Human biomonitoring of environmental contaminants in Gulf Countries - current status and future directions.

BACKGROUND: This systematic review aimed to evaluate the status of Human Biomonitoring (HBM) in the Gulf Cooperation Council (GCC) region and provide recommendations for future research, considering the increased environmental contaminants that pose a threat to human health in this rapidly industrializing area. METHODS: A thorough search was performed in PubMed and Web of Science databases up to February 2023 to identify biomonitoring studies on human exposure and levels in the GCC region. Two independent reviewers assessed study eligibility, conducted data extraction and risk of bias assessment. The NIH Quality Assessment Tools and PRISMA guidelines were utilized for quality evaluation and reporting of results. RESULTS: A total of 38 eligible articles were included in this systematic review out of 662 articles screened. The majority of the publications were from Saudi Arabia (n = 24) and Kuwait (n = 10), while limited representation was found from Qatar (n = 3) and the UAE (n = 1). No articles were identified from Oman and Bahrain. The studies focused on metals, organohalogen compounds, pesticides, polycyclic aromatic hydrocarbons, and phthalates. The findings revealed elevated levels of metals and established correlations between metal exposure and adverse health effects, including infant neurodevelopmental issues, vitamin D deficiency, and oxidative stress. The presence of organohalogen compounds and pesticides was prevalent in the GCC region, with significant associations between exposure to these compounds and negative health outcomes. Notably, high levels of perchlorate were observed in the Kuwaiti population, and a study from Saudi Arabia found an association between per- and polyfluorinated substances and increased odds of osteoporosis. CONCLUSIONS: This review emphasizes the need to address environmental health challenges in the GCC region through improved HBM research methods and strategies. Implementing biomonitoring programs, conducting cohort studies, investing in tools and expertise, promoting collaboration, and engaging the community are crucial for reliable HBM data in the GCC.

Pilot study on the concentrations of organochlorine compounds and potentially toxic elements in pregnant women and local food items from the Finnish Lapland.

In the Arctic, main sources of persistent organic pollutants and potentially toxic elements are industry and agriculture in the lower latitudes. However, there are also local sources of pollution. Our study was focused on possible pollution in the Finnish Lapland, transferred from the Pechenganikel industrial complex located in the borders of Russia, Finland and Norway. Local food items and blood samples of pregnant women from the Inari municipality were collected and organochlorine compounds (OCs) and metal(oid)s analyzed. Most of the examined food samples showed detectable levels of these compounds. The mean concentrations of DDTs and polychlorobiphenyls (PCBs) were higher in fish (0.18-0.32 ng/g and 0.34-0.64 ng/g, respectively), than in the other food groups (0.027-0.047 ng/g and 0.11-0.20 ng/g, respectively). PCBs were found at the highest concentrations in blood samples of the pregnant women, and congeners 153 and 118 were dominant. The mean concentration of PCB153, 0.29 µg/kg serum lipid, was lower than those described in many other studies. Concerning DDTs, the 4,4'-DDT/4,4'-DDE ratio, 0.092, in the blood samples was lower than that observed in the food items, 0.25-0.71, reflecting old uses of the DDT pesticide. None of the observed levels of selected potentially toxic elements in blood samples and in food items exceeded the known safe limits. Higher concentrations of PCB52 and γ-HCH were observed in the serum of pregnant women who consumed greater amounts of meat, and berries and mushrooms, respectively. The OC concentrations from the pregnant women currently studied were lower than those observed fourteen years ago with pregnant women from the same municipality. Compounds whose occurrence is likely related to a long-distance transport showed clear decreases, e.g., 63% for PCBs, and for those from pesticides, decreases were 93% and 97% for 4,4'-DDE and ß-HCH, respectively. No obvious influence from the Pechenganikel complex is observed from the results.

Monitoring temporal trends of dioxins, organochlorine pesticides and chlorinated paraffins in pooled serum samples collected from Northern Norwegian women: The MISA cohort study.

The ubiquitous presence of legacy and emerging persistent organic pollutants (POPs) in the environmental matrices poses a potential hazard to the humans and creating public health concerns. The present study aimed to evaluate dioxins, dioxin-like polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and chlorinated paraffins (CPs) concentrations in serum of women (postpartum, pregnant and non-pregnant) from Northern Norway to better understand their exposure and contamination status as well as temporal trends across 2007-2009 (MISA 1) to 2019 (MISA 2). Sixty-two blood samples from the MISA 1 cohort and 38 samples from MISA 2 were randomly selected in this study (n = 100). Ninety samples from postpartum (MISA 1) and pregnant women (MISA 2) were randomly combined into 9 pools, with 9-11 individual samples contributing to each pool keeping the groups of pregnant and postpartum women. Remaining 10 samples from non-pregnant women (MISA 2) were allocated into separate group. Geometric mean, minimum and maximum were used to describe the serum concentrations of pooled POPs in MISA cohort. Mann-Whitney U test and independent sample t-test were applied for trend analysis of blood levels of POPs between MISA 1 and MISA 2. We found the serum concentrations of selected POPs in this study to be at lower range. Serum concentrations of dibenzo-p-dioxins (PCDDs) (p = 0.010), polychlorinated dibenzofurans (PCDFs) (p = 0.002), dioxins-like PCBs (p = 0.001), hexachlorobenzene (HCB) (p < 0.001) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) (p = 0.002) were decreased between the studied time. In contrast, the serum concentrations of medium chain chlorinated paraffins showed an increasing trend between 2007 and 2009 and 2019 (p = 0.019). Our findings report a particular concern of emerging contaminant medium chain chlorinated paraffin exposure to humans. Future observational studies with repeated measurements of chlorinated paraffins in general populations worldwide and large sample size are warranted.

The EDCMET Project: Metabolic Effects of Endocrine Disruptors.

Endocrine disruptors (EDs) are defined as chemicals that mimic, block, or interfere with hormones in the body's endocrine systems and have been associated with a diverse array of health issues. The concept of endocrine disruption has recently been extended to metabolic alterations that may result in diseases, such as obesity, diabetes, and fatty liver disease, and constitute an increasing health concern worldwide. However, while epidemiological and experimental data on the close association of EDs and adverse metabolic effects are mounting, predictive methods and models to evaluate the detailed mechanisms and pathways behind these observed effects are lacking, thus restricting the regulatory risk assessment of EDs. The EDCMET (Metabolic effects of Endocrine Disrupting Chemicals: novel testing METhods and adverse outcome pathways) project brings together systems toxicologists; experimental biologists with a thorough understanding of the molecular mechanisms of metabolic disease and comprehensive in vitro and in vivo methodological skills; and, ultimately, epidemiologists linking environmental exposure to adverse metabolic outcomes. During its 5-year journey, EDCMET aims to identify novel ED mechanisms of action, to generate (pre)validated test methods to assess the metabolic effects of Eds, and to predict emergent adverse biological phenotypes by following the adverse outcome pathway (AOP) paradigm.

An investigation into the formation of tebufenozide's toxic aromatic amine metabolites in human in vitro hepatic microsomes.

Tebufenozide is a nonsteroid ecdysone agonist that causes premature and incomplete molting in Lepidoptera. Studies conducted so far have shown the low toxicity of tebufenozide in mammals, birds and invertebrates. Tebufenozide potential metabolites such as aromatic amines are known to induce methemoglobinemia disorder in humans, most likely by the formation of N-hydroxy metabolites; therefore, the aim of this research is to investigate the formation of the potential toxic N-hydroxy derivatives in pooled human hepatic microsomal fractions. Analyses of metabolites by high performance liquid chromatography equipped by a time-of-flight detector (HPLC/TOF) indicated the formation of a hydroxylated metabolite (exact mass=369; retention time: 6.65min) and two de-dimethylethyl metabolites (exact masses=313; retention times: 5.76 and 6.22min). Hydroxylated tebufenozide metabolite resulted from hydroxylation at either the 3 or 5 position of the dimethylbenzoic acid moiety to form either 3-hydroxymethyl-5-methylbenzoic acid 1-(1,1-dimethylethyl)-2-(4-ethylbenzoyl) or 3-methyl-5-hydroxymethylbenzoic acid 1-(1,1-dimethylethyl)-2-(4-ethylbenzoyl), respectively. The two de-dimethylethyl-tebufenozide derivatives were 3,5-dimethylbenzoic acid-2-(4-hydroxyethylbenzoyl) and 3-hydroxymethyl-5-methylbenzoic acid-2-(4-ethylbenzoyl) or 3-methyl-5-hydroxymethylbenzoic acid-2-(4-ethylbenzoyl). Generally the metabolite formation rates increased with incubation time. The rate of hydroxylation of the dimethylbenzoic acid moiety was approximately 12 times higher than the hydroxylation of the ethylbenzoyl moiety. Tebufenozide does not appear to produce the toxic aromatic amine metabolites in human in vitro hepatic microsomes. This suggests that the fate of tebufenozide in humans is a process of detoxification rather than activation.

Statistically Non-significant Papers in Environmental Health Studies included more Outcome Variables.

OBJECTIVE: The number of analyzed outcome variables is important in the statistical analysis and interpretation of research findings. This study investigated published papers in the field of environmental health studies. We aimed to examine whether differences in the number of reported outcome variables exist between papers with non-significant findings compared to those with significant findings. Articles on the maternal exposure to mercury and child development were used as examples. METHODS: Articles published between 1995 and 2013 focusing on the relationships between maternal exposure to mercury and child development were collected from Medline and Scopus. RESULTS: Of 87 extracted papers, 73 used statistical significance testing and 38 (43.7%) of these reported 'non-significant' (P>0.05) findings. The median number of child development outcome variables in papers reporting 'significant' (n=35) and 'non-significant' (n=38) results was 4 versus 7, respectively (Mann-Whitney test P-value=0.014). An elevated number of outcome variables was especially found in papers reporting non-significant associations between maternal mercury and outcomes when mercury was the only analyzed exposure variable. CONCLUSION: Authors often report analyzed health outcome variables based on their P-values rather than on stated primary research questions. Such a practice probably skews the research evidence.

One health in the Arctic - connections and actions.

There is growing awareness and recognition of the importance of the One Health paradigm to address existing environmental threats and recognise emerging ones at an early stage among Arctic residents, public health agencies, and wildlife resource managers. The One Health approach, emphasising the interconnectedness of human, animal, and ecosystem health, plays a pivotal role in addressing these multifaceted issues. Warming climate and permafrost thaw may influence both contaminant exposure and the spread of zoonotic infectious diseases and have impacts on water and food security. Migration from rural regions to larger communities and urban centres along with increased tourism may be accompanied by changes in exposure to contaminants and zoonotic diseases. Universities have developed educational programmes and research projects on One Health in the Arctic, and under the Arctic Council there is running a project of One Arctic, One Health. These arctivities have produced interdisciplinary information and practical solutions for local communities, decision-makers, and in scientific forums. There is a need for epidemiological zoonotic/human disease models, as well as new approaches to integrate existing and future surveillance data to climatic and environmental data. This requires not only regional and international collaboration but also multi-agency and transdisciplinary research.

Environmental contaminants in Arctic human populations: Trends over 30 years.

INTRODUCTION: Arctic Monitoring and Assessment Programme (AMAP) monitors persistent organic pollutant (POP) levels in the Arctic populations and assesses health effects related to exposure to them. Many internationally regulated POPs persist in humans and biota, while new Emerging Contaminants of Arctic Concern (ECAC), many of which are unregulated, present additional challenges. Biomonitoring offers valuable insights into temporal trends within human matrices, revealing critical information not only about the efficacy of international regulations but also serving as an early warning system for exposure and risks for human health. METHODS: Data analyzed in this study is aggregated data presented in the AMAP Human Health in the Arctic assessments, which provide data on contaminant concentrations measured in human matrices from adults, and children across various population studies conducted in the Arctic since the 1980 s. Linear regression analyses were used to assess trends of various POPs including organochlorine (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and per- and polyfluoroalkyl substances (PFAS), measured over time from the Arctic populations in Finland, Norway, Sweden, Denmark, Iceland, Canada and Alaska (USA). RESULTS: Overall, decreasing trends were observed for PCBs and OCPs. Regulated PFAS showed decreasing trends, but increasing trends were observed for unregulated PFAS in certain populations. PBDEs showed decreasing or inconsistent trends in certain Arctic populations. CONCLUSIONS: Decreasing trends are observed for legacy POPs, but the trends for new emerging contaminants are inconsistent. More focus is needed on biomonitoring the new emerging contaminants of concern in the Arctic and their implications on human health.

Assessment of elemental chemistry, spatial distribution, and potential risks of road-deposited dusts in Sharjah, United Arab Emirates.

Road dust is a major source of pollution in the environment, carrying different pollutants, including heavy metals and metalloids, from one location to another. This study assesses the concentrations of eight heavy metals and one metalloid (Zn, Pb, Mn, Fe, Cr, Cu, Cd, Ni, and As) in dust samples collected from sixty-eight streets of Sharjah, United Arab Emirates using ICP-OES, as well as investigates their effects on both the environment and humans. Mean concentrations of the elements in µg/g across the sites were 392 ± 46 (Zn), 68.28 ± 11.3 (Pb), 1437 ± 67 (Mn), 39,481 ± 4611 (Fe), 460 ± 31 (Cr), 150 ± 44 (Cu), 1.25 ± 0.65 (Cd), 856 ± 72 (Ni), and 0.97 ± 0.28 (As). The Cdeg and ERI calculated from the study were 54.79 and 573, respectively, suggesting varying pollution levels. The highest contributions were from Ni, Cd, Zn, Cu, Cr, and Pb, especially in areas with heavy traffic. The non-carcinogenic risk assessments were generally low for the three routes of exposure, except HQoral that was slightly higher for children. Similarly, none of the elements exhibited any carcinogenic risk except chromium. Overall, the cancer risk is considered low. In view of the limited studies from UAE in relation to the metal content of road-deposited dusts, the current study serves as novel knowledge, especially in the context of geographical areas with a higher occurrence of sandstorms and the presence of particulate matter. The study also adds to the global understanding of the contribution of street dust to environmental pollution and its implications for human health.

Applying a modified systematic review and integrated assessment framework (SYRINA) - a case study on triphenyl phosphate.

This work presents a case study in applying a systematic review framework (SYRINA) to the identification of chemicals as endocrine disruptors. The suitability and performance of the framework is tested with regard to the widely accepted World Health Organization definition of an endocrine disruptor (ED). The endocrine disrupting potential of triphenyl phosphate (TPP), a well-studied flame retardant reported to exhibit various endocrine related effects was assessed. We followed the 7 steps of the SYRINA framework, articulating the research objective via Populations, Exposures, Comparators, Outcomes (PECO) statements, performed literature search and screening, conducted study evaluation, performed data extraction and summarized and integrated the evidence. Overall, 66 studies, consisting of in vivo, in vitro and epidemiological data, were included. We concluded that triphenyl phosphate could be identified as an ED based on metabolic disruption and reproductive function. We found that the tools used in this case study and the optimizations performed on the framework were suitable to assess properties of EDs. A number of challenges and areas for methodological development in systematic appraisal of evidence relating to endocrine disrupting potential were identified; significant time and effort were needed for the analysis of in vitro mechanistic data in this case study, thus increasing the workload and time needed to perform the systematic review process. Further research and development of this framework with regards to grey literature (non-peer-reviewed literature) search, harmonization of study evaluation methods, more consistent evidence integration approaches and a pre-defined method to assess links between adverse effect and endocrine activity are recommended. It would also be advantageous to conduct more case studies for a chemical with less data than TPP.

Thujone and thujone-containing herbal medicinal and botanical products: toxicological assessment.

Thujone, a major component of the notoriously famous absinthe drink, is neurotoxic, although the current view rather downgrades its risk to humans. In animal studies, thujone inhibits the gamma-aminobutyric acid A (GABA(A)) receptor causing excitation and convulsions in a dose-dependent manner, although there are uncertainties about the doses required in humans. Toxicity of thujone has been extensively studied. Neurotoxicity is the principal toxic outcome in acute and chronic studies. There is some equivocal evidence of carcinogenicity in rats. Metabolism of thujone has been elucidated both in vitro and in vivo in several species and in vitro in human liver preparations. CYP2A6 is the principal metabolic enzyme, followed by CYP3A4 and, to a lesser extent, CYP2B6. CYP-associated metabolism may give rise to some potential pharmacogenetic and metabolic interaction consequences. Although the data base for determining exposure limits is of variable usefulness, the best estimates for allowable daily intakes via herbal preparations and diet are of the order of 3-7 mg/day. There are still important gaps in the knowledge required to assess thujone toxicity, the most important ones being human dose-concentration-effect relationships including the elucidation of bioavailability, and the actual toxicological consequences of potential pharmacogenetic variations and environmental factors.

Inter-species differences between humans and other mammals in the in vitro metabolism of carbofuran and the role of human CYP enzymes.

This study investigated the metabolic transformation of carbofuran in seven species of mammals using LC-MS/MS and liver microsomes. The results revealed species-specific differences in metabolite formation, indicating the potential role of metabolic pathways in toxicity and risk assessment. The majority of carbofuran was metabolized through the 3-hydroxycarbofuran pathway, with the highest levels observed in dogLM and the lowest in humanLM. Further analysis was conducted to investigate the human cytochrome P450-mediated metabolism of carbofuran, with CYP3A4 being found to be the most efficient enzyme with the highest contribution to the 3-hydroxycarbofuran pathway. Inhibition of CYP3A4 with ketoconazole resulted in a substantial decrease in carbofuran metabolism. In addition, carbofuran exhibited inhibitory effects on human CYP3A4 and CYP2B6, demonstrating the potential for carbofuran to interact with these enzymes. The findings highlight the importance of in vitro screening for metabolic processes and provide insights into the biotransformation of carbofuran.

Investigating the relationship between non-occupational pesticide exposure and metabolomic biomarkers.

The relationship between pesticide exposures and metabolomics biomarkers is not well understood. We examined the changes in the serum metabolome (early biomarkers) and the metabolic pathways associated with various pesticide exposure scenarios (OPE: overall exposure, PEM: exposure in months, PEY: exposure in years, and PEU: reported specific pesticides use) using data from the Northern Finland Birth Cohort 1966 31-year cross-sectional examination. We utilized questionnaire data on pesticide exposures and serum samples for nuclear magnetic resonance (NMR)-based metabolomics analyses. For exposures and metabolites associations, participants size varied between 2,361 and 5,035. To investigate associations between metabolomics biomarkers and exposure to pesticide scenarios compared to those who reported no exposures multivariable regression analyses stratified by sex and adjustment with covariates (season of pesticide use, socioeconomic position (SEP), alcohol consumption, BMI, and latitude of residence) were performed. Multiple testing by Benjamini-Hochberg false discovery rate (FDR) correction applied. Pesticide exposures differed by sex, season of pesticide use, alcohol, SEP, latitude of residence. Our results showed that all pesticide exposure scenarios were negatively associated with decreased HDL concentrations across all lipoprotein subclasses in women. OPE, PEY, and PEU were associated with decreased branched-chain amino acid concentrations in men and decreased albumin concentrations in women. OPE, PEY and PEU were also associated with changes in glycolysis metabolites and ketone bodies in both sexes. Specific pesticides exposure was negatively associated with sphingolipids and inflammatory biomarkers in men. In women, OPE, PEM, and PEU were associated with decreased apolipoprotein A1 and increased apolipoprotein B/apolipoprotein A1 ratio. Our findings suggest that identification of early biomarkers of disease risk related to pesticide exposures can inform strategies to reduce exposure and investigate causal pathways. Women may be more susceptible to non-occupational pesticide exposures when compared to men, and future sex-specific studies are warranted.

Metabolites in the regulatory risk assessment of pesticides in the EU.

A large majority of chemicals is converted into metabolites through xenobiotic-metabolising enzymes. Metabolites may present a spectrum of characteristics varying from similar to vastly different compared with the parent compound in terms of both toxicokinetics and toxicodynamics. In the pesticide arena, the role of metabolism and metabolites is increasingly recognised as a significant factor particularly for the design and interpretation of mammalian toxicological studies and in the toxicity assessment of pesticide/metabolite-associated issues for hazard characterization and risk assessment purposes, including the role of metabolites as parts in various residues in ecotoxicological adversities. This is of particular relevance to pesticide metabolites that are unique to humans in comparison with metabolites found in in vitro or in vivo animal studies, but also to disproportionate metabolites (quantitative differences) between humans and mammalian species. Presence of unique or disproportionate metabolites may underlie potential toxicological concerns. This review aims to present the current state-of-the-art of comparative metabolism and metabolites in pesticide research for hazard and risk assessment, including One Health perspectives, and future research needs based on the experiences gained at the European Food Safety Authority.

Characterization of furathiocarb metabolism in in-vitro human liver microsomes and recombinant cytochrome P450 enzymes.

Furathiocarb is a carbamate insecticide detected in ecosystems. Its main metabolite carbofuran has been alluded to affect birth outcomes and disturb hormone levels in humans. The metabolism of furathiocarb in humans has not been characterized. The metabolism studies were performed using hepatic microsomes from ten donors and fifteen human cDNA-expressed CYPs. The initial screening and identification of the metabolites were performed by LC-TOF. Quantifications and fragmentations were performed by LC/MS-MS. Furathiocarb was metabolized to eight phase I metabolites via two general pathways, carbofuran metabolic pathway and furathiocarb oxidation pathway. Six metabolites in the carbofuran metabolic pathway (carbofuran, 3-hydroxycarbofuran, 3-ketocarbofuran, 3-keto-7-phenolcarbofuran, 3-hydroxy-7-phenolcarbofuran, and 7-phenolcarbofuran) were identified with the help of authentic standards. The two unidentified metabolites in the furathiocarb oxidation pathway are probably hydroxylated and sulfoxidated derivatives of furathiocarb. The carbofuran metabolic pathway was more predominant than the furathiocarb oxidation pathway, ratios ranged from 24- to 115-fold in a 10-donor panel of hepatic microsomes. On the basis of recombinant CYP studies, the carbofuran pathway was dominated by CYP3A4 (95.9%); contributions by CYP1A2 (1.3%) and CYP2B6 (2.0%) were minor. The minor furathiocarb oxidation pathway was catalyzed by CYP2C19 and CYP2D6 (hydroxylated/sulfoxidated metabolite A) and by CYP3A5, CYP3A4 and CYP2A6 (metabolite B). High and significant correlation between carbofuran metabolic pathway and CYP3A4 marker activities (midazolam-1'-hydroxylation and omeprazole-sulfoxidation) were observed. Ketoconazole, a CYP3A4-inhibitor, inhibited the carbofuran pathway by 32-86% and hydroxylated/sulfoxidated metabolite-B formations by 41-62%. The data suggest that in humans, the carbofuran metabolic pathway is dominant, and CYP3A4 is the major enzyme involved. These results provide useful scientific information for furathiocarb risk assessment in humans.

Metabolic profiling and in vitro-in vivo extrapolation of furathiocarb in mammalian hepatic microsomes.

Furathiocarb is a carbamate insecticide found in marine ecosystems as well as river water and sediments. The aim of this study was to characterize species differences in the in vitro metabolism of furathiocarb in seven mammalian species (human, monkey, minipig, rat, mouse, dog, rabbit) analyzed by LC-TOF-MS/MS, in order to provide qualitative and quantitative chemical-specific data to enhance toxicological risk assessment. Furathiocarb was mainly biotransformed to carbofuran metabolic pathway via (N-S) bond-cleavage. Two hydroxylated and sulfoxidated metabolites of furathiocarb were also detected (oxidation pathway). No unique human metabolites were detected. The carbofuran metabolic pathway was more predominant than the furathiocarb oxidation pathway in all species studied; differences based on hepatic clearance rates (CL H ), were up to 9.4-fold in monkey and 7-fold in rats, while it was 4.3-fold in human. Animal to human differences in the carbofuran pathway are within the default toxicokinetic uncertainty factor, except for mouse (3.9-fold). Our findings on metabolic profiling and in vitro-in vivo extrapolations are helpful for the interpretation of toxicological findings and chemical risk assessment of furathiocarb.

The impact of mercury contamination on human health in the Arctic: A state of the science review.

The 2021 Arctic Monitoring and Assessment Programme (AMAP) Mercury (Hg) Assessment is motivated by Arctic populations, and most notably Indigenous Peoples in the region, who are particularly vulnerable to Hg pollution. The objective of this review paper is to answer the following AMAP policy-relevant question: what is the human health impact of Hg pollution in the Arctic? In doing so, this state of the science review paper builds on information published 10 years ago in the last AMAP Hg assessment. The synthesized results demonstrate that: a) global influences (e.g., sources and transport pathways, biogeochemical processes, climate change, globalization) drive Hg exposures into human communities; b) Hg exposures are realized through dietary intake of certain country food items, and that new exposure science approaches are helping to deepen understandings; c) the nutritional and cultural benefits of country foods are immense, though a dietary transition is underway raising concerns over metabolic syndrome and broader issues of food security as well as cultural and social well-being; d) blood Hg measures are among the highest worldwide based on the results of human biomonitoring studies; e) Hg exposures are associated with adverse health outcomes across life stages (e.g., neurodevelopmental outcomes in young children to cardiovascular disease in adults); and f) risk communication needs to be balanced, targeted and clear, culturally appropriate, and be done collaboratively. These synthesized findings are particularly timely and policy-relevant given that the Minamata Convention entered into legal force worldwide in 2017 as a regulatory scheme to reduce the use and environmental release of Hg in order to protect human health and the environment. The Convention was influenced by health concerns raised by northern populations as indicated in the preamble text which makes reference to "the particular vulnerabilities of Arctic ecosystems and Indigenous communities".

Research on Selected Wildlife Infections in the Circumpolar Arctic-A Bibliometric Review.

One Health, a multidisciplinary approach to public health, which integrates human, animal, and environmental studies, is prudent for circumpolar Arctic health research. The objective of our bibliometric review was to identify and compare research in select infectious diseases in Arctic wildlife species with importance to human health indexed in English language databases (PubMed, Scopus) and the Russian database eLibrary.ru. Included articles (in English and Russian languages) needed to meet the following criteria: (1) data comes from the Arctic, (2) articles report original research or surveillance reports, (3) articles were published between 1990 and 2018, and (4) research relates to naturally occurring infections. Of the included articles (total n = 352), most were from Russia (n = 131, 37%), Norway (n = 58, 16%), Canada (n = 39, 11%), and Alaska (n = 39, 11%). Frequently reported infectious agents among selected mammals were Trichinella spp. (n = 39), Brucella spp. (n = 25), rabies virus (n = 11), Echinococcus spp. (n = 10), and Francisella tularensis (n = 9). There were 25 articles on anthrax in eLibrary.ru, while there were none in the other two databases. We identified future directions where opportunities for further research, collaboration, systematic reviews, or monitoring programs are possible and needed.

A Children's Health Perspective on Nano- and Microplastics.

BACKGROUND: Pregnancy, infancy, and childhood are sensitive windows for environmental exposures. Yet the health effects of exposure to nano- and microplastics (NMPs) remain largely uninvestigated or unknown. Although plastic chemicals are a well-established research topic, the impacts of plastic particles are unexplored, especially with regard to early life exposures. OBJECTIVES: This commentary aims to summarize the knowns and unknowns around child- and pregnancy-relevant exposures to NMPs via inhalation, placental transfer, ingestion and breastmilk, and dermal absorption. METHODS: A comprehensive literature search to map the state of the science on NMPs found 37 primary research articles on the health relevance of NMPs during early life and revealed major knowledge gaps in the field. We discuss opportunities and challenges for quantifying child-specific exposures (e.g., NMPs in breastmilk or infant formula) and health effects, in light of global inequalities in baby bottle use, consumption of packaged foods, air pollution, hazardous plastic disposal, and regulatory safeguards. We also summarize research needs for linking child health and NMP exposures and address the unknowns in the context of public health action. DISCUSSION: Few studies have addressed child-specific sources of exposure, and exposure estimates currently rely on generic assumptions rather than empirical measurements. Furthermore, toxicological research on NMPs has not specifically focused on child health, yet children's immature defense mechanisms make them particularly vulnerable. Apart from few studies investigating the placental transfer of NMPs, the physicochemical properties (e.g., polymer, size, shape, charge) driving the absorption, biodistribution, and elimination in early life have yet to be benchmarked. Accordingly, the evidence base regarding the potential health impacts of NMPs in early life remains sparse. Based on the evidence to date, we provide recommendations to fill research gaps, stimulate policymakers and industry to address the safety of NMPs, and point to opportunities for families to reduce early life exposures to plastic. https://doi.org/10.1289/EHP9086.

Metabolism of α-thujone in human hepatic preparations in vitro.

This study aims to characterize the metabolism of α-thujone in human liver preparations in vitro and to identify the role of cytochrome P450 (CYP) and possibly other enzymes catalyzing α-thujone biotransformations. With a liquid chromatography-mass spectrometry (LC-MS) method developed for measuring α-thujone and four potential metabolites, it was demonstrated that human liver microsomes produced two major (7- and 4-hydroxy-thujone) and two minor (2-hydroxy-thujone and carvacrol) metabolites. Glutathione and cysteine conjugates were detected in human liver homogenates, but not quantified. No glucuronide or sulphate conjugates were detected. Major hydroxylations accounted for more than 90% of the primary microsomal metabolism of α-thujone. Screening of α-thujone metabolism with CYP recombinant enzymes indicated that CYP2A6 was principally responsible for the major 7- and 4-hydroxylation reactions, although CYP3A4 and CYP2B6 participated to a lesser extent and CYP3A4 and CYP2B6 catalyzed minor 2-hydroxylation. Based on the intrinsic efficiencies of different recombinant CYP enzymes and average abundances of these enzymes in human liver microsomes, CYP2A6 was calculated to be the most active enzyme in human liver microsomes, responsible for 70-80% of the metabolism on average. Inhibition screening indicated that α-thujone inhibited both CYP2A6 and CYP2B6, with 50% inhibitory concentration values of 15.4 and 17.5 µM, respectively.