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Physiologically based pharmacokinetic (PBPK) models are commonly used in risk assessments to perform inter- and intraspecies extrapolations as well as to extrapolate between different dosing scenarios; however, they must first undergo quality assurance review, which can be a time-consuming process, especially when model code is not readily available. We developed and implemented (using R and MCSim) a PBPK model template capable of replicating published model results for several chemical-specific PBPK models. This model template allows for faster quality assurance review because the general model equations only need to be reviewed once, and application to a specific chemical then only requires reviewing input parameters. The model template can implement PBPK models with oral and intravenous exposure routes, varying numbers of tissue compartments, renal reabsorption, and multiple elimination pathways, including fecal, urinary, and biliary. Using the model template, we reproduced published model simulation results for perfluorohexanesulfonic acid, perfluorononanoic acid, perfluorodecanoic acid, perfluorooctanoate, and perflouorooctane sulfonate. We also show that the template can be a useful tool for identifying potential model errors. Thus, the model template allows for faster evaluation and review of published PBPK models and provides a proof of concept for using this approach with broader classes of chemical-specific PBPK models.

Per/polyfluoroalkyl substances (PFAS) are contaminants of emerging concern that can impair immune function, yet few studies have tested whether exposure increases infection risk. Using laboratory experiments, we found that exposure to 10 ppb of perfluorohexanesulfonic acid increased trematode (Echinoparyphium lineage 3) infections in larval northern leopard frogs (Lithobates pipiens). However, there was no effect of perfluorooctanesulfonic acid. Our results demonstrate that PFAS can potentially enhance infection risk in natural systems. Environ Toxicol Chem 2021;40:689-694. © 2020 SETAC.

Activated carbon is a versatile sorbent and effective contaminant removal media due to its complex porous structure and high surface area. The main purpose of this research is to increase ...

Background Perfluoroalkyl substances (PFASs) have been related to neurodevelopmental toxicity in animals. However, human studies are inconclusive. Objectives To evaluate the association between prenatal PFAS exposure and neuropsychological development during childhood. Methods 1240 mother–child pairs from the Spanish INMA Project were analyzed. Perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA) were measured in first-trimester maternal plasma. Neuropsychological development was assessed at 14 months, 4–5 and 7 years covering four domains: general cognitive, general motor, attention, and working memory. Associations were studied by means of multivariable regression analyses. Results PFHxS, PFOA, PFOS, and PFNA medians were: 0.6, 2.4, 6.1, and 0.7 ng/mL. Higher PFAS prenatal exposure was associated with worse motor development at 14 months, especially in the case of PFHxS (β[95%CI]: −1.49[−2.73, −0.24]) and to a lesser extent PFOS (−1.25[−2.62, 0.12]). There was also a marginal positive association between general cognitive development at 4–5 years and PFOS (1.17[−0.10, 2.43]) and PFNA (0.99[−0.13, 2.12]). No clear associations for other neuropsychological outcomes or any sex differences were found. Discussion This study shows no clear-cut evidence of an association between prenatal PFAS exposure and adverse neuropsychological development in children up to the age of 7 years.

Per- and polyfluoroalkyl substances (PFASs) are used in a wide range of consumer products for their water- and grease-resistant properties, but few studies have explored this exposure route. We used multiple regression to investigate associations between six self-reported behaviors hypothesized to influence PFAS exposure and serum concentrations of six PFAS chemicals in 178 middle-aged women enrolled in the Child Health and Development Studies, about half of whom are African American. Blood samples were collected in 2010-2013, and participants were interviewed about behavior in 2015-2016. Results showed that African American women had lower levels of perfluorooctanoic acid (PFOA) and perfluorohexanesulfonic acid (PFHxS) compared with non-Hispanic white women. In African Americans, but not others, frequent consumption of prepared food in coated cardboard containers was associated with higher levels of four PFASs. Flossing with Oral-B Glide, having stain-resistant carpet or furniture, and living in a city served by a PFAS-contaminated water supply were also associated with higher levels of some PFASs. Product testing using particle-induced γ-ray emission (PIGE) spectroscopy confirmed that Oral-B Glide and competitor flosses contained detectable fluorine. Despite the delay between blood collection and interview, these results strengthen the evidence for exposure to PFASs from food packaging and implicate exposure from polytetrafluoroethylene (PTFE)-based dental floss for the first time.

A first global emission inventory of C4–C10 perfluoroalkanesulfonic acids (PFSAs) released during the life cycle of perfluorohexanesulfonyl fluoride (PHxSF)- and perfluorodecanesulfonyl fluoride (PDSF)-based products is presented. This study complements previous research on emissions of PFSAs that focused largely on the life cycle of perfluorooctanesulfonyl fluoride (POSF) and its derivatives. It reviews and integrates existing information about the life cycle of PHxSF, PDSF, and their derivatives; the limited data available in the public domain point to potentially significant global production, uses, and releases of these substances. Between 1958 and 2015, ranges of total emissions of perfluorohexanesulfonic acid (PFHxS) and perfluorodecanesulfonic acid (PFDS) are estimated to be 120–1022 and 38–378 metric tons, respectively. With the new emission estimates as inputs in a global multimedia environmental fate model (CliMoChem), the model-derived environmental concentrations well capture the reported fiel...

Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) are found in the blood of humans and wildlife worldwide. Since the beginning of the 21st century, a downward trend in the human body burden, especially for PFOS and PFOA, has been observed while there is no clear temporal trend in wildlife. The inconsistency between the concentration decline in human serum and in wildlife could be indicative of a historical exposure pathway for humans linked to consumer products that has been reduced or eliminated. In this study, we reconstruct the past human exposure trends in two different regions, USA and Australia, by inferring the historical intake from cross-sectional biomonitoring data of PFOS, PFOA and PFHxS using a population-based pharmacokinetic model. For PFOS in the USA, the reconstructed daily intake peaked at 4.5 ng/kg-bw/day between 1988 and 1999 while in Australia it peaked at 4.0 ng/kg-bw/day between 1984 and 1996. For PFOA in the USA and Australia, the peak reconstructed daily intake was 1.1 ng/kg-bw/day in 1995 and 3.6 ng/kg-bw/day in 1992, respectively, and started to decline in 2000 and 1995, respectively. The model could not be satisfactorily fitted to the biomonitoring data for PFHxS within reasonable boundaries for its intrinsic elimination half-life, and thus reconstructing intakes of PFHxS was not possible. Our results indicate that humans experienced similar exposure levels and trends to PFOS and PFOA in the USA and Australia. Our findings support the hypothesis that near-field consumer product exposure pathways were likely dominant prior to the phase-out in industrialized countries. The intrinsic elimination half-life, which represents elimination processes that are common for all humans, and elimination processes unique to women (i.e., menstruation, cord-blood transfer and breastfeeding) were also investigated. The intrinsic elimination half-lives for PFOS and PFOA derived from model fitting for men were 3.8 and 2.4 years, respectively, for the USA, and 4.9 and 2 years respectively for Australia. Our results show that menstruation is a depuration pathway for PFOA for women, similarly but to a lesser extent compared to previous reports for PFOS. However menstruation, cord-blood transfer and breastfeeding together do not fully explain the apparently more rapid elimination of PFOA and PFOS by women compared to men; the intrinsic elimination half-lives in women were up to 13% lower for PFOS and up to 12% lower for PFOA compared to the corresponding half-lives in men.

In recent years, environmental issues emerging from per- and polyfluoroalkyl substances (PFAS) have raised high concern worldwide. Levels of human exposure to PFAS remain unknown in India. Biomonitoring data obtained from hair analysis have been evidenced to provide insight into retrospective human exposure to PFAS. In this study, 25 PFAS, including perfluoroalkyl acids and their precursors, were measured in 39 human hair samples collected from 14 cities in India. The inuflence of gender on the PFAS levels was also examined. To our knowledge, this is the first attempt to provide preliminary indicative data (due to the limited sample size and variability in hair-length sampling) on the levels of PFAS in Indian hair. The concentrations of total PFAS in hair varied from below matrix-specific limit of quantification (

A total of 201 sewage sludge and 45 biowaste samples were examined for 14 different perfluoroalkyl acids (PFAA). For perfluorooctanesulfonic acid, maximum concentrations of 698 μg/kg dry weight were measured in sewage sludge and for perfluorohexanesulfonic acid 29.0 μg/kg dry weight were found in biowaste. Looking at the fingerprints of both these matrixes it can be see that long-chain PFAA make up 85.9% of the total concentration in sewage sludge whereas short-chain PFAA only account for 14.1%. In contrast, the trend in biowaste is just the opposite, with 53.2% long-chain and 46.8% short-chain PFAA. These results lead to the conclusion that sewage sludge functions as a sink for long-chain PFAA, and the plants preferentially take up short-chain PFAA from the sludge/soil, as seen by the concentrations found in biowaste. It can be calculated that the total yearly amount of PFAA spread onto agricultural lands amount to 15.3 kg.

Background Humans are exposed to poly- and perfluoroalkyl substances (PFASs) from diverse sources and this has been associated with negative health impacts. Advances in analytical methods have enabled routine detection of more than 15 PFASs in human sera, allowing better profiling of PFAS exposures. The composition of PFASs in human sera reflects the complexity of exposure sources but source identification can be confounded by differences in toxicokinetics affecting uptake, distribution, and elimination. Common PFASs, such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) and their precursors are ubiquitous in multiple exposure sources. However, their composition varies among sources, which may impact associated adverse health effects. Methods We use available PFAS concentrations from several demographic groups in a North Atlantic seafood consuming population (Faroe Islands) to explore whether chemical fingerprints in human sera provide insights into predominant exposure sources. We compare serum PFAS profiles from Faroese individuals to other North American populations to investigate commonalities in potential exposure sources. We compare individuals with similar demographic and physiological characteristics and samples from the same years to reduce confounding by toxicokinetic differences and changing environmental releases. Results Using principal components analysis (PCA) confirmed by hierarchical clustering, we assess variability in serum PFAS concentrations across three Faroese groups. The first principal component (PC)/cluster consists of C9-C12 perfluoroalkyl carboxylates (PFCAs) and is consistent with measured PFAS profiles in consumed seafood. The second PC/cluster includes perfluorohexanesulfonic acid (PFHxS) and the PFOS precursor N-ethyl perfluorooctane sulfonamidoacetate (N-EtFOSAA), which are directly used or metabolized from fluorochemicals in consumer products such as carpet and food packaging. We find that the same compounds are associated with the same exposure sources in two North American populations, suggesting generalizability of results from the Faroese population. Conclusions We conclude that PFAS homologue profiles in serum provide valuable information on major exposure sources. It is essential to compare samples collected at similar time periods and to correct for demographic groups that are highly affected by differences in physiological processes (e.g., pregnancy). Information on PFAS homologue profiles is crucial for attributing adverse health effects to the proper mixtures or individual PFASs. Electronic supplementary material The online version of this article (10.1186/s12940-018-0355-4) contains supplementary material, which is available to authorized users.

In 2012, drinking water contaminated with per- and polyfluoroalkyl substances (PFASs), foremost perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) at levels over 20ng/L and 40ng/L, respectively, was confirmed in Uppsala, Sweden.We assessed how a longitudinally sampled cohort's temporal trend in PFAS plasma concentration was influenced by their residential location and determined the plausible association or disparity between the PFASs detected in the drinking water and the trend in the study cohort.The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort provided plasma samples three times from 2001 to 2014. Individuals maintaining the same zip code throughout the study (n = 399) were divided into a reference (no known PFAS exposure), low, intermediate and high exposure area depending on the proportion of contaminated drinking water received. Eight PFASs detected in the majority (75%) of the cohort's plasma samples were evaluated for significant changes in temporal PFAS concentrations using a random effects (mixed) model.PFHxS plasma concentrations continued to significantly increase in individuals living in areas receiving the largest percentage of contaminated drinking water (p0.0001), while PFOS showed an overall decrease. The temporal trend of other PFAS plasma concentrations did not show an association to the quality of drinking water received.The distribution of contaminated drinking water had a direct effect on the trend in PFHxS plasma levels among the different exposure groups, resulting in increased concentrations over time, especially in the intermediate and high exposure areas. PFOS and the remaining PFASs did not show the same relationship, suggesting other sources of exposure influenced these PFAS plasma trends.

Persistent organic pollutants (POPs) are widespread in the environment and some may be neurotoxic. As we are exposed to complex mixtures of POPs, we aimed to investigate how a POP mixture based on Scandinavian human blood data affects behaviour and neurodevelopment during early life in zebrafish. Embryos/larvae were exposed to a series of sub-lethal doses and behaviour was examined at 96 h post fertilization (hpf). In order to determine the sensitivity window to the POP mixture, exposure models of 6 to 48 and 48 to 96 hpf were used. The expression of genes related to neurological development was also assessed. Results indicate that the POP mixture increases the swimming speed of larval zebrafish following exposure between 48 to 96 hpf. This behavioural effect was associated with the perfluorinated compounds, and more specifically with perfluorooctanesulfonic acid (PFOS). The expression of genes related to the stress response, GABAergic, dopaminergic, histaminergic, serotoninergic, cholinergic systems and neuronal maintenance, were altered. However, there was little overlap in those genes that were significantly altered by the POP mixture and PFOS. Our findings show that the POP mixture and PFOS can have a similar effect on behaviour, yet alter the expression of genes relevant to neurological development differently.

Hot spots of drinking water contaminated with toxic fluorocarbons in Australia, the Netherlands, Italy, and the US grabbed headlines last year. In 2019, expect scientists to look for—and find—more areas polluted with nonpolymeric per- and polyfluoroalkyl substances (PFAS) in those countries and across the world. “It’s going to seem to the public like the problem is getting worse,” says Ginny Yingling, a research scientist at the Minnesota Department of Health and a PFAS expert. But scientists will just be identifying existing contamination through better analytical methods, says Yingling, who coleads the US Interstate Technology and Regulatory Council’s PFAS team. Scientists are also likely to identify additional PFAS besides well-known legacy compounds, such as perfluorooctanoic acid and perfluorohexanesulfonic acid, that were used industrially for decades, Yingling adds. Data indicate that at least some of these legacy chemicals, which have been found in people’s blood, can cause reproductive, developme...