ABSTRACT
Populations consuming saline drinking water are at greater risk of high blood pressure and potentially other adverse health outcomes. We modelled data and used available datasets to identify countries of higher vulnerability to future saltwater intrusion associated with climate change in 2050 under Representative Concentration Pathways (RCP)4.5 and RCP8.5. We developed three vulnerability criteria to capture geographies with: (1) any coastal areas with projected inland saltwater intrusion of ≥ 1 km inland, (2) > 50% of the population in coastal secondary administrative areas with reliance on groundwater for drinking water, and 3) high national average sodium urinary excretion (i.e., > 3 g/day). We identified 41 nations across all continents (except Antarctica) with ≥ 1 km of inland saltwater intrusion by 2050. Seven low- and middle-income countries of higher vulnerability were all concentrated in South/Southeast Asia. Based on these initial findings, future research should study geological nuances at the local level in higher-risk areas and co-produce with local communities contextually appropriate solutions to secure equitable access to clean drinking water.
Subject(s)
Climate Change , Drinking Water , Humans , Drinking Water/analysis , Groundwater/analysis , Water Supply , Hypertension/epidemiologyABSTRACT
BACKGROUND: Cancer is one of the leading causes of morbidity and mortality, worldwide. Little information is available for the temporal trends of cancer in the Mediterranean region, including Cyprus. AIMS: We aimed to analyze cancer incidence trends overall and by sex for the period 2004-2017 regarding the five most common cancer sites for the population of Cyprus. METHODS AND RESULTS: Data were obtained from the nationwide cancer registry dataset that included 27 017 total cancer cases in Cyprus (2004-2017). We estimated the crude, sex-, and age-specific, as well as age-standardized (ASR) cancer incidence rates and we analyzed the time trends of ASR using the joinpoint regression program. For the general population (0-85+ years of age), the most common cancer sites in descending order, were breast, prostate, lung, colorectal, and thyroid cancer. During the study period, breast and thyroid cancer ASR presented a significant (p < .05) increasing temporal trend. Lung cancer ASRs seemed to stabilize (no increase or decrease) during the more recent years (2009 onwards) for both sexes; a similar pattern was observed for colorectal cancer in males. The ASRs of prostate cancer in men were in steady decline from 2012 onwards and the same was observed for the female ASRs of colorectal cancer from 2007 onwards. The colorectal cancer ASR temporal patterns overall, during the whole study period appeared unchanged. CONCLUSION: This temporal analysis would feed into cancer surveillance and control programs that focus on prevention, early detection, and treatment, particularly for cancer sites of higher mortality rates or those with temporally increasing trends.
Subject(s)
Neoplasms , Registries , Humans , Cyprus/epidemiology , Male , Female , Incidence , Aged , Middle Aged , Adult , Neoplasms/epidemiology , Neoplasms/mortality , Adolescent , Registries/statistics & numerical data , Young Adult , Child, Preschool , Aged, 80 and over , Child , Infant , Infant, Newborn , Age Distribution , Time FactorsABSTRACT
Introduction: Men are vulnerable to ambient heat-related kidney disease burden; however, limited evidence exists on how vulnerable women are when exposed to high ambient heat. We evaluated the sex-specific association between ambient temperature and urine electrolytes, and 24-hour urine total protein, and volume. Methods: We pooled a longitudinal 5624 person-visits data of 1175 participants' concentration and 24-hour excretion of urine electrolytes and other biomarkers (24-hour urine total protein and volume) from southwest coastal Bangladesh (Khulna, Satkhira, and Mongla districts) during November 2016 to April 2017. We then spatiotemporally linked ambient temperature data from local weather stations to participants' health outcomes. For evaluating the relationships between average ambient temperature and urine electrolytes and other biomarkers, we plotted confounder-adjusted restricted cubic spline (RCS) plots using participant-level, household-level, and community-level random intercepts. We then used piece-wise linear mixed-effects models for different ambient temperature segments determined by inflection points in RCS plots and reported the maximum likelihood estimates and cluster robust standard errors. By applying interaction terms for sex and ambient temperature, we determined the overall significance using the Wald test. Bonferroni correction was used for multiple comparisons. Results: The RCS plots demonstrated nonlinear associations between ambient heat and urine biomarkers for males and females. Piecewise linear mixed-effects models suggested that sex did not modify the relationship of ambient temperature with any of the urine parameters after Bonferroni correction (P < 0.004). Conclusion: Our findings suggest that women are as susceptible to the effects of high ambient temperature exposure as men.
ABSTRACT
Around the world, groundwater salinity levels are increasing in coastal areas, as a result of its systematic overexploitation for domestic, agricultural and industrial demand and potentially due to climate change manifestations (such as, sea level rise). We hypothesized that the groundwater quality of many Mediterranean coastal areas is already being perturbed, especially for water salinity, depending on the groundwater distance from the seafront. The objectives of this study were: i) to evaluate the magnitude and temporal variance of drinking water sodium (Na) as a metric of salt intake used for public health purposes using drinking water data in Cyprus; and ii) to examine the degree of Na enrichment in drinking water as defined by the seawater coastline distance of each sampling point. Open access governmental data of drinking water Na (n = 3304), daily max ambient air temperature and total rainfall were obtained for the period of 2009-2020 from governmental repositories. Linear mixed-effect regression models of drinking water Na with unsupervised covariance matrix were used. After adjusting for temperature and rainfall data, there was a significant annual increase in drinking water Na levels over time (beta = 0.01; 95 % CI: 0.00, 0.02; p = 0.02) for the coastal areas (<10 km from coastline, cutoff used by the EU Environment Agency), but this was not the case for non-coastal areas (>10 km distance from coastline). The distance of each sampling point from the coastline in Cyprus was negatively associated with drinking water Na in coastal areas (beta = -0.04, 95%CI: -0.06, -0.01; p = 0.002); this was not the case for non-coastal areas. More research is warranted to better understand the impacts of global environmental change on water quality in association with the burden of disease in coastal areas.
Subject(s)
Drinking Water , Environmental Monitoring , Sodium , Cyprus , Drinking Water/chemistry , Sodium/analysis , Salinity , Groundwater/chemistry , Water Pollutants, Chemical/analysis , Climate Change , Seawater/chemistryABSTRACT
Organic food consumption in children has been shown to reduce the body burden of chemical pesticides. However, there is little evidence of human health benefits associated with the consumption of organic foods. The objectives were to i) determine the effectiveness of an organic food intervention treatment in reducing the magnitude of an inflammation biomarker (C-reactive protein, CRP) in children (10-12 years) and ii) assess the association between the urinary biomarkers of exposure to pesticides and CRP. This work was part of the ORGANIKO cluster-randomized cross-over trial entailing a 40-day organic food treatment in healthy children. Urinary biomarkers of exposure to pesticides and inflammation (CRP) were measured using tandem mass spectrometry and ELISA immunoassay, respectively. Linear mixed-effect regression models of CRP were used to account for the effect and duration of organic food treatment. Multiple comparisons were handled using Benjamini-Hochberg correction. Results supported an anti-inflammatory effect of organic food treatment in children, albeit with mixed results, depending on the creatinine adjustment method; biomarker levels were divided by urinary creatinine (method a1), or urinary creatinine was used as a fixed effect variable (a2). In the a1 method, a time-dependent reduction for creatinine-adjusted CRP (ß = -0.019; 95% CI: -0.031, -0.006; q = 0.045) was observed during the organic food intervention period. A statistically significant association (ß = 0.104; 95% CI: 0.035, 0.173; q = 0.045) was found between the biomarker of pyrethroids exposure (3-PBA) and CRP inflammatory biomarker, but not for 6-CN. In the a2 method, similar trend of time-dependent reduction for creatinine-adjusted CRP (ß = -0.008; 95% CI: -0.021, 0.004; p = 0.197) was observed during the organic food intervention period, but did not reach statistical significance (q > 0.05); the associations of pyrethroid and neonicotinoid biomarkers with CRP were not statistically significant (q > 0.05). More studies are warranted to sufficiently understand the potential anti-inflammatory response of an organic food treatment.
Subject(s)
Biomarkers , C-Reactive Protein , Cross-Over Studies , Food, Organic , Pesticides , Humans , Child , Male , Female , C-Reactive Protein/analysis , Biomarkers/urine , Pesticides/urine , Inflammation/urine , Environmental Exposure/analysisABSTRACT
This paper explores the exposome concept and its role in elucidating the interplay between environmental exposures and human health. We introduce two key concepts critical for exposomics research. Firstly, we discuss the joint impact of genetics and environment on phenotypes, emphasizing the variance attributable to shared and nonshared environmental factors, underscoring the complexity of quantifying the exposome's influence on health outcomes. Secondly, we introduce the importance of advanced data-driven methods in large cohort studies for exposomic measurements. Here, we introduce the exposome-wide association study (ExWAS), an approach designed for systematic discovery of relationships between phenotypes and various exposures, identifying significant associations while controlling for multiple comparisons. We advocate for the standardized use of the term "exposome-wide association study, ExWAS," to facilitate clear communication and literature retrieval in this field. The paper aims to guide future health researchers in understanding and evaluating exposomic studies. Our discussion extends to emerging topics, such as FAIR Data Principles, biobanked healthcare datasets, and the functional exposome, outlining the future directions in exposomic research. This abstract provides a succinct overview of our comprehensive approach to understanding the complex dynamics of the exposome and its significant implications for human health.
ABSTRACT
Background: Noncommunicable diseases (NCDs) are the leading cause of morbidity and mortality worldwide. The aim of this study was to determine the prevalence of NCDs among the population of Cyprus and to identify the distribution of the socioeconomic and demographic determinants among individuals with the most frequent NCDs. Methods: A cross-sectional study was conducted using stratified sampling. Socioeconomic and demographic characteristics and the presence of NCDs were collected through a standardized questionnaire. The diseases were classified using the 10th revision of the International Classification of Diseases (ICD-10). Results: In total, 1140 individuals participated in the study, among whom 590 (51.7%) had at least one chronic disease. The most prevalent NCDs were hyperlipidemia (17.4%), hypertension (12.9%), and thyroid diseases (8.4%). We identified more males than females with hyperlipidemia aged 25-44 years old and >65 years old (p = 0.024), more males compared to females with hypertension (p = 0.001) and more females compared to males with thyroid diseases (p < 0.001). Individuals with hypertension and hyperlipidemia were more likely to be married, to have completed a higher education, and to have a high annual income. Discussion: In Cyprus, the majority of the general population had at least one NCD. Hyperlipidemia, hypertension, and thyroid disease are relatively common, even at younger ages, highlighting the need for the development of public health programs aimed at addressing and preventing NCDs.
ABSTRACT
During recent years, we are moving away from the 'one exposure, one disease'-approach in occupational settings and towards a more comprehensive approach, taking into account the totality of exposures during a life course by using an exposome approach. Taking an exposome approach however is accompanied by many challenges, one of which, for example, relates to the collection of biological samples. Methods used for sample collection in occupational exposome studies should ideally be minimally invasive, while at the same time sensitive, and enable meaningful repeated sampling in a large population and over a longer time period. This might be hampered in specific situations e.g., people working in remote areas, during pandemics or with flexible work hours. In these situations, using self-sampling techniques might offer a solution. Therefore, our aim was to identify existing self-sampling techniques and to evaluate the applicability of these techniques in an occupational exposome context by conducting a literature review. We here present an overview of current self-sampling methodologies used to characterize the internal exposome. In addition, the use of different biological matrices was evaluated and subdivided based on their level of invasiveness and applicability in an occupational exposome context. In conclusion, this review and the overview of self-sampling techniques presented herein can serve as a guide in the design of future (occupational) exposome studies while circumventing sample collection challenges associated with exposome studies.
Subject(s)
Exposome , Humans , Environmental ExposureABSTRACT
BACKGROUND: Oxidative stress and tissue damage (OSD) play a pivotal role as an early-stage process in chronic disease pathogenesis. However, there has been little research to better understand the temporal (χρÏνος[chronos]) dimensions of OSD process associated with environmental (non-genetic, including behaviors/lifestyle) and/or occupational stressors, like night shift work. OSD processes have recently attracted attention in relation to time-resolved external stressor trajectories in personalized medicine (prevention) initiatives, as they seem to interact with circadian clock systems towards the improved delineation of the early stages of (chronic) disease process. OBJECTIVES: This work critically reviewed human studies targeting the temporal dynamics of OSD and circadian clock system's activity in response to environmental/occupational stressors; the case of night shift work was examined. METHODS: Being a key stressor influencing OSD processes and circadian rhythm, night shift work was evaluated as part of a scoping review of research in OSD, including inflammatory and metabolic processes to determine the extent of OSD research undertaken in human populations, methodologies, tools and biomarkers used and the extent that the temporal dimensions of exposure and biological effect(s) were accounted for. Online databases were searched for papers published from 2000 onwards, resulting in the selection of 53 original publications. RESULTS AND DISCUSSION: The majority of studies (n = 41) took place in occupational settings, while the rest were conducted in the general population or patient groups. Most occupational studies targeted outcomes of oxidative stress/damage (n = 19), followed by the combination of OSD with inflammatory response (n = 10), and studies focused on metabolic outcomes (n = 12). Only a minor fraction of the studies measured biomarkers related to circadian rhythm, such as, melatonin, its metabolite, or cortisol. Night shift work was associated with select biomarkers of OSD and inflammation, albeit with mixed results. Although much progress in delineating the biological mechanisms of OSD process has been made, an equally thorough investigation on the temporal trajectory of OSD processes as triggered by environmental/occupational stressors in human studies has yet to fully evolve.
Subject(s)
Shift Work Schedule , Humans , Shift Work Schedule/adverse effects , Circadian Rhythm , Biomarkers/metabolism , Oxidative Stress , HydrocortisoneABSTRACT
Tailoring medical models to the right person or risk subgroups delivered at the right time is important in personalized medicine/prevention initiatives. The CIRCA-CHEM randomized 2x2 crossover pilot trial investigated whether the consumption of fruits/vegetables within a time-restricted daily window would affect urinary biomarkers of exposure to neonicotinoids (6-chloronicotinic acid, 6-CN) and pyrethroids (3-phenoxybenzoic acid, 3-PBA) pesticides, a biomarker of oxidative damage (4-hydroxynonenal, 4-HNE) and the associated urinary NMR metabolome. A statistically significant difference (p < 0.001) in both creatinine-adjusted 6-CN and 3-PBA levels was observed between the two-time dietary intervention windows (morning vs. evening). In the evening intervention period, pesticides biomarker levels were higher compared to the baseline, whereas in the morning period, pesticide levels remained unchanged. Positive associations were observed between pesticides and 4-HNE suggesting a diurnal chrono-window of pesticide toxicity. The discovery of a chronotoxicity window associated with chrono-disrupted metabolism of food contaminants may find use in personalized medicine initiatives.
ABSTRACT
Human biomonitoring (HBM) data measured in specific contexts or populations provide information for comparing population exposures. There are numerous health-based biomonitoring guidance values, but to locate these values, interested parties need to seek them out individually from publications, governmental reports, websites and other sources. Until now, there has been no central, international repository for this information. Thus, a tool is needed to help researchers, public health professionals, risk assessors, and regulatory decision makers to quickly locate relevant values on numerous environmental chemicals. A free, on-line repository for international health-based guidance values to facilitate the interpretation of HBM data is now available. The repository is referred to as the "Human Biomonitoring Health-Based Guidance Value (HB2GV) Dashboard". The Dashboard represents the efforts of the International Human Biomonitoring Working Group (i-HBM), affiliated with the International Society of Exposure Science. The i-HBM's mission is to promote the use of population-level HBM data to inform public health decision-making by developing harmonized resources to facilitate the interpretation of HBM data in a health-based context. This paper describes the methods used to compile the human biomonitoring health-based guidance values, how the values can be accessed and used, and caveats with using the Dashboard for interpreting HBM data. To our knowledge, the HB2GV Dashboard is the first open-access, curated database of HBM guidance values developed for use in interpreting HBM data. This new resource can assist global HBM data users such as risk assessors, risk managers and biomonitoring programs with a readily available compilation of guidance values.
Subject(s)
Biological Monitoring , Environmental Monitoring , Humans , Environmental Monitoring/methods , Global Health , Public HealthABSTRACT
BACKGROUND: Food contaminants, such as, pesticides and metals are ubiquitous in the food chain. Studies routinely report on the metals content of organic and conventional food crops. However, comparative human studies on the body burden of metals associated with organic food consumption are currently lacking. OBJECTIVES: The objectives were to i) determine the effectiveness of an organic food intervention in reducing the body burden of urinary concentration of lead (Pb) and cadmium (Cd) and ii) evaluate the association between metal exposures and biomarkers of oxidative damage in primary school children in Cyprus. METHODS: This study was part of the ORGANIKO cluster-randomized crossover trial, a 40-day organic food treatment to 149 healthy children (10-12 years) in Cyprus. Urinary biomarkers of Pb and Cd were determined using inductively coupled plasma mass spectrometry. Linear mixed-effect regression models were used to account for the effect and duration of the organic food treatment. Multiple comparisons were handled using Benjamini-Hochberg correction. RESULTS: A time-dependent reduction for creatinine-adjusted Pb during the intervention period was observed (ß = -0.021; 95% CI: -0.034, -0.008; p-adjusted = 0.01). A similar trend was observed for creatinine-adjusted Cd, but it was not significant (ß = -0.013; 95% CI: -0.026, 0.000; p-adjusted = 0.15). The creatinine-adjusted oxidative damage biomarkers were significantly associated with both metal biomarkers; Pb (8-OHdG: ß = 0.388, 95% CI: 0.303, 0.472; p-adjusted<0.001; MDA: ß = 0.187, 95% CI: 0.109, 0.265; p-adjusted<0.001; 8-iso-PGF2a: ß = 0.320, 95% CI: 0.244, 0.397; p-adjusted<0.001), and Cd (8-OHdG: ß = 0.148, 95% CI: 0.063, 0.233; p-adjusted = 0.003; MDA: ß = 0.107, 95% CI: 0.030, 0.184; p-adjusted = 0.018; 8-iso-PGF2a: ß = 0.263, 95% CI: 0.186, 0.339; p-adjusted<0.001). DISCUSSION: A 40-day organic food treatment reduced primary school children's exposures to Pb over time. More human studies in settings with high food contaminant profiles across common crops are warranted.
Subject(s)
Cadmium , Lead , Child , Humans , Cadmium/analysis , Lead/analysis , Food, Organic/analysis , Environmental Exposure/analysis , Cross-Over Studies , Creatinine , Cyprus , Biomarkers/analysis , SchoolsABSTRACT
Environmental factors affecting health and vulnerability far outweigh genetics in accounting for disparities in health status and longevity in US communities. The concept of the exposome, the totality of exposure from conception onwards, provides a paradigm for researchers to investigate the complex role of the environment on the health of individuals. We propose a complementary framework, community-level exposomics, for population-level exposome assessment. The goal is to bring the exposome paradigm to research and practice on the health of populations, defined by various axes including geographic, social, and occupational. This framework includes the integration of community-level measures of the built, natural and social environments, environmental pollution-derived from conventional and community science approaches, internal markers of exposure that can be measured at the population-level and early responses associated with health status that can be tracked using population-based monitoring. Primary challenges to the implementation of the proposed framework include needed advancements in population-level measurement, lack of existing models with the capability to produce interpretable and actionable evidence and the ethical considerations of labeling geographically-bound populations by exposomic profiles. To address these challenges, we propose a set of recommendations that begin with greater engagement with and empowerment of affected communities and targeted investment in community-based solutions. Applications to urban settings and disaster epidemiology are discussed as examples for implementation.
ABSTRACT
Non-pharmacological interventions (e.g., stay-at-home orders, school closures, physical distancing) implemented during the COVID-19 pandemic are expected to have modified routines and lifestyles, eventually impacting key exposome parameters, including, among others, physical activity, diet and cleaning habits. The objectives were to describe the exposomic profile of the general Cypriot population and compliance to the population-wide measures implemented during March-May 2020 to lower the risk of SARS-CoV-2 transmission, and to simulate the population-wide measures' effect on social contacts and SARS-CoV-2 spread. A survey was conducted in March-May 2020 capturing different exposome parameters, e.g., individual characteristics, lifestyle/habits, time spent and contacts at home/work/elsewhere. We described the exposome parameters and their correlations. In an exposome-wide association analysis, we used the number of hours spent at home as an indicator of compliance to the measures. We generated synthetic human proximity networks, before and during the measures using the dynamic-[Formula: see text]1 model and simulated SARS-CoV-2 transmission (i.e., to identify possible places where higher transmission/number of cases could originate from) on the networks with a dynamic Susceptible-Exposed-Infectious-Recovered model. Overall, 594 respondents were included in the analysis (mean age 45.7 years, > 50% in very good health and communicating daily with friends/family via phone/online). The median number of contacts at home and at work decreased during the measures (from 3 to 2 and from 12 to 0, respectively) and the hours spent at home increased, indicating compliance with the measures. Increased time spent at home during the measures was associated with time spent at work before the measures (ß= -0.87, 95% CI [-1.21,-0.53]) as well as with being retired vs employed (ß= 2.32, 95% CI [1.70, 2.93]). The temporal network analysis indicated that most cases originated at work, while the synthetic human proximity networks adequately reproduced the observed SARS-CoV-2 spread. Exposome approaches (i.e., holistic characterization of the spatiotemporal variation of multiple exposures) would aid the comprehensive description of population-wide measures' impact and explore how behaviors and networks may shape SARS-CoV-2 transmission.
Subject(s)
COVID-19 , Exposome , Humans , Middle Aged , COVID-19/epidemiology , SARS-CoV-2 , Pandemics , Cyprus/epidemiologyABSTRACT
The urban overheating phenomenon in Mediterranean cities is a societal challenge with vast implications for the protection of public health. An additional analysis of the pilot TEMP randomized 2 × 2 cross-over trial was set up, using wearable sensor-based skin temperature measurements (n = 14). The study objectives were to: (i) assess the recurrence patterns of skin temperature measurements in individuals spending time in two climatologically contrasting settings (urban versus mountainous), and (ii) evaluate the association between the diurnal nonlinear recurrence quantification analysis (RQA) metrics and metabolic hormone levels. The intervention was a short-term stay (5-7 days) in a mountainous, climate-cooler setting (range 600-900 m altitude), which is about a 1 h drive from the main urban centres of Cyprus. The RQA analysis showed a blunting phenomenon on the nonlinear temporal dynamics of skin temperature time series observed in the urban setting. Compared with the mountainous setting, a more stable (and thus less adaptive) profile of skin temperature dynamics in the urban setting appeared, being less deterministic and with a smaller degree of complexity. No significant (p > 0.05) associations were observed between the leptin or cortisol and any of the skin temperature dynamical descriptors. However, there were marginal associations between the adiponectin and laminarity (beta = 0.24, 95%CI: -0.02, 0.50, p = 0.07) and with determinism (beta = 0.23, 95%CI: -0.037, 0.50, p = 0.09). We found dysregulations in skin temperature temporal dynamics of the study population while residing in the urban setting when compared with the cooler mountainous setting; these dysregulations took the form of reduced cycle duration and complexity, while skin temperature dynamics became less responsive to perturbations and less regular in magnitude. More research is needed to better understand heat stress temporal dynamics and their influence on human health. Trial registration: This trial is registered with ClinicalTrials.gov; number: NCT03625817.
Subject(s)
Heat Stress Disorders , Skin Temperature , Humans , Cross-Over Studies , Climate , Heat Stress Disorders/epidemiology , HormonesABSTRACT
Pyrethroids are a major insecticide class, suitable for biomonitoring in humans. Due to similarities in structure and metabolic pathways, urinary metabolites are common to various active substances. A tiered approach is proposed for risk assessment. Tier I was a conservative screening for overall pyrethroid exposure, based on phenoxybenzoic acid metabolites. Subsequently, probabilistic approaches and more specific metabolites were used for refining the risk estimates. Exposure was based on 95th percentiles from HBM4EU aligned studies (2014-2021) covering children in Belgium, Cyprus, France, Israel, Slovenia, and The Netherlands and adults in France, Germany, Israel, and Switzerland. In all children populations, the 95th percentiles for 3-phenoxybenzoic acid (3-PBA) exceeded the screening value. The probabilistic refinement quantified the risk level of the most exposed population (Belgium) at 2% or between 1-0.1% depending on the assumptions. In the substance specific assessments, the 95th percentiles of urinary concentrations in the aligned studies were well below the respective human biomonitoring guidance values (HBM-GVs). Both information sets were combined for refining the combined risk. Overall, the HBM data suggest a low health concern, at population level, related to pyrethroid exposure for the populations covered by the studies, even though a potential risk for highly exposed children cannot be completely excluded. The proposed tiered approach, including a screening step and several refinement options, seems to be a promising tool of scientific and regulatory value in future.
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Few data are available on the exposure of children to glyphosate (Gly) in Europe. Within HBM4EU, new HBM exposure data were collected from aligned studies at five sampling sites distributed over Europe (studies: SLO CRP (SI); ORGANIKO (CY); GerES V-sub (DE); 3XG (BE); ESTEBAN (FR)). Median Gly concentrations in urine were below or around the detection limit (0.1 µg/L). The 95th percentiles ranged between 0.18 and 1.03 µg Gly/L. The ratio of AMPA (aminomethylphosphonic acid; main metabolite of Gly) to Gly at molar basis was on average 2.2 and the ratio decreased with higher Gly concentrations, suggesting that other sources of AMPA, independent of metabolism of Gly to AMPA in the monitored participants, may concurrently operate. Using reverse dosimetry and HBM exposure data from five European countries (east, west and south Europe) combined with the proposed ADI (acceptable daily intake) of EFSA for Gly of 0.1 mg/kg bw/day (based on histopathological findings in the salivary gland of rats) indicated no human health risks for Gly in the studied populations at the moment. However, the absence of a group ADI for Gly+AMPA and ongoing discussions on e.g., endocrine disrupting effects cast some uncertainty in relation to the current single substance ADI for Gly. The carcinogenic effects of Gly are still debated in the scientific community. These outcomes would influence the risk conclusions presented here. Finally, regression analyses did not find clear associations between urinary exposure biomarkers and analyzed potential exposure determinants. More information from questionnaires targeting exposure-related behavior just before the sampling is needed.
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The risk assessment of pesticide residues in food is a key priority in the area of food safety. Most jurisdictions have implemented pre-marketing authorization processes, which are supported by prospective risk assessments. These prospective assessments estimate the expected residue levels in food combining results from residue trials, resembling the pesticide use patterns, with food consumption patterns, according to internationally agreed procedures. In addition, jurisdictions such as the European Union (EU) have implemented large monitoring programs, measuring actual pesticide residue levels in food, and are supporting large-scale human biomonitoring programs for confirming the actual exposure levels and potential risk for consumers. The organophosphate insecticide chlorpyrifos offers an interesting case study, as in the last decade, its acceptable daily intake (ADI) has been reduced several times following risk assessments by the European Food Safety Authority (EFSA). This process has been linked to significant reductions in the use authorized in the EU, reducing consumers' exposure progressively, until the final ban in 2020, accompanied by setting all EU maximum residue levels (MRL) in food at the default value of 0.01 mg/kg. We present a comparison of estimates of the consumer's internal exposure to chlorpyrifos based on the urinary marker 3,5,6-trichloro-2-pyridinol (TCPy), using two sources of monitoring data: monitoring of the food chain from the EU program and biomonitoring of European citizens from the HB4EU project, supported by a literature search. Both methods confirmed a drastic reduction in exposure levels from 2016 onwards. The margin of exposure approach is then used for conducting retrospective risk assessments at different time points, considering the evolution of our understanding of chlorpyrifos toxicity, as well as of exposure levels in EU consumers following the regulatory decisions. Concerns are presented using a color code, and have been identified for almost all studies, particularly for the highest exposed group, but at different levels, reaching the maximum level, red code, for children in Cyprus and Israel. The assessment uncertainties are highlighted and integrated in the identification of levels of concern.
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Human biomonitoring has become a pivotal tool for supporting chemicals' policies. It provides information on real-life human exposures and is increasingly used to prioritize chemicals of health concern and to evaluate the success of chemical policies. Europe has launched the ambitious REACH program in 2007 to improve the protection of human health and the environment. In October 2020 the EU commission published its new chemicals strategy for sustainability towards a toxic-free environment. The European Parliament called upon the commission to collect human biomonitoring data to support chemical's risk assessment and risk management. This manuscript describes the organization of the first HBM4EU-aligned studies that obtain comparable human biomonitoring (HBM) data of European citizens to monitor their internal exposure to environmental chemicals. The HBM4EU-aligned studies build on existing HBM capacity in Europe by aligning national or regional HBM studies. The HBM4EU-aligned studies focus on three age groups: children, teenagers, and adults. The participants are recruited between 2014 and 2021 in 11 to 12 primary sampling units that are geographically distributed across Europe. Urine samples are collected in all age groups, and blood samples are collected in children and teenagers. Auxiliary information on socio-demographics, lifestyle, health status, environment, and diet is collected using questionnaires. In total, biological samples from 3137 children aged 6-12 years are collected for the analysis of biomarkers for phthalates, HEXAMOLL® DINCH, and flame retardants. Samples from 2950 teenagers aged 12-18 years are collected for the analysis of biomarkers for phthalates, Hexamoll® DINCH, and per- and polyfluoroalkyl substances (PFASs), and samples from 3522 adults aged 20-39 years are collected for the analysis of cadmium, bisphenols, and metabolites of polyaromatic hydrocarbons (PAHs). The children's group consists of 50.4% boys and 49.5% girls, of which 44.1% live in cities, 29.0% live in towns/suburbs, and 26.8% live in rural areas. The teenagers' group includes 50.6% girls and 49.4% boys, with 37.7% of residents in cities, 31.2% in towns/suburbs, and 30.2% in rural areas. The adult group consists of 52.6% women and 47.4% men, 71.9% live in cities, 14.2% in towns/suburbs, and only 13.4% live in rural areas. The study population approaches the characteristics of the general European population based on age-matched EUROSTAT EU-28, 2017 data; however, individuals who obtained no to lower educational level (ISCED 0-2) are underrepresented. The data on internal human exposure to priority chemicals from this unique cohort will provide a baseline for Europe's strategy towards a non-toxic environment and challenges and recommendations to improve the sampling frame for future EU-wide HBM surveys are discussed.
Subject(s)
Biological Monitoring , Environmental Pollutants , Adolescent , Adult , Cadmium/analysis , Child , Environmental Exposure/analysis , Environmental Monitoring , Environmental Pollutants/analysis , Europe , Female , Humans , Male , Risk AssessmentABSTRACT
Excess weight is a public health challenge affecting millions worldwide, including younger age groups. The human exposome concept presents a novel opportunity to comprehensively characterize all non-genetic disease determinants at susceptible time windows. This study aimed to describe the association between multiple lifestyle and clinical exposures and body mass index (BMI) in adolescents using the exposome framework. We conducted an exposome-wide association (ExWAS) study using U.S. National Health and Nutrition Examination Survey (NHANES) 2003-2004 wave for discovery of associations between study population characteristics and zBMI, and used the 2013-2014 wave to replicate analysis. We included non-diabetic and non-pregnant adolescents aged 12-18 years. We performed univariable and multivariable linear regression analysis adjusted for age, sex, race/ethnicity, household smoking, and income to poverty ratio, and corrected for false-discovery rate (FDR). A total of 1899 and 1224 participants were eligible from 2003-2004 and 2013-2014 survey waves. Weighted proportions of overweight were 18.4% and 18.5% whereas those for obese were 18.1% and 20.6% in 2003-2004 and 2013-2014, respectively. Retained exposure agents included 75 laboratory (clinical and biomarkers of environmental chemical exposures) and 64 lifestyle (63 dietary and 1 physical activity) variables. After FDR correction, univariable regression identified 27 and 12 predictors in discovery and replication datasets, respectively, while multivariable regression identified 22 and 9 predictors in discovery and replication datasets, respectively. Six were significant in both datasets: alanine aminotransferase, gamma glutamyl transferase, segmented neutrophils number, triglycerides; uric acid and white blood cell count. In this ExWAS study using NHANES data, we described associations between zBMI, nutritional, clinical and environmental factors in adolescents. Future studies are warranted to investigate the role of the identified predictors as early-stage biomarkers of increased BMI and associated pathologies among adolescents and to replicate findings to other populations.