Toxicokinetics of perfluorocarboxylate isomers in rainbow trout

Perfluorooctanoate (PFOA) and other perfluorocarboxylates (PFCAs) are widely dispersed in the environment. Current and/or historical production of PFOA and fluorochemical precursors was conducted by telomerization and electrochemical fluorination (ECF). Telomer products typically contain linear chains of perfluorocarbons, and ECF products are a mixture of linear and branched isomers. The objective of the present study was to examine the role of toxicokinetics on PFCA isomer profiles in fish since monitoring studies have revealed a predominance of n-isomers of PFCAs in biota. Using dietary exposure, rainbow trout were administered technical ECF PFOA isomers (6.9 microg/kg/d), linear perfluorononanoate (1.4 microg/kg/d n-PFNA), and isopropyl PFNA (1.1 microg/kg/d iso-PFNA) for 36 d and then switched to a 40-d clean diet. Throughout exposure and depuration phases, blood and tissue sampling ensued. The accumulation ratio (AR) revealed similar accumulation propensity of n-PFOA and two minor branched PFOA isomers; however, the majority of branched isomers had lower AR values than n-PFOA. Enrichment of n-PFOA and n-PFNA relative to most branched isomers was consistent in all tissues. First-order elimination (k(d)) and half-life (t1/2) values were calculated. The largest t1/2 corresponded to n-PFNA followed by iso-PFNA. In ECF PFOA isomers, both n-PFOA and one minor branched isomer had the largest t1/2, suggesting that this minor isomer could be diagnostic of ECF exposure using environmental PFOA isomer patterns. Results of lower-dose ECF PFOA exposure showed similar results to the high-dose study; it is possible that both scenarios resulted in saturation of processes involved in PFCA transport. As such, the toxicokinetics of PFCA isomers at environmentally realistic levels may deviate from the results of the present study.     

Disposition of perfluorinated acid isomers in Sprague-Dawley rats; part 1: single dose

Perfluorinated acids (PFAs) and their precursors (PFA-precursors) exist in the environment as linear and multiple branched isomers. These isomers are hypothesized to have different biological properties, but no isomer-specific data are currently available. The present study is the first in a two-part project examining PFA isomer-specific uptake, tissue distribution, and elimination in a rodent model. Seven male Sprague-Dawley rats were administered a single gavage dose of approximately 500 microg/kg body weight perfluorooctane sulfonate (C(8)F(17)SO(3)(-), PFOS), perfluorooctanoic acid (C(7)F(15)CO(2)H, PFOA), and perfluorononanoic acid (C(8)F(17)CO(2)H, PFNA) and 30 microg/kg body weight perfluorohexane sulfonate (C(6)F(13)SO(3)(-), PFHxS). Over the subsequent 38 d, urine, feces, and tail-vein blood samples were collected intermittently, while larger blood volumes and tissues were collected on days 3 and 38 for isomer analysis by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). For all PFAs, branched isomers generally had lower blood depuration half-lives than the corresponding linear isomer. The most remarkable exception was for the PFOS isomer containing an alpha-perfluoromethyl branch (1m-PFOS), which was threefold more persistent than linear PFOS, possibly due to steric shielding of the hydrophilic sulfonate moiety. For perfluoromonomethyl-branched isomers of PFOS, a structure-property relationship was observed whereby branching toward the sulfonate end of the perfluoroalkyl chain resulted in increased half-lives. For PFHxS, PFOA, and PFOS, preferential elimination of branched isomers occurred primarily via urine, whereas for PFNA preferential elimination of the isopropyl isomer occurred via both urine and feces. Changes in the blood isomer profiles over time and their inverse correlation to isomer elimination patterns in urine, feces, or both provided unequivocal evidence of significant isomer-specific biological handling. Source assignment based on PFA isomer profiles in biota must therefore be conducted with caution, because isomer profiles are unlikely to be conserved in biological samples.     

Isomer profiles of perfluorochemicals in matched maternal, cord, and house dust samples: manufacturing sources and transplacental transfer

Background: Perfluorochemicals (PFCs) are detectable in the general population and in the human environment, including house dust. Sources are not well characterized, but isomer patterns should enable differentiation of historical and contemporary manufacturing sources. Isomer-specific maternal–fetal transfer of PFCs has not been examined despite known developmental toxicity of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in rodents.Objectives: We elucidated relative contributions of electrochemical (phased out in 2001) and telomer (contemporary) PFCs in dust and measured how transplacental transfer efficiency (TTE; based on a comparison of maternal and cord sera concentrations) is affected by perfluorinated chain length and isomer branching pattern.Methods: We analyzed matching samples of house dust (n = 18), maternal sera (n = 20), and umbilical cord sera (n = 20) by isomer-specific high-performance liquid chromatography tandem mass spectrometry.Results: PFOA isomer signatures revealed that telomer sources accounted for 0–95% of total PFOA in house dust (median, 31%). This may partly explain why serum PFOA concentrations are not declining in some countries despite the phase-out of electrochemical PFOA. TTE data indicate that total branched isomers crossed the placenta more efficiently than did linear isomers for both PFOS (p < 0.01) and PFOA (p = 0.02) and that placental transfer of branched isomers of PFOS increased as the branching point moved closer to the sulfonate (SO₃^–) end of the molecule.Conclusions: Results suggest that humans are exposed to telomer PFOA, but larger studies that also account for dietary sources should be conducted. The exposure profile of PFOS and PFOA isomers can differ between the mother and fetus—an important consideration for perinatal epidemiology studies of PFCs.     

Isomer-specific accumulation of perfluorooctane sulfonate in the liver of chicken embryos exposed in ovo to a technical mixture

Prior to its recent phaseout, perfluorooctane sulfonate (PFOS) was produced by electrochemical fluorination processes, which yielded technical mixtures composed of linear isomer (～65-79%) and several branched isomers (～21-35%). Because PFOS can biomagnify in wildlife, birds that occupy higher trophic levels are at increased risk of exposure. We hypothesized that the pharmacokinetic properties of PFOS are isomer-specific in developing chicken (Gallus gallus domesticus) embryos exposed to technical grade PFOS (T-PFOS). In the present study, T-PFOS was composed of 62.7% linear isomer (L-PFOS), and 37.3% branched isomer, including six mono(trifluoromethyl)-branched isomers and four bis(trifluoromethyl)-branched isomers. Concentrations of 0.1, 5, or 100?μg/g of T-PFOS were injected into the air cell of chicken eggs prior to incubation. After pipping, compared with T-PFOS, the PFOS isomer profile in embryonic liver tissue for the 0.1?μg/g dose group showed 21% enrichment in the proportion of L-PFOS with a corresponding decrease in the proportion of branched isomers. Not all branched isomers were discriminated against at equal rates. The proportion of two mono(trifluoromethyl)-branched isomers and three bis(trifluoromethyl)-branched isomers decreased to a greater degree than other branched isomers. In contrast, the mono-branched isomer, P6MHpS, was overrepresented in the low-dose group. In the higher dose groups, L-PFOS was still enriched but only by approximately 10%, which indicated a dose-dependent change in isomer composition relative to T-PFOS. These results show that accumulation of PFOS in chicken embryo livers is dependent on the presence and position of branches on the alkyl backbone. This supports the hypothesis that the pharmacokinetics of PFOS are isomer-specific in biota, and may help explain why wildlife PFOS burdens are dominated by L-PFOS relative to T-PFOS mixtures.     

Toxicity of perfluorooctane sulfonic acid and perfluorooctanoic acid on freshwater macroinvertebrates (Daphnia magna and Moina macrocopa) and fish (Oryzias latipes)

Because of their global distribution, persistence, and tendency to bioaccumulate, concerns about perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are growing. We determined the toxicity of PFOS and PFOA in several freshwater organisms, including two cladocerans, Daphnia magna and Moina macrocopa, and the teleost Oryzias latipes. In general, PFOS is approximately 10 times more toxic than PFOA in these organisms. In M. macrocopa, the median lethal concentration (LC50) was 17.95 mg/L for PFOS and 199.51 mg/L for PFOA. Moina macrocopa exhibited greater sensitivity than D. magna to both perfluorinated compounds in both acute and chronic exposures. In the 48-h acute toxicity test, M. macrocopa was approximately two times more sensitive than D. magna. In the 7-d chronic toxicity test, M. macrocopa showed significant reproductive changes at 0.31 mg/L for PFOS, which was approximately seven times lower than the effect concentrations observed over the 21-d exposure in D. magna. Two-generation fish toxicity tests showed that parental exposure to both compounds affected the performance of offspring. Unexposed progeny-generation (F1) fish exhibited elevated mortality and histopathological changes that were correlated with exposure in the parental generation (F0). Continuous exposure from F0 through F1 generations increased the extent of adverse effects. Considering the persistent nature of PFOS and PFOA, more research is required to determine potential consequences of long-term exposure to these compounds in aquatic ecosystems.     

Perfluoroalkyl Substances in the Blood of Wild Rats and Mice from 47 Prefectures in Japan: Use of Samples from Nationwide Specimen Bank

Numerous studies have reported on the global distribution, persistence, fate, and toxicity of perfluoroalkyl and polyfluoroalkyl substances (PFASs). However, studies on PFASs in terrestrial mammals are scarce. Rats can be good sentinels of human exposure to toxicants because of their habitat, which is in close proximity to humans. Furthermore, exposure data measured for rats can be directly applied for risk assessment because many toxicological studies use rodent models. In this study, a nationwide survey of PFASs in the blood of wild rats as well as surface water samples collected from rats’ habitats from 47 prefectures in Japan was conducted. In addition to known PFASs, combustion ion chromatography technique was used for analysis of total fluorine concentrations in the blood of rats. In total, 216 blood samples representing three species of wild rats (house rat, Norway rats, and field mice) were analyzed for 23 PFASs. Perfluorooctanesulfonate (PFOS; concentration range <0.05-148 ng/mL), perfluorooctane sulfonamide (PFOSA; <0.1–157), perfluorododecanoate (<0.05–5.8), perfluoroundecanoate (PFUnDA; <0.05–51), perfluorodecanoate (PFDA; <0.05–9.7), perfluorononanoate (PFNA; <0.05–249), and perfluorooctanoate (PFOA) (<0.05–60) were detected >80 % of the blood samples. Concentrations of several PFASs in rat blood were similar to those reported for humans. PFSAs (mainly PFOS) accounted for 45 % of total PFASs, whereas perfluoroalkyl carboxylates (PFCAs), especially PFUnDA and PFNA, accounted for 20 and 10 % of total PFASs, respectively. In water samples, PFCAs were the predominant compounds with PFOA and PFNA found in >90 % of the samples. There were strong correlations (p < 0.001 to p < 0.05) between human population density and levels of PFOS, PFNA, PFOA, and PFOSA in wild rat blood.     

Pilot study on the perfluorooctanesulfonate and perfluorooctanoate exposure of the German general population

Perfluorinated chemicals (PFCs) are used in a wide variety of consumer products. Major fields of application include surfactants, surface protection (e.g., for textiles, carpets, and upholstery), paper treatment (e.g., for food packages), and lubricants. Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are raw materials or manufacturing aids for some PFCs and can be released of those by biotic and/or metabolic decomposition. Due to their widespread use, persistence and bioaccumulative properties they are taken up by the general population from different sources. This might be a problem for environmental medicine because in animal studies PFOS and PFOA provoked various types of cancer and showed developmental toxic potential besides other adverse health effects.

We determined the PFOS and PFOA plasma concentrations of 105 non-smokers out of the German general population as a first estimate of the exposure situation in Germany. We employed an analytical method based on serum protein precipitation followed by HPLC with MS/MS-detection. The median plasma concentrations of all participants were 22.3 and 6.8 μg/l, the 95th percentiles 54.3 and 14.6 μg/l for PFOS and PFOA, respectively. These values are comparable with those of other biomonitoring studies. In our study, men were higher burdened both with PFOS (median: 27.1 vs. 19.9 μg/l) and PFOA (median: 8.3 vs. 5.8 μg/l) than women. No significant influence of age on PFOS and PFOA plasma concentrations could be observed. A strong correlation (r=0.82) between PFOS and PFOA plasma levels indicates the same exposure sources. The ubiquitous internal exposure of the general population to PFOS and PFOA must lead to further activities primarily regarding clarification of sources, metabolism, pharmacokinetics, and health effects.     

Recent experimental results of effects of perfluoroalkyl substances in laboratory animals – Relation to current regulations and guidance values

The detection of perfluoroalkyl substances (PFAS) in surface and drinking water from various countries raised the attention to the presence of these chemicals in environmental probes and led to several regulatory actions to limit exposure in human beings. There was particular concern about perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), due to their former wide-spread use. Recently, several institutions published revisions of former regulatory or recommended maximum concentrations in drinking water and food, which are markedly lower than the former values. The present short overview describes the current regulations for PFAS and compares them with the outcome of several experimental studies in laboratory animals at low-level exposure to PFOA and PFOS. In addition, regulations for short-chain PFAS are presented which, due to lack of toxicological information, are evaluated according to the concepts of Threshold of Toxicological Concern (TTC) or the Health-related Indication Values (HRIV).     

The influence of time, sex and geographic factors on levels of perfluorooctane sulfonate and perfluorooctanoate in human serum over the last 25 years

Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are important perfluorochemicals (PFCs) in various applications. Recently, it has been shown that these chemicals are widespread in the environment, wildlife and humans. But the kinds of factors that affect their levels in serum are unclear, and it is also not clear whether exposure to them is increasing or not. To investigate the impacts of time, geographical location and sex on the levels of these chemicals, we measured PFOS and PFOA concentrations in human sera samples collected both historically and recently in Miyagi, Akita and Kyoto Prefectures in Japan. The PFOS and PFOA levels in sera [Geometric Mean (Geometric Standard Deviation)] (microg/L) in 2003 ranged from 3.5 (2.9) in Miyagi to 28.1 (1.5) in Kyoto for PFOS and from 2.8 (1.5) to 12.4 (1.4) for PFOA. Historical samples collected from females demonstrated that PFOS and PFOA concentrations have increased by factors of 3 and 14, respectively, over the past 25 yr. There are large sex differences in PFOS and PFOA concentrations in serum at all locations. Furthermore, there are predominant regional differences for both PFOS and PFOA concentrations. In Kyoto the concentrations of PFOA in dwellers who had lived in the Kinki area for more than 2 yr were significantly higher than in people who had recently moved into the area, in both sexes. This finding suggests that there are sources of PFOA in the Kinki area that have raised the PFOA serum levels of its inhabitants. Further studies are needed to elucidate these sources in the Kinki area of Japan.     

Occurrence of Perfluoroalkyl Surfactants in Water, Fish, and Birds from New York State

Concentrations of perfluorooctanesulfonate (PFOS) and several other perfluoroalkyl surfactants (PASs) were determined in nine major water bodies (n = 51) of New York State (NYS). These PASs were also measured in the livers of two species of sport fish (n = 66) from 20 inland lakes in NYS. Finally, perfluorinated compounds were measured in the livers of 10 species of waterfowl (n = 87) from the Niagara River region in NYS. PFOS, perfluorooctanoic acid (PFOA), and perfluorohexanesulfonate (PFHS) were ubiquitous in NYS waters. PFOA was typically found at higher concentrations than were PFOS and PFHS. Elevated concentrations of PFOS were found in surface waters of Lake Onondaga, and elevated concentrations of PFOA were found in the Hudson River. PFOS was the most abundant perfluorinated compound in all fish and bird samples. PFOS concentrations in the livers of fishes ranged from 9 to 315 ng/g wet weight. PFOS, PFOA, and PFOSA (perfluorooctanesulfonamide) concentrations in smallmouth and largemouth bass (taken together) caught in remote mountain lakes with no known point sources of PAS contamination were 14 to 207, < 1.5 to 6.1, and < 1.5 to 9.8 ng/g wet weight, respectively. PFOS concentrations in the livers of birds ranged from 11 to 882 ng/g wet weight. PFOS concentrations were 2.5-fold greater (p = 0.001) in piscivorous birds than in non-piscivorous birds. However, PFOA, PFOSA, and PFHS were not found in bird livers. Overall, average concentrations of PFOS in fish were 8850-fold greater than those in surface water. An average biomagnification factor of 8.9 was estimated for PFOS in common merganser relative to that in fish. This study highlights the significance of dietary fish in PFOS accumulation in the food chain. Furthermore, our results provide information on the distribution of PASs in natural waters, fish, and several bird species in NYS.     

Excretion of PFOA and PFOS in Male Rats During a Subchronic Exposure

Perfluorinated compounds (PFCs), a class of synthetic surfactants that are widely used, have become global environmental contaminants because of their high persistence and bioaccumulation. An increasing number of studies have described the pharmacokinetics of PFCs following in vivo exposure, however, few papers have focused on the excretion of these compounds during a period of consecutive exposure. In this study, the excretions of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in male Sprague–Dawley rats gavaged consecutively for 28 days were investigated and compared. The faster elimination rate in urine compared to feces indicated that urinary excretion is the primary clearance route in rats for either PFOA or PFOS. During the first 24 h after administration of PFOA (5 and 20 mg/kg body weight/day), about 24.7–29.6% of the oral dose was excreted through urine and feces, while for PFOS, the excretion amounts were only 2.6–2.8% of the total gavaged doses (5 and 20 mg/kg body weight/day). The excretion rates of both PFCs increased with increasing exposure doses. The higher elimination rate of PFOA through excretion indicated its lower accumulation in rats, thus inducing possible lower toxicities compared to PFOS.     

Perfluorinated compounds--exposure assessment for the general population in Western countries

Perfluorinated compounds (PFCs) can currently be detected in many environmental media and biota, as well as in humans. Because of their persistence and their potential to accumulate they are of toxicological concern. The present review presents the current knowledge of PFC monitoring data in environmental media relevant for human exposure. In this context, PFC concentrations in indoor and ambient air, house dust, drinking water and food are outlined. Furthermore, we summarize human biomonitoring data of PFC levels in blood, breast milk, and human tissues. An estimate of the overall exposure of the general adult population is provided and compared with tolerable intake values. Using a simplified model, the average (and upper) level of daily exposure including all potential routes amounts to 1.6 ng/kg(body weight) (8.8 ng/kg(body weight)) for PFOS and 2.9 ng/kg(body weight) (12.6 ng/kg(body weight)) for PFOA in adults in the general population. The majority of exposure can be attributed to the oral route, mainly to diet. Overall, the contribution of PFOS and PFOA precursors to total exposure seems to be limited. Besides this background exposure of the general population, a specific additional exposure may occur which causes an increased PFC body burden. This has been observed in populations living near PFC production facilities or in areas with environmental contamination of PFCs. The consumption of highly contaminated fish products may also cause an increase in PFC body burdens.     

Impacts of two perfluorinated compounds (PFOS and PFOA) on human hepatoma cells: cytotoxicity but no genotoxicity?

Perfluorinated compounds (PFCs) and particularly two of them, perfluoroctanoate (PFOA) and perfluorooctanesulfonate (PFOS), have been widely produced and used since 1950. They both persist in the environment and accumulate in wildlife and humans. The toxicity of PFOS and PFOA has been studied extensively in rodents with several adverse effects mainly a hepatocarcinogenic potential. Carcinogenic effects are not highlighted in humans' studies. In this study, we investigated the cytotoxic and genotoxic effects of PFOA and PFOS using human HepG2 cells after 1 or 24h of exposure. The cytotoxic and genotoxic potential was evaluated by MTT assay, single cell gel electrophoresis (SCGE) assay and micronucleus assay respectively. We measured the intracellular generation of reactive oxygen species (ROS) using dichlorofluorescein diacetate to identify a potential mechanism of toxicity. We observed a cytotoxic effect of PFOA and PFOS after 24h of exposure starting from a concentration of 200 μM (MTT: -14.6%) and 300 μM (MTT: -51.2%) respectively. We did not observe an increase of DNA damage with the comet assay or micronucleus with the micronucleus assay after exposure to the two PFCs. After 24h of exposure, both PFOA and PFOS highlight a decrease of ROS generation (-5.9% to -23%). We did not find an effect after an hour of exposure. Our findings show that PFOA and PFOS exert a cytotoxic effect on the human cells line HepG2 but nor PFOA or PFOS could induce an increase of DNA damage (DNA strand breaks and micronucleus) or reactive oxygen species at the range concentration tested. Our results do not support that oxidative stress and DNA damage are relevant for potential adverse effects of PFOA and PFOS. These results tend to support epidemiological studies that do not show evidence of carcinogenicity.     

Prenatal exposure to perfluoroalkyl substances,immune-related outcomes,and lung function in children from a Spanish birth cohort study

BackgroundPrenatal exposure to perfluoroalkyl substances (PFASs) has been associated with impaired immune and respiratory health during childhood but the evidence is inconsistent and limited for lung function. We studied the association between prenatal PFASs exposure and immune and respiratory health, including lung function, up to age 7 years in the Spanish INMA birth cohort study.MethodsWe assessed four PFASs in maternal plasma samples collected during the 1st trimester of pregnancy (years: 2003–2008): perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorononanoate (PFNA). Mothers reported the occurrence (yes/no) of lower respiratory tract infections, wheezing, asthma, and eczema in the previous 12 months at 1.5 and 4 years of the child (n = 1188) and at 7 years (n = 1071). At ages 4 (n = 503) and 7 (n = 992) years lung function was assessed using spirometry tests.ResultsThe most abundant PFASs were PFOS and PFOA (geometric means: 5.80 and 2.31 ng/mL, respectively). The relative risk of asthma during childhood per each doubling in PFNA concentration was 0.74 (95 CI%: 0.57, 0.96). The relative risk of eczema during childhood per every doubling in PFOS concentration was 0.86 (95 CI%: 0.75, 0.98). Higher PFOA concentrations were associated with lower forced vital capacity and lower forced expiratory volume in 1 s z-scores at 4 years [β (95 CI %): −0.17 (−0.34, −0.01) and −0.13 (−0.29, 0.03), respectively], but not at 7 years.ConclusionThis longitudinal study suggests that different PFASs may affect the developing immune and respiratory systems differently. Prenatal exposure to PFNA and PFOS may be associated with reduced risk of respiratory and immune outcomes, particularly asthma and eczema whereas exposure to PFOA may be associated with reduced lung function in young children. These mixed results need to be replicated in follow-up studies at later ages.     

Relationships of perfluorooctanoate and perfluorooctane sulfonate serum concentrations between mother-child pairs in a population with perfluorooctanoate exposure from drinking water

Background: There are limited data on the associations between maternal or newborn and child exposure to perfluoroalkyl acids (PFAAs), including perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS). This study provides an opportunity to assess the association between PFAA concentrations in mother–child pairs in a population exposed to PFOA via drinking water.Objectives: We aimed to determine the relationship between mother–child PFAA serum concentrations and to examine how the child:mother ratio varies with child’s age, child’s sex, drinking-water PFOA concentration, reported bottled water use, and mother’s breast-feeding intention.Methods: We studied 4,943 mother–child pairs (children, 1–19 years of age). The child:mother PFAA ratio was stratified by possible determinants. Results are summarized as geometric mean ratios and correlation coefficients between mother–child pairs, overall and within strata.Results: Child and mother PFOA and PFOS concentrations were correlated (r = 0.82 and 0.26, respectively). Up to about 12 years of age, children had higher serum PFOA concentrations than did their mothers. The highest child:mother PFOA ratio was found among children ≤ 5 years (44% higher than their mothers), which we attribute to in utero exposure and to exposure via breast milk and drinking water. Higher PFOS concentrations in children persisted until at least 19 years of age (42% higher than their mothers). Boys > 5 years of age had significantly higher PFOA and PFOS child:mother ratios than did girls.Conclusion: Concentrations of both PFOA and PFOS tended to be higher in children than in their mothers. This difference persisted until they were about 12 years of age for PFOA and at least 19 years of age for PFOS.     

Developmental neurotoxicity of perfluorinated chemicals modeled in vitro

BACKGROUND: The widespread detection of perfluoroalkyl acids and their derivatives in wildlife and humans, and their entry into the immature brain, raise increasing concern about whether these agents might be developmental neurotoxicants. OBJECTIVES: We evaluated perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonamide (PFOSA), and perfluorobutane sulfonate (PFBS) in undifferentiated and differentiating PC12 cells, a neuronotypic line used to characterize neurotoxicity. METHODS: We assessed inhibition of DNA synthesis, deficits in cell numbers and growth, oxidative stress, reduced cell viability, and shifts in differentiation toward or away from the dopamine (DA) and acetylcholine (ACh) neurotransmitter phenotypes. RESULTS: In general, the rank order of adverse effects was PFOSA > PFOS > PFBS approximately PFOA. However, superimposed on this scheme, the various agents differed in their underlying mechanisms and specific outcomes. Notably, PFOS promoted differentiation into the ACh phenotype at the expense of the DA phenotype, PFBS suppressed differentiation of both phenotypes, PFOSA enhanced differentiation of both, and PFOA had little or no effect on phenotypic specification. CONCLUSIONS: These findings indicate that all perfluorinated chemicals are not the same in their impact on neurodevelopment and that it is unlikely that there is one simple, shared mechanism by which they all produce their effects. Our results reinforce the potential for in vitro models to aid in the rapid and cost-effective screening for comparative effects among different chemicals in the same class and in relation to known developmental neurotoxicants.     

Perfluoroalkyl acids in children and their mothers: Association with drinking water and time trends of inner exposures—Results of the Duisburg birth cohort and Bochum cohort studies

BackgroundPerfluoroalkyl acids (PFAAs) are widely distributed in the environment and humans are globally exposed with them. Contaminated drinking water can considerably contribute to the inner exposure levels.ObjectivesWe report the results of a human biomonitoring study with mother–child pairs living in two German cities, one city with PFAA contaminated drinking water in the sub μg/l-range (Bochum) and the other one without contamination (Duisburg). Furthermore, we studied time trends of exposure levels within the Duisburg cohort study.MethodsWe measured seven PFAAs (PFOS, PFOA, PFHxS, PFNA, PFBS, PFDeA, PFDoA) in blood samples by high performance liquid chromatography and tandem mass spectrometry. Samples were taken during pregnancy, from umbilical cord blood (2000–2002), 6–7 years (5th follow-up) and 8–10 years after birth (7th follow-up). The consumption of drinking water was recorded by a standardized questionnaire. Statistical analyses were calculated with multiple linear regression models.ResultsChildren and mothers from Bochum showed higher PFOS and PFOA plasma concentrations than from Duisburg. The median concentrations (μg/l) for children were: PFOS 4.7 vs. 3.3; PFOA 6.0 vs. 3.6 μg/l (p ≤ 0.05). Consumption of >0.7 l (children) and >0.9 l (mothers) drinking water/day was associated with 13–18% higher PFOS, PFOA and PFHxS concentrations in children (p ≤ 0.01), and 22% higher PFOA in mothers (p ≤ 0.05). Within the Duisburg cohort, PFAA levels in children peaked in the 5th follow-up study (medians (μg/l): cord plasma: 2.7 (PFOS); 1.9 (PFOA); 5th follow-up: 3.6 (PFOS); 4.6 (PFOA); 7th follow-up: 3.3 (PFOS); 3.6 (PFOA)). PFOS concentrations in mothers declined from pregnancy to the 5th follow-up (medians: 8.7 vs. 4.0 μg/l).ConclusionResidents exposed to PFOS and PFOA through drinking water showed significantly higher PFOS and PFOA concentrations in blood plasma. Although PFAA concentrations in the children slightly decreased from the 5th to the 7th follow-up, we detected increasing exposure trends with increasing age in the 7th follow-up.     

Bioaccumulation and distribution of perfloroalkyl acids in seafood products from Bohai Bay, China

Ten perfluoroalkyl acids (PFAAs) were measured in seafood collected from Bohai Bay, China in 2010. The summed concentrations of the PFAAs were in the ranges of not detected to 194?ng/g dry weight and 4.0 to 304?ng/g dry weight for invertebrates and fish, respectively. The levels of perflurooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) in the seafood were lower than those from North America, the Mediterranean Sea, and South Korea. Living habitat, trophic level, and feeding habits had important impacts on the bioaccumulation and distribution of PFAAs in the seafood. The species at higher trophic levels had the potential to accumulate more PFAAs than benthic invertebrates. Tidal-flat organisms tended to accumulate more PFOA than PFOS, whereas the opposite was seen for shallow-water species. For all the species, PFOS and PFOA were partitioned preferentially in the liver or viscera. Risk assessment indicated that the current level of PFAAs in the seafood of Bohai Bay does not represent an immediate source of harm to public health. Environ. Toxicol. Chem. 2012; 31: 1972-1979. ? 2012 SETAC.