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Exposure to methylmercury (MeHg) and perfluorooctanoic acid (PFOA) can occur simultaneously as both contaminants are found in the same food sources, especially fish, seafood, marine mammals and milk. The aim of this study was to assess the effects of exposure to MeHg (10μgmL⁻¹ in drinking water) and PFOA (10μgmL⁻¹ in drinking water) from gestational day 1 to postnatal day (PND) 21, alone and in combination, on neurobehavioral development and the expression of c-Fos/Jun in different brain regions in the offspring. Our findings showed that exposure to MeHg alone, and exposure to MeHg combined with PFOA significantly induced cliff avoidance reflexes and negative geotaxis reflexes. And these effects appeared to be greater following exposure to MeHg alone. MeHg and/or PFOA exposure did not significantly impair motor coordination functions, or cause significant changes in c-Fos expression in the hippocampus and cerebellum, and spatial learning tests were similar to those in the controls, thus it was impossible to determine whether combined exposure to MeHg and PFOA had any additional effects on both hippocampus and cerebellum regions. However, a significant increase in the frequency of line crossing was observed in rats treated with MeHg or PFOA alone, and there were no significant differences between the MeHg+PFOA-treated group and the controls, suggesting that PFOA was antagonistic to MeHg toxicity in the locomotor activity test. Co-exposure to MeHg and PFOA decreased all tissue Hg concentrations in pups compared to the group exposed to MeHg only, suggesting that PFOA impaired Hg retention in different tissues.

▼ The steroidogenic cytochrome P450 17 (CYP17) enzyme produces dehydroepiandrosterone (DHEA), which is the most abundant circulating endogenous sex steroid precursor. DHEA plays a key role in e.g. sexual functioning and development. To date, no rapid screening assay for effects on CYP17 is available. In this study, a novel assay using porcine adrenal cortex microsomes (PACMs) was described. Effects of twenty-eight suggested endocrine disrupting compounds (EDCs) on CYP17 activity were compared with effects in the US EPA validated H295R (human adrenocorticocarcinoma cell line) steroidogenesis assay. In the PACM assay DHEA production was higher compared with the H295R assay (4.4 versus 2.2nmol/h/mg protein). To determine the additional value of a CYP17 assay, all compounds were also tested for interaction with CYP19 (aromatase) using human placental microsomes (HPMs) and H295R cells. 62.5% of the compounds showed enzyme inhibition in at least one of the microsomal assays. Only the cAMP inducer forskolin induced CYP17 activity, while CYP19 was induced by four test compounds in the H295R assay. These effects remained unnoticed in the PACM and HPM assays. Diethylstilbestrol and tetrabromobisphenol A inhibited CYP17 but not CYP19 activity, indicating different mechanisms for the inhibition of these enzymes. From our results it becomes apparent that CYP17 can be a target for EDCs and that this interaction differs from interactions with CYP19. Our data strongly suggest that research attention should focus on validating a specific assay for CYP17 activity, such as the PACM assay, that can be included in the EDC screening battery.

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Perfluorooctanoic acid (PFOA), a persistent perfluorinated compound, is distributed widely in wildlife and humans. Recent studies showed that PFOA is a suspected endocrine disruptor. But the results are somewhat contradictory and the mechanisms are unclear. In this study, we investigated the endocrine-related effects of PFOA using a series of assays. The lower dose effect of PFOA on development and endocrine-related gene expression were assessed in a short-term zebrafish assay in vivo. To clarify the mechanism of PFOA, in vitro assays were performed. We tested the hormone receptor activities of ER, AR, and TR against PFOA using reporter gene assays. The hormone levels of estradiol (E2) and testosterone (T), the expression of major steroidogenic genes and the key steroidogenic gene regulator steroidogenic factors 1 (SF-1) were measured after PFOA exposure in H295R steroidogenesis assay. Exposure of zebrafish embryo to PFOA resulted in higher expression of esr1, hhex and pax. PFOA is able to interfere with hormone receptor ER and TR. In H295R cells, PFOA could increase the E2 production and decrease the T production, altered the expression of major steroidogenic genes and regulator SF-1. The current findings indicated the potential endocrine-related effects of PFOA and provided novel information for human risk assessment.

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Perfluorooctanoic acid (PFOA), a persistent perfluorinated compound, is distributed widely in wildlife and humans. Recent studies showed that PFOA is a suspected endocrine disruptor. But the results are somewhat contradictory and the mechanisms are unclear. In this study, we investigated the endocrine-related effects of PFOA using a series of assays. The lower dose effect of PFOA on development and endocrine-related gene expression were assessed in a short-term zebrafish assay in vivo. To clarify the mechanism of PFOA, in vitro assays were performed. We tested the hormone receptor activities of ER, AR, and TR against PFOA using reporter gene assays. The hormone levels of estradiol (E2) and testosterone (T), the expression of major steroidogenic genes and the key steroidogenic gene regulator steroidogenic factors 1 (SF-1) were measured after PFOA exposure in H295R steroidogenesis assay. Exposure of zebrafish embryo to PFOA resulted in higher expression of esr1, hhex and pax. PFOA is able to interfere with hormone receptor ER and TR. In H295R cells, PFOA could increase the E2 production and decrease the T production, altered the expression of major steroidogenic genes and regulator SF-1. The current findings indicated the potential endocrine-related effects of PFOA and provided novel information for human risk assessment.

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The composition of impurities in perfluorooctanoic acid (PFOA) was measured and determined to be notably different between lots. Since the purity of PFOA varied, the accuracy of prepared calibration solution concentrations was reduced. In this study, factors influencing the purity were investigated using a Karl Fischer titrator and a LC/MS to support the development of reference materials. The results showed variances of water and isomer/homologue contents under different ambient conditions during sample handling. Moreover, these variances, especially for water, greatly affected the purity of PFOA (0.95–0.99 kg kg⁻¹). Therefore, PFOA of reliable purity should be used for the preparation of calibration solutions.

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The composition of impurities in perfluorooctanoic acid (PFOA) was measured and determined to be notably different between lots. Since the purity of PFOA varied, the accuracy of prepared calibration solution concentrations was reduced. In this study, factors influencing the purity were investigated using a Karl Fischer titrator and a LC/MS to support the development of reference materials. The results showed variances of water and isomer/homologue contents under different ambient conditions during sample handling. Moreover, these variances, especially for water, greatly affected the purity of PFOA (0.95–0.99 kg kg⁻¹). Therefore, PFOA of reliable purity should be used for the preparation of calibration solutions.

▼ The breast cancer resistance protein (Bcrp) is an efflux transporter that participates in the biliary and renal excretion of drugs and environmental chemicals. Recent evidence suggests that pharmacological activation of the peroxisome proliferator activated receptor alpha (PPARα) can up-regulate the hepatic expression of Bcrp. The current study investigated the regulation of hepatic and renal Bcrp mRNA and protein in mice treated with the PPARα agonist perfluorooctanoic acid (PFOA) and the ability of PFOA to alter human BCRP function in vitro. Bcrp mRNA and protein expression were quantified in the livers and kidneys of male C57BL/6 mice treated with vehicle or PFOA (1 or 3mg/kg/day oral gavage) for 7 days. PFOA treatment increased liver weights as well as the hepatic mRNA and protein expression of the PPARα target gene, cytochrome P450 4a14. Compared to vehicle-treated control mice, PFOA increased hepatic Bcrp mRNA and protein between 1.5- and 3-fold. Immunofluorescent staining confirmed enhanced canalicular Bcrp staining in liver sections from PFOA-treated mice. The kidney expression of cytochrome P450 4a14 mRNA, but not Bcrp, was increased in mice treated with PFOA. Micromolar concentrations of PFOA decreased human BCRP ATPase activity and inhibited BCRP-mediated transport in inverted membrane vesicles. Together, these studies demonstrate that PFOA induces hepatic Bcrp expression in mice and may inhibit human BCRP transporter function at concentrations that exceed levels observed in humans.

▼ This study investigates the concentrations and distributions of perfluoroalkyl acids (PFAAs), including perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkane sulphonates (PFSAs), in surface sediments from Laizhou Bay and its adjacent rivers. PFAAs showed much higher levels in the river sediment (with a mean of 5.25ng/g dw) than in the coastal sediment (with a mean of 0.76ng/g dw). Perfluorooctanoic acid (PFOA) was the predominant compound, accounting for 50% to 97% of PFAA concentrations in 70% of the samples. The highest concentrations were detected in the Xiaoqing River, possibly due to the rapid development of the nearby fluorochemical industry. Hydrodynamics strongly influenced the distribution of PFAAs in Laizhou Bay. The hydrophilic property of shorter-chained PFAAs (C 8) allowed them to be transported to the inner bay via currents, to adsorb onto suspended sediment and then to be deposited. The Xiaoqing River showed the highest PFOA concentration (76.9ng/g dw) among the bodies of sediment that had been studied worldwide, which might pose a potential threat for the benthic organisms of this river.

▼ Perfluoroalkyl substances (PFASs) are ubiquitous in the environment world-wide. Our overall objective was to assess the exposure to PFASs experienced by delivering women and their new-borns in the industrial city of Norilsk (arctic Russia) and the rural Aral Sea region of Uzbekistan, with the secondary objective of evaluating the distribution of PFASs between blood cell and plasma fractions. Six PFASs were detected in every sample from Norilsk city with the plasma concentration sequence of: PFOS PFOA>PFNA>FOSA>PFHxS>PFUnDA. In the Uzbekistani samples, only PFOS was reported above the MDL (0.08ng/mL). The median plasma concentrations of PFOS of 11.0ng/mL for the Norilsk mothers was comparable to that reported for western countries, while that for Uzbekistan was considerably lower (0.23ng/mL). Apparent increases in the maternal-cord concentration ratios for both whole blood and plasma were evident with the length of the carbon chain for both the carboxylate and the sulfonate PFASs. The median value of this ratio for FOSA in plasma was the lowest, while that for whole blood was the highest. Other than for FOSA, the observed plasma-whole blood concentration ratios for maternal and umbilical cord blood were consistent with a priori calculations using appropriate packed cell and plasma volumes for neonates and pregnant women at term. Clearly FOSA favored whole blood, and acid-base equilibrium calculations suggested that the resonance-stabilized sulfonamidate ion resides in the blood cell fraction. Thus for PFASs and related compounds with pK_a values with magnitudes comparable to physiological pH, it is pertinent to measure the cell-associated fraction (separately or as whole blood). Our study illustrates that consideration of both the physico-chemical properties of the contaminants and the physiological attributes of blood matrices were helpful in the interpretation of our findings.

▼ This study investigates the concentrations and distributions of perfluoroalkyl acids (PFAAs), including perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkane sulphonates (PFSAs), in surface sediments from Laizhou Bay and its adjacent rivers. PFAAs showed much higher levels in the river sediment (with a mean of 5.25ng/g dw) than in the coastal sediment (with a mean of 0.76ng/g dw). Perfluorooctanoic acid (PFOA) was the predominant compound, accounting for 50% to 97% of PFAA concentrations in 70% of the samples. The highest concentrations were detected in the Xiaoqing River, possibly due to the rapid development of the nearby fluorochemical industry. Hydrodynamics strongly influenced the distribution of PFAAs in Laizhou Bay. The hydrophilic property of shorter-chained PFAAs (C 8) allowed them to be transported to the inner bay via currents, to adsorb onto suspended sediment and then to be deposited. The Xiaoqing River showed the highest PFOA concentration (76.9ng/g dw) among the bodies of sediment that had been studied worldwide, which might pose a potential threat for the benthic organisms of this river.

▼ Perfluoroalkyl substances (PFASs) are ubiquitous in the environment world-wide. Our overall objective was to assess the exposure to PFASs experienced by delivering women and their new-borns in the industrial city of Norilsk (arctic Russia) and the rural Aral Sea region of Uzbekistan, with the secondary objective of evaluating the distribution of PFASs between blood cell and plasma fractions. Six PFASs were detected in every sample from Norilsk city with the plasma concentration sequence of: PFOS PFOA>PFNA>FOSA>PFHxS>PFUnDA. In the Uzbekistani samples, only PFOS was reported above the MDL (0.08ng/mL). The median plasma concentrations of PFOS of 11.0ng/mL for the Norilsk mothers was comparable to that reported for western countries, while that for Uzbekistan was considerably lower (0.23ng/mL). Apparent increases in the maternal-cord concentration ratios for both whole blood and plasma were evident with the length of the carbon chain for both the carboxylate and the sulfonate PFASs. The median value of this ratio for FOSA in plasma was the lowest, while that for whole blood was the highest. Other than for FOSA, the observed plasma-whole blood concentration ratios for maternal and umbilical cord blood were consistent with a priori calculations using appropriate packed cell and plasma volumes for neonates and pregnant women at term. Clearly FOSA favored whole blood, and acid-base equilibrium calculations suggested that the resonance-stabilized sulfonamidate ion resides in the blood cell fraction. Thus for PFASs and related compounds with pK_a values with magnitudes comparable to physiological pH, it is pertinent to measure the cell-associated fraction (separately or as whole blood). Our study illustrates that consideration of both the physico-chemical properties of the contaminants and the physiological attributes of blood matrices were helpful in the interpretation of our findings.

▼ Perfluoroalkyl acids (PFAAs) and polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants representing two classes of environmental contaminants of toxicological concern, especially for infants. Canadian biomonitoring data on these chemicals are limited. The objectives of this study were to measure PFAAs and PBDEs in umbilical cord blood from approximately 100 hospital deliveries in Ottawa (Ontario, Canada) and examine associations with characteristics of the mother and infant. Geometric means were 1.469ng/mL for perfluorooctanoate (PFOA) (95% confidence interval of 1.292-1.671ng/mL), 4.443ng/mL for perfluorooctane sulfonate (PFOS) (95% CI of 3.735-5.285ng/mL), 0.359ng/mL for perfluorononanoic acid (PFNA) (95% CI of 0.318-0.404ng/mL), and 0.579ng/mL for perfluorohexanesulfonate (PFHxS) (95% CI of 0.473-0.709ng/mL). The final multiple regression models indicated that lower gravida, term gestational age, smoking during pregnancy and vaginal delivery were significantly associated with higher levels of PFOS. Similarly, a vaginal delivery was significantly associated with higher PFOA, while weak associations were found with lower gravida and birth weight less than 2500g. Furthermore, higher PFNA concentrations were significantly associated with older mothers, and vaginal delivery, while weakly associated with term gestational age. Elevated PFHxS concentrations were significantly associated with smoking during pregnancy and lower gravida. Similar to reports from other countries, the preponderant PBDE congener measured in the cord blood was PBDE-47. Questions remain on why various studies have reported conflicting results on the association between PFAAs and birth weight.

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The aggregation of multi-walled carbon nanotubes (MWCNTs) in the aqueous phase not only inhibits their extensive utilization in various aspects but also dominates their environmental fate and transport. The role of surfactants at low concentration in the aggregation of MWCNTs has been studied, however the effect of perfluorinated surfactants at low concentration is uncertain. To understand this interfacial phenomenon, the influences of perfluorooctanoic acid (PFOA), and sodium dodecyl sulfate (SDS) as a control, on MWCNT aggregation in the aqueous phase were examined by the UV absorbency method. Influences of pH and cationic species on the critical coagulation concentration (CCC) value were evaluated. The CCC values were dependent on the concentration of PFOA, however a pronounced effect of SDS concentration on the CCC values was not observed. The CCC values of the MWCNTs were 51.6 mmol/L in NaCl and 0.28 mmol/L in CaCl₂ solutions, which suggested pronounced differences in the effects of Na⁺ and Ca²⁺ ions on the aggregation of the MWCNTs. The presence of both PFOA and SDS significantly decreased the CCC values of the MWCNTs in NaCl solution. The aggregation of the MWCNTs took place under acidic conditions and was not notably altered under neutral and alkaline conditions due to the electrostatic repulsion of deprotonated functional groups on the surface of the MWCNTs.

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The aggregation of multi-walled carbon nanotubes (MWCNTs) in the aqueous phase not only inhibits their extensive utilization in various aspects but also dominates their environmental fate and transport. The role of surfactants at low concentration in the aggregation of MWCNTs has been studied, however the effect of perfluorinated surfactants at low concentration is uncertain. To understand this interfacial phenomenon, the influences of perfluorooctanoic acid (PFOA), and sodium dodecyl sulfate (SDS) as a control, on MWCNT aggregation in the aqueous phase were examined by the UV absorbency method. Influences of pH and cationic species on the critical coagulation concentration (CCC) value were evaluated. The CCC values were dependent on the concentration of PFOA, however a pronounced effect of SDS concentration on the CCC values was not observed. The CCC values of the MWCNTs were 51.6 mmol/L in NaCl and 0.28 mmol/L in CaCl₂ solutions, which suggested pronounced differences in the effects of Na⁺ and Ca²⁺ ions on the aggregation of the MWCNTs. The presence of both PFOA and SDS significantly decreased the CCC values of the MWCNTs in NaCl solution. The aggregation of the MWCNTs took place under acidic conditions and was not notably altered under neutral and alkaline conditions due to the electrostatic repulsion of deprotonated functional groups on the surface of the MWCNTs.

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This study analyzed the concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS) in maternal and umbilical cord sera at delivery from the general population in Korea. Seventy samples were analyzed with ion-pairing and LC/MS/MS. PFOS, PFOA and PFHxS were detected in both maternal and umbilical cord sera. There was a high correlation of PFC concentrations between maternal and cord serum samples, implying transplacental transport. Ranking of transplacental transfer efficiency was PFOA>PFHxS>PFOS. Student’s t-tests revealed that concentrations of maternal PFOA were related with decreases in birth weight, birth length and ponderal index, suggesting a possible impact on fetal growth. With multiple logistic regression models, maternal PFOS concentration showed a significant inverse association with ponderal index (OR=0.22; 95% CI, 0.05–0.90). Umbilical cord PFHxS concentration showed a significant inverse association with birth weight (OR=0.26; 95% CI, 0.08–0.85) or a marginally significant inverse association with birth length (OR=0.33; 95% CI, 0.09–1.17). This is the first report demonstrating an inverse association of birth outcomes with PFHxS exposure. Concentrations of maternal PFOA were decreased with parity, implying that delivery is one of the major routes for PFOA elimination in women. This study demonstrated prenatal exposure of PFCs through placental transfer which could result in possible developmental effects in the population sampled. Our results may provide data basis to conduct a larger scale investigation into developmental effects of PFCs in the future and contribute to understanding levels of PFC contaminations from a variety of populations in the globe.

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The fluorotelomer alcohols (FTOHs) have been detected in various environmental compartments, including indoor and outdoor air, in North America and Europe. In our previous studies, FTOHs were detected at a relative higher concentration in outdoor air in the Keihan (Kyoto–Osaka, one of the major industrial zones) area, Japan compared to reported data. The exposure level of FTOHs in indoor air in the Keihan area remains unclear. In the present study, indoor air FTOH concentrations were investigated using a passive air sampler containing activated carbon felts. The indoor air sampling was conducted in 49 households of the Keihan area, during winter and summer 2008. Most samples contained 6:2 FTOH, 8:2 FTOH, 10:2 FTOH and 8:2 FTOAc. The median concentration of 8:2 FTOH (5.84ngm⁻³) was highest among fluorotelomers, followed by those of 10:2 FTOH (1.12ngm⁻³), 6:2 FTOH (0.29ngm⁻³), and others. Significant correlations among fluorotelomers were observed in collected samples. The association between housing conditions and 8:2 FTOH concentrations showed that samples collected from bed rooms have higher 8:2 FTOH concentrations than those collected from other locations. In addition, samples collected in winter showed lower levels of 8:2 FTOH than those collected in summer. These findings suggest that 8:2 FTOH is the predominant component among fluorotelomers in indoor air, and that there are emission sources of fluorotelomers in indoor environments of the Keihan area. Further investigations into the origins of fluorotelomers are needed to evaluate indoor contamination with fluorotelomers.

▼ Background: Disruption of developing immune and respiratory systems by early-life exposure to persistent organic pollutants (POPs) could result into reduced capacity to fight infections and increased risk to develop allergic manifestations later in life. Objectives: To systematically review the epidemiologic literature on the adverse effects of early-life exposure to POPs on respiratory health, allergy and the immune system in infancy, childhood and adolescence. Methods: Based on published guidelines for systematic reviews, two independent researchers searched for published articles in MEDLINE and SCOPUS using defined keywords on POPs and respiratory health, immune function and allergy. Study eligibility criteria were defined to select the articles. Results: This review of 41 studies finds limited evidence for prenatal exposure to DDE, PCBs and dioxins and risk of respiratory infections. Evidence was limited also for postnatal exposure to PCBs, specifically ndl-PCBs, and reduced immune response after vaccination in childhood. The review indicates lack of association between postnatal exposure to PCBs/ndl-PCBs and risk of asthma-related symptoms. For the other exposure-outcome associations reviewed evidence was inadequate. Discussion and conclusion: Current epidemiological evidence suggests that early-life exposure to POPs can adversely influence immune and respiratory systems development. Heterogeneity between studies in exposure and outcome assessment and the small number of studies for any given exposure-outcome relationship currently make comparisons difficult and meta-analyses impossible. Also, mechanisms remain largely unexplored. Recommendations for significantly improving our understanding thus include harmonization of exposure and outcome assessment between studies, conduct of larger studies, long-term assessment of respiratory infections and asthma symptoms in order to identify critical periods of susceptibility, integration of the potential immunotoxic mechanisms of POPs, and use of new statistical tools to detangle the role of multiple exposures on multiple outcomes.

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This study analyzed the concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS) in maternal and umbilical cord sera at delivery from the general population in Korea. Seventy samples were analyzed with ion-pairing and LC/MS/MS. PFOS, PFOA and PFHxS were detected in both maternal and umbilical cord sera. There was a high correlation of PFC concentrations between maternal and cord serum samples, implying transplacental transport. Ranking of transplacental transfer efficiency was PFOA>PFHxS>PFOS. Student’s t-tests revealed that concentrations of maternal PFOA were related with decreases in birth weight, birth length and ponderal index, suggesting a possible impact on fetal growth. With multiple logistic regression models, maternal PFOS concentration showed a significant inverse association with ponderal index (OR=0.22; 95% CI, 0.05–0.90). Umbilical cord PFHxS concentration showed a significant inverse association with birth weight (OR=0.26; 95% CI, 0.08–0.85) or a marginally significant inverse association with birth length (OR=0.33; 95% CI, 0.09–1.17). This is the first report demonstrating an inverse association of birth outcomes with PFHxS exposure. Concentrations of maternal PFOA were decreased with parity, implying that delivery is one of the major routes for PFOA elimination in women. This study demonstrated prenatal exposure of PFCs through placental transfer which could result in possible developmental effects in the population sampled. Our results may provide data basis to conduct a larger scale investigation into developmental effects of PFCs in the future and contribute to understanding levels of PFC contaminations from a variety of populations in the globe.

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The fluorotelomer alcohols (FTOHs) have been detected in various environmental compartments, including indoor and outdoor air, in North America and Europe. In our previous studies, FTOHs were detected at a relative higher concentration in outdoor air in the Keihan (Kyoto–Osaka, one of the major industrial zones) area, Japan compared to reported data. The exposure level of FTOHs in indoor air in the Keihan area remains unclear. In the present study, indoor air FTOH concentrations were investigated using a passive air sampler containing activated carbon felts. The indoor air sampling was conducted in 49 households of the Keihan area, during winter and summer 2008. Most samples contained 6:2 FTOH, 8:2 FTOH, 10:2 FTOH and 8:2 FTOAc. The median concentration of 8:2 FTOH (5.84ngm⁻³) was highest among fluorotelomers, followed by those of 10:2 FTOH (1.12ngm⁻³), 6:2 FTOH (0.29ngm⁻³), and others. Significant correlations among fluorotelomers were observed in collected samples. The association between housing conditions and 8:2 FTOH concentrations showed that samples collected from bed rooms have higher 8:2 FTOH concentrations than those collected from other locations. In addition, samples collected in winter showed lower levels of 8:2 FTOH than those collected in summer. These findings suggest that 8:2 FTOH is the predominant component among fluorotelomers in indoor air, and that there are emission sources of fluorotelomers in indoor environments of the Keihan area. Further investigations into the origins of fluorotelomers are needed to evaluate indoor contamination with fluorotelomers.

▼ Background: Disruption of developing immune and respiratory systems by early-life exposure to persistent organic pollutants (POPs) could result into reduced capacity to fight infections and increased risk to develop allergic manifestations later in life. Objectives: To systematically review the epidemiologic literature on the adverse effects of early-life exposure to POPs on respiratory health, allergy and the immune system in infancy, childhood and adolescence. Methods: Based on published guidelines for systematic reviews, two independent researchers searched for published articles in MEDLINE and SCOPUS using defined keywords on POPs and respiratory health, immune function and allergy. Study eligibility criteria were defined to select the articles. Results: This review of 41 studies finds limited evidence for prenatal exposure to DDE, PCBs and dioxins and risk of respiratory infections. Evidence was limited also for postnatal exposure to PCBs, specifically ndl-PCBs, and reduced immune response after vaccination in childhood. The review indicates lack of association between postnatal exposure to PCBs/ndl-PCBs and risk of asthma-related symptoms. For the other exposure-outcome associations reviewed evidence was inadequate. Discussion and conclusion: Current epidemiological evidence suggests that early-life exposure to POPs can adversely influence immune and respiratory systems development. Heterogeneity between studies in exposure and outcome assessment and the small number of studies for any given exposure-outcome relationship currently make comparisons difficult and meta-analyses impossible. Also, mechanisms remain largely unexplored. Recommendations for significantly improving our understanding thus include harmonization of exposure and outcome assessment between studies, conduct of larger studies, long-term assessment of respiratory infections and asthma symptoms in order to identify critical periods of susceptibility, integration of the potential immunotoxic mechanisms of POPs, and use of new statistical tools to detangle the role of multiple exposures on multiple outcomes.

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Simultaneous determination of bisphenol A, tetrabromobisphenol A, and perfluorooctanoic acid in small household electronics appliances by accelerated solvent extraction-ultra-performance liquid chromatography-tandem mass spectrometry was established. Samples, heated for 5 min, were extracted by toluene/methanol (10:1, v/v) under the pressure 1500 psi at 100°C, and were extracted 3 static cycles with 20 min per cycle. And then 15 mL extractant solvent was used to wash the samples, and at last the sample was purged by nitrogen for 100 s. The partial extractant (10 mL) was concentrated by nitrogen and re-dissolved with 1 mL methanol/water (1:1, v/v). The three compounds were separated by BEH C18 column effectively in 3 min and detected by electrospray ionization mode mass spectrometry. The linear ranges for bisphenol A, perfluorooctanoic acid, and tetrabromobisphenol A were 1–100, 10–1000 ng/mL, and 0.1–10 μg/mL, respectively. The correlation coefficient was greater than 0.996. The LOD and limit of quantitation for three compounds were 0.1, 10, 1 ng/mL, and 0.5, 50, 5 ng/mL, respectively. And the recoveries were 84–92, 76–82, and 72–74%, respectively, with RSD < 5%. The method was successfully used in determining the real samples. The method and the result were confirmed by liquid chromatography-ion trap-time of flight mass spectrometry.

▼ Concentrations, distributions, fate, and partitioning of perfluoroalkyl acids (PFAAs) were investigated in surface water (n=34) collected from the Youngsan and Nakdong River Estuaries of South Korea. Thirteen individual PFAAs in water and suspended solids (SS) were quantified by use of HPLC-MS/MS. PFAAs were detected in all samples, which indicated that they were widely distributed in the study area. Greater concentrations of PFAAs were found at some inland sites which seemed to be affected by direct input from point sources, such as wastewater treatment plants, and/or indirect diffusive sources, such as surface runoff. Spatial distributions of PFAAs in estuaries along transects toward the open sea demonstrated that these chemicals were transported to the outer region primarily by water discharged during the rainy season. Field-based partition coefficients (K_d) for long-chain PFAAs (C>=8) were significantly correlated with salinity (r^2=0.48 to 0.73, p<0.01); K_d values increased exponentially as a function of salinity. Due to the 'salting-out' effect, PFAAs were largely scavenged by adsorption onto SS and/or sediments in estuarine environments. In addition, values for K_d of those PFAAs were directly proportional to the number of carbon atoms in the PFAAs. Salting constants of selected PFAAs were notably greater than those of other environmental organic contaminants, which indicated that adsorption of PFAAs is largely associated with salinity. Overall, the results of the present study will provide better understanding of the fate and transport of PFAAs in the zone of salinity boundary that can be used for developing fate models of PFAAs in the coastal marine environment.

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Simultaneous determination of bisphenol A, tetrabromobisphenol A, and perfluorooctanoic acid in small household electronics appliances by accelerated solvent extraction-ultra-performance liquid chromatography-tandem mass spectrometry was established. Samples, heated for 5 min, were extracted by toluene/methanol (10:1, v/v) under the pressure 1500 psi at 100°C, and were extracted 3 static cycles with 20 min per cycle. And then 15 mL extractant solvent was used to wash the samples, and at last the sample was purged by nitrogen for 100 s. The partial extractant (10 mL) was concentrated by nitrogen and re-dissolved with 1 mL methanol/water (1:1, v/v). The three compounds were separated by BEH C18 column effectively in 3 min and detected by electrospray ionization mode mass spectrometry. The linear ranges for bisphenol A, perfluorooctanoic acid, and tetrabromobisphenol A were 1–100, 10–1000 ng/mL, and 0.1–10 μg/mL, respectively. The correlation coefficient was greater than 0.996. The LOD and limit of quantitation for three compounds were 0.1, 10, 1 ng/mL, and 0.5, 50, 5 ng/mL, respectively. And the recoveries were 84–92, 76–82, and 72–74%, respectively, with RSD < 5%. The method was successfully used in determining the real samples. The method and the result were confirmed by liquid chromatography-ion trap-time of flight mass spectrometry.

▼ Concentrations, distributions, fate, and partitioning of perfluoroalkyl acids (PFAAs) were investigated in surface water (n=34) collected from the Youngsan and Nakdong River Estuaries of South Korea. Thirteen individual PFAAs in water and suspended solids (SS) were quantified by use of HPLC-MS/MS. PFAAs were detected in all samples, which indicated that they were widely distributed in the study area. Greater concentrations of PFAAs were found at some inland sites which seemed to be affected by direct input from point sources, such as wastewater treatment plants, and/or indirect diffusive sources, such as surface runoff. Spatial distributions of PFAAs in estuaries along transects toward the open sea demonstrated that these chemicals were transported to the outer region primarily by water discharged during the rainy season. Field-based partition coefficients (K_d) for long-chain PFAAs (C>=8) were significantly correlated with salinity (r^2=0.48 to 0.73, p<0.01); K_d values increased exponentially as a function of salinity. Due to the 'salting-out' effect, PFAAs were largely scavenged by adsorption onto SS and/or sediments in estuarine environments. In addition, values for K_d of those PFAAs were directly proportional to the number of carbon atoms in the PFAAs. Salting constants of selected PFAAs were notably greater than those of other environmental organic contaminants, which indicated that adsorption of PFAAs is largely associated with salinity. Overall, the results of the present study will provide better understanding of the fate and transport of PFAAs in the zone of salinity boundary that can be used for developing fate models of PFAAs in the coastal marine environment.

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Editor’s Highlight: Species-specific toxicity of chemicals is usually demonstrated in adult animal models. These authors demonstrated the species-specific toxicity of the peroxisome proliferator perfluorooctanoic acid (PFOA) in a developing mouse model. Using wild-type, PPARα-null and PPARα—humanized mice, the authors demonstrated that the developmental/postnatal effects of PFOA are differentially mediated by mouse compared to human PPARα.

▼  Background

Perfluorinated compounds (PFCs) are man-made chemicals that are heat stable, non-flammable and able to repel both water and oils. Biomonitoring research shows global distribution in human, animal and aquatic environments of these chemicals. PFCs have been shown to activate the peroxisome proliferator-activated receptors which play a large role in metabolism and the regulation of energy homeostasis. Previous epidemiological research has also suggested a potential role of PFCs on lipid and glucose metabolism.

Objectives

The objectives of this study were to examine the association between the levels of perfluorinated compounds perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonate (PFHxS) in plasma and metabolic function and plasma lipid levels.

Methods

Using cross-sectional data from the Canadian Health Measures Survey (Cycle 1 2007–2009) we examined the association in adults between plasma levels of PFOA, PFOS and PFHxS (n=2700) on cholesterol outcomes, metabolic syndrome and glucose homeostasis using multivariate linear and logistic regression models.

Results

We found some evidence of a significant association between perfluoroalkyl substances, notably PFHxS, with total cholesterol (TC), low-density lipoprotein cholesterol (LDL), total cholesterol/high density lipoprotein cholesterol ratio (TC/HDL) and non-HDL cholesterol as well as an elevated odds of high cholesterol. We found some associations with PFOA and PFOS in our unweighted models but these results did not remain significant after weighting for sampling strategy. We found no association with metabolic syndrome, or glucose homeostasis parameters.

Conclusions

This study showed lower levels of PFOA and PFOS and slightly higher levels of PFHxS than other published population studies. Our results did not give significant evidence to support the association with cholesterol outcomes with PFOS and PFOA. However, we did observe several significant associations with the PFHxS and cholesterol outcomes (LDL, TC, NON-HDL, TC/HDL ratio).

▼ Background

Perfluorinated compounds (PFCs) are man-made chemicals that are heat stable, non-flammable and able to repel both water and oils. Biomonitoring research shows global distribution in human, animal and aquatic environments of these chemicals. PFCs have been shown to activate the peroxisome proliferator-activated receptors which play a large role in metabolism and the regulation of energy homeostasis. Previous epidemiological research has also suggested a potential role of PFCs on lipid and glucose metabolism.

Objectives

The objectives of this study were to examine the association between the levels of perfluorinated compounds perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonate (PFHxS) in plasma and metabolic function and plasma lipid levels.

Methods

Using cross-sectional data from the Canadian Health Measures Survey (Cycle 1 2007–2009) we examined the association in adults between plasma levels of PFOA, PFOS and PFHxS (n=2700) on cholesterol outcomes, metabolic syndrome and glucose homeostasis using multivariate linear and logistic regression models.

Results

We found some evidence of a significant association between perfluoroalkyl substances, notably PFHxS, with total cholesterol (TC), low-density lipoprotein cholesterol (LDL), total cholesterol/high density lipoprotein cholesterol ratio (TC/HDL) and non-HDL cholesterol as well as an elevated odds of high cholesterol. We found some associations with PFOA and PFOS in our unweighted models but these results did not remain significant after weighting for sampling strategy. We found no association with metabolic syndrome, or glucose homeostasis parameters.

Conclusions

This study showed lower levels of PFOA and PFOS and slightly higher levels of PFHxS than other published population studies. Our results did not give significant evidence to support the association with cholesterol outcomes with PFOS and PFOA. However, we did observe several significant associations with the PFHxS and cholesterol outcomes (LDL, TC, NON-HDL, TC/HDL ratio).

▼ 

Editor’s Highlight: Species-specific toxicity of chemicals is usually demonstrated in adult animal models. These authors demonstrated the species-specific toxicity of the peroxisome proliferator perfluorooctanoic acid (PFOA) in a developing mouse model. Using wild-type, PPARα-null and PPARα—humanized mice, the authors demonstrated that the developmental/postnatal effects of PFOA are differentially mediated by mouse compared to human PPARα.

▼ In this work, we illustrate the ability of the prokaryotic potassium channel KcsA to assemble into a variety of supramolecular clusters of defined sizes containing the tetrameric KcsA as the repeating unit. Such clusters, particularly the larger ones, are markedly detergent-labile and thus, disassemble readily upon exposure to the detergents commonly used in protein purification or conventional electrophoresis analysis. This is a reversible process, as cluster re-assembly occurs upon detergent removal and without the need of added membrane lipids. Interestingly, the dimeric ensemble between two tetrameric KcsA molecules are quite resistant to detergent disassembly to individual KcsA tetramers and along with the latter, are likely the basic building blocks through which the larger clusters are organized. As to the proteins domains involved in clustering, we have observed disassembly of KcsA clusters by SDS-like alkyl sulfates. As these amphiphiles bind to inter-subunit, ''non-annular'' sites on the protein, these observations suggest that such sites also mediate channel-channel interactions leading to cluster assembly.

▼ In this work, we illustrate the ability of the prokaryotic potassium channel KcsA to assemble into a variety of supramolecular clusters of defined sizes containing the tetrameric KcsA as the repeating unit. Such clusters, particularly the larger ones, are markedly detergent-labile and thus, disassemble readily upon exposure to the detergents commonly used in protein purification or conventional electrophoresis analysis. This is a reversible process, as cluster re-assembly occurs upon detergent removal and without the need of added membrane lipids. Interestingly, the dimeric ensemble between two tetrameric KcsA molecules are quite resistant to detergent disassembly to individual KcsA tetramers and along with the latter, are likely the basic building blocks through which the larger clusters are organized. As to the proteins domains involved in clustering, we have observed disassembly of KcsA clusters by SDS-like alkyl sulfates. As these amphiphiles bind to inter-subunit, ''non-annular'' sites on the protein, these observations suggest that such sites also mediate channel-channel interactions leading to cluster assembly.