d(-1)), PFNA (0.2ng.kg(-1) bw.d(-1)) and PFHxS (0.06ng.kg(-1) bw.d(-1)). For all considered populations, the major exposure contributors are fish, seafood and water under LB hypothesis, while dairy products, bread and crispbread are the main contributors under upper bound (UB) hypothesis. Besides this food exposure assessment, further studies are needed to assess the more global PFAA exposure, taking into account indoor and outdoor air, dust and cutaneous contact, which could be other important contributors for this particular class of chemicals.

Abstract  Perfluoroalkyl substances (PFASs) are protein-binding blood-accumulating contaminants that may have detrimental toxicological effects on the early phases of mammalian development. To enable an evaluation of the potential health risks of PFAS exposure for polar bears (Ursus maritimus), an exposure assessment was made by examining plasma levels of PFASs in polar bear mothers in relation to their suckling cubs-of-the-year (~4 months old). Samples were collected at Svalbard in 1998 and 2008, and we investigated the between-year differences in levels of PFASs. Seven perfluorinated carboxylic acids (∑₇PFCAs: PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, and PFTrDA) and two perfluorinated sulfonic acids (∑₂PFSAs: PFHxS and PFOS) were detected in the majority of the mothers and cubs from both years. In mothers and cubs, most PFCAs were detected in higher concentrations in 2008 than in 1998. On the contrary, levels of PFOS were lower in 2008 than in 1998, while levels of PFHxS did not differ between the two sampling years. PFOS was the dominating compound in mothers and cubs both in 1998 and in 2008. Concentration of PFHpA did not differ between mothers and cubs, while concentrations of PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFHxS, and PFOS were higher in mothers than in their cubs. Except from PFHpA, all compounds correlated significantly between mothers and their cubs. The mean cub to mother ratios ranged from 0.15 for PFNA to 1.69 for PFHpA. On average (mean±standard error of mean), the levels of ∑₇PFCAs and ∑₂PFSAs in cubs were 0.24±0.01 and 0.22±0.01 times the levels in their mothers, respectively. Although maternal transfer appears to be a substantial source of exposure for the cubs, the low cub to mother ratios indicate that maternal transfer of PFASs in polar bears is relatively low in comparison with hydrophobic contaminants (e.g. PCBs). Because the level of several PFASs in mothers and cubs from both sampling years exceeded the levels associated with health effects in humans, our findings raise concern on the potential health effects of PFASs in polar bears from Svalbard. Effort should be made to examine the potential health effects of PFASs in polar bears.

Abstract  The ivory gull is a high Arctic seabird species threatened by climate change and contaminant exposure. High levels of contaminants have been reported in ivory gull Pagophila eburnea eggs from Svalbard and the Russian Arctic. The present study investigated associations between high levels of contaminants (organochlorinated pesticides (OCPs), polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs), perfluorinated alkyl substances (PFASs) and mercury (Hg)) and three response variables: eggshell thickness, retinol (vitamin A) and α-tocopherol (vitamin E). Negative associations were found between levels of OCPs, PCBs and BFRs and eggshell thickness (p<0.021) and α-tocopherol (p<0.023), but not with retinol (p>0.1). There were no associations between PFASs and mercury and the three response variables. Furthermore, the eggshell thickness was 7-17% thinner in the present study than in archived ivory gull eggs (≤1930). In general, a thinning above 16 to 20% has been associated with a decline in bird populations, suggesting that contaminant-induced eggshell thinning may constitute a serious threat to ivory gull populations globally.

Abstract  BACKGROUND: Breast cancer (BC) is the most common cancer for women in the western world. From very few cases an extraordinary increase in BC was observed in the Inuit population of Greenland and Canada although still lower than in western populations. Previous data suggest that exposure to persistent organic pollutants (POPs) might contribute to the risk of BC. Rat studies showed that perfluorinated compounds (PFCs) cause significantly increase in mammary fibroadenomas. This study aimed at evaluating the association between serum levels of POPs/PFCs in Greenlandic Inuit BC cases and their controls, and whether the combined POP related effect on nuclear hormone receptors affect BC risk.

METHODS: Thirty-one BC cases and 115 controls were sampled during 2000-2003 from various Greenlandic districts. The serum levels of POPs, PFCs, some metals and the combined serum POP related effect on estrogen- (ER), androgen- (AR) and Ah-receptor (AhR) transactivity were determined. Independent student t-test was used to compare the differences and the odds ratios were estimated by unconditional logistic regression models.

RESULTS: We observed for the very first time a significant association between serum PFC levels and the risk of BC. The BC cases also showed a significantly higher concentration of polychlorinated biphenyls at the highest quartile. Also for the combined serum POP induced agonistic AR transactivity significant association to BC risk was found, and cases elicited a higher frequency of samples with significant POP related hormone-like agonistic ER transactivity. The AhR toxic equivalent was lowest in cases.

CONCLUSIONS: The level of serum POPs, particularly PFCs, might be risk factors in the development of BC in Inuit. Hormone disruption by the combined serum POP related xenoestrogenic and xenoandrogenic activities may contribute to the risk of developing breast cancer in Inuit. Further investigations are needed to document these study conclusions.

Abstract  A well-defined subsample of 128 subadult (3-5 years) polar bears (Ursus maritimus) from 19 sampling years within the period 1984-2006 was investigated for perfluoroalkyl contaminants (PFCs), Linear regression analysis of logarithmic-transformed median concentrations showed significant annual increases for PFOS (4.7%), PFNA (6.1%), PFUnA (5.9%), PFDA (4.3%), PFTrA (8.5%), PFOA (2.3%), and PFDoA (5.2%). For four of the PFCs, a LOESS smoother model provided significantly better descriptions, revealing steeper linear annual increases for PFOSA of 9.2% after 1990 and between 18.6 and 27.4% for PFOS, PFDA, and PFTrA after 2000. Concentrations of Sigma PFCs, by 2006, exceeded the concentrations of all conventional OHCs (organohalogen compounds), of which several have been documented to correlate with a number of negative health effects. If the PFC concentrations in polar bears continue to increase with the steepest observed trends, then the lowest no-adverse-effect level (NOAEL) and lowest-adverse-effect level (LOAEL) detected for rats and monkeys will be exceeded in 2014-2024. In addition, the rapidly increasing concentrations of PFCs are likely to cause cumulative and combined effects on the polar bear, compounding the already detected threats from OHCs.

Abstract  Lake Ontario water and sediment collected from tributary, nearshore, and open lake sites were analyzed for perfluoroalkyl substances (PFASs), namely perfluoroalkyl carboxylic acids (PFCAs, F(CF(2))(n)CO(2)(-); n=6-11,13) and perfluoroalkane sulfonic acids (PFSAs, F(CF(2))(n)SO(3)(-); n=6,8,10). Survey results of surface sediment and water indicated that shorter chained PFASs were predominant in and near urban/industrial area watersheds, while longer chained PFASs were predominant in fine-grained sediment from major depositional basins. Niagara River suspended solids (1981-2006) demonstrated temporal trends that may have been influenced by recent changes in North American production and use of PFASs. Perfluorooctane sulfonate (PFOS) reached a peak concentration in 2001 of 1.1 ng/g, followed by a decrease from 2001 to 2006 (half-life=9 years). Perfluorooctanoic acid (PFOA) increased from 2001 to 2006 (doubling time= 2 years) reaching a peak concentration of 0.80 ng/g. In contrast, three sediment cores from western, central, and eastern Lake Ontario showed increasing temporal trends to surface sediment for all PFASs. PFOA and PFOS concentrations increased from 1988 to 2004 (doubling time= ~ 4 years) in the western Lake Ontario core. The observed variations in temporal trends from different environmental compartments may be a result of the physico-chemical properties of PFASs, ongoing emissions, and the environmental transformation and degradation of PFAS precursor compounds.

Abstract  A total of 27 per- and polyfiuorinated compounds (PFCs) were determined in both house dust (n = 10) and indoor air (n = 10) from selected homes in Catalonia, Spain. Concentrations were found to be similar or lower than those previously reported for household microenvironments in other countries. Ten PFCs were detected in all house dust samples. The highest mean concentrations corresponded to perfluorodecanoic acid (PFDA) and perfluorononanoic acid (PFNA), 10.7 ng/g (median: 1.5 ng/g) and 10.4 ng/g (median: 5.4 ng/g), respectively, while the 8:2 fluorotelomer alcohol (FTOH) was the dominating neutral PFC at a concentration of 0.41 ng/g (median: 0.35 ng/g). The indoor air was dominated by the FTOHs. especially the 8:2 FTOH at a mean (median) concentration of 51 pg/m(3) (median: 42 pg/m(3)). A limited number of ionic PFCs were also detected in the indoor air samples. Daily intakes of PFCs were estimated for average and worst case scenarios of human exposure from indoor sources. For toddlers, this resulted in average intakes of Sigma ionic PFCs of 4.9 ng/day (0.33 ng/kg(bw)/day for a 15 kg toddlers) and Sigma neutral PFCs of 0.072 ng/day (0.005 ng/kg(bw)/day) from house dust. For adults, the average daily intakes of dust were 3.6 and 0.053 ng/day (0.05 and 0.001 ng/kg(bw)/day for a 70 kg adult) for Sigma ionic and Sigma neutral PFCs, respectively. The average daily inhalation of Sigma neutral PFCs was estimated to be 0.9 and 1.3 ng/day (0.06 and 0.02 ng/kg(bw)/day) for toddlers and adults, respectively. For PFOS, the main ionic PFC detected in indoor air samples, the median intakes (based on those samples where PFOS was detected), resulted in indoor exposures of 0.06 and 0.11 ng/day (0.004 and 0.002 ng/kg(bw)/day) for toddlers and adults, respectively. Based on previous studies on dietary intake and drinking water consumption, both house dust and indoor air contribute significantly less to PFC exposure within this population. (C) 2011 Elsevier Ltd. All rights reserved.

Abstract  Eleven perfluorinated alkyl acids (PFAAs) were analyzed in plasma from a total of 600 American Red Cross adult blood donors from six locations in 2010. The samples were extracted by protein precipitation and quantified by using liquid chromatography tandem mass spectrometry (HPLC/MS/MS). The anions of the three perfluorosulfonic acids measured were perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS). The anions of the eight perfluorocarboxylic acids were perfluoropentanoate (PFPeA), perfluorohexanoate (PFHxA), perfluoroheptanoate (PFHpA), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnA), and perfluorododecanoate (PFDoA). Findings were compared to results from different donor samples analyzed at the same locations collected in 2000-2001 (N = 645 serum samples) and 2006 (N = 600 plasma samples). Most measurements in 2010 were less than the lower limit of quantitation for PFBS, PFPeA, PFHxA, and PFDoA. For the remaining analytes, the geometric mean concentrations (ng/mL) in 2000-2001, 2006, and 2010 were, respectively, PFHxS: (2.25, 1.52, 1.34); PFOS (34.9, 14.5, 8.3); PFHpA (0.13, 0.09, 0.05); PFOA (4.70, 3.44, 2.44); PFNA (0.57, 0.97, 0.83); PFDA (0.16, 0.34, 0.27), and PFUnA (0.10, 0.18, 0.14). The percentage decline (parentheses) in geometric mean concentrations from 2000-2001 to 2010 were PFHxS (40%), PFOS (76%), and PFOA (48%). The decline in PFOS suggested a population halving time of 4.3 years. This estimate is comparable to the geometric mean serum elimination half-life of 4.8 years reported in individuals. This similarity supports the conclusion that the dominant PFOS-related exposures to humans in the United States were greatly mitigated during the phase-out period.

Abstract  Precise age-specific average body weight estimates are necessary for deterministic risk assessments, and an accurate body weight distribution is equally important in probabilistic risk assessments. Age-specific body weight distributions for U.S. residents are estimated using NHANES (National Health and Nutrition Examination Survey) data collected in four surveys over the last 24 years. The weighted mean and standard deviation of natural log-transformed body weights are computed for single-year age groups and population age-specific weight patterns further described using piece-wise polynomial spline functions and nonparametric age-smoothed trend lines. These functions are used to compare distributional changes in age-specific body weight in the United States from the first NHANES survey in 1976?1980 to the most recent in 1999?2002. Analysis demonstrates that age- and sex-specific average body weight changes over this time period are not uniform. Use of these functions to compute body weight distributions for selected child-age categories is demonstrated.

Abstract  Perfluorononanoic acid (PFNA,C9),a synthetic perfluorinated chemical containing nine carbons, accumulates and is biomagnified through food webs. This compound has been detected in the serum of humans and wildlife and has the potential for reproductive interference. Few studies, however, have reported the effects of PFNA exposure on male reproduction. To determine this, male rats were orally dosed for 1, 3 and 5 mg/kg day PFNA or with vehicle for 14 days. In the present study, serum testosterone levels were decreased. while estradiol levels were increased dramatically in rats receiving 5 mg PFNA/kg day. Spermatogenic cells from rats that received 5 mg PFNA/kg day exhibited apoptotic features including crescent chromatin condensation and chromatin margination. Flow cytometric analysis and TUNEL assays revealed a dose-dependent increase of apoptotic cell numbers. In addition, expression of Fas and Bax mRNA levels were upregulated significantly, and Bcl-2 mRNA levels were downregulated markedly in the 3 and 5 mg/kg day groups. A dose-dependent increase in levels of active caspase-8 and no significant changes of active caspase-9 were observed. Our results indicate that PFNA exposure can lead to cell apoptosis in rat testis, and this apoptosis was probably associated with the Fas death receptor-dependent apoptotic pathway. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Abstract  Some pesticides may interfere with the female hormonal function, which may lead to negative effects on the reproductive system through disruption of the hormonal balance necessary for proper functioning. Previous studies primarily focused on interference with the estrogen and/or androgen receptor, but the hormonal function may be disrupted in many more ways through pesticide exposure. The aim of this review is to give an overview of the various ways in which pesticides may disrupt the hormonal function of the female reproductive system and in particular the ovarian cycle. Disruption can occur in all stages of hormonal regulation: 1. hormone synthesis; 2. hormone release and storage; 3. hormone transport and clearance; 4. hormone receptor recognition and binding; 5. hormone postreceptor activation; 6. the thyroid function; and 7. the central nervous system. These mechanisms are described for effects of pesticide exposure in vitro and on experimental animals in vivo. For the latter, potential effects of endocrine disrupting pesticides on the female reproductive system, i.e. modulation of hormone concentrations, ovarian cycle irregularities, and impaired fertility, are also reviewed. In epidemiological studies, exposure to pesticides has been associated with menstrual cycle disturbances, reduced fertility, prolonged time-to-pregnancy, spontaneous abortion, stillbirths, and developmental defects, which may or may not be due to disruption of the female hormonal function. Because pesticides comprise a large number of distinct substances with dissimilar structures and diverse toxicity, it is most likely that several of the above-mentioned mechanisms are involved in the pathophysiological pathways explaining the role of pesticide exposure in ovarian cycle disturbances, ultimately leading to fertility problems and other reproductive effects. In future research, information on the ways in which pesticides may disrupt the hormonal function as described in this review, can be used to generate specific hypotheses for studies on the effects of pesticides on the ovarian cycle, both in toxicological and epidemiological settings.

Abstract  Background: Evidence of associations between prenatal exposure to perfluoroalkyl substances (PFASs) and fetal thyroid hormones (THs) is controversial, and few studies have estimated the associations, while addressing the high correlations among multiple PFASs. We aimed to examine the associations between prenatal PFAS exposure and thyroid hormone concentrations in cord blood. Methods: A total of 300 mother-infant pairs from the Shanghai-Minhang Birth Cohort Study were included. We measured the concentrations of eight PFASs in maternal plasma samples collected at 12–16 gestational weeks, as well as those of total thyroxine (T4), free T4 (FT4), total triiodothyronine (T3), free T3 (FT3), and thyroid stimulating hormone (TSH) in cord plasma. We estimated the associations between maternal PFAS concentrations and TH concentrations using linear regression and Bayesian kernel machine regression (BKMR) models. Results: In BKMR models, higher PFAS mixture concentrations were associated with increased T3 concentrations, and there were suggestive associations with increased FT3 concentrations. For single-exposure effects in BKMR models, a change in PFDA, PFUdA, and PFOA concentrations from the 25th to 75th percentile was associated with a 0.04 (95%CrI: − 0.01, 0.09), 0.02 (95%CrI: − 0.03, 0.07), and 0.03 (95%CrI: − 0.001, 0.06) nmol/L increase in T3 concentrations, respectively. PFOA, PFNA, and PFDA were the predominant compounds in PFASs-FT3 associations, and the corresponding estimates were 0.11 (95% CrI: 0.02, 0.19), − 0.17 (95% CrI: − 0.28, − 0.07), and 0.12 (95% CrI: − 0.004, 0.24) pmol/L, respectively. A change in PFNA and PFOA concentrations from the 25th to 75th percentile was associated with a − 1.69 (95% CrI: − 2.98, − 0.41) μIU/mL decrease and a 1.51 (95% CrI: 0.48, 2.55) μIU/mL increase in TSH concentrations. The associations of PFOA and PFNA with T3/FT3 were more pronounced in boys, while those with TSH were more pronounced in girls. Conclusion: Our results suggest that prenatal exposure to multiple PFASs was associated with thyroid hormones in cord blood. However, individual PFAS had varied effects—differing in magnitude and direction—on fetal thyroid hormones.

Abstract  Previous years, the incidence of autoimmune thyroid diseases has increased worldwide. The presence of many pollutants in the environment suspected to be thyroid disruptors may have contributed to the observed increase. Unfortunately, the results from epidemiological studies assessing the association between pollution and thyroid disorders remain inconsistent, maybe due to a nearly complete neglect of the mixture effect. The blood levels of 12 brominated flame retardants, 3 polychlorinated biphenyls, 16 organochlorine pesticides, 7 perfluoroalkyl substances and 16 phenolic organohalogens were measured in 35 hypothyroid and 44 hyperthyroid volunteers and in 160 individuals from the general population designed as controls. Weighted quantile sum (WQS) regressions were performed to compute indexes representing the mixture of POPs, and we assessed the relations with thyroid disorders. Nineteen pollutants were detected in more than 40% of the individuals and were thus included in the WQS indexes. The WQS index was statistically significantly associated with an increased odds of hypothyroidism (odds ratio (OR) = 98.1; 95% CI: 5.51-1747) with the highest weights attributed to PCB 138 (w = 0.210), 3-OH-CB 180 (w = 0.197), 4-OH-CB 146 (w = 0.188), 4',4-DDE (w = 0.156) while there were no evidence of a relation with increased odds of hyperthyroidism. Given the relative low number of individuals included in the present investigation, standard WQS methodology could not be used, this study should thus be considered as a preliminary, hypothesis-generating study. Nevertheless, these results highlighted the importance of considering the potential effect of chemical mixture when studying endocrine disruptors.

Abstract  Poly- and perfluoroalkyl substances (PFAS) are a broad class of synthetic compounds produced since the 1940s that are found in environment and in most consumer products, including food and drinking water. PFAS induce several toxicological effects, as the epidemiological studies have revealed immunotoxicity and neurotoxicity effects included. Although epidemiological studies have shown that the long-term exposure would affect various organisms and human health, the intimate molecular mechanisms are yet to be elucidated. Appropriate adverse outcome pathways can be used in the future to develop mechanistic assays to predict adverse effects upon human's exposure to PFAS and bring new information on interspecies circulation of these ubiquitous compounds.

Abstract  In 2013 a contamination of drinking water by perfluoroalkylated substances (PFASs) was discovered in areas of the Veneto Region (northern Italy). In this study the exposure to PFASs of people living in the aforesaid areas was characterized: contaminant serum concentrations were measured and compared with those of a control population group living in neighboring areas at background exposure (based on available drinking water data). The enrolled population was also genotyped for the OATP1A2*3 allelic variant, possibly affecting PFAS excretion and hence the internal dose. The difference in PFAS concentrations between exposed and not exposed subjects was significantly larger for nine of the 12 substances analyzed, and confirmed that water contamination had resulted in an appreciable high exposure of the residing population over time. Within the group of exposed subjects, subgroups at different exposure levels were identified. The contamination of drinking water of the residence area was found to be the main factor influencing PFAS serum levels; in addition to water contamination, other relevant influencing factors were sex, the years of residence and raising own livestock. No relationship with the genetic trait for the studied renal transporter was evidenced. These results provide a baseline characterization of PFAS exposure of the monitored population groups for further studies, planned to be carried out in the near future.

Abstract  BACKGROUND: Perfluoroalkyl substances (PFASs) are persistent chemicals with suspected endocrine disrupting abilities applied in consumer products. PFASs have potentially modulating effects on glucose homeostasis. Insulin resistance prevails during third trimester of pregnancy, and this challenge of glucose homeostasis may reveal putative effects of PFAS concentrations on glycemic status.

OBJECTIVE: To investigate associations between five serum PFASs and glucose-related outcomes in pregnant Danish women based on their risk of gestational diabetes mellitus (GDM).

METHODS: In the prospective Odense Child Cohort serum concentrations of five PFASs - perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) - were measured at median gestational week (GW) 11 in pregnant women. An oral glucose tolerance test (OGTT) was performed at GW 28. The statistical analysis was conducted among 158 women with high GDM risk and 160 women with low GDM risk matched by gestational age. Multiple linear regression models were performed to estimate associations between PFAS concentrations and glucose, insulin, C-peptide, homeostatic model of assessment of insulin resistance (HOMA-IR) and beta cell function (HOMA-%β), and insulin sensitivity (Matsuda index) during the 2-h OGTT.

RESULTS: In women with high risk for GDM, a two-fold increase in PFHxS concentration was significantly associated with increased fasting glucose, fasting insulin and HOMA-IR after adjusting for age, parity, educational level and pre-pregnancy BMI. Adjusting for the same confounders, a doubling in PFNA concentration was associated with higher fasting insulin and HOMA-%β. In women with low GDM risk, no associations were found between PFAS concentrations and glucose-related outcomes.

CONCLUSION: PFHxS and PFNA concentrations were associated with impaired glycemic status in metabolically vulnerable pregnant women and might further enhance the risk of developing GDM.

Abstract  As a result of their ubiquitous presence in the environment perfluoroalkyl acids (PFAAs) have been demonstrated in numerous organisms worldwide, in particular in those of higher trophic levels. The fact that PFAAs have been detected in various human matrices, together with the resultant potential human health risks, knowledge of possible paths of entry and distribution in various ecosystems, is of great importance. In this context pooled samples of terrestrial ecosystems - roe deer liver (n = 141), earthworms (n = 44) as well as leaves from beech and poplar trees (n = 70) - from the year 1989-2015 were obtained from the German Environmental Specimen Bank and examined for the presence of 11 PFAAs for the first time. In addition to determining individual and total PFAA concentrations, temporal trends have been deduced in order to determine the effectiveness of regulatory measures. The highest total mean concentration of PFAAs (sum of the concentrations of the 11 analytes) were 9.9 μg/kg in the roe deer liver samples, followed by earthworm samples with a mean PFAA concentration of 3.5 μg/kg and leaves with a mean total concentration of 2.5 μg/kg. In regard to temporal trends there was a significant reduction of concentrations for perfluorooctane sulfonate, perfluorooctanoic acid, perfluorononanoic acid and perfluorodecanoic acid in roe deer liver from 2003 to 2015, an indication of the effectiveness of regulatory measures. The same is true for the perfluorooctane sulfonate concentrations in earthworms and for perfluorooctanoic acid concentrations in the leaves. In contrast, an increase in perfluorobutanoic acid concentrations was observed from 2003 to 2015 in all three matrices. In summary it must be noted that in spite of the discernible effectiveness of minimization strategies, PFAAs are still detectable in terrestrial matrices and concentrations of other PFAAs as perfluorobutanoic acid appear to be increasing.