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With its inclusion under Action 3 in the Environment and Health Action Plan 2004-2010 of the European Commission, human biomonitoring is currently receiving an increasing amount of attention from the scientific community as a tool to better quantify human exposure to, and health effects of, environmental stressors. Despite the policy support, however, there are still several issues that restrict the routine application of human biomonitoring data in environmental health impact assessment. One of the main issues is the obvious need to routinely collect human samples for large-scale surveys. Particularly the collection of invasive samples from susceptible populations may suffer from ethical and practical limitations. Children, pregnant women, elderly, or chronically-ill people are among those that would benefit the most from non-invasive, repeated or routine sampling. Therefore, the use of non-invasively collected matrices for human biomonitoring should be promoted as an ethically appropriate, cost-efficient and toxicologically relevant alternative for many biomarkers that are currently determined in invasively collected matrices. This review illustrates that several non-invasively collected matrices are widely used that can be an valuable addition to, or alternative for, invasively collected matrices such as peripheral blood sampling. Moreover, a well-informed choice of matrix can provide an added value for human biomonitoring, as different non-invasively collected matrices can offer opportunities to study additional aspects of exposure to and effects from environmental contaminants, such as repeated sampling, historical overview of exposure, mother-child transfer of substances, or monitoring of substances with short biological half-lives. [ABSTRACT FROM AUTHOR]

This study provides evidence of fine-grained genetic structuring in Mediterranean mussels (Mytilus galloprovincialis) from the Strait of Istanbul, caused by barriers to gene flow via contaminant-mediated selection. In this study, mitochondrial D-loop sequences were analyzed in mussels from 8 localities, all less than 30 kilometers apart, with differing contaminant loads. The results were: 1) Intra-population genetic differentiation (Φ ST ) between sites with high and low contaminant loads was high (up to 0.459), even at distances of only a few kilometers. 2) Genetic diversity was negatively correlated with the contaminant load ("genetic erosion"). 3) There was evidence of selection, based on haplotype frequencies and neutrality tests (Tajima's D), with purifying selection at the most contaminated site and balancing selection at the least contaminated. 4) Genetic distance was not correlated with geographic distance (no isolation-by-distance), but was correlated with contaminant load at each site. 5) Population dendrograms and Bayesian estimators of migration indicated that gene flow between sites was affected by contamination. For the dendrograms of the sampling sites, the clades clustered according to contaminant load more than geographic distance. Overall, these results suggest that 1) contamination may serve as a genotype-dependent dispersal barrier (i.e., contamination may not affect total number of migrants, just the relative proportions of the haplotypes in the established immigrants), leading strong population differentiation over short distances, and 2) genetic erosion may occur by a combination of selection and altered patterns of haplotype-specific gene flow. These effects may be more pronounced in the Strait of Istanbul than in other locations because of the riverine nature and strong, uni-directional current of the strait., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The Allan-Herndon Dudley Syndrome (AHDS) is a rare disease caused by the progressive loss of monocarboxylate transporter 8 (MCT8). In patients with AHDS, the absence of MCT8 impairs transport of thyroid hormones (TH) through the blood brain barrier, leading to a central state of TH deficiency. In mice, the AHDS is mimicked by simultaneous deletion of the TH transporters MCT8 and the solute carrier organic anion transporter family member 1c1 (OATP1C1). To support preclinical mouse studies, an analytical methodology was developed and successfully applied for quantifying selected thyroid hormones in mouse whole brain and in specific regions using liquid chromatography tandem mass-spectrometry (LC-MS/MS). An important requirement for the methodology was its high sensitivity since a very low concentration of THs was expected in MCT8/OATP1C1 double-knockout (dko) mouse brain. Seven THs were targeted: L-thyroxine (T4), 3,3´,5-triiodo-L-thyronine-thyronine (T3), 3,3´,5´-triiodo-L-thyronine-thyronine (rT3), 3,3´-diiodo-L-thyronine (3,3´-T2, T2), 3,5-diiodo-L-thyronine (rT2, 3,5-T2), 3-iodo-L-thyronine (T1), 3-iodothyronamine (T1AM). Isotope dilution liquid chromatography triple-quadrupole mass spectrometry methodology was applied for detection and quantification. The method was validated in wild-type animals for mouse whole brain and for five different brain regions (hypothalamus, hippocampus, prefrontal cortex, brainstem and cortex). Instrumental calibration curves ranged from 0.35 to 150 pg/µL with good linearity (r 2 >0.996). The limit of quantification was from 0.08 to 0.6 pg/mg, with an intra- and inter-day precision of 4.2-14.02% and 0.4-17.9% respectively, and accuracies between 84.9% and 114.8% when the methodology was validated for the whole brain. In smaller, distinct brain regions, intra- and inter-day precision were 0.6-20.7% and 2.5-15.6% respectively, and accuracies were 80.2-128.6%. The new methodology was highly sensitive and allowed for the following quantification in wild-type mice: (i) for the first time, four distinct thyroid hormones (T4, T3, rT3 and 3,3´-T2) in only approximately 100 mg of mouse brain were detected; (ii) the quantification of T4 and T3 for the first time in distinct mouse brain regions were reported. Further, application of our method to MCT8/OATP1C1 dko mice revealed the expected, relative lack of T3 and T4 uptake into the brain, and confirmed the utility of our analytical method to study TH transport across the blood brain barrier in a preclinical model of central TH deficiency., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

To explore the etiology of diseases is one of the major goals in epidemiological study. Meet-in-metabolite analysis reconstitutes biomonitoring-based adverse outcome (AO) pathways from environmental exposure to a disease, in which the chemical exposome-related metabolism responses are transmitted to incur the AO-related metabolism phenotypes. However, the ongoing data-dependent acquisition of non-targeted biomonitoring by high-resolution mass spectrometry (HRMS) is biased against the low abundance molecules, which forms the major of molecular internal exposome, i.e., the totality of trace levels of environmental pollutants and/or their metabolites in human samples. The recent development of data-independent acquisition protocols for HRMS screening has opened new opportunities to enhance unbiased measurement of the extremely low abundance molecules, which can encompass a wide range of analytes and has been applied in metabolomics, DNA, and protein adductomics. In addition, computational MS for small molecules is urgently required for the top-down exposome databases. Although a holistic analysis of the exposome and endogenous metabolites is plausible, multiple and flexible strategies, instead of "putting one thing above all" are proposed., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Thyroid hormones (TH) are known to play a critical role in regulating many biological processes including growth and development, energy homeostasis, thermogenesis, lipolysis and metabolism of cholesterol. Severe TH deficiency especially during fetal development results in cretinism, but can also lead to an imbalance in metabolism with, among others, an alteration in body weight composition. Over the past two decades, increasing evidence has shown that certain persistent organic pollutants (POP) can interfere with the endocrine system. These POP referred to as "endocrine disrupting chemicals" are widely present in the environment and populations are exposed globally. Moreover, epidemiological studies have shown that a particularly sensitive period is the pre- and postnatal time. Indeed, perinatal exposure to such chemicals could lead to the onset diseases in later life. It is known, that, maternal thyroid hormones are transported by the placenta to the fetus from 6 weeks of gestation and it seems that during the first trimester, and part of the second, the fetus is entirely dependent on maternal TH supply for its development. Interferences in the TH-network as a consequence of the exposure to such pollutants could cause variations in TH concentration. Only small changes in maternal thyroid hormone levels in early stages of pregnancy can influence fetal neurological and cardiovascular development, as well as according to recent studies, have effect on childhood body composition. With this review, we will report the most recent and important studies concerning the association between thyroid hormone concentration and POP levels measured during the perinatal period. We will mostly focus on the data recently reported on placenta and breastmilk as main sources for understanding the potential consequences of exposure. The possible link between exposure to pollutants, TH dysregulation and possible adverse outcome will also be briefly discussed. From our literature search, several studies support the hypothesis that pre- and postnatal exposure to different pollutants might play a role in causing variation in thyroid hormone concentration. However, few research papers have so far studied the relationship linking exposure to pollutants, TH concentration and possible health consequences. Therefore, this review highlights the need for further research in this direction., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The mediobasal hypothalamus (MBH) is the central region in the physiological response to metabolic stress. The FK506-binding protein 51 (FKBP51) is a major modulator of the stress response and has recently emerged as a scaffolder regulating metabolic and autophagy pathways. However, the detailed protein-protein interactions linking FKBP51 to autophagy upon metabolic challenges remain elusive. We performed mass spectrometry-based metabolomics of FKBP51 knockout (KO) cells revealing an increased amino acid and polyamine metabolism. We identified FKBP51 as a central nexus for the recruitment of the LKB1/AMPK complex to WIPI4 and TSC2 to WIPI3, thereby regulating the balance between autophagy and mTOR signaling in response to metabolic challenges. Furthermore, we demonstrated that MBH FKBP51 deletion strongly induces obesity, while its overexpression protects against high-fat diet (HFD)-induced obesity. Our study provides an important novel regulatory function of MBH FKBP51 within the stress-adapted autophagy response to metabolic challenges.

Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring. C57Bl6/N mouse dams (F0) were exposed to DE-71 via oral administration of 0 (VEH/CON), 0.1 (L-DE-71) or 0.4 (H-DE-71) mg/kg bw/d from 3 wk prior to gestation through end of lactation. Mass spectrometry analysis indicated in utero and lactational transfer of PBDEs (in ppb) to F1 female offspring brain tissue at postnatal day (PND) 15 which was reduced by PND 110. Neurobehavioral testing of social novelty preference (SNP) and social recognition memory (SRM) revealed that adult L-DE-71 F1 offspring display deficient short- and long-term SRM, in the absence of reduced sociability, and increased repetitive behavior. These effects were concomitant with reduced olfactory discrimination of social odors. Additionally, L-DE-71 exposure also altered short-term novel object recognition memory but not anxiety or depressive-like behavior. Moreover, F1 L-DE-71 displayed downregulated mRNA transcripts for oxytocin (Oxt) in the bed nucleus of the stria terminalis (BNST) and supraoptic nucleus, and vasopressin (Avp) in the BNST and upregulated Avp1ar in BNST, and Oxtr in the paraventricular nucleus. Our work demonstrates that developmental PBDE exposure produces ASD-relevant neurochemical, olfactory processing and behavioral phenotypes that may result from early neurodevelopmental reprogramming within central social and memory networks., (© 2021. The Author(s).)

Morphine can be synthesized endogenously by mammals from dopamine via the intermediate norlaudanosoline. Previously, both compounds have been detected separately in whole brains of mice and brain regions of rats, and in urine of humans. Here, we report a novel method for the analysis of both compounds in single murine brain regions. Initially, a variant of dispersive liquid-liquid microextraction was established by using methanol as an extractant, cyclohexane as solvent, and tributylphosphate as disperser. The extraction method was applied to murine brain regions homogenized with perchloric acid while the subsequent detection was carried out by HPLC with electrochemical detection. In the thalamus of C57Bl/6J mice (n = 3, male, age 4-8 months), morphine and norlaudanosoline could be detected at levels of 19 ± 3.9 and 7.2 ± 2.3 pg/mg, respectively. Overall, we provide a novel method for the simultaneous extraction and detection of both morphine and norlaudanosoline in single murine brain regions., (Copyright © 2021. Published by Elsevier Ltd.)

The metabolites of gut microbiome are important host-health regulating factors and can be interrupted when the host is exposed to environmental pollutant via ingestion route. Arsenic contaminated drinking water is one of the most serious environmental health problems worldwide. Therefore, the arsenic-induced alterations of gut microbiome and metabolome, especially the persistence and reversibility of the alterations after the long-term arsenic exposure will be interesting to know. In this study, we investigated the relationship between gut microbiota and metabolites in male rats both after the 30-days arsenic treatment and 30-days recovery duration. The composition and diversity of gut microbiota were affected significantly by the treatment, but they presented partial improvement in recovery duration. Moreover, arsenic exposure induced the significant changes of 73 metabolites, which involved in the metabolism of glycerophospholipid, linoleic acid, as well as the biosynthesis of phenylalanine, tyrosine and tryptophan. Although it had a persistent effect, the restoration of glycerophospholipid metabolism was observed in the 30-days recovery. Integration analysis further correlated the arsenic impacting microbes with some important differential metabolites. Lactobacillus associated with the decreases of phosphatidylethanolamine(34:1), 16alpha-hydroxydehydroepiandrosterone 3-sulfate, seryltryptophan and alanyltyrosine in recovery duration. Lactobacillus strains have potential to work as protective agents against arsenic toxicity by restoring perturbed glycerophospholipid metabolism. In summary, arsenic significantly disrupted gut microbiome and metabolome, but the disruptions are reversible to some extent after a 30-days recovery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Concentrations of persistent organic pollutants (POPs) have been associated with an increased type 2 diabetes (T2D) risk. It remains unclear whether POPs are also associated with the risk of diabetes complications including neuropathy and evidence on this topic is scarce. We aimed to investigate the hypothesis that low-dose background concentrations of POPs were positively associated with distal sensorimotor polyneuropathy (DSPN)., Methods: This cross-sectional study was based on data from the second follow-up (FF4, 2013-2014, N = 2279) of the population-based KORA S4 study (Augsburg, Germany). The study sample consisted of 200 participants, including four groups of 50 persons each with known T2D, prediabetes, newly diagnosed diabetes, and normal glucose tolerance (NGT) based on an oral glucose tolerance test. We analyzed the association of six most abundant serum concentrations of POPs, including polychlorinated biphenyls (PCBs) as well as organochlorine (OC) pesticides, with DSPN by multivariable logistic regression adjusted for age, sex, glycaemic status, body mass index, physical activity, smoking and alcohol consumption. We assessed effect modification by age, sex, glycaemic status and obesity and conducted two-pollutant models to check the robustness of the estimates., Results: For all pollutants, the main models indicated no significant association of having DSPN but pointed to rather decreased odds for DSPN. Two-pollutant models supported these findings, though only the association between the combination of PCB-138 and beta-hexachlorocyclohexane (β-HCH) (OR: 0.59; 95% CI: 0.35-0.99) with DSPN became significant. No effect modification was found by age, sex, glycaemic status and obesity., Conclusion: Low-dose concentrations of POPs were not associated with increased odds of having DSPN in T2D, prediabetes and NGT., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Persistent organic pollutants (POPs) are ubiquitous contaminants with adverse health effects in the ecosystem. One of such effects is endocrine disruption in humans and wildlife even at background exposure concentrations. This study assessed maternal breastmilk concentrations of POPs; brominated flame retardants (BFRs), polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), and the potential health risks posed to the nursing infants. We also evaluated the association of these POPs with total 3,3',5-triiodo-L-thyronine (T 3 ), L-thyroxine (T 4 ), and 3,3',5'-triiodo-L-thyronine (rT 3 ) levels measured in human breast milk. Thirty breastmilk samples were collected from Kampala, Uganda between August and December 2018. Hexabromobenzene was not detected while the maximum level of 2,2',4,4',5,5'-hexabrombiphenyl was 64.7 pg/g lw. The median levels of total indicator PCBs, PBDEs, dioxin-like PCBs, and PCDD/Fs in the samples were 159 pg/g lw, 511 pg/g lw, 1.16 pg TEQ/g lw, and 0.4 pg TEQ/g lw, respectively. These levels were lower than those reported in other countries. Owing to their bio accumulative nature, PCBs -81, -169, and ∑PCDD/Fs increased with increase in maternal age. Estimated dietary intakes for dioxin-like PCBs and PCDD/Fs were lower than those reported elsewhere but were higher than the WHO tolerable daily intakes suggesting potential health risks to nursing infants. In adjusted single pollutant models, PCB-126, PCB-169, and ∑PCB TEQ were negatively associated with T 3 , while 1,2,3,4,5,7,8-HpCDF was positively associated with rT 3 . Although these associations did not persist in multipollutant models, our findings suggest potential thyroid hormone disruption by POPs in mothers. This may reduce the levels of thyroid hormones transferred from the mother to the neonates and, hence, adversely influence infant growth. A temporal study with a bigger sample size is required to corroborate these findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Meeting ecological and water quality standards in lotic ecosystems is often failed due to multiple stressors. However, disentangling stressor effects and identifying relevant stressor-effect-relationships in complex environmental settings remain major challenges. By combining state-of-the-art methods from ecotoxicology and aquatic ecosystem analysis, we aimed here to disentangle the effects of multiple chemical and non-chemical stressors along a longitudinal land use gradient in a third-order river in Germany. We distinguished and evaluated four dominant stressor categories along this gradient: (1) Hydromorphological alterations: Flow diversity and substrate diversity correlated with the EU-Water Framework Directive based indicators for the quality element macroinvertebrates, which deteriorated at the transition from near-natural reference sites to urban sites. (2) Elevated nutrient levels and eutrophication: Low to moderate nutrient concentrations together with complete canopy cover at the reference sites correlated with low densities of benthic algae (biofilms). We found no more systematic relation of algal density with nutrient concentrations at the downstream sites, suggesting that limiting concentrations are exceeded already at moderate nutrient concentrations and reduced shading by riparian vegetation. (3) Elevated organic matter levels: Wastewater treatment plants (WWTP) and stormwater drainage systems were the primary sources of bioavailable dissolved organic carbon. Consequently, planktonic bacterial production and especially extracellular enzyme activity increased downstream of those effluents showing local peaks. (4) Micropollutants and toxicity-related stress: WWTPs were the predominant source of toxic stress, resulting in a rapid increase of the toxicity for invertebrates and algae with only one order of magnitude below the acute toxic levels. This toxicity correlates negatively with the contribution of invertebrate species being sensitive towards pesticides (SPEAR pesticides index), probably contributing to the loss of biodiversity recorded in response to WWTP effluents. Our longitudinal approach highlights the potential of coordinated community efforts in supplementing established monitoring methods to tackle the complex phenomenon of multiple stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Accidental spills or illegal discharges of pesticides in aquatic ecosystems can lead to exposure levels that strongly exceed authorized pesticide concentrations, causing major impacts on aquatic ecosystems. Such short-term events often remain undetected in regular monitoring programs with infrequent sampling. In early spring 2015, we identified a catastrophic pesticide spill with the insecticide cypermethrin in the Holtemme River, Germany. Based on existing pre-event macroinvertebrate community data, we monitored the effects and recovery of the macroinvertebrate community for more than two years after the spill. Strong short-term effects were apparent for all taxa with the exception of Chironomidae and Tubificidae. Effects could also be observed on the community level as total abundance, taxa number and biomass strongly decreased. Total abundance and taxa number showed a fast recovery. Regarding long-term effects, the total biomass remained substantially below the pre-contamination level (76%) until the end of the study. Also the abundances of three taxa (Gammarus, Leuctra, Limnius Ad.) did not return to levels prior to the spill even after 26 months. This lack of the taxon-specific recovery was likely due to their long generation time and a low migration ability due to a restricted connectivity between the contaminated site and uncontaminated stream sections. These factors proved to be stronger predictors for the recovery than the pesticide tolerance. We revealed that the biological indicators SPEARpesticides and share of Ephemeroptera, Plecoptera and Trichoptera (EPT) are not suitable for the identification of such extreme events, when nearly all taxa are eradicated. Both indicators are functioning only when repeated stressors initiate long-term competitive replacement of sensitive by insensitive taxa. We conclude that pesticide spills can have significant long-term effects on stream macroinvertebrate communities. Regular ecological monitoring is imperative to identify such ecosystem impairments, combined with analytical chemistry methods to identify the potential sources of spills., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

3-iodothyronamine (3-T 1 AM) has been suggested as a novel chemical messenger and potent trace amine-associated receptor 1 ligand in the CNS that occurs naturally as endogenous metabolite of the thyroid hormones. Discrepancies and variations in 3-T 1 AM plasma and tissue concentrations have nonetheless caused controversy regarding the existence and biological role of 3-T 1 AM. These discussions are at least partially based on potential analytical artefacts caused by differential decay kinetics of 3-T 1 AM and the widely used deuterated quantification standard D 4 -T 1 AM. Here, we report a novel LC-MS/MS method for the quantification of 3-T 1 AM in biological specimens using stable isotope dilution with 13 C 6 -T 1 AM, a new internal standard that showed pharmacodynamic properties comparable to endogenous 3-T 1 AM. The method detection limit (MDL) and method quantification limit (MQL) of 3-T 1 AM were 0.04 and 0.09 ng/g, respectively. The spike-recoveries of 3-T 1 AM were between 85.4% and 94.3%, with a coefficient of variation of 3.7-5.8%. The intra-day and inter-day variations of 3-T 1 AM were 8.45-11.2% and 3.58-5.73%, respectively. Endogenous 3-T 1 AM liver values in C57BL/6J mice were 2.20 ± 0.49 pmol/g with a detection frequency of 50%. Higher liver 3-T 1 AM values were found when C57BL/6J mice were treated with N-acetyl-3-iodothyronamine or O-acetyl-3-iodothyronamine. Overall, our new stable isotope dilution LC-MS/MS method improves both the sensitivity and selectivity compared with existing methods. The concomitant possibility to quantify additional thyroid hormones such as thyroxine, 3,5,3'-triiodo- L -thyronine, 3,3',5'-triiodo- L -thyronine, 3,3'-diiodo- L -thyronine, and 3,5-diiodo- L -thyronine further adds to the value of our novel method in exploring the natural occurrence and fate of 3-T 1 AM in biological tissues and fluids., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Sampling points belonging to the Harz National Park river system, Germany, were selected between the period of 2014 and 2017 for monitoring polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in water, air, and sediment. Triolein-containing Virtual Organisms (VO) were employed to assess the levels of chemicals in water, air and triolein as surrogate for natural fat. To avoid overestimation of the concentrations 20 performance reference compounds (PRCs)-16 PRCs-PAHs and 4 PRCs-PCBs were covering the range of properties of native compounds. Results manifested the highest concentration of individual PAH as follows: 31 ng fluoranthene/L water, 3600 ng pyrene/g fat, 62 ng phenanthrene/m 3 air and 2800 ng fluoranthene/g dw sediment. All PCBs and OCPs values were below above mentioned PAH concentrations and far below EU-limit levels. Environmental partition of chemicals was investigated by calculating fugacity, suggesting a mass transport from water to air. Only quite volatile compounds such as hexachlorobutadiene showed higher fugacity in air. Ratios of sediment/water concentrations and log Kow within individual sampling periods at Holtemme River exhibited strong linear relationships. Interestingly, during summer months of the years water and fat contents well correlate to the flow rates of Holtemme River. Our results show that VO can be successfully used as a tool for ongoing exposure assessment studies and predictions of worst case levels in food and nutrition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Per- and polyfluoroalkyl substances (PFASs) are known organic pollutants with adverse health effects on humans and the ecosystem. This paper synthesises literature about the status of the pollutants and their precursors, identifies knowledge gaps and discusses future perspectives on the study of PFASs in Africa. Limited data on PFASs prevalence in Africa is available because there is limited capacity to monitor PFASs in African laboratories. The levels of PFASs in Africa are higher in samples from urban and industrialized areas compared to rural areas. Perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are the dominant PFASs in human samples from Africa. Levels of PFOS and PFOA in these samples are lower than or comparable to those from industrialized countries. PFOA and PFOS levels in drinking water in Africa are, in some cases, higher than the EPA drinking water guidelines suggesting potential risk to humans. The levels of PFASs in birds' eggs from South Africa are higher, while those in other environmental media from Africa are lower or comparable to those from industrialized countries. Diet influences the pollutant levels in fish, while size and sex affect their accumulation in crocodiles. No bioaccumulation of PFASs in aquatic systems in Africa could be confirmed due to small sample sizes. Reported sources of PFASs in Africa include municipal landfills, inefficient wastewater treatment plants, consumer products containing PFASs, industrial wastewater and urban runoff. Relevant stakeholders need to take serious action to identify and deal with the salient sources of PFASs on the African continent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Reliability in the use of placentome (including placenta, umbilical cord, and cord blood) biomarkers requires an understanding of their distributions. Here we aim to develop a simple and proper placenta sampling scheme, and to evaluate the placental distributions of biomarkers., Methods: We developed a continuous cooling chain protocol off delivery room and cryo-subsampling method for placenta sampling. The levels of thyroid hormones (THs), elements, persistent organic pollutants (POPs), monoamines, and vitamin E were measured using UPLC-Q-TOF-MS, HPLC-ICP-MS, HPLC-EcD, and HRGC-HRMS, respectively. The distributions of biomarkers were assessed., Results: In human placentome, l -thyroxine (T 4 ), Cd, Se, Zn, Cu, Fe, Ca, K, Mg, α-tocopherol, β-tocopherol, and β-tocotrienol levels were higher in placenta than in umbilical cord, while Pb and Mn were concentrated in human cord. In porcine placentome, T 4 , 3,3',5'-triiodo- l -thyronine (rT 3 ), 3,3'-diiodo- l -thyronine, Cd, Pb, Zn, K, and Al levels were higher in the cord. The intraclass correlation coefficient (ICC) was <0.4 for 3,3',5-triiodo- l -thyronine, rT 3 , α-tocopherol, and 7 elements in human basal plate, indicating low reliability. rT 3 , Cd, Zn, Mn, and Cu were significantly concentrated in the central region in human placenta, while higher levels of As, Cd, Cr, and Al were found in the periphery region in porcine placenta. Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) showed moderate reliability (ICC: 0.40-0.98) except PCB-81, -126, and BDE-208, while polychlorinated dibenzo-p-doixins/furans (PCDD/Fs) showed poor reliability (ICC: 0.07-0.31)., Discussion: These results highlight the complexity of placenta sampling. This study provides a novel and simple sampling approach in investigating placental exposomics., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aims/hypothesis: Treatment with the α3β4 nicotinic acetylcholine receptor (nAChR) agonist, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), improves glucose tolerance in diet-induced obese (DIO) mice, but the physiological and molecular mechanisms are unknown., Methods: DMPP (10 mg/kg body weight, s.c.) was administered either in a single injection (acute) or daily for up to 14 days (chronic) in DIO wild-type (WT) and Chrnb4 knockout (KO) mice and glucose tolerance, tissue-specific tracer-based glucose metabolism, and insulin signalling were assessed., Results: In WT mice, but not in Chrnb4 KO mice, single acute treatment with DMPP induced transient hyperglycaemia, which was accompanied by high plasma adrenaline (epinephrine) levels, upregulated hepatic gluconeogenic genes, and decreased hepatic glycogen content. In contrast to these acute effects, chronic DMPP treatment in WT mice elicited improvements in glucose tolerance already evident after three consecutive days of DMPP treatment. After seven days of DMPP treatment, glucose tolerance was markedly improved, also in comparison with mice that were pair-fed to DMPP-treated mice. The glycaemic benefit of chronic DMPP was absent in Chrnb4 KO mice. Chronic DMPP increased insulin-stimulated glucose clearance into brown adipose tissue (+69%), heart (+93%), gastrocnemius muscle (+74%) and quadriceps muscle (+59%), with no effect in white adipose tissues. After chronic DMPP treatment, plasma adrenaline levels did not increase following an injection with DMPP. In glucose-stimulated skeletal muscle, we detected a decreased phosphorylation of the inhibitory Ser640 phosphorylation site on glycogen synthase and a congruent increase in glycogen accumulation following chronic DMPP treatment., Conclusions/interpretation: Our data suggest that DMPP acutely induces adrenaline release and hepatic glycogenolysis, while chronic DMPP-mediated activation of β4-containing nAChRs improves peripheral insulin sensitivity independently of changes in body weight via mechanisms that could involve increased non-oxidative glucose disposal into skeletal muscle.

Celastrol is a natural pentacyclic triterpene extracted from the roots of Tripterygium wilfordi (thunder god vine). Celastrol was reported as a powerful anti-obesity drug with leptin sensitizing properties that decreases food consumption and mediates body weight loss when administered to diet-induced obese mice at 100 μg/kg body weight. The weight lowering properties of celastrol are likely mediated by the CNS, in particular, by the hypothalamus, but the final proof for the accumulation of celastrol in the brain and hypothalamus remains to be established. Here, we aimed to demonstrate that intraperitoneal celastrol administration at 100 μg/kg can rapidly reach the brain and, in particular, the hypothalamus of mice. We developed and validated a sensitive liquid chromatography mass spectrometry method for the quantitative determination of celastrol in murine tissues, namely liver, brain and hypothalamus. Chow-fed lean mice were randomly assigned to the vehicle vs. celastrol groups, injected with saline or 100 μg/kg body weight of celastrol, and sacrificed 30 min or 120 min post injection. Celastrol was extracted from homogenized tissue using ethyl acetate as organic solvent, and quantified using a matrix-matched calibration curve with glycyrrhetinic acid as internal standard. Liver celastrol concentrations were 32.60 ± 8.21 pg/mg and 40.52 ± 15.6 pg/mg, 30 and 120 min after injection, respectively. We found 4.70 ± 0.31 pg/mg celastrol after 30 min, and 16.22 ± 3.33 pg/mg after 120 min in whole brain lysates, and detectable amounts in the hypothalamus. These results corroborate the validity of our methodology, demonstrate the accumulation of celastrol in the brain of mice injected intraperitoneally with a dose of 100 μg/kg, and confirm the CNS as possible site of action for the weight lowering properties of celastrol., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Endocrine disrupting chemicals (EDCs) are xenobiotics that mimic the interaction of natural hormones and alter synthesis, transport, or metabolic pathways. The prospect of EDCs causing adverse health effects in humans and wildlife has led to the development of scientific and regulatory approaches for evaluating bioactivity. This need is being addressed using high-throughput screening (HTS) in vitro approaches and computational modeling., Objectives: In support of the Endocrine Disruptor Screening Program, the U.S. Environmental Protection Agency (EPA) led two worldwide consortiums to virtually screen chemicals for their potential estrogenic and androgenic activities. Here, we describe the Collaborative Modeling Project for Androgen Receptor Activity (CoMPARA) efforts, which follows the steps of the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP)., Methods: The CoMPARA list of screened chemicals built on CERAPP's list of 32,464 chemicals to include additional chemicals of interest, as well as simulated ToxCast™ metabolites, totaling 55,450 chemical structures. Computational toxicology scientists from 25 international groups contributed 91 predictive models for binding, agonist, and antagonist activity predictions. Models were underpinned by a common training set of 1,746 chemicals compiled from a combined data set of 11 ToxCast™/Tox21 HTS in vitro assays., Results: The resulting models were evaluated using curated literature data extracted from different sources. To overcome the limitations of single-model approaches, CoMPARA predictions were combined into consensus models that provided averaged predictive accuracy of approximately 80% for the evaluation set., Discussion: The strengths and limitations of the consensus predictions were discussed with example chemicals; then, the models were implemented into the free and open-source OPERA application to enable screening of new chemicals with a defined applicability domain and accuracy assessment. This implementation was used to screen the entire EPA DSSTox database of ∼ 875,000 chemicals, and their predicted AR activities have been made available on the EPA CompTox Chemicals dashboard and National Toxicology Program's Integrated Chemical Environment. https://doi.org/10.1289/EHP5580.

Epidemiological studies have indicated the thyroid-disrupting effects of persistent organic pollutants (POPs). However, the association of low-exposure POPs with thyroid hormones (THs) remains unclear. Here, we aim to assess the association of low exposure of POPs, including polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polychlorinated dibenzo- p -dioxins and furans (PCDD/Fs), and polybrominated dibenzo- p -dioxins and furans, with THs [total L -thyroxine (TT 4 ), total 3,3',5-triiodo- L -thyronine (TT 3 ), and total 3,3',5'-triiodo- L -thyronine (TrT 3 )] measured in human breast milk. Ninety-nine breast milk samples were collected from the LUPE cohort (2015-2016, Bavaria, Germany). Fourteen PBDEs, 17 PCBs, and 5 PCDD/Fs had quantification rates of >80%. Nonmonotonic associations were observed. In adjusted single-pollutant models, (1) TT 4 was inversely associated with BDE-99, -154, and -196; (2) TT 3 was inversely associated with BDE-47, -99, -100, -197, -203, -207, and OCDD; and (3) TrT 3 was inversely associated with BDE-47, -99, -183, and -203. Multipollutant analysis using principal component analysis and hierarchical clustering revealed inverse associations of PBDEs (BDE-28, -47, -99, -100, -154, -183, and -197) with TT 4 and TrT 3 . These results indicate that POPs at low levels might be related to reduced THs. This study shows that human breast milk might be an appropriate specimen to evaluate the thyroid disruption of POPs.

Organochlorine pesticides (OCPs) were analyzed in three different ages (half-, 1.5-, 2.5-year-old) for needles and semi permeable membrane devices (SPMDs) at three deployment periods from sea level to 1881 meter above sea level. Individual HCHs concentrations ranged between 1.4 and 129 pg/g fw depending on the age and sampling season while 2.5-year-old needles showed higher HCHs levels compared to half and 1.5- year-old. Correlation between elevation and HCH concentration in SPMDs was found but not in needle samples. Concentrations of HCHs in SPMDs indicated clearly cold condensation effect on accumulation in winter period and increased with altitude. Concentrations of DDTs in half and 1.5-year-old needles were lower than 2.5-year-old needles. The highest total concentration of DDTs was detected in 1-year-period SPMD. Higher concentrations were found in 2.5-year-old needles for other OCPs. Seasonal and altitude-dependent changes were not observed for other OCPs in SMPDs. Total accumulation of OCPs in SPMDs were found higher than in needles. On the contrary, an increased accumulation rate was observed for HCHs in SPMD. In general, Total concentrations of DDTs and HCHs were similar to total of other OCPs in all altitudes when dominating endosulfan wasnot taken into account in the computation of total concentration of other OCPs.

Exposomics is assessment of organism exposure to high priority environmental pollutants in an ecosystem using OMIC technologies. A virtual organism (VO) is an artificial property-tool (OMIC) reflecting exposomic process in compartments of real organisms. The exposomics of aquatic organisms inhabiting Lake Victoria (L.V.) and Three Gorges Reservoir (TGR) were compared using VOs. The two reservoirs are heavily depended on for food and water both in Africa and China. The target priority pollutants in the reservoirs were polyclic aromatic hydrocarbons (PAHs) and persistent organic pollutants such as polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), medium chain chlorinated paraffins (MCCPs) and short chain chlorinated paraffins (SCCPs). The VOs showed that in a period of 28 days, aquatic organisms in TGR were exposed to total (∑) PAHs of 8.71 × 10 -6  mg/L, PCBs of 2.81 × 10 -6  mg/L, OCPs of 2.80 × 10 -6  mg/L, MCCPs of 8.9 × 10 -10  mg/L and SCCPs of 1.13 × 10 -7  mg/L. While in a period of 48 days, organisms in L. V. were exposed to total (∑) PAHs of 7.45 × 10 -6  mg/L, PCBs of 4.70 × 10 -6  mg/L, OCPs of 3.39 × 10 -8  mg/L, MCCPs of 4.6 × 10 -10  mg/L and SCCPs of 3.6 × 10 -9  mg/L. The exposomic levels in TGR after 28 days were higher than those in Lake Victoria after 48 days. In both reservoirs, bioaccumulation levels are above set standards for aquatic organisms. The sources of the pollutants into the reservoirs were diagnostically determined to originate from anthropogenic processes such as petrogenic, diesel emissions, biomass burning, coal combustion, electronic wastes, traffic emissions and historic uses., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Serum thyroid state in older adults correlates with extended longevity. We hypothesized that age impacts not only systemic but also organ-specific thyroid state and response to thyroxine (T4). Methods: Young (3 months) and old (23 months) male mice were analyzed at baseline and after acute T4 challenge. Age effects on circulating thyrotropin (TSH) and thyroid hormone (TH) concentrations, transcript expression in the pituitary and thyroid were compared with organ-specific responses characterized by hepatic and cardiac content of TH and TH metabolites and expression of TH-target genes, as well as hepatic deiodinase 1 activity. Results: Circulating TH concentrations and hepatic and cardiac TH content were lower in old versus young mice. After injection with T4, conversion of T4 to triiodothyronine was decreased in old mice while TH transport in liver and heart was not affected. Organ-specific TH response was augmented in old mice in liver but not heart, indicating age- and tissue-specific sensitivity to TH. A compensatory increase of thyroid stimulating hormone subunit beta expression in the pituitary and increased serum TSH concentrations, but reduced expression of thyroid differentiation markers were found in old mice. Conclusions: We suggest that a reduced activity of the aged thyroid is responsible for the systemic low TH state in old mice. Further, divergent TH metabolism and tissue response in liver and heart occur after T4 treatment in an aged organism. These rodent data are in agreement with a much narrower window for T4 substitution in the older adults to avoid overtreatment.

Titanium dioxide nanoparticles (TiO 2 -NPs) are widely distributed in the environment. It has been demonstrated that TiO 2 -NPs could modify the environmental fate and bioavailability of organic pollutants, which affects ecological risks of TiO 2 -NPs and organic pollutants. In this study, the uptake, translocation and accumulation of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) in pumpkin plants was investigated in the presence of TiO 2 -NPs. We reported for the first time the negligible effects of TiO 2 -NPs at environmentally relevant concentrations (0.05-5 mg/L) on the uptake and accumulation of PFOA and PFOS in hydroponically grown pumpkin seedlings regardless of root, stem and leaf. This phenomenon was independent of the initial concentrations of PFOA/PFOS and TiO 2 -NPs in the exposure solution. Also, seedling mass and contents of chlorophyll and anthocyanin were not affected by the co-exposure. Adsorption tests demonstrated the negligible adsorption of PFOA/PFOS on TiO 2 -NPs in the exposure solution. Moreover, uptake of PFOA/PFOS was insensitive to aquaporin inhibitor AgNO 3 but significantly inhibited by niflumic acid (anion channel blocker) and 2,4-dinitrophenol (metabolic inhibitor) whereas Ti concentration in root was not affected by niflumic acid and 2,4-dinitrophenol but significantly decreased by AgNO 3 , indicating that transport of PFOA/PFOS and TiO 2 -NPs were via different routes into the pumpkin seedling. It was proposed that different pathways by which TiO 2 -NPs and PFOA/PFOS transported into the pumpkin seedling and negligible adsorption of PFOA/PFOS on TiO 2 -NPs contributed to the negligible effects of TiO 2 -NPs on the uptake, translocation and accumulation of PFOA/PFOS in pumpkin seedlings. In total, this work would improve our understanding of the ecological risks of TiO 2 -NPs in the environment., (Copyright © 2019. Published by Elsevier B.V.)

Background: Associations between several persistent organic pollutants (POPs) and type 2 diabetes have been found in humans, but the relationship has rarely been investigated in the general population. The current nested case-control study examined internal exposure to polychlorinated biphenyls (PCB) and pesticides and the incidence of type 2 diabetes among participants of two population-based German cohort studies., Methods: We retrospectively selected 132 incident cases of type 2 diabetes and 264 age- and sex-matched controls from the CARdiovascular Living and Aging in Halle (CARLA) study (2002-2006, East Germany) and the Cooperative Health Research in the Region of Augsburg (KORA) study (1999-2001, South Germany) based on diabetes status at follow-up examinations in 2007-2010 and 2006-08, respectively (60% male, mean age 63 and 54 years). We assessed the association between baseline POP concentrations and incident diabetes by conditional logistic regression adjusted for cohort, BMI, cholesterol, alcohol, smoking, physical activity, and parental diabetes. Additionally, we examined effect modification by sex, obesity, parental diabetes and cohort., Results: In both cohorts, diabetes cases showed a higher BMI, a higher frequency of parental diabetes, and higher levels of POPs. We observed an increased chance for incident diabetes for PCB-138 and PCB-153 with an odds ratio (OR) of 1.50 (95%CI: 1.07-2.11) and 1.53 (1.15-2.04) per interquartile range increase in the respective POP. In addition, explorative results suggested higher OR for women and non-obese participants., Conclusions: Our results add to the evidence on diabetogenic effects of POPs in the general population, and warrant both policies to prevent human exposure to POPs and additional research on the adverse effects of more complex chemical mixtures., (Copyright © 2019. Published by Elsevier Ltd.)

Celastrol is a natural pentacyclic triterpene used in traditional Chinese medicine with significant weight-lowering effects. Celastrol-administered mice at 100 μg/kg decrease food consumption and body weight via a leptin-dependent mechanism, yet its molecular targets in this pathway remain elusive. Here, we demonstrate in vivo that celastrol-induced weight loss is largely mediated by the inhibition of leptin negative regulators protein tyrosine phosphatase (PTP) 1B (PTP1B) and T-cell PTP (TCPTP) in the arcuate nucleus (ARC) of the hypothalamus. We show in vitro that celastrol binds reversibly and inhibits noncompetitively PTP1B and TCPTP. NMR data map the binding site to an allosteric site in the catalytic domain that is in proximity of the active site. By using a panel of PTPs implicated in hypothalamic leptin signaling, we show that celastrol additionally inhibited PTEN and SHP2 but had no activity toward other phosphatases of the PTP family. These results suggest that PTP1B and TCPTP in the ARC are essential for celastrol's weight lowering effects in adult obese mice.

Recent European regulations have indicated the need for new bioanalytical screening methods capable of monitoring dioxin and dioxin-like compounds in foodstuffs and environmental samples, cost-effectively and with a quicker turnaround. Cryo-cells of the hepatic H4IIE line preserved in 96-well plates were exposed to sample extracts prepared from various foodstuffs and analysed for their content of dioxins and dioxin-like compounds by means of the 7-Ethoxyresorufin-O-Deethylase (EROD)-assay in two laboratories. Assay data were compared between both laboratories and results from instrumental analysis used as a confirmatory method. Additionally, cut-off values for the different studied matrices were derived. The current European regulation regarding methods of analysis for the control of foodstuffs was applied with the aim of determining the feasibility of the cryo-methodology. Results obtained in both laboratories were in congruence with the required validation parameters of the Commission Regulation (EU) No 2017/644. Cut-off values should be established matrix-dependent to reduce the rate of false compliant results and to keep the rate of false non-compliant results under control. In summary, the ready-to-use cryo-assay method for the bioanalytical screening of foodstuffs in control laboratories without cell-culture facilities has successfully proven to be accurate, far quicker and more cost effective than current methods., (Copyright © 2018. Published by Elsevier Ltd.)

Celastrol, a plant-derived constituent of traditional Chinese medicine, has been proposed to offer significant potential as an antiobesity drug. However, the molecular mechanism for this activity is unknown. We show that the weight-lowering effects of celastrol are driven by decreased food consumption. Although young Lep ob mice respond with a decrease in food intake and body weight, adult Lep db and Lep ob mice are unresponsive to celastrol, suggesting that functional leptin signaling in adult mice is required to elicit celastrol's catabolic actions. Protein tyrosine phosphatase 1 (PTP1B), a leptin negative-feedback regulator, has been previously reported to be one of celastrol's targets. However, we found that global PTP1B knockout (KO) and wild-type (WT) mice have comparable weight loss and hypophagia when treated with celastrol. Increased levels of uncoupling protein 1 (UCP1) in subcutaneous white and brown adipose tissue suggest celastrol-induced thermogenesis as a further mechanism. However, diet-induced obese UCP1 WT and KO mice have comparable weight loss upon celastrol treatment, and celastrol treatment has no effect on energy expenditure under ambient housing or thermoneutral conditions. Overall, our results suggest that celastrol-induced weight loss is hypophagia driven and age-dependently mediated by functional leptin signaling. Our data encourage reconsideration of therapeutic antiobesity strategies built on leptin sensitization., (© 2018 by the American Diabetes Association.)

In utero exposure to persistent organic pollutants (POPs) can result in thyroid function disorder, leading to concerns about their impact on fetal and neonatal development. The associations between placental levels of various POPs and thyroid hormones (THs) were investigated. In a prospective Danish study initially established for assessing congenital cryptorchidism, 58 placenta samples were collected from mothers of boys born with (n = 28) and without (n = 30) cryptorchidism. The concentrations of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), organotin chemicals (OTCs), organochlorine pesticides (OCPs), T4, T3, and rT3 were measured. The associations between placental THs and various POPs were analyzed using multiple linear regression. Five PBDEs, 35 PCBs, 14 PCDD/Fs, 3 OTCs, 25 OCPs, T4, T3, and rT3 were measured. No correlation between THs and the odds of cryptorchidism was found. Several POPs were significantly associated with THs: (1) T4 was inversely associated with BDEs 99, 100, ΣPBDE, and 2378-TeCDD, and positively associated with 1234678-HpCDF; (2) T3 was positively associated with 2378-TeCDF and 12378-PeCDF; and (3) rT3 was positively associated with PCB 81, 12378-PeCDF, and 234678-HxCDF, and inversely associated with tributyltin, ΣOTC, and methoxychlor. These results revealed that POP exposures were associated with TH levels in placenta, which may be a possible mechanism for the impacts of POP exposures on children's growth and development. This study provides new insight into the complexity of thyroid-disrupting properties of POPs. More research is needed to elucidate the biological consequences of POP exposures.

Monoamines, acting as hormones and neurotransmitters, play a critical role in multiple physiological processes ranging from cognitive function and mood to sympathetic nervous system activity, fight-or-flight response and glucose homeostasis. In addition to brain and blood, monoamines are abundant in several tissues, and dysfunction in their synthesis or signaling is associated with various pathological conditions. It was our goal to develop a method to detect these compounds in peripheral murine tissues. In this study, we employed a high-performance liquid chromatography method using electrochemical detection that allows not only detection of catecholamines but also a detailed analysis of nine monoamines and metabolites in murine tissues. Simple tissue extraction procedures were optimized for muscle (gastrocnemius, extensor digitorum longus and soleus), liver, pancreas and white adipose tissue in the range of weight 10-200 mg. The system allowed a limit of detection between 0.625 and 2.5 pg μL -1 for monoamine analytes and their metabolites, including dopamine, 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine, homovanillic acid, norepinephrine, epinephrine, 3-methoxy-4-hydroxyphenylglycol, serotonin and 5-hydroxyindoleacetic acid. Typical concentrations for different monoamines and their metabolization products in these tissues are presented for C57Bl/6 J mice fed a high-fat diet., (Copyright © 2017 John Wiley & Sons, Ltd.)

Dioxins and dioxin-like compounds can be analyzed by bioanalytical screening methods to evaluate their biotoxicity. In vitro bioassays, based on 7-ethoxyresorufin-O-deethylase (EROD) and the activity of cytochrome P450 1A1 and the aryl hydrogen receptor (AhR) pathway, are employed for the evaluation of bioanalytical equivalents (BEQ) of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) from a wide variety of sample matrices. Here, we present the evaluation of 11 humic soil samples derived from forest stands across Germany and a comparison of the BEQ values against toxic equivalents (TEQ, PCDD/Fs+PCBs) derived by chemical analysis. BEQ values ranged from 8.8 to 34.1 while TEQ values from 13.9 to 60.5 pg/g dry weight. Additional two subsequent mineral layers were analyzed to identify the BEQ/TEQ gradient vertically, showing a TEQ decrease of 85.1 and 93.8 % from the humic to the first and second mineral layers, respectively. For BEQ values, a decrease as well as an increase was detected. BEQ measurements were performed with and without sample clean-up. Omitting clean-up revealed about 20 times increased BEQ values presumably due to non-persistent bioactive compounds not detected by chemical analysis. The results we present suggest that the EROD assay can be used for the screening of large sample quantities for the identification of samples showing dioxin and dioxin-like contaminations even at low levels, which can then be further analyzed by chemical analysis to identify the congener composition. The study also shows that EROD results give a qualitative image of the contamination. EROD seems to be interfered with cross-contaminants specifically for soils with high biological activity as forest layers.

The transplacental passage of thyroid hormones (THs) is of great significance since the maternal THs are vitally important in ensuring the normal fetal development. In this paper, we determined the concentrations of seven THs, viz. L-thyroxine (T 4 ), 3,3',5-triiodo-l-thyronine (T 3 ), 3,3',5'-triiodo-l-thyronine (rT 3 ), 3,3'-diiodo-l-thyronine (T 2 ), 3,5-diiodo-l-thyronine (rT 2 ), 3-iodo-l-thyronine (T 1 ) and 3-iodothyronamine (T 1 AM), in placenta using isotope dilution liquid chromatography quadrupole time-of-flight mass spectrometry. We optimized the method using isotopically labeled quantification standards ( 13 C 6 -T 4 , 13 C 6 -T 3 , 13 C 6 -rT 3 and 13 C 6 -T 2 ) and recovery standard ( 13 C 12 -T 4 ) in combination with solid-liquid extraction, liquid-liquid extraction and solid phase extraction. The linearity was obtained in the range of 0.5-150 pg uL -1 with R 2 values >0.99. The method detection limits (MDLs) ranged from 0.01 ng g -1 to 0.2 ng g -1 , while the method quantification limits (MQLs) were between 0.04 ng g -1 and 0.7 ng g -1 . The spike-recoveries for THs (except for T 1 and T 1 AM) were in the range of 81.0%-112%, with a coefficient of variation (CV) of 0.5-6.2%. The intra-day CVs and inter-day CVs were 0.5%-10.3% and 1.19%-8.88%, respectively. Concentrations of the THs were 22.9-35.0 ng g -1  T 4 , 0.32-0.46 ng g -1  T 3 , 2.86-3.69 ng g -1 rT 3 , 0.16-0.26 ng g -1  T 2 , and < MDL for other THs in five human placentas, and 2.05-3.51 ng g -1  T 4 , 0.37-0.62 ng g -1  T 3 , 0.96-1.3 ng g -1 rT 3 , 0.07-0.13 ng g -1  T 2 and < MDL for other THs in five mouse placentas. The presence of T 2 was tracked in placenta for the first time. This method with improved selectivity and sensitivity allows comprehensive evaluation of TH homeostasis in research of metabolism and effects of environmental contaminant exposures., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) were detected in 86 humic topsoil layers and in a subset of 11 randomly selected top mineral forest soils at the depths of 0-5cm and 5-10cm collected from different federal states of Germany. The distribution of these persistent organic pollutants (POPs) in humic topsoils with respect to vegetation cover (coniferous vs. deciduous vs. mixed), total organic carbon (TOC), altitude and latitude data was investigated. There is cross correlation between the contents and TOC while the correlation with latitude indicates higher abundances of POPs in central Germany where there is high population density accompanied with industrial activities. The calculated stocks suggest that humus type (mor, mull, or moder) in conjunction with forest type can explain the relative POPs abundances in different soil layers. Generally, humic topsoils show highest contents of POPs compare to the two mineral soils with a ratio of 100:10:1. However, the stock humic layers of coniferous stands contribute about 50% to the total stock, whereas at deciduous stands the stock is mainly located in the upper mineral soil layer (0-5cm). The soil-water distribution coefficients (Kd) were calculated to estimate the potential translocation in the different soil types. The Kd values vary among the PCBs and PCDD/Fs congeners and are most variable for humic topsoils. There is pronounced chemical abundance in the top mineral soils with increasing Kd and this points to non-water bound transport processes for superlipophilic compounds., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Bromocarbazoles and chlorocarbazoles are emerging environmental contaminants that have been reported to be persistent and possessing dioxin-like toxicity; however, their photodegradative fate in water is unknown. The photodegradation of 3-bromocarbazole, 3-chlorocarbazole, and 3,6-dichlorocarbazole was determined in ultrapure water. They proceeded by direct photolysis and followed first-order kinetics. The rate constants (k) were 0.4838, 0.3454, and 0.4422 h -1 corresponding to half-lives (t 1/2 ) 1.81, 2.01, and 1.62, while the quantum yields (Ф) were 0.232, 0.180, and 0.295 respectively. The maximum wavelengths of absorption (λ max ) were in the near ultraviolet region (295, 296, 299, and 301 nm) implying these compounds are likely to degrade slowly under sunlight in natural aquatic environment. The molar extinction coefficients (ε) determined in acetonitrile were 18,573, 17,028, 13,385, and 14,010 L mol -1  cm -1 , respectively, the latter being 3,6-dibromocarbazole. A bathochromic shift was observed with halogen addition on their respective mono-substituted congeners. Bromocarbazoles were observed to degrade faster in water than chlorocarbazoles. In addition, photodegradation was estimated to proceed faster in summer than in winter, in natural water system at 50° N latitude. In the absence of light, hydrolytic degradation occurred but proceeded very slowly. Hexahydroxybenzene and trihydroxycarbazole were positively identified as the likely photoproducts with the former being a known toxic compound. Dehalogenation, oxidative cleavage, hydroxylation, and hydrolysis are suggested as the major photodegradation mechanisms in water, yielding phototoxic products that may be of enhanced toxicity than the parent compounds.

Detoxification of cigarette smoke employing copper compounds has a potential for the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans and should not be practiced before the degree of formation has been shown to be harmless.

Performance reference compounds (PRCs) are neutral organic compounds, introduced in a passive sampler prior deployment for the assessment of in situ sampling rate. In this study, evaluation of in situ sampling rates of 16 13 C-PAH-PRCs with moderate and high hydrophobicity was established to provide an overall correction factor for variations in virtual organism (VO) uptake rates of the analytes of interest. In situ sampling rate was compared to an empirical model during sampling campaign in 2011 with VO in 12 different sites along the Three Gorges Reservoir (TGR) in China. A discrepancy was observed for high hydrophobic compounds with log K ow ranging from 5.18 to 6.63 where ΣPAH concentration in TGR from Huckins model (305,624 pg/L) was resulted to be roughly 2-fold higher than the alternative procedure (182,292 pg/L). A relationship between in situ sampling rates of the 16 13 C-PAH-PRCs (Rs, PRC ) and log K ow was set up to allow then calculation of analyte sampling rate Rs analyte (N) of various organic pollutants with log K ow  ≤ 6.63.