Abstract  Perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA), which are classified as perfluoroalkyl and polyfluoroalkyl substances (PFASs), have been widely used in industrial applications as a surface protectant. PFASs have been detected in wildlife and in humans around the globe. The purposes of this study are to develop and validate a physiologically based pharmacokinetic (PBPK) model for detecting PFNA and PFDA in male and female rats, and to apply the model to a human health risk assessment regarding the sex difference. A PBPK model of PFNA and PFDA was established based on an in vivo study in male and female rats. Analytes in biological samples (plasma, nine tissues, urine, and feces) were determined by ultra-liquid chromatography coupled tandem mass spectrometry (UPLC-MS/MS) method. PFNA and PFDA showed a gender differences in the elimination half-life and volume of distribution. The tissue-plasma partition coefficients were the highest in the liver in both male and female rats. The predicted rat plasma and urine concentrations simulated and fitted were in good agreement with the observed values. The PBPK models of PFNA and PFDA in male and female rats were then extrapolated to a human PBPK model based on human physiological parameters. The external doses were calculated at 3.35 ng/kg/day (male) and 17.0 ng/kg/day (female) for PFNA and 0.530 ng/kg/day (male) and 0.661 ng/kg/day (female) for PFDA. Human risk assessment was estimated using Korean biomonitoring values considering the gender differences. This study provides valuable insight into human health risk assessment regarding PFNA and PFDA exposure.

Abstract  BACKGROUND: Emerging work has examined neurodevelopmental outcomes following prenatal exposure to per- and polyfluoroalkyl substances (PFAS), but few studies have assessed associations with autism spectrum disorder (ASD).

OBJECTIVES: Our objective was to estimate associations of maternal prenatal PFAS concentrations with ASD and intellectual disability (ID) in children.

METHODS: Participants were from a population-based nested case-control study of children born from 2000 to 2003 in southern California, including children diagnosed with ASD (n=553), ID without autism (n=189), and general population (GP) controls (n=433). Concentrations of eight PFAS from stored maternal sera collected at 15-19 wk gestational age were quantified and compared among study groups. We used logistic regression to obtain adjusted odds ratios for the association between prenatal PFAS concentrations (parameterized continuously and as quartiles) and ASD versus GP controls, and separately for ID versus GP controls.

RESULTS: Geometric mean concentrations of most PFAS were lower in ASD and ID groups relative to GP controls. ASD was not significantly associated with prenatal concentrations of most PFAS, though significant inverse associations were found for perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) [adjusted ORs for the highest vs. lowest quartiles 0.62 (95% CI: 0.41, 0.93) and 0.64 (95% CI: 0.43, 0.97), respectively]. Results for ID were similar.

CONCLUSIONS: Results from this large case-control study with prospectively collected prenatal measurements do not support the hypothesis that prenatal exposure to PFAS is positively associated with ASD or ID. https://doi.org/10.1289/EHP1830.

Abstract  Evidence has shown that leukocyte telomere length (LTL) at birth is related to the susceptibility to various diseases in later life and the setting of newborn LTL is influenced by the intrauterine environment. Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as a kind of persistent organic pollutants, are commonly used in commercial and domestic applications and are capable of crossing the maternal-fetal barrier during pregnancy. We hypothesized that intrauterine exposure to PFASs may affect fetal LTL by increasing oxidative stress. To verify this hypothesis, LTL, concentrations of PFASs and reactive oxygen species (ROS) were measured in umbilical cord blood of 581 newborns from a prospective cohort. Our results showed that there were interactions between PFOS/PFDA and sex on LTL and ROS. The LTL was significantly shorter (0.926 ± 0.053 vs 0.945 ± 0.054, P = .023 for PFOS; 0.919 ± 0.063 vs 0.940 ± 0.059, P = .011 for PFDA) and the ROS levels were extremely higher (252.9 ± 60.5 [M] vs 233.5 ± 53.6 [M], P = .031 for PFOS; 255.2 ± 62.9 [M] vs 232.9 ± 58.3 [M], P = .011 for PFDA) in the female newborns whose PFOS or PFDA concentrations fell in the upmost quartile compared with those in the lowest quartile after adjusting for potential confounders. ROS levels were inversely associated with LTL in female newborns (β = -1.42 × 10-4, P = .022). 13% of the effect of PFOS on female LTL was mediated through ROS approximately by the mediation analyses. However, in male newborns, no relationships among PFASs, ROS and LTL were observed. Our findings suggest a "programming" role of PFASs on fetal telomere biology system in females in intrauterine stage.

Abstract  Perfluoroalkyl acids (PFAAs) have been widely used in human environment, and their exposure among general population has been frequently reported. However, extent of PFAAs exposure and their potential effects among children are not well characterized. In this study, children of between 3 and 18 years of age (n = 150) were recruited in Seoul and Gyeonggi, Korea, and the serum levels of 16 PFAAs along with lipids and thyroid hormones were measured. Questionnaire survey was conducted for dietary and behavioral characteristics of the children. Among the measured PFAAs, PFOA, PFNA, PFHxS, and PFOS were detected in all the samples, and PFUnDA and PFDA were detected in over 75% of the samples. PFOS was detected at the highest concentration with a median of 5.68 ng/mL. PFUnDA was detected at higher levels (median of 0.652 ng/mL) compared to those reported for children in USA. Serum PFAA levels were not different by sex among the children of <10 years of age, but in older children, those of boys are significantly higher than girls. Physiological characteristics like menstruation may explain lower PFAAs levels of the girls. In addition, breastmilk consumption, fish/shellfish consumption, non-stick frying pan use, and waterproof cloth use were identified as potential sources of PFAAs exposure. Serum PFUnDA level was positively associated with total cholesterol and low-density lipoprotein level of the children. PFNA was positively associated with free T4 level. High levels of PFUnDA among children and its association with serum lipids warrant replication and confirmation in other populations and/or supports by experimental studies.

Abstract  The development of integrated ecotoxicological approaches is of great interest in the investigation of global concerns such as impacts of municipal wastewater effluents on aquatic ecosystems. The objective of this study was to investigate the effects of a major wastewater municipal effluent on fish using a multi-level biological approach, from gene transcription and enzyme activities to histological changes. Yellow perch (Perca flavescens) were selected based on their wide distribution, their commercial and recreational importance, and the availability of a customized microarray. Yellow perch were sampled upstream of a major municipal wastewater treatment plant (WWTP) and 4 km and 10 km downstream from its point of discharge in the St. Lawrence River (Quebec, Canada). Concentrations of perfluoroalkyl substances (PFASs), polybrominated diphenyl ethers (PBDEs) and metals/trace elements in whole body homogenates were comparable to those from other industrialized regions of the world. Genomic results indicated that the transcription level of 177 genes was significantly different (p<0.024) between exposed and non-exposed fish. Among these genes, 38 were found to be differentially transcribed at both downstream sites. Impacted genes were associated with biological processes and molecular functions such as immunity, detoxification, lipid metabolism/energy homeostasis (e.g., peroxisome proliferation), and retinol metabolism suggesting impact of WWTP on these systems. Moreover, antioxidant enzyme activities were more elevated in perch collected at the 4 km site. Biomarkers of lipid metabolism, biosynthetic activity, and aerobic capacities were significantly lower (p<0.05) in fish residing near the outfall of the effluent. Histological examination of the liver indicated no differences between sites. Correlations between PFAS, PBDE, and metal/trace element tissue concentrations and markers of peroxisomal proliferation, oxidative stress, and retinoid metabolism were found at the gene and cellular levels. Present results suggest that relating transcriptomic analyses to phenotypic responses is important to better understand impacts of environmental contamination on wild fish populations.

Abstract  Oxygen sensing properties of optical sensor using layer of 1-pyrenedecanoic acid and perfluorodecanoic acid chemisorbed onto anodic oxidized aluminium plate was investigated. The ratio I-0/I-100, where I-0 and I-100 represent the detected fluorescence intensities from a substrate exposed to 100% argon and 100% oxygen, respectively, is used as an indicator of the sensitivity of the sensing film. The I-0/I-100 value of 1-pyrenedecanoic acid and perfluorodecanoic acid layer chemisorbed onto the anodic oxidized aluminium plate is estimated to be 18.6. On the other hand, the I-0/I-100 value of 1-pyrenedecanoic acid chemisorbed onto the anodic oxidized aluminiurn plate is 20.2. The response time of the 1-pyrenedecanoic acid layer is 8.5 s on going from argon to oxygen and the recovery time is 40 s on going from oxygen to argon, respectively. In contrast, the response and recovery times of the 1-pyrenedecanoic acid and perfluorodecanoic acid chemisorbed layer are 3.0 and 22 s, respectively. Thus, the optical oxygen sensor using 1-pyrenedecanoic acid and perfluorodecanoic acid chemisorbed layer has rapid response and recovery times. (C) 2003 Elsevier B.V. All rights reserved.

Abstract  Simultaneous exposure of Au and In2O3/SnO2 (ITO) electrodes to an equimolar solution of a thiol and a carboxylic acid or a thiol and phosphonic acid results in the selective attachment of the thiol to the Au electrode and the carboxylic or phosphonic acid to the ITO electrode. This selective surface-attachment chemistry is termed ''orthogonal self-assembly'' (OSA) and can be used to direct the spontaneous assembly of molecular reagents onto Au and ITO microstructures. The selectivity of the thiols for Au and the carboxylic or phosphonic acids for ITO:is determined by a combination of cyclic voltammetry experiments using ferrocene-tagged molecules, scanning Auger microscopy, and imaging secondary ion mass spectrometry (SIMS) to map the distribution of thiols, carboxylic acids, and phosphonic acids on derivatized Au and ITO microstructures. Simultaneous exposure of Au and ITO electrodes for 30 min to an equimolar solution of 11-mercaptoundecanoylferrocene (I) and 12-ferrocenyldodecanoic acid (III) results in a coverage ratio I:LII of approximately 100:1 on Au and 1:45 on ITO, as determined by cyclic voltammetry. A 30-min exposure of Au and ITO electrodes to an equimolar solution of I and 6-ferrocenylhexyl- phosphonic acid (V) yields a coverage ratio of I:V of 30:1 on Au and better than 1:100 on ITO. The coverages of I, III, and V on the Au and ITO electrodes can be determined using cyclic voltammetry by virtue of the difference in redox potential between the acylferrocene center in I and the alkylferrocene centers in III and V. Typical converages of I on Au (4 x 10(-10) mol/cm(2)) and PPI and V on ITO (6 x 10(-10) and 3 x 10(-10) mol/cm2, respectively) after 30 min of derivatization correspond to approximately a monolayer of redox-active molecules in each case. Long derivatization times' (12-15 h) result in small or insignificant changes in the coverage ratios of these reagents on both Au and ITO electrodes, demonstrating that the OSA is essentially complete within 30 min. Surface analysis by X-ray photoelectron spectroscopy, scanning Auger microscopy, and imaging SIMS of Au and ITO microstructures and Si3N4 surfaces exposed to equimolar solutions of I and perfluorodecanoic acid (IV), or 12,12, 12-trifluorodode-canethiol (II) and V, reveal the selective assembly of these reagents on the Au and ITO microstructures and their absence on the insulating Si3N4 substrate. The orthogonal self-assembly process described here provides a promising method by which individual molecules could be spontaneously oriented and connected between closely-spaced, externally-addressable electrodes.

Abstract  Perfluoroalkyl substances (PFASs) are environmentally persistent chemicals widely used in many consumer products due to water and oil proofing and fire-resistant properties. Several PFASs are recognized as environmental pollutants. This study investigated serum concentrations of 18 different PFASs and their associations with diet and lifestyle variables in 940 adolescents (age 15-19 years) who participated in the Fit Futures 1 study in the Troms arctic district of Norway. Serum concentrations of PFASs were analyzed by ultrahigh pressure liquid chromatography coupled to a triple quadrupole mass spectrometer (UHPLC-MS/MS). The most abundant PFASs in this population were perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), perfluorononanoate (PFNA) and perfluorodecanoate (PFDA) that were found in 99% of the participants. Perfluoroheptane sulfonate (PFHpS) was found in 98% of the participants. Median concentrations were: PFOS 6.20 ng/mL, PFOA 1.92 ng/mL, PFHxS 0.71 ng/mL, PFNA 0.50 ng/mL, PFDA 0.21 ng/mL and PFHpS 0.15 ng/mL. Median of PFASs sum concentration (∑PFAS) was 10.7 ng/mL, the concentration range was 2.6-200.8 ng/mL. Intake of fat fish, fish liver, seagull eggs, reindeer meat and drinks with sugar were the main dietary predictors of several PFASs. Intake of junk food (pizza, hamburger, sausages) was positively associated with PFNA, intake of canned food was positively associated with PFHxS. Intake of fruits and vegetables, milk products, snacks and candy was not associated with PFASs concentrations. Lean fish intake was positively associated with PFUnDA, but not with other PFASs. There was a positive association of ∑PFAS, PFHxS, PFOA, PFNA and PFDA with chewed tobacco use.

Abstract  This study demonstrated the 10-year trend of 13 perfluoroalkyl substances (PFASs) serum levels among 786 adults living in Seoul, Korea. PFAS levels gradually increased from 2006 to 2013, decreasing thereafter. We found that PFAS levels were higher in male than in female participants and were positively correlated with age. PFASs were not significantly correlated with body mass index, although we observed positive correlations with total cholesterol, low-density lipoprotein cholesterol, and triglycerides and negative correlations with high-density lipoprotein cholesterol. Uric acid and free thyroxine (fT4) also showed positive correlations with major congeners while correlations between thyroid stimulating hormone and PFASs were inconsistent. We demonstrated significant correlations between fT4 and perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorodecanoic acid (PFDA). There were significant differences in PFHxS and perfluorododecanoic acid (PFDoDA) levels between participants with and without diabetes. Furthermore, principal component analysis suggested possible differences in disease manifestation based on the congener distribution of PFASs. This study is the first study of temporal trends of 13 PFAS congeners in serum samples obtained from the Korean general population; it is currently longest and largest scale study of this type.

Abstract  This study investigated wild caught striped mullet (Mugil cephalus) at Merritt Island National Wildlife Refuge (MINWR) for levels of 15 perfluoroalkyl acids (PFAA) in tandem with individual fecundity measurements (Oocyte sub-stage 2 late, n=42) and oocyte reproductive stages (Stages 1-5, n=128). PFAA measurements were quantified in striped mullet liver (n=128), muscle (n=49), and gonad (n=10). No significant negative impacts of liver PFAA burden on wild-caught, mullet fecundity endpoints were observed in this study; however, changes in PFAA were observed in the liver as mullet progressed through different sub-stages of oocyte development. Of the PFAA with significant changes by sub-stage of oocyte development, the carboxylic acids (perfluorooctanoic acid, perfluorononanoic acid, and perfluorotridecanoic acid) increased in the liver with increasing sub-stage while the sulfonic acid and its precursor (perfluorooctanesulfonic acid (PFOS) and perfluorooctanesulfonamide, respectively) decreased in the liver with increasing sub-stage of oocyte development. This is a unique find and suggests PFAA change location of compartmentalization as mullet progress towards spawning. Investigations also revealed higher than expected median muscle and gonad levels of PFOS in striped mullet collected at MINWR (9.01ng/g and 80.2ng/g, respectively).

Abstract  Perfluorochemicals produce hepatotoxic effects via activation of PPARα and CAR nuclear receptors in animals. Bile formation is one major liver function. But it remains unknown whether perfluorochemicals alter metabolism of bile acids (BAs) in liver. The present study was designed to determine the impact of perfluorononanoic acid (PFNA) on BA and cholesterol homeostasis in mice. A single dose of PFNA (0.1 mmol/kg) was intraperitoneally administered to adult male wild-type (WT), PPARα-null, and CAR-null mice. PFNA caused cholestasis in the WT mice, indicated by increased serum ALT, hyperbilirubinemia, elevated BA concentrations in mouse serum, and appearance of bile plugs in mouse liver. In addition, PFNA decreased total and some individual BAs in mouse liver. PFNA increased the concentrations of total and taurine-conjugated, as well as some individual BAs in the serum of WT and CAR-null mice but not in PPARα-null mice, indicating a PPARα-dependent mechanism. PFNA decreased mRNA expression of most BA-related transporters (Ntcp, Oatp1a1, Oatp1b2, and Bsep) and BA biosynthetic enzymes (Cyp7a1, 7b1, 8b1, and 27a1) in mouse liver, but increased mRNA expression of some efflux transporters (Bcrp, Mdr2, Mrp2, 3, and 4), primarily via a PPARα-dependent mechanism. Moreover, PFNA increased free and total cholesterol in mouse liver but not in mouse serum. Furthermore, PFNA increased mRNA expression of sterol transporters, namely Abca1, g1, g5/g8, and StAR via PPARα. In conclusion, PFNA produced cholestasis in mouse liver, and the activation of PPARα plays a central role in regulating BA and cholesterol metabolism and transport in mouse serum and liver.

Abstract  The toxicity of long chained perfluoroalkyl acids (PFAAs) has previously been reported to be related to the length of the perfluorinated carbon chain and functional group attached. In the present study, we compared the cytotoxicity of six PFAAs, using primary cultures of rat cerebellar granule neurons (CGNs). Two perfluoroalkyl sulfonic acids (PFSAs, chain length C6and C8) and four perfluoroalkyl carboxylic acids (PFCAs, chain length C8-C11) were studied. These PFAAs have been detected in human blood and the brain tissue of mammals. The cell viability trypan blue and MTT assays were used to determine toxicity potencies (based on LC50values) after 24h exposure (in descending order): perfluoroundecanoic acid (PFUnDA)≥perfluorodecanoic acid (PFDA)>perfluorooctanesulfonic acid potassium salt (PFOS)>perfluorononanoic acid (PFNA)>perfluorooctanoic acid (PFOA)>perfluorohexanesulfonic acid potassium salt (PFHxS). Concentrations of the six PFAAs that produced equipotent effects after 24h exposure were used to further explore the dynamics of viability changes during this period. Therefore viability was assessed at 10, 30, 60, 90, 120 and 180min as well as 6, 12, 18 and 24h. A difference in the onset of reduction in viability was observed, occurring relatively quickly (30-60min) for PFOS, PFDA and PFUnDA, and much slower (12-24h) for PFHxS, PFOA and PFNA. A slight protective effect of vitamin E against PFOA, PFNA and PFOS-induced reduction in viability indicated a possible involvement of oxidative stress. PFOA and PFOS did not induce lipid peroxidation on their own, but significantly accelerated cumene hydroperoxide-induced lipid peroxidation. When distribution of the six PFAAs in the CGN-membrane was investigated using NanoSIMS50 imaging, two distinct patterns appeared. Whereas PFHxS, PFOS and PFUnDA aggregated in large hotspots, PFOA, PFNA and PFDA showed a more dispersed distribution pattern. In conclusion, the toxicity of the investigated PFAAs increased with increasing carbon chain length. For molecules with a similar chain length, a sulfonate functional group led to greater toxicity than a carboxyl group.

Abstract  INTRODUCTION: The liver plays a central role in transforming and clearing foreign substances. The continuous exposure of the liver to xenobiotics sometimes leads to impaired liver function, referred to as drug-induced liver injury (DILI). The pregnane X receptor (PXR) tightly regulates the expression of genes in the hepatic drug-clearance system and its undesired activation plays a role in DILI.

AREAS COVERED: This review focuses on the recent progress in understanding PXR-mediated DILI and highlights the efforts made to assess and manage PXR-mediated DILI during drug development.

EXPERT OPINION: Future efforts are needed to further elucidate the mechanisms of PXR-mediated liver injury, including the epigenetic regulation and polymorphisms of PXR. Novel in vitro models containing functional PXR could improve our ability to predict and assess DILI during drug development. PXR inhibitors may provide chemical tools to validate the potential of PXR as a therapeutic target and to develop drugs to be used in the clinic to manage PXR-mediated DILI.

Abstract  The Universal Waste Management System (UWMS) is an improved Waste Collection System for astronauts living and working in low Earth orbit spacecraft. Polymeric materials used in water recovery on International Space Station are regularly exposed to phosphoric acid-treated 'pretreated' urine. Polymeric materials used in UWMS are not only exposed to pretreated urine, but also to concentrated phosphoric acid with oxidizer before dilution known as 'pure pretreat.' Samples of five different polymeric materials immersed in pure pretreat for 1 year were tested for liquid compatibility by measuring changes in storage modulus with a dynamic mechanical analyzer.

Abstract  Per-/polyfluoroalkyl substances (PFASs), which are widely used in industrial and commercial products, have been identified as global and ubiquitous pollutants. Despite this, limited data are available regarding the impacts of PFAS exposure and intake in non-human primates. Here, we report for the first time on the occurrence of PFASs in the blood and dietary sources of two rare and endangered primate species, namely, the golden snub-nosed monkey (Rhinopithecus roxellana) and Francois' leaf monkey (Trachypithecus francoisi). Results showed that perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) were dominant and found at the highest proportions in the blood of both species at the four study sites. The ∑PFAS levels in blood samples from captive golden snub-nosed monkeys in Tongling Zoo (mean: 2.51 ng/mL) and Shanghai Wild Zoo (3.52 ng/mL) near urbanized areas were one order of magnitude higher than the levels in wild monkeys from Shennongjia Nature Reserve (0.27 ng/mL). Furthermore, significant age positive relationships for perfluorodecanoic acid (PFDA), perfluorooctane sulfonate (PFOS), and 6:2 chlorinated polyfluorinated ether sulfonates (6:2 Cl-PFESA) were observed in both golden snub-nosed monkeys at Shanghai Wild Zoo and Francois' leaf monkeys at Wuzhou Breeding Center. In addition, PFAS levels in frequently consumed food and drinking water were analyzed for Francois' leaf monkeys. Results showed that tree leaves accounted for the highest percentage of total daily intake of PFASs, especially PFOA, thus highlighting tree leaf consumption as a primary PFAS exposure route for this species. Overall, however, dietary exposure to PFASs was of relatively low risk to Francois' leaf monkey health.

Abstract  Perfluorochemicals (PFC's) are widely spread in the environment and have been detected in blood of wildlife and humans world-wide. Recently, various toxic effects of PFC's in laboratory rats have been demonstrated, resulting in increased government concerns regarding the presence of PFC's in the environment and the implications they have on human health. In the last decade, various analytical methods have been developed for the analysis of PFC's in different matrices whereby the majority of methods have utilised liquid chromatography coupled with mass spectrometry (LC-MS). Here we describe an optimized method for the quantitation of PFC's, including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), in food packaging, polytetrafluoroethylene (PTFE) sealant tape and drinking water. The method involved PFC's extraction via off-line SPE followed by separation using reversed-phase liquid chromatography on a Phenyl-Hexyl column coupled with ion-trap (IT) mass spectrometric detection. The optimized approach minimized ion-suppression effects commonly seen with conventional elution buffers, improving detection limits down to 25 pg/mL and allowed effective quantitation down to 50 pg/mL for PFOA and PFOS. The optimized LC-MS method detected PFOA and other PFC's in microwave popcorn packaging and PFOA in PTFE sealant tape in the low μg/kg. In all samples, PFOS was not detected.

Abstract  The exposure of infants to per and polyfluoroalkyl substances (PFAS) through breast-feeding is of global concern owing to their numerous detrimental health effects. This study investigated the occurrence of eleven perfluorocarboxylic acids (PFCAs) and four perfluorosulfonates (PFSAs) in breast milk of nursing mothers from South Africa. The concentrations of PFAS in these samples were measured by using a validated UHPLC – MS/MS method. The median concentrations of Σ15 PFAS ranged from

Abstract  The global problem of groundwater being contaminated with per- and polyfluoroalkyl substances (PFASs) originating from highly contaminated soils has created a need to remediate these locations. In situ immobilisation of PFASs in soil by applying sorbents is often a preferred low-cost technique to reduce their mobility and leaching to groundwater, but the long-term efficacy of sorbents has not yet been investigated. In this study, the longevity of remediation of two different soils by two common sorbents (RemBind®, and pulverized activated carbon, Filtrasorb™ 400) was assessed. Regulatory agencies often rely on standardised leaching procedures to assess the risk of contaminant mobility in soils. Hence, the Australian Standard Leaching Procedure and the U.S. EPA Leaching Environmental Assessment Framework were applied to quantify the desorption/leaching of a wide range of PFASs from unremediated and remediated soils under a range of pH conditions (pH 2 to 12). Ease of desorption and subsequent leaching from the unremediated soils was related to C-chain length; while short-chain PFASs were easily desorbed and leached, long-chain PFASs were more difficult to desorb. Desorption of long-chain PFASs was also pH dependent in unremediated soils, with desorption being greater at high pH. Both sorbents retained PFASs strongly in the remediated soils (> 99% for most PFASs) across a broad range of pH conditions, with only small differences between the sorbents in terms of efficacy. Both sorbents showed better retention of PFASs under low pH conditions. Remediation of PFAS-contaminated soils with these sorbents could be considered robust and durable in terms of changes in soil pH, with little risk of subsequent PFASs desorption under normal environmental pH conditions. Ultimately, to give regulators and site owners the greatest level of confidence that immobilisation is stable for the longer term, it should also be tested under repeated cycles of leaching and under different conditions. © 2020 Elsevier B.V.

Abstract  The development of high-throughput screening methodologies may decrease the need for laboratory animals for toxicity testing. Here, we investigate the potential of assessing immunotoxicity with high-throughput screening data from the U.S. Environmental Protection Agency ToxCast program. As case studies, we analyzed the most common chemicals added to food as well as per-and polyfluoroalkyl substances (PFAS) shown to migrate to food from packaging materials or processing equipment. The antioxidant preservative tert-butylhydroquinone (TBHQ) showed activity both in ToxCast assays and in classical immunological assays, suggesting that it may affect the immune response in people. From the PFAS group, we identified eight substances that can migrate from food contact materials and have ToxCast data. In epidemiological and toxicological studies, PFAS suppress the immune system and decrease the response to vaccination. However, most PFAS show weak or no activity in immune-related ToxCast assays. This lack of concordance between toxicological and high-throughput data for common PFAS indicates the current limitations of in vitro screening for analyzing immunotoxicity. High-throughput in vitro assays show promise for providing mechanistic data relevant for immune risk assessment. In contrast, the lack of immune-specific activity in the existing high-throughput assays cannot validate the safety of a chemical for the immune system. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Abstract  The liver is the largest internal organ in the human body and it is the main site for the metabolism of endogenous molecules and xenobiotics. Drug-induced liver injury is one of the leading causes of drug attrition during drug development and post-marketing drug withdrawal. Current biomarkers can detect liver injury but there are many inadequacies that make them less than ideal. For example, the serum level of alanine aminotransferase (ALT) is the most commonly used biomarker of hepatocellular injury, but its elevation can also reflect muscle injury. Therefore, more sensitive and specific biomarkers are needed to better predict liver toxicity. The omics technologies including genomics, proteomics, and metabolomics have been employed in hepatotoxicity studies to identify new biomarkers. This chapter evaluates the existing and emerging hepatotoxicity biomarkers from the omics platforms as well as from analysis of microRNAs in human body fluids. A brief description of the qualification of biomarker candidates is also given.