Germ-free status but not subacute polychlorinated biphenyl (PCB) exposure altered hepatic phosphatidylcholine and ether-phosphatidylcholine levels in mice.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that pose a current ecosystem and human health concern. PCB exposure impacts the gut microbiome in animal models, suggesting a mechanistic link between PCB exposure and adverse health outcomes. The presence and absence of the microbiome and exposure to PCBs independently affect the lipid composition in the liver, which in turn affects the PCB disposition in target tissues, such as the liver. Here, we investigated microbiome × subacute PCB effects on the hepatic lipid composition of conventional and germ-free female mice exposed to 0, 6, or 30 mg/kg body weight of an environmental PCB mixture in sterile corn oil once daily for 3 consecutive days. Hepatic triacylglyceride and polar lipid levels were quantified using mass spectrometric methods following the subacute PCB exposure. The lipidomic analysis revealed no PCB effect on the hepatic levels. No microbiome effect was observed on levels of triacylglyceride and most polar lipid classes. The total hepatic levels of phosphatidylcholine (PC) and ether-phosphatidylcholine (ePC) lipids were lower in germ-free mice than the conventional mice from the same exposure group. Moreover, levels of several unsaturated PCs, such as PC(36:5) and PC(42:10), and ePCs, such as ePC(36:2) and ePC(4:2), were lower in germ-free than conventional female mice. Based on a KEGG pathway meta-analysis of RNA sequencing data, the ether lipid metabolism pathway is altered in the germ-free mouse liver. In contrast to the liver, extractable lipid levels, determined gravimetrically, differed in several tissues from naïve conventional vs. germ-free mice. Overall, microbiome × subacute PCB exposure effects on hepatic lipid composition are unlikely to affect PCB distribution into the mouse liver. Further studies are needed to assess how the different extractable lipid levels in other tissues alter PCB distribution in conventional vs. germ-free mice.

Distribution of 2,2',5,5'-Tetrachlorobiphenyl (PCB52) Metabolites in Adolescent Rats after Acute Nose-Only Inhalation Exposure.

Inhalation of PCB-contaminated air is increasingly recognized as a route for PCB exposure. Because limited information about the disposition of PCBs following inhalation exposure is available, this study investigated the disposition of 2,2',5,5'-tetrachlorobiphenyl (PCB52) and its metabolites in rats following acute, nose-only inhalation of PCB52. Male and female Sprague-Dawley rats (50-58 days of age, 210 ± 27 g; n = 6) were exposed for 4 h by inhalation to approximately 14 or 23 µg/kg body weight of PCB52 using a nose-only exposure system. Sham animals (n = 6) were exposed to filtered lab air. Based on gas chromatography-tandem mass spectrometry (GC-MS/MS), PCB52 was present in adipose, brain, intestinal content, lung, liver, and serum. 2,2',5,5'-Tetrachlorobiphenyl-4-ol (4-OH-PCB52) and one unknown monohydroxylated metabolite were detected in these compartments except for the brain. Liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis identified several metabolites, including sulfated, methoxylated, and dechlorinated PCB52 metabolites. These metabolites were primarily found in the liver (7 metabolites), lung (9 metabolites), and serum (9 metabolites) due to the short exposure time. These results demonstrate for the first time that complex mixtures of sulfated, methoxylated, and dechlorinated PCB52 metabolites are formed in adolescent rats following PCB52 inhalation, laying the groundwork for future animal studies of the adverse effects of inhaled PCB52.

Predicted versus observed activity of PCB mixtures toward the ryanodine receptor.

Non-dioxin-like polychlorinated biphenyls (NDL PCBs) alter the activity of the ryanodine receptor (RyR), and this activity is linked to developmental neurotoxicity. Most work to date has focused on the activity of single congeners rather than relevant mixtures. The current study assessed the RyR activity of single congeners or binary, tertiary, and complex PCB mixtures. Observed mixture activity was then compared to the expected activity calculated using the concentration addition (CA) model or a RyR-specific neurotoxic equivalency scheme (rNEQ). The predictions of the CA model were consistent with the observed activity of binary mixtures at the lower portion of the concentration-response curve, supporting the additivity of RyR1 active PCBs. Findings also show that minimally active congeners can compete for the RyR1 binding site, and congeners that do not activate the RyR1 do not interfere with the activity of a full agonist. Complex PCB mixtures that mimic PCB profiles detected in indoor air, fish tissue, and the serum of mothers and children activated the RyR1 and displayed similar efficacy and potency regardless of varying congener profiles. Neither the CA model nor the rNEQ perfectly predicted the observed activity of complex mixtures, but predictions were often within one magnitude of change from the observed response. Importantly, PCB mixtures approximating profiles found in environmental samples or human serum displayed RyR1 activity at concentrations reported in published research. The work presented will aid in the development of risk assessment platforms for NDL PCBs and similar compounds toward RyR1 activation and related neurotoxicity.

Use of a polymeric implant system to assess the neurotoxicity of subacute exposure to 2,2',5,5'-tetrachlorobiphenyl-4-ol, a human metabolite of PCB 52, in male adolescent rats.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) that ubiquitously exist in the environment. PCB exposure has been linked to cancer and multi-system toxicity, including endocrine disruption, immune inhibition, and reproductive and neurotoxicity. 2,2',5,5'-Tetrachlorobiphenyl (PCB 52) is one of the most frequently detected congeners in the environment and human blood. The hydroxylated metabolites of PCB 52 may also be neurotoxic, especially for children whose brains are still developing. However, it is challenging to discern the contribution of these metabolites to PCB neurotoxicity because the metabolism of PCB is species-dependent. In this study, we evaluated the subacute neurotoxicity of a human-relevant metabolite, 2,2',5,5'-tetrachlorobiphenyl-4-ol (4-52), on male adolescent Sprague Dawley rats, via a novel polymeric implant drug delivery system grafted subcutaneously, at total loading concentrations ranging from 0%, 1%, 5%, and 10% of the implant (w/w) for 28 days. Y-maze, hole board test, open field test, and elevated plus maze were performed on exposure days 24-28 to assess their locomotor activity, and exploratory and anxiety-like behavior. 4-52 and other possible hydroxylated metabolites in serum and vital tissues were quantified using gas chromatography with tandem mass spectrometry (GC-MS/MS). Our results demonstrate the sustained release of 4-52 from the polymeric implants into the systemic circulation in serum and tissues. Dihydroxylated and dechlorinated metabolites were detected in serum and tissues, depending on the dose and tissue type. No statistically significant changes were observed in the neurobehavioral tasks across all exposure groups. The results demonstrate that subcutaneous polymeric implants provide a straightforward method to expose rats to phenolic PCB metabolites to study neurotoxic outcomes, e.g., in memory, anxiety, and exploratory behaviors.

Predicted Versus Observed Activity of PCB Mixtures Toward the Ryanodine Receptor.

Non-dioxin-like polychlorinated biphenyls (NDL PCBs) alter the activity of the ryanodine receptor (RyR), and this activity is linked to developmental neurotoxicity. Most work to date has focused on the activity of single congeners rather than relevant mixtures. The current study assessed the RyR activity of single congeners or binary, tertiary, and complex PCB mixtures. Observed mixture activity was then compared to the expected activity calculated using the concentration addition (CA) model or a RyR-specific neurotoxic equivalency scheme (rNEQ). The predictions of the CA model were consistent with the observed activity of binary mixtures at the lower portion of the concentration-response curve, supporting the additivity of RyR1 active PCBs. Findings also show that minimally active congeners can compete for the RyR1 binding site, and congeners that do not activate the RyR1 do not interfere with the activity of a full agonist. Complex PCB mixtures that mimic PCB profiles detected in indoor air, fish tissue, and the serum of mothers and children activated the RyR1 and displayed similar efficacy and potency regardless of varying congener profiles. Neither the CA model nor the rNEQ perfectly predicted the observed activity of complex mixtures, but predictions were often within one magnitude of change from the observed response. Importantly, PCB mixtures approximating profiles found in environmental samples or human serum displayed RyR1 activity at concentrations reported in published research. The work presented will aid in the development of risk assessment platforms for NDL PCBs, and similar compounds, towards RyR1 activation and related neurotoxicity.

Disposition and Metabolomic Effects of 2,2',5,5'-Tetrachlorobiphenyl in Female Rats Following Intraperitoneal Exposure.

The disposition and toxicity of lower chlorinated PCBs (LC-PCBs) with less than five chlorine substituents have received little attention. This study characterizes the distribution and metabolomic effects of PCB 52, an LC-PCB found in indoor and outdoor air, three weeks after intraperitoneal exposure of female Sprague Dawley rats to 0, 1, 10, or 100 mg/kg BW. PCB 52 exposure did not affect overall body weight. Gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis identified PCB 52 in all tissues investigated. Hydroxylated, sulfated, and methylated PCB metabolites, identified using GC-MS/MS and nontarget liquid chromatography-high resolution mass spectrometry (Nt-LCMS), were primarily found in the serum and liver of rats exposed to 100 mg/kg BW. Metabolomic analysis revealed minor effects on L-cysteine, glycine, cytosine, sphingosine, thymine, linoleic acid, orotic acid, L-histidine, and erythrose serum levels. Thus, the metabolism of PCB 52 and its effects on the metabolome must be considered in toxicity studies. Highlights: PCB 52 was present in adipose, brain, liver, and serum 3 weeks after PCB exposureLiver and serum contained hydroxylated, sulfated, and methylated PCB 52 metabolitesMetabolomics analysis revealed minor changes in endogenous serum metabolitesLevels of dopamine and its metabolites in the brain were not affected by PCB 52.

Disposition and metabolomic effects of 2,2',5,5'-tetrachlorobiphenyl in female rats following intraperitoneal exposure.

The disposition and toxicity of lower chlorinated PCBs (LC-PCBs) with less than five chlorine substituents have received little attention. This study characterizes the distribution and metabolomic effects of PCB 52, an LC-PCB found in indoor and outdoor air, three weeks after intraperitoneal exposure of female Sprague Dawley rats to 0, 1, 10, or 100 mg/kg BW. PCB 52 exposure did not affect overall body weight. Gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis identified PCB 52 in all tissues investigated. Hydroxylated, sulfated, and methylated PCB metabolites, identified using GC-MS/MS and nontarget liquid chromatography-high resolution mass spectrometry (Nt-LCMS), were primarily found in the serum and liver of rats exposed to 100 mg/kg BW. Metabolomic analysis revealed minor effects on L-cysteine, glycine, cytosine, sphingosine, thymine, linoleic acid, orotic acid, L-histidine, and erythrose serum levels. Thus, the metabolism of PCB 52 and its effects on the metabolome must be considered in toxicity studies.

Design of Proanthocyanidins and TiO2 Nanoparticles-Based Novel Emulsions as a Platform for UV Protection.

A white oil-in-water novel emulsion stabilized by TiO2 nanoparticles with UVB shielding properties and proanthocyanidins with antioxidant activity was prepared, where the proanthocyanidins aggregated at the oil-water interface to reduce interfacial tension while TiO2 nanoparticles were dispersed in the continuous water phase to hinder droplet coalescence. It was found that the average oil droplet size was less than 10 µm and decreased with the increase of proanthocyanidins concentration, but the increase of the content of TiO2 nanoparticles had little effect on it. The combination of TiO2 nanoparticles and proanthocyanidins was versatile for oil phases with different polarities, and the resulting emulsion exhibited high stability in the face of centrifugation, heating and prolonging storage time. After encapsulating the UVA filter avobenzone in white oil, the emulsion was endowed with the ability to resist UVB and UVA. Further, the emulsion showed great free radical scavenging ability for superoxide anion radical (⋅O2 - ), hydroxyl radical (⋅OH) with the clearance rate of over 70 %, indicating the good antioxidant activity. The ingenious combination of UVB, UVA filter and antioxidant with emulsion as carrier provides a new idea for the preparation of full-band sunscreen emulsion.

Enantiomeric Fractions Reveal Differences in the Atropselective Disposition of 2,2',3,5',6-Pentachlorobiphenyl (PCB 95) in Wildtype, Cyp2abfgs-Null, and CYP2A6-Humanized Mice.

Polychlorinated biphenyls (PCBs) are environmental contaminants that can cause neurotoxicity. PCBs, such as PCB 95 (2,2',3,5',6-pentachlorobiphenyl), can be metabolized by cytochrome P450 enzymes into neurotoxic metabolites. To better understand how the metabolism of PCB 95 affects neurotoxic outcomes, we conducted a study on the disposition of PCB 95 in transgenic mouse models. The mice were given a single oral dose of PCB 95 (1.0 mg/kg) and were euthanized 24 h later for analysis. PCB 95 levels were highest in adipose tissue, followed by the liver, brain, and blood. Adipose tissue levels were significantly higher in wild-type (WT) mice than in Cyp2abfgs-null (KO) or CYP2A6-transgenic (KI) mice. We also observed genotype-dependent differences in the enrichment of aS-PCB 95 in female mice, with a less pronounced enrichment in KO than WT and KI mice. Ten hydroxylated PCB 95 metabolites were detected in blood and tissue across all exposure groups. The metabolite profiles differed across tissues, while sex and genotype-dependent differences were less pronounced. Total OH-PCB levels were highest in the blood, followed by the liver, adipose tissue, and brain. Total OH-PCB blood levels were lower in KO than in WT mice, while the opposite trend was observed in the liver. In male mice, total OH-PCB metabolite levels were significantly lower in KI than in WT mice in blood and the liver, while the opposite trend was observed in female mice. In conclusion, the study highlights the differences in the atropselective disposition of PCB 95 and its metabolites in different types of mice, demonstrating the usefulness of these transgenic mouse models for characterizing the role of PCB metabolism in PCB neurotoxicity.

Photolysis of 3-Nitro-1,2,4-triazol-5-one: Mechanisms and Products.

Insensitive munitions formulations that include 3-nitro-1,2,4-triazol-5-one (NTO) are replacing traditional explosive compounds. While these new formulations have superior safety characteristics, the compounds have greater environmental mobility, raising concern over potential contamination and cleanup of training and manufacturing facilities. Here, we examine the mechanisms and products of NTO photolysis in simulated sunlight to further inform NTO degradation in sunlit surface waters. We demonstrate that NTO produces singlet oxygen and that dissolved oxygen increases the NTO photolysis rate in deionized water. The rate of NTO photolysis is independent of concentration and decreases slightly in the presence of Suwannee River Natural Organic Matter. The apparent quantum yield of NTO generally decreases as pH increases, ranging from 2.0 × 10-5 at pH 12 to 1.3 × 10-3 at pH 2. Bimolecular reaction rate constants for NTO with singlet oxygen and hydroxyl radical were measured to be (1.95 ± 0.15) × 106 and (3.28 ± 0.23) × 1010 M-1 s-1, respectively. Major photolysis reaction products were ammonium, nitrite, and nitrate, with nitrite produced in nearly stoichiometric yield upon the reaction of NTO with singlet oxygen. Environmental half-lives are predicted to span from 1.1 to 5.7 days. Taken together, these data enhance our understanding of NTO photolysis under environmentally relevant conditions.

Networks of placental DNA methylation correlate with maternal serum PCB concentrations and child neurodevelopment.

BACKGROUND: Gestational exposure to polychlorinated biphenyls (PCBs) has been associated with elevated risk for neurodevelopmental disorders. Placental epigenetics may serve as a potential mechanism of risk or marker of altered placental function. Prior studies have associated differential placental DNA methylation with maternal PCB exposure or with increased risk of autism spectrum disorder (ASD). However, sequencing-based placental methylomes have not previously been tested for simultaneous associations with maternal PCB levels and child neurodevelopmental outcomes. OBJECTIVES: We aimed to identify placental DNA methylation patterns associated with maternal PCB levels and child neurodevelopmental outcomes in the high-risk ASD MARBLES cohort. METHODS: We measured 209 PCB congeners in 104 maternal serum samples collected at delivery. We identified networks of DNA methylation from 147 placenta samples using the Comethyl R package, which performs weighted gene correlation network analysis for whole genome bisulfite sequencing data. We tested placental DNA methylation modules for association with maternal serum PCB levels, child neurodevelopment, and other participant traits. RESULTS: PCBs 153 + 168, 170, 180 + 193, and 187 were detected in over 50% of maternal serum samples and were highly correlated with one another. Consistent with previous findings, maternal age was the strongest predictor of serum PCB levels, alongside year of sample collection, pre-pregnancy BMI, and polyunsaturated fatty acid levels. Twenty seven modules of placental DNA methylation were identified, including five which significantly correlated with one or more PCBs, and four which correlated with child neurodevelopment. Two modules associated with maternal PCB levels as well as child neurodevelopment, and mapped to CSMD1 and AUTS2, genes previously implicated in ASD and identified as differentially methylated regions in mouse brain and placenta following gestational PCB exposure. CONCLUSIONS: Placental DNA co-methylation modules were associated with maternal PCBs and child neurodevelopment. Methylation of CSMD1 and AUTS2 could be markers of altered placental function and/or ASD risk following maternal PCB exposure.

Toxicity Impacts on Human Adipose Mesenchymal Stem/Stromal Cells Acutely Exposed to Aroclor and Non-Aroclor Mixtures of Polychlorinated Biphenyl.

Polychlorinated biphenyl (PCB) accumulates in adipose where it may impact the growth and function of cells within the tissue. This is particularly concerning during adolescence when adipocytes expand rapidly. Herein, we sought to understand how exposure to PCB mixtures found in U.S. schools affects human adipose mesenchymal stem/stromal cell (MSC) health and function. We investigated how exposure to Aroclor 1016 and Aroclor 1254, as well as a newly characterized non-Aroclor mixture that resembles the PCB profile found in cabinets, Cabinet Mixture, affects adipose MSC growth, viability, and function in vitro. We found that exposure to all three mixtures resulted in two distinct types of toxicity. At PCB concentrations >20 µM, the majority of MSCs die, while at 1-10 µM, MSCs remained viable but display numerous alterations to their phenotype. At these sublethal concentrations, the MSC rate of expansion slowed and morphology changed. Further assessment revealed that PCB-exposed MSCs had impaired adipogenesis and a modest decrease in immunosuppressive capabilities. Thus, exposure to PCB mixtures found in schools negatively impacts the health and function of adipose MSCs. This work has implications for human health due to MSCs' role in supporting the growth and maintenance of adipose tissue.

Ryanodine receptor-active non-dioxin-like polychlorinated biphenyls cause neurobehavioral deficits in larval zebrafish.

Although their production was banned in the United States in 1977, polychlorinated biphenyls (PCBs) continue to pose significant risks to the developing nervous system. Perinatal exposure to PCBs is associated with increased risk of neuropsychiatric disorders, perhaps due to altered patterns of dendritic arborization of central neurons. Non-dioxin-like (NDL) PCB congeners enhance dendritic arborization of developing mammalian neurons via sensitization of ryanodine receptors (RYR). Structure-activity relationships (SAR) of RYR sensitization by PCBs have been demonstrated using mammalian and rainbow trout (Oncorhynchus mykiss) tissue homogenates. The purpose of this study is to determine whether this SAR translates to developmental neurotoxicity (DNT) of PCBs in vivo, a question that has yet to be tested. To address this gap, we leveraged a zebrafish model to evaluate the developmental neurotoxicity potential of PCBs 28, 66, 84, 95, 138, and 153, congeners previously shown to have broadly different potencies towards sensitizing RYR. We first confirmed that these PCB congeners exhibited differing potency in sensitizing RYR in zebrafish muscle ranging from negligible (PCB 66) to moderate (PCB 153) to high (PCB 95) RYR activity. Next, enzymatically dechorionated embryos were statically exposed to varying concentrations (0.1-10 µM) of each PCB congener from 6 h post-fertilization to 5 days post-fertilization (dpf). Embryos were observed daily using stereomicroscopy to assess mortality and gross malformations and photomotor behavior was assessed in larval zebrafish at 3, 4, and 5 dpf. The body burden of each PCB was measured by gas chromatography. The key findings are: 1) None of these PCBs caused death or overt teratology at the concentrations tested; 2) A subset of these PCB congeners altered photomotor behavior in larval zebrafish and the SAR for PCB behavioral effects mirrored the SAR for RYR sensitization; and 3) Quantification of PCB levels in larval zebrafish ruled out the possibility that congener-specific effects on behavior were due to differential uptake of PCB congeners. Collectively, the findings from this study provide in vivo evidence in support of the hypothesis that RYR sensitization contributes to the DNT of PCBs.

Machine Learning-Assisted Identification and Quantification of Hydroxylated Metabolites of Polychlorinated Biphenyls in Animal Samples.

Laboratory studies of the disposition and toxicity of hydroxylated polychlorinated biphenyl (OH-PCB) metabolites are challenging because authentic analytical standards for most unknown OH-PCBs are not available. To assist with the characterization of these OH-PCBs (as methylated derivatives), we developed machine learning-based models with multiple linear regression (MLR) or random forest regression (RFR) to predict the relative retention times (RRT) and MS/MS responses of methoxylated (MeO-)PCBs on a gas chromatograph-tandem mass spectrometry system. The final MLR model estimated the retention times of MeO-PCBs with a mean absolute error of 0.55 min (n = 121). The similarity coefficients cos θ between the predicted (by RFR model) and experimental MS/MS data of MeO-PCBs were >0.95 for 92% of observations (n = 96). The levels of MeO-PCBs quantified with the predicted MS/MS response factors approximated the experimental values within a 2-fold difference for 85% of observations and 3-fold differences for all observations (n = 89). Subsequently, these model predictions were used to assist with the identification of OH-PCB 95 or OH-PCB 28 metabolites in mouse feces or liver by suggesting candidate ranking information for identifying the metabolite isomers. Thus, predicted retention and MS/MS response data can assist in identifying unknown OH-PCBs.

Metabolism of 3-Chlorobiphenyl (PCB 2) in a Human-Relevant Cell Line: Evidence of Dechlorinated Metabolites.

Lower chlorinated polychlorinated biphenyls (LC-PCBs) and their metabolites make up a class of environmental pollutants implicated in a range of adverse outcomes in humans; however, the metabolism of LC-PCBs in human models has received little attention. Here we characterize the metabolism of PCB 2 (3-chlorobiphenyl), an environmentally relevant LC-PCB congener, in HepG2 cells with in silico prediction and nontarget high-resolution mass spectrometry. Twenty PCB 2 metabolites belonging to 13 metabolite classes, including five dechlorinated metabolite classes, were identified in the cell culture media from HepG2 cells exposed for 24 h to 10 µM or 3.6 nM PCB 2. The PCB 2 metabolite profiles differed from the monochlorinated metabolite profiles identified in samples from an earlier study with PCB 11 (3,3'-dichlorobiphenyl) under identical experimental conditions. A dechlorinated dihydroxylated metabolite was also detected in human liver microsomal incubations with monohydroxylated PCB 2 metabolites but not PCB 2. These findings demonstrate that the metabolism of LC-PCBs in human-relevant models involves the formation of dechlorination products. In addition, untargeted metabolomic analyses revealed an altered bile acid biosynthesis in HepG2 cells. Our results indicate the need to study the disposition and toxicity of complex PCB 2 metabolites, including novel dechlorinated metabolites, in human-relevant models.

Assessment of Polychlorinated Biphenyls and Their Hydroxylated Metabolites in Postmortem Human Brain Samples: Age and Brain Region Differences.

Exposure to polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) has been implicated in neurodevelopmental disorders. However, the distribution of PCBs and OH-PCBs in the human brain has not been characterized. This study investigated the age-, sex-, and brain region-specific distribution of all 209 PCBs using gaschromatography-tandem mass spectrometry (GC-MS/MS) in neonatal (N = 7) and adult (N = 7) postmortem brain samples. OH-PCB analyses were performed by GC-MS/MS (as methylated derivatives) and, in a subset of samples, by nontarget liquid chromatography high-resolution mass spectrometry (Nt-LCMS). Fourteen higher chlorinated PCB congeners were observed with a detection frequency >50%. Six lower chlorinated PCBs were detected with a detection frequency >10%. Higher chlorinated PCBs were observed with higher levels in samples from adult versus younger donors. PCB congener profiles from adult donors showed more similarities across brain regions and donors than younger donors. We also assess the potential neurotoxicity of the PCB residues in the human brain with neurotoxic equivalency (NEQ) approaches. The median ΣNEQs, calculated for the PCB homologues, were 40-fold higher in older versus younger donors. Importantly, lower chlorinated PCBs made considerable contributions to the neurotoxic potential of PCB residues in some donors. OH-PCBs were identified for the first time in a small number of human brain samples by GC-MS/MS and Nt-LCMS analyses, and all contained four or fewer chlorine.

The disposition of polychlorinated biphenyls (PCBs) differs between germ-free and conventional mice.

The disposition of toxicants, such as polychlorinated biphenyls (PCBs), in germ-free (GF) vs. conventional (CV) mice has received little attention to date. Here, we investigate PCB levels in three-month-old female CV and GF mice exposed orally daily for 3 days to 0, 6, or 30 mg/kg body weight of the Fox River Mixture (FRM), an environmental PCB mixture. We euthanized animals 24 h after the final dose. PCB profiles in tissues differed from the FRM profile but were similar in tissues across all 4 PCB exposure groups. PCB levels in CV but not GF mice followed the difference in PCB dose. Importantly, PCB levels were higher in CV than GF mice exposed to the same dose. Hepatic cytochrome P450 enzyme or lipid levels did not explain these trends in PCB tissue levels. Thus, toxicity studies with CV and GF animals need to assess the toxicokinetics of the toxicant investigated. CAPSULE: PCB levels are typically higher in conventional than germ-free mice exposed to the same dose of PCBs.

Hydroxylated Polychlorinated Biphenyls Are Emerging Legacy Pollutants in Contaminated Sediments.

We measured the concentrations of 837 hydroxylated polychlorinated biphenyls (OH-PCBs, in 275 chromatographic peaks) and 209 polychlorinated biphenyls (PCBs, in 174 chromatographic peaks) in sediments from New Bedford Harbor in Massachusetts, Altavista wastewater lagoon in Virginia, and the Indiana Harbor and Ship Canal in Indiana, USA and in the original commercial PCB mixtures Aroclors 1016, 1242, 1248, and 1254. We used the correlation between homologues and the peak responses to quantify the full suite of OH-PCBs including those without authentic standards available. We found that OH-PCB levels are approximately 0.4% of the PCB levels in sediments and less than 0.0025% in Aroclors. The OH-PCB congener distributions of sediments are different from those of Aroclors and are different according to sites. We also identified a previously unknown compound, 4-OH-PCB52, which together with 4'-OH-PCB18 made up almost 30% of the OH-PCBs in New Bedford Harbor sediments but less than 1.2% in the Aroclors and 3.3% in any other sediments. This indicates site-specific environmental transformations of PCBs to OH-PCBs. We conclude that the majority of OH-PCBs in these sediments are generated in the environment. Our findings suggest that these toxic breakdown products of PCBs are prevalent in PCB-contaminated sediments and present an emerging concern for humans and ecosystems.