Environment International

BackgroundSeveral studies revealed an implication of air pollution in neurodegenerative disorders, although this link and the potential underlying mechanisms remain unclear. ObjectivesTo analyze the impact of air pollution on neurodegenerative risk by testing multiple pollutants simultaneously, along with other potential risk/protective factors, and the role of circulating inflammation. MethodsIn the Moli-sani cohort (N=24,325; [&ge;]35 years; 51.9% women, baseline 2005-2010), we estimated yearly levels of exposure to nitrogen oxides, ozone, particulate matter (PM10), sulfur dioxide and BTX hydrocarbons in 2006-2018, applying residence geo-localization of participants and Kriging interpolation algorithm to land measurements of air pollutants. We performed a principal component (PC) analysis of pollutant levels and tested associations of the resulting PC scores with the incident risk of dementia (AD) and Parkinsons disease/parkinsonism (PD), through multivariable Cox PH regressions adjusted for age, sex, education level, and several professional and lifestyle exposures. Moreover, we tested whether a composite biomarker of circulating inflammation (INFLA-score) may explain part of these associations. ResultsOver 24,308 subjects with pollution data available (51.9% women, mean age 55.8(12.0) years), we extracted three PCs explaining [&ge;]5% of pollution exposure variance: PC1 (38.2%, tagging PM10), PC2 (19.5%, O3/CO/SO2), PC3 (8.5%, NOx/BTX hydrocarbons). Over a median (IQR) follow-up of 11.2(2.0) years, we observed statistically significant associations of PC1 with an increased risk of both AD (HR[CI] = 1.06[1.04-1.08]; 218 cases) and PD (1.05[1.03-1.06]; 405 incident cases), independent on other covariates. These associations were confirmed testing average PM10 levels during follow-up time (25[19-31]% and 19[15-24]% increase of AD and PD risk, per 1 g/m3 of PM10). INFLA-score explained a negligible (<1%) proportion of these associations. DiscussionAir pollution - especially PM10 - is associated with increased neurodegenerative risk in the Italian population, independent on concurring risk factors, suggesting its reduction as a potential public health target.

Neonatal meconium provides a non-invasive matrix for assessing prenatal or near-birth exposure to environmental contaminants. Although microplastics and metals have each been reported in human biological samples, integrated assessments of concurrent particle and metal exposure in meconium remain scarce, particularly in South Asia. In this cross-sectional biomonitoring study, meconium from 30 Cesarean-delivered neonates born in Dhaka, Bangladesh, was analyzed for microplastic occurrence, morphology, and polymer composition using stereomicroscopy, scanning electron microscopy, and Raman spectroscopy, and for fifteen metals using inductively coupled plasma mass spectrometry. Maternal breast milk from a subset of lactating mothers was analyzed as a complementary maternal exposure context. Microplastics were detected in all analyzable meconium samples (n=28), with a median burden of 149 particles/g wet weight, dominated by polyethylene terephthalate fragments and nylon fibers. All fifteen measured metals were also detected in all analyzable meconium samples, with median Pb and Cr concentrations of 1.18 and 3.92 ug/g dry weight, respectively. No microplastic-metal associations remained significant after multiple-testing correction, suggesting partly distinct exposure or accumulation pathways. Here, we show that neonatal meconium captures concurrent microplastic and metal exposure in an urban South Asian birth cohort. This study provides one of the first integrated meconium-based assessments of concurrent microplastic and metal exposure from the region and highlights meconium as a practical matrix for early-life biomonitoring.

Pesticide gestational exposure may contribute to the development of allergies in childhood, yet evidence on its health impact on urban populations remains limited. This study investigates the association between prenatal exposure to individual and mixed pesticides and allergic outcomes, including asthma, wheezing, and eczema, at age 6 in 387 mother-child pairs from the LiNA cohort. Forty pesticides and metabolites were detected in urine during pregnancy through non-targeted screening, and 11 were selected (detection rate[&ge;]17%) for further analysis. Multivariable logistic regression models adjusted for covariates revealed statistically significant associations between dihydroxy-pyrimethanil and asthma (aOR=1.36, 95% CI: 1.04-1.80), and fluazifop-desbuthyl and wheezing (aOR=1.15, 95% CI: 1.01-1.31). No significant associations were observed for eczema. The mixture effect analysis with weighted quantile sum (WQS) regression showed that higher pesticide co-exposures significantly increased wheezing odds (aOR=2.08, 95% CI: 1.21-3.56). The main components of the WQS index were fluazifop-desbuthyl, flonicamid, hydroxy-metazachlor, and terbuthylazine, accounting for 67% of the overall dose-additive effect. These findings suggest that prenatal exposure to pesticides at dietary levels may increase the risk of childhood asthma and wheezing. Further epidemiological studies should replicate our findings by considering exposures to other pesticides of concern and their metabolites. SynopsisRisk assessment of chemical mixtures should cover dietary exposure to non-persistent pesticides in urban populations by screening for compound-specific metabolites.

The human toxicological risk assessment of per- and polyfluoroalkyl substances (PFAS) is challenging, due to their sheer number and structural diversity, but also the paucity of the toxicity data required to characterize them. The development of Next Generation Physiologically Based Kinetic (NG-PBK) models may assist in overcoming this challenge. The mechanistic nature of NG-PBK models allows for their extrapolation from data-rich PFAS, such as perfluorooctanoic acid (PFOA), to data-poor ones, facilitating their application in Next Generation Risk Assessment (NGRA). The present study proposes a NG-PBK model for PFOA in humans, parametrized exclusively using in vitro-, and in silico-derived data. The model describes the toxicokinetic processes of 1) partitioning to plasma and tissue proteins, 2) partitioning to cell membrane lipids, 3a) transporter-mediated entero-hepatic circulation and 3b) renal elimination and reabsorption, and 4) elimination via menstruation. Global sensitivity analysis indicated that the model was most sensitive to the fraction unbound in plasma, active-transport parameters, and tissue-plasma partition coefficients. The model was equivalent to already available validated human PFOA-PBK models, while compared to those, it is not calibrated to observed animal, nor human data, illustrating its strength in being mechanistic. The serum concentrations and half-lives predicted by the NG-PBK model were within the ranges of those reported in human volunteer and biomonitoring (HBM) studies, demonstrating the models capacity to accurately predict PFOA toxicokinetics on exposure estimates. Extrapolation of the NG-PBK model to other PFAS, in conjunction with its integration with HBM data, will facilitate the NGRA of PFAS. This is particularly relevant given the paucity of in vivo data for most PFAS, ensuring compliance with the 3R principles.

BackgroundHousehold air pollution is a major contributor to cardiovascular disease burden in women in Sub-Saharan Africa. However, little is known about exposures during pregnancy or the effect of clean cooking interventions on postpartum blood pressure trajectories. MethodsThe Ghana Randomized Air Pollution and Health Study (GRAPHS) randomized 1414 non-smoking women in the first and second trimesters to liquefied petroleum gas (LPG) or improved biomass stoves - vs control (traditional three-stone open fire). Personal exposure to carbon monoxide was measured at four prenatal timepoints and three times over the first postpartum year. Participants were prospectively followed with annual resting BP measurements at 2, 4, 5, 6, 7, and 8 years postpartum. We employed linear mixed effects models to determine effect of GRAPHS interventions on postpartum BP, and to examine associations between prenatal and postnatal CO and postpartum BP. ResultsLPG intervention was associated with 3.54mmHg (95% CI-5.55,-1.53) lower change in systolic BP from enrolment through 8 years postpartum, and 2.27mmHg (95% CI-3.61,-0.93) lower change in diastolic BP from enrolment through 8 years postpartum, as compared to control. In exposure-response analysis, average prenatal CO was positively associated with change in systolic BP from enrolment ({beta}=0.71mmHg, 95% CI 0.08, 1.30, per doubling of CO) ConclusionsLPG cookstove intervention initiated in early pregnancy and maintained through the first postpartum year was associated with lower systolic and diastolic BP trajectories through 8 years postpartum. These findings support the need to integrate clean cooking solutions into existing antenatal care packages.

The presence of microplastic in the environment has become a matter of significant concern regarding its impact on the food chain and, moreover, human health. The potential ways in which humans may be exposed to microplastic include ingestion, inhalation, or dermal contact. To facilitate initial estimates of the potential for human exposure, a model has been developed that incorporates all of the major stages in the transfer of microplastic from its sources to direct human contact. Due to the scarcity of data available, a simplified gradation of exposure probability has been applied. Building on the results of published mass flow models for microplastics, the model is based on normalized values for the release of microplastics from different types of applications into environmental compartments, also considering the degradation of macroplastic. Published data investigating the contamination of different foods and beverages are evaluated, and the inhalation probability is assessed using air pollution data and breathing rates. In the final step, the potential for resorption through the gastrointestinal and the respiratory tract is estimated. The results obtained from this modelling indicate a high exposure potential for microplastic from tire wear via outdoor air and for various PET applications via indoor air. Furthermore, the results demonstrate a high potential for exposure via ingestion of food for plastics used in agriculture. The models results represent an initial attempt to estimate exposure probabilities for humans across all application categories of plastics and the most common polymers, taking into account the uncertainty of current research.

Introductioncurrent evidence on the short-term effects of air pollution on mortality often overlooks potential temporal variation and non-linear exposure-response relationships, which may bias effect estimates and limit the accuracy of health risk assessments. Methodsthis study addresses these gaps by examining temporal changes and non-linear associations between daily concentrations of PM10, PM2.5, NO2, and SO2 and mortality from natural, cardiovascular, and respiratory causes across eight municipalities in Tuscany, Italy, from 2008 to 2019. Environmental and mortality data were obtained from official sources; missing environmental data were handled through multiple imputation. Time-invariant and time-varying linear effects were estimated using Poisson regression models, and non-linear dose-response curves were assessed using splines. ResultsPM2.5 and SO2 were positively associated with natural and respiratory mortality, while PM10 and NO2 showed weaker or no associations. Stronger effects were observed during 2012-2015, despite lower pollutant concentrations. SO2 also exhibited a non-linear relationship with cardiovascular mortality, with greater effects at lower concentrations. Conclusionthese findings suggest that reductions in pollutant levels do not necessarily imply reduced health risks, potentially due to changes in pollutant composition or interactions with meteorological factors. This study underscores the importance of accounting for both temporal variation and potential non-linearity in air pollution health impact assessments. What is already known on this topicThere is strong evidence that short-term exposure to air pollutants such as PM10, PM2.5, NO2, and SO2 is associated with increased risks of natural, cardiovascular, and respiratory mortality. However, most existing studies rely on the assumption that these effects are constant over time and that the exposure-response relationship is linear. The possibility that health effects vary across time due to changing environmental or contextual factors - and that such variation may be non-linear - has received limited attention. What this study addsThis study investigates short-term mortality effects of air pollution over a 12-year period in eight municipalities in Tuscany, Italy, using both linear and non-linear models. It demonstrates that the effects of PM10, PM2.5, and SO2 on mortality are not temporally constant and that stronger associations are observed in periods with lower average pollutant levels. While SO2 shows a clear non-linear relationship, non-linearity alone does not fully explain the time variation observed for particulates, suggesting that changes in pollutant composition or environmental conditions may also play a role. How this study might affect research, practice or policyBy revealing that pollutant-related health risks can vary significantly over time and may not follow a simple linear pattern, this study underscores the importance of integrating temporal variability and non-linearity into air pollution epidemiology. These insights could improve the accuracy of health impact assessments, support more responsive air quality regulations, and inform future policies aimed at protecting public health under evolving environmental conditions.

Given Chinas recent introduction of the "three-child policy" in response to population ageing1, safeguarding perinatal health has become an urgent priority2. Previous epidemiological research seldom explored the risk factors of maternal cardiovascular and haematological diseases, or its impact on adverse pregnancy outcomes (APO). To fill the literature gap, here we conducted systematic epidemiological analyses on 121,090 pregnant women and their neonates from the ZEBRA Chinese prospective maternity cohort. We find that incremental exposure in PM2.5, O3, and green space modify the risks of APO, including congenital heart disease, by 11.2%, 7.8%, and -5.5%, respectively. Maternal cardiovascular and haematological complications during pregnancy significantly aggravate the risk of APO by 66.2%, and also modify the environment-APO risk associations by amplifying the hazards of air pollution and weakening the protective effect of greenness accessibility. Our research findings support the Sustainable Development Goals (e.g. SDG3)3,4 by providing first-hand epidemiological evidence and clinical guidance for protecting maternal and neonatal health.

Dietary exposure to heavy metals (HMs) via animal-source foods is a critical environmental health pathway. In rapidly industrializing Bangladesh, contamination of the bovine food chain from agricultural feeds and industrial emissions poses an unquantified public health burden. This study evaluated exposure pathways, spatial distribution, mass-transfer dynamics, and health risks of six HMs (Cr, Cu, Cd, Pb, As, and Hg) across the fodder-cattle-human continuum. Samples of beef (n = 76), raw milk (n = 76), commercial cattle feed (n = 40), and fodder (n = 88) were collected from eight sites across industrial and non-industrial zones in Bangladesh and analysed by atomic absorption spectroscopy. Probabilistic Monte Carlo simulations (10,000 iterations) quantified estimated daily intake, target hazard quotients (THQ), cumulative hazard index (HI), and lifetime carcinogenic risk (CR) for adult and pediatric receptors. Copper (Cu) was the dominant contaminant across all matrices, peaking in beef (103.89 {+/-} 15.87 mg/kg) and milk (13.67 {+/-} 1.53 mg/L). Spatial analysis revealed distinct contamination profiles: Pb burden peaked in industrial zones while Cr was elevated in non-industrial sectors. Monte Carlo modelling identified commercial feed as the most efficient transfer vector into beef. Pediatric THQ for Cu significantly exceeded the safety threshold (THQ > 1), and upper-bound lifetime carcinogenic risk from As approached the critical USEPA 10- regulatory ceiling. These findings demonstrate that industrial and agricultural externalities efficiently contaminate the bovine food supply chain in Bangladesh, with copper and arsenic representing the most critical non-carcinogenic and carcinogenic dietary hazards, respectively. Children are disproportionately vulnerable due to lower body weight. The results underscore the need for targeted upstream interventions in commercial feed production and provide evidence to support feed-quality regulation and environmental monitoring in rapidly industrializing settings.

PFAS are ubiquitous endocrine-disrupting pollutants that cross the placenta and impact offspring health, but the extent and timing of their transfer to both placental and fetal compartments remain poorly understood. We aimed to characterize the relationship between trimester-specific maternal serum levels of prenatal PFAS and paired placental and cord levels at term. Data came from Glowing, a prospective birth cohort (n=151). Seventeen PFAS were measured in maternal serum, cord serum, and pulverized flash-frozen villous placenta with liquid chromatography-tandem mass spectrometry. Mixed effects models tested transplacental transfer efficiency (TTE) over pregnancy. Regularization models, stochastic intervention, and quantile g-computation models tested the association between maternal and placental or cord PFAS levels. TTE increased linearly across trimesters for all PFAS (p<0.001). Quartile increases in maternal PFAS were strongly associated with placental levels (0.018-0.24 ng/g, p<0.001). Stochastic intervention identified T1 PFNA and PFDA; T2 PFOS, PFOA, PFHxS, and PFNA; and T3 PFHxS as robust predictors (p<0.001) of placental levels, consistent with quantile-based contributions. Quartile increases in maternal and placental PFAS concentrations were associated with cord levels (0.08 ng/g-0.55 ng/g, p<0.001). Stochastic intervention identified T1 PFOS and PFHxS; T2 PFOS and PFNA; T3 PFOA; and placental PFOA as important predictors (p<0.05) of cord levels, consistent with quantile-based contributions. Early-to-mid gestation, especially 2nd trimester PFAS measures, were the strongest sentinels of placental and cord serum levels, apart from PFOA which was best reflected by 3rd trimester or placental levels. Placental PFOS and PFOA strongly influenced cord levels. Our findings underscore the heterogeneity in PFAS transfer or metabolism across pregnancy and the placenta.

BackgroundPer- and polyfluoroalkyl substances (PFAS) have been reported in human milk. However, prior U.S. studies have not included novel PFAS alternatives of emerging concern or infants Estimated Daily Intake (EDI) of PFAS. MethodsHuman milk was collected between 2019 and 2020 at 6 weeks after delivery from 100 Cincinnati, Ohio, nursing women participants in the IMPRINT study; 29 PFAS congeners were measured using ultrahigh performance liquid chromatography-mass spectrometry. We performed descriptive exposure analyses and assessed infants PFAS EDI from human milk. ResultsAll human milk samples contained PFAS. Of the 19 PFAS detected, 5 congeners were concurrently found in [&ge;] 50% of the samples. Legacy PFAS had the highest detection frequencies and concentrations: 97.7% for perfluorooctanesulfonic acid (PFOS) (median concentration: 14.5 ng/L) and 89.8% for perfluorooctanoic acid (PFOA) (median: 17.4 ng/L), 71.6% for perfluorohexanesulfonic acid (PFHxS) (median: 3.7 ng/L), and 70.0% for perfluorohexanoic acid (PFHxA) (median: 10.4 ng/L). An emerging PFAS, dodecafluoro-3H-4,8-dioxanonanoate (ADONA), was detected in 68.0% of samples (median: 3.5 ng/L). The PFAS with the highest EDI included PFOA (median: 8.6 ng), PFOS (median: 7.1 ng), and PFHxA (median: 5.8 ng). About 98% of samples had PFAS levels above the European Food Safety Authority (EFSA) tolerable weekly intake of 4.4 ng/kg body weight/week for the sum of PFOA, PFOS, PFHxS and perfluorononanoate (PFNA). ConclusionsHuman milk from women in Cincinnati, Ohio, contained both legacy and emerging PFAS and infants PFAS consumption through breastfeeding exceeded EFSA tolerable weekly intakes.

Background: Preeclampsia is a leading cause of maternal morbidity and mortality in sub Saharan Africa. Lead exposure remains widespread across the region, yet its contribution to preeclampsia risk has not been quantified at the population level. The World Health Organization (WHO, 2025) estimated that in 2023, there were approximately 182,000 maternal deaths in SSA (70 % of global deaths), and that approximately 16% of these deaths were due to hypertensive disorders of pregnancy (HDP) (Say et al, 2014). This implies that there were approximately 29,000 HDP related maternal deaths annually in the SSA (with preeclampsia/eclampsia constituting a substantial fraction). Methods: We synthesized maternal blood lead level (BLL) data from pregnancy biomonitoring studies conducted in sub-Saharan Africa and supplemented these with soil derived exposure scenarios representing severely contaminated settings. Using published meta analytic evidence indicating a 1.6% increase in the odds of preeclampsia per 1 microgram/dL increase in maternal BLL, we modelled relative odds and predicted absolute preeclampsia risk under a range of plausible baseline prevalence assumptions. Sensitivity analyses examined uncertainty related to exposure extrapolation and baseline preeclampsia prevalence, and population attributable fractions were estimated across baseline scenarios. Results: Biomonitoring derived maternal BLLs were associated with modest but consistent increases in predicted preeclampsia risk across baseline scenarios. Soil derived exposure scenarios representing severe environmental contamination yielded sharply increasing predicted risks under uncapped extrapolation. Sensitivity analyses demonstrated that relative exposure response gradients were robust to modelling assumptions, while absolute risk and attributable burden estimates varied with baseline prevalence. The mean maternal blood lead level from fifteen (15) separate studies in SSA was 26.24 microgram/dL (Range: 0.83 to 99 microgram/dL) (Bede et al., 2016) while the mean or geometric mean BLL in of women the United States, Canada, Germany, South Korea, China, and Mexico were between 0.5 and 2.4 microgram/dL. Conclusion: Maternal lead exposure may contribute meaningfully to preeclampsia risk in sub Saharan Africa, with modest effects at commonly observed exposure levels and potentially substantial effects in severely contaminated settings. These findings support the inclusion of environmental lead exposure prevention within broader maternal health strategies.

BackgroundCardiometabolic multimorbidity (CMM) with at least two cardiometabolic diseases (CMDs) including type II diabetes (T2D), ischemic heart disease (IHD), and stroke, is a global health problem with multiplicative mortality risk and deserves to be investigated as a top priority. Although air pollution is a leading modifiable environmental risk for individual CMD, its impacts on CMM progression were poorly understood. ObjectiveTo elucidate the impact of air pollution on CMM progression, individually and in the context of genetic preposition. DesignMulti-state modeling cohort study. SettingData were extracted from the UK Biobank. Participants415,855 eligible UK Biobank adults that were free of CMDs at baseline. MeasurementsAnnual concentrations of particulate matter (PM) with a diameter of [&le;]2.5 m (PM2.5), 2.5-10 m (PM2.5-10), and [&le;]10 m (PM10), and nitrogen oxides (NOx and NO2) were estimated using Land Use Regression model. ResultsDuring a median follow-up of 8.93 years, 33,375 participants had a first CMD (FCMD), and 3,257 subsequently developed CMM. PM2.5, PM10, NO2, and NOx levels, as well as their combined exposure were associated with increased FCMD risks and even higher risks of CMM. Particularly, per a 5-g/m3 increase in PM2.5, risks for FCMD and CMM increased by 27% (95% confidence interval: 20%-34%) and 41% (18%-68%), respectively. By FCMD types, participants with IHD had a higher risk of CMM than those with T2D or stroke. Eighty-five CMD-related genetic variants were associated with CMM trajectories in our study and associations of air pollution with FCMD and CMM risks could be aggravated progressively with increasing genetic risks. LimitationsOther major air pollutants including ozone and SO2 were not considered due to the data availability. ConclusionsAir pollution has profound adverse health impacts on the progression of CMM through multi-stage dynamics, especially for individuals with IHD and high genetic risk.

Background: Urban environmental and lifestyle factors during early life may influence pubertal timing, but the combined effects of multiple environmental exposures within an exposome analytical framework remain poorly understood. Objective: To examine the association between early-life urban environmental exposures and pubertal timing, and to explore whether these exposures interact with early-life nutritional factors, namely breastfeeding duration and childhood diet quality. Methods: Data from two European population-based birth cohorts were analysed: Generation XXI (G21, Portugal; n=5263; 51.5% girls) and INfancia y Medio Ambiente (INMA, Spain; n=1019; 50.1% girls). Urban environmental exposures including indicators of air pollution, traffic, built environment, and natural spaces were estimated at 4 early-life stages at both cohorts: pregnancy (INMA only), birth, 1 year, and 4-5 years of age. Pubertal development timing was assessed using Tanner staging and/or the Pubertal Development Scale (PDS), and age at menarche was self-reported. Exposome-Wide Association Study (ExWAS) models and unsupervised clustering followed by ordinal logistic regression models were used to examine single- and multi-exposure associations, respectively. Regression models were fitted adjusting for relevant child characteristics, maternal factors, and household socioeconomic conditions, and corrected for multiple testing. Results: Individuals living in more unfavourable urban environments characterised by higher building density, air pollution, and lower access to natural spaces showed earlier pubertal timing according to multiple outcomes, across multiple early-life exposure periods, and in both cohorts. In the G21 cohort, these environmental profiles were associated with earlier age at menarche, particularly for exposures at 1-1.5 and 4-5 years (e.g., 1-1.5y: {beta}=-0.172, FDR-adjusted p-value=0.041), while in the INMA cohort, boys exposed to more unfavourable environmental profiles showed more advanced pubertal development, also particularly for exposures at 1-1.5 and 4-5 years of age (e.g., 1-1.5y; {beta}=0.572, FDR-adjusted p-value=0.008). Among environmental domains, air pollution and traffic were the factors most consistently associated with pubertal timing. Regarding early-life nutritional factors, longer duration of exclusive breastfeeding was associated with a lower Tanner stage among girls in G21. No significant interactions between breastfeeding duration and environmental exposure clusters were observed. Conclusion: Early-life urban environmental exposures, particularly air pollution and traffic, may influence pubertal timing. Exclusive breastfeeding may have a protective role against earlier pubertal development. These findings highlight the importance of improving urban environmental conditions and promoting breastfeeding to support healthy developmental trajectories.

The co-occurrence of per- and polyfluoroalkyl substances (PFAS) and volatile organic compounds (VOCs) in industrial environments poses complex toxicological risks that standard additive models fail to capture. This study elucidates a novel "metabolic blockade" mechanism wherein PFAS competitively inhibits the renal excretion of VOC metabolites, thereby amplifying neurotoxic burdens. Utilizing a Double Machine Learning (DML) framework on data from National Health and Nutrition Examination Survey (2005-2020), we analyzed a final intersectional cohort of 1,975 participants. We identified a robust inhibition of VOC metabolite clearance by serum PFAS. Specifically, PFNA significantly suppressed the excretion of the benzene metabolite URXPMA (Causal {beta}TMLE = -0.219, p < 0.001), with efficacy dependent on perfluorinated chain length. Molecular docking simulations revealed the biophysical basis of this antagonism: long-chain PFNA exhibited superior binding affinity to the Organic Anion Transporter 1 (OAT1) ({Delta}G = -6.333 kcal/mol) compared to native VOC metabolites ({Delta}G = -4.957 kcal/mol), confirming high-affinity competitive inhibition at the renal interface. In a neurocognitive sub-cohort (N = 1,200), this interference translated into functional synergism; high-PFNA exposure magnified VOC-associated cognitive impairment by 1.5-fold and significantly exacerbated the negative association between VOC burden and processing speed ({beta}int = -0.263, p = 0.004). These findings define PFAS as a "metabolic amplifier" of co-contaminant toxicity, necessitating a paradigm shift toward mixture-based hazardous material regulations that account for transporter-level interactions.

Background: Lead exposure is estimated to cause approximately 3.5 million premature deaths a year, yet the key ongoing sources of lead exposure are unclear. Methods: We estimated the contribution of dietary lead intake to global blood lead levels (BLLs) for 7-year-old children and 22-year-old adults by applying the All-Ages Lead Model (AALM) to calculate blood lead levels (BLLs) based on 25 total diet studies (TDS) that quantify dietary lead intake across 46 countries. Results: For children, the population-weighted average dietary lead intake in low- and middle-income countries (LMICs) (32.0 g/day) was found to be more than three times higher than in high-income countries (HICs) (9.3 g/day), and more than 10 times higher than the FDA reference level for children (2.2 g/day). The average impact on BLLs for children is estimated to be near 29 g/L in LMICs and near 12 g/L in HICs. Averaged across the TDS data, vegetables (27%) and cereals (24%) were found to contribute the most to dietary lead. Conclusions: While there are limitations associated with biokinetic modelling and the TDS data from LMICs, these results suggest that the contribution of dietary lead intake to global lead exposure is in the region of 40 to 50%, suggesting, in turn, that dietary lead intake is likely a major global driver of lead poisoning. Lead absorbed from the environment into food crops is expected to be the key driver of dietary lead. Current regulatory levels for maximum lead concentrations in foods (0.05-0.3 mg/kg) are out-of-date and may imply a dietary lead intake of 200 g/day, far higher than the FDA reference level (2.2 g/day). Collecting representative TDS data in high lead burden countries should be a priority. Further research is also recommended on upstream lead sources and pathways of lead uptake in plants, driving global food contamination.

Phthalates and bisphenol A (BPA) are plasticizers used in many industrial products that can act as endocrine disruptors. In the frame of the LIFE PERSUADED project, we measured the urinary concentrations of BPA and Di (2-ethylhexyl) phthalate (DEHP) metabolites in 900 Italian women enrolled between 2015 and 2017 and living in North, Centre and South of Italy in both rural and urban areas. The whole cohort, representative of the Italian female adult population, was exposed to DEHP and BPA with measurable levels above the limit of detection (LOD) in more than 99% and 95% of the samples, respectively. The exposure patterns differed for the two chemicals in the three macro-areas with the highest urinary levels for DEHP in South compared to Central and Northern Italy and for BPA in Northern compared to Central and Southern Italy. BPA levels were higher in women living in urban areas, whereas no difference between areas was observed for DEHP. The estimated daily intake of BPA was 0.11 g/kg per day, about 36-fold below the current temporary Tolerable Daily Intake of 4 g/kg per day established by the European Food Safety Authority in 2015. The analysis of cumulative exposure showed a positive correlation between DEHP and BPA. These results suggest to further limit the exposure to DEHP and BPA through specific legislative measures.

BackgroundAir pollution has been associated with increased rates of hospital admissions and general-practitioner (GP) visits. Yet, more research is to be done to reveal the spatial-temporal dimension of this association and whether ethnic minorities experience greater effects from exposure to air pollution compared to the rest of population. This study investigates the spatial-temporal effect of air pollution on GP visits and hospital admissions by ethnicity in the United-Kingdom (UK). MethodsWe used individual-level longitudinal data from the "UK Household Longitudinal Study" including 46,442 adult individuals who provided 140,466 responses across five years (2015-2019). This data was linked to yearly concentrations of NO2, SO2, and particulate-matter (PM10, PM2.5) pollution using the Lower-Super-Output-Area (LSOA) of residence for each individual. We distinguished between spatial (between areas) and temporal (across time within each area) effects of air pollution on GP visits and hospital admissions and we used multilevel mixed-effects ordered logistic models for analysis. ResultsResults showed higher odds of outpatient hospital admissions with increasing concentrations of NO2 (OR=1.009; 95%CI=1.006-1.013), SO2 (OR=1.063; 95%CI=1.030-1.097), PM10 (OR=1.013; 95%CI=1.006-1.021), and PM2.5 (OR=1.022; 95%CI=1.012-1.032) pollutants. Higher odds of GP visits were also observed with increasing concentrations of NO2 (OR=1.011; 95%CI=1.007-1.015) and SO2 (OR=1.123; 95%CI=1.087-1.160) pollutants. Decomposing air pollution into between (spatial: across LSOAs) and within (temporal: across years within each LSOA) effects, showed significant between effects for air pollution on GP visits and hospital admissions, but not within effects. We observed no differences between ethnic minorities and British-white for the association between air pollution and hospital admissions and GP visits. ConclusionUsing individual-level longitudinal data, our study supports the presence of a spatial-temporal association between air pollution and hospital admissions and GP visits. However, ethnic minorities do not seem to experience greater health-related effects from exposure to air pollution compared to the rest of population.

BackgroundBisphenols (BP) AF, B, E, F, M, and S have been introduced as substitutes for bisphenol A (BPA) and are increasingly used in consumer products. Despite widespread human exposure and potential adverse health outcomes related to BPF, BPB, BPS, and BPAF, their physiological disposition in humans is poorly characterized, which hinders assessment of associated risks. ObjectivesOur goal was to simulate the kinetic behavior of prevalent bisphenol analogs in organs of toxicological interest. To enable predictions of physiologically relevant internal concentrations of a family of structurally similar compounds with limited available human data, we aim to establish a reproducible framework using multimodal parameterization methods. MethodsHerein we developed physiologically based kinetic (PBK) models, following oral exposure. Their parametrization was primarily based on structural, physiological and experimental values, as well as quantitative structure-activity relationship (QSAR) predictions. Outputs were evaluated against available biomonitoring data for BPA and BPS. Critical parameters were identified by sensitivity analysis and iteratively re-sampled in Monte Carlo (MC) simulations to quantify uncertainties. ResultsAmong human models parametrized for males and females of different ages, we predicted that bisphenols reached the highest concentrations in 5-year-old males. Environmentally relevant exposure levels resulted in maximum concentrations in the blood and testes for BPS, and in the thyroid for BPM. After 96 hours, steady-state concentrations were not yet reached in the breasts for BPA, BPAF, BPB, BPE, BPF and BPM. ConclusionsThe data from this study suggest significant variability in internal concentrations for identical exposures to different bisphenols analogs that further depend on age, sex and organ. This diversity in toxicokinetic behavior should be considered for health risk assessment of these substitutes.

BackgroundLiving in areas with high air pollution concentrations is associated with all-cause and cause-specific mortality. Exposure in sensitive developmental periods might be long-lasting but studies with very long follow-up are rare, and mediating pathways between early life exposure and life-course mortality are not fully understood. MethodsData were drawn from the Scottish Longitudinal Study Birth Cohort of 1936, a representative record-linkage study comprising 5% of the Scottish population born in 1936. Participants had valid age 11 cognitive ability test scores along with linked mortality data until age 86. Fine particle (PM2.5) concentrations estimated with the EMEP4UK atmospheric chemistry transport model were linked to participants residential address from the National Identity Register in 1939 (age 3). Confounder-adjusted Cox regression estimated associations between PM2.5 and mortality; regression-based causal mediation analysis explored mediation through childhood cognitive ability. ResultsThe final sample consisted of 2734 individuals with 1608 deaths registered during the 1,833,517 person-months at risk follow-up time. Higher early life PM2.5 exposure increased the risk of all-cause mortality (HR=1.03, 95% CI: 1.01-1.04 per 10g m-3 increment), associations were stronger for mortality between age 65 and 86. PM2.5 increased the risk of cancer-related mortality (HR=1.05, 95% CI: 1.02-1.08), especially for lung cancer among females (HR=1.11, 95% CI: 1.02-1.21), but not for cardiovascular and respiratory diseases. Higher PM2.5 in early life ([&ge;]50g m-3) was associated with lower childhood cognitive ability, which, in turn, increased the risk of all-cause mortality and mediated 25% of the total associations. ConclusionsIn our life-course study with 75-year of continuous mortality records, we found that exposure to air pollution in early life was associated with higher mortality in late adulthood, and that childhood cognitive ability partly mediated this relationship. Findings suggest that past air pollution concentrations will likely impact health and longevity for decades to come. HIGHLIGHTSO_LIWe explored PM2.5 at age 3 and mortality between age 11 and 86 in a Scottish cohort C_LIO_LIPM2.5 increased the risk of all-cause mortality, especially between the age of 65 and 86 C_LIO_LIChildhood cognitive ability mediated 25% of the total association C_LIO_LIAssociations were prominent for (lung) cancer mortality, especially among females C_LIO_LIAir pollution in early life may affect health and longevity across the life course C_LI