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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 s

The human population is exposed to organophosphate and pyrethroid pesticides due to their extensive use in agriculture and household products. Once up-taken, these compounds are metabolized relatively quickly by cytochrome P450 enzymes and excreted via the urine. The measurement of a metabolite allows thus to identify its precursor compound. Some pesticides are suspected metabolism-disrupting chemicals (MDCs) and are associated, amongst others, with the onset of diabetes. Since validated test methods for the identification of MDCs are still lacking, the European Union is funding several projects that aim to develop and establish (pre-) validated test methods, one of the being EDCMET (Metabolic effects of endocrine disrupting chemicals: novel test methods and adverse outcome pathways). Here, we recently finalized an in vitro assay for hepatic triglyceride accumulation (TGA), which is currently under pre-validation with the PEPPER platform. This high-throughput assay uses the metabolically competent human hepatoma cell line HepaRG, known for its high expression of major cytochrome P450 enzymes, which is comparable to primary human hepatocytes. Using this assay, we already screened more than 100 compounds regarding their potential to induce steatosis in vitro and further extended our database including 12 organophosphate and pyrethroid pesticides and their metabolites, which we measured in urine and serum samples of different cohorts. In parallel to the TGA assay, we determined the half-life of both, the parent compound and metabolite, under the HepaRG treatment conditions aiming to clarify the contribution of either of them to the development of steatosis in vitro.

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.

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

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.

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 (CLH), 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.

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 provi

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

Chloro-s-triazines-atrazine, cyanazine, propazine, simazine, and terbuthylazine-are structurally similar herbicides, differing only in specific s-triazine4-and 6-N alkyl substituents. It is generally regarded that their toxicokinetics, such as, metabolic pathways, biological effects and toxicities, also share more similar features than the differences. Consequently, it is useful to compare their characteristics to potentially find useful structure-activity relationships or other similarities or differences regarding different active compounds, their metabolites, and biological effects including toxic outcomes. The ultimate goal of these exercises is to apply the summarized knowledge-as far as it is possible regarding a patchy and often inadequate database-to cross the in vitro-in vivo and animal-human borders and integrate the available data to enhance toxicological risk assessment for the benefit of humans and ecosystems.

Thawing permafrost creates risks to the environment, economy and culture in Arctic coastal communities. Identification of these risks and the inclusion of the societal context and the relevant stakeholder involvement is crucial in risk management and for future sustainability, yet the dual dimensions of risk and risk perception is often ignored in conceptual risk frameworks. In this paper we present a risk framework for Arctic coastal communities. Our framework builds on the notion of the dual dimensions of risk, as both physically and socially constructed, and it places risk perception and the coproduction of risk management with local stakeholders as central components into the model. Central to our framework is the importance of multidisciplinary collaboration. A conceptual model and processual framework with a description of successive steps is developed to facilitate the identification of risks of thawing permafrost in a collaboration between local communities and scientists. Our conceptual framework motivates coproduction of risk management with locals in the identification of these risks from permafrost thaw and the development of adaptation and mitigation strategies.

For the last two and a half decades, a network of human health experts under the Arctic Monitoring and Assessment Program (AMAP) has produced several human health assessment reports. These reports have provided a base of scientific knowledge regarding environmental contaminants and their impact on human health in the Arctic. These reports provide scientific information and policy-relevant recommendations to Arctic governments. They also support international agreements such as the Stockholm Convention on Persistent Organic Pollutants (POPs) and the Minamata Convention on Mercury. Key topics discussed in this paper regarding future human health research in the circumpolar Arctic are continued contaminant biomonitoring, health effects research and risk communication. The objective of this paper is to describe knowledge gaps and future priorities for these fields.

For the last two and a half decades, a network of human health experts under the Arctic Monitoring and Assessment Program (AMAP) has produced several human health assessment reports. These reports have provided a base of scientific knowledge regarding environmental contaminants and their impact on human health in the Arctic. These reports provide scientific information and policy-relevant recommendations to Arctic governments. They also support international agreements such as the Stockholm Convention on Persistent Organic Pollutants (POPs) and the Minamata Convention on Mercury. Key topics discussed in this paper regarding future human health research in the circumpolar Arctic are continued contaminant biomonitoring, health effects research and risk communication. The objective of this paper is to describe knowledge gaps and future priorities for these fields.

The first Arctic Monitoring and Assessment Programme (AMAP) report was published in 1998 and followed by three assessment reports of human health (AMAP 2003, 2009 and 2015). The focus area of the AMAP reports was to monitor levels of environmental contaminants in the Arctic and to assess the health effects connected with detected levels in Arctic countries. This review gives an overview of temporal trends of contaminants and their health effects in humans of the Arctic based on data published by AMAP, as well as Russian scientific literature. Several time series of 31 contaminants in humans of the Arctic from different cohorts are reported. The lengths of time series and periods covered differ from each other. International restrictions have decreased the levels of most persistent organic pollutants in humans and food webs. Percentage changes for contaminants in human biological matrices (blood samples from children, mothers and males and breast milk samples) for the period of sampling showed declining trends in most of the monitored Arctic locations, with the exception of oxychlordane, hexachlorobenzene (HCB), 2,2′,4,4′,5,5′-hexabromodiphenyl ether (PBDE153) and perfluorinated compounds (PFCs).

Climatic factors, especially temperature, precipitation, and humidity play an important role in disease transmission. As the Arctic changes at an unprecedented rate due to climate change, understanding how climatic factors and climate change affect infectious disease rates is important for minimizing human and economic costs. The purpose of this systematic review was to compile recent studies in the field and compare the results to a previously published review. English language searches were conducted in PubMed, ScienceDirect, Scopus, and PLOS One. Russian language searches were conducted in the Scientific Electronic Library “eLibrary.ru”. This systematic review yielded 22 articles (51%) published in English and 21 articles (49%) published in Russian since 2012. Articles about zoonotic and vector-borne diseases accounted for 67% (n = 29) of the review. Tick-borne diseases, tularemia, anthrax, and vibriosis were the most researched diseases likely to be impacted by climatic factors in the Arctic. Increased temperature and precipitation are predicted to have the greatest impact on infectious diseases in the Arctic.

Polychlorinated biphenyls (PCBs) can be used as chemical sentinels for the assessment of anthropogenic influences on Arctic environmental change. We present an overview of studies on PCBs in the Arctic and combine these with the findings from ArcRisk—a major European Union-funded project aimed at examining the effects of climate change on the transport of contaminants to and their behaviour of in the Arctic—to provide a case study on the behaviour and impact of PCBs over time in the Arctic. PCBs in the Arctic have shown declining trends in the environment over the last few decades. Atmospheric long-range transport from secondary and primary sources is the major input of PCBs to the Arctic region. Modelling of the atmospheric PCB composition and behaviour showed some increases in environmental concentrations in a warmer Arctic, but the general decline in PCB levels is still the most prominent feature. ‘Within-Arctic’ processing of PCBs will be affected by climate change-related processes such as changing wet deposition. These in turn will influence biological exposure and uptake of PCBs. The pan-Arctic rivers draining large Arctic/sub-Arctic catchments provide a significant source of PCBs to the Arctic Ocean, although changes in hydrology/sediment transport combined with a changing marine environment remain areas of uncertainty with regard to PCB fate. Indirect effects of climate change on human exposure, such as a changing diet will influence and possibly reduce PCB exposure for indigenous peoples. Body burdens of PCBs have declined since the 1980s and are predicted to decline further.