Human molybdenum exposure risk in industrial regions of China: New critical effect indicators and reference dose.

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.

Exposure to synthesized tribromobisphenol A and critical effects: Metabolic pathways, disease signature, and benchmark dose derivation.

2,2',6-Tribromobisphenol A (Tri-BBPA), the main debrominated congener of tetrabromobisphenol A (TBBPA), is ubiquitous in the environment and human body but with unknown toxicity. Tri-BBPA was synthesized and applied to investigate its sub-chronic exposure effects on 28 organ coefficients and clinical health indicators related to liver function, kidney function, and cardiovascular system function in female mice. Results showed that the liver was the targeted organ of Tri-BBPA exposure. Compared to the control group, the changes in liver coefficient, cholinesterase, total protein, albumin, γ-glutamyl transpeptidase, lactate dehydrogenase, and creatine kinase levels ranged from -61.2 % to 35.5 % in the high-exposed group. Creatine kinase was identified as a critical effect indicator of Tri-BBPA exposure. Using the Bayesian benchmark dose derivation method, a lower reference dose than TBBPA was established for Tri-BBPA (10.6 µg/kg-day). Serum metabolomics revealed that Tri-BBPA exposure may primarily damage the liver by disrupting tryptophan metabolism related to L-alanine, tryptamine, 5-hydroxyindoleacetic acid, and 5-methoxyindoleacetate in liver cells and leading to liver dysfunction. Notably, epilepsy, schizophrenia, early preeclampsia, and late-onset preeclampsia were the top six enriched diseases, suggesting that the nervous system may be particularly affected by Tri-BBPA exposure. Our findings hinted a non-negligible health risk of exposure to debrominated products of TBBPA.

Perturbation of lipid metabolism in 3T3-L1 at different stages of preadipocyte differentiation and new insights into the association between changed metabolites and adipogenesis promoted by TBBPA or TBBPS.

Tetrabromobisphenol A (TBBPA) and tetrabromobisphenol S (TBBPS) are widely distributed brominated flame retardants. While TBBPA has been demonstrated to stimulate adipogenesis, TBBPS is also under suspicion for potentially inducing comparable effects. In this study, we conducted a non-targeted metabolomics to examine the metabolic changes in 3T3-L1 cells exposed to an environmentally relevant dose of TBBPA or TBBPS. Our findings revealed that 0.1 µM of both TBBPA and TBBPS promoted the adipogenesis of 3T3-L1 preadipocytes. Multivariate analysis showed significant increases in glycerophospholipids, sphingolipids, and steroids relative levels in 3T3-L1 cells exposed to TBBPA or TBBPS at the final stage of preadipocyte differentiation. Metabolites set composed of glycerophospholipids was found to be highly effective predictors of adipogenesis in 3T3-L1 cells exposed to TBBPA or TBBPS (revealed from the receiver operating characteristic curve with an area under curve > 0.90). The results from metabolite set enrichment analysis suggested both TBBPA and TBBPS exposures significantly perturbed steroid biosynthesis in adipocytes. Moreover, TBBPS additionally disrupted the sphingolipid metabolism in the adipocytes. Our study presents new insights into the obesogenic effects of TBBPS and provides valuable information about the metabolites associated with adipogenesis induced by TBBPA or TBBPS.

Construction of Models To Predict the Effectiveness of E-Waste Control through Capture of Volatile Organic Compounds and Metals/Metalloids Exposure Fingerprints: A Six-Year Longitudinal Study.

The significant health implications of e-waste toxicants have triggered the global tightening of regulation on informal e-waste recycling sites (ER) but with disparate governance that requires effective monitoring. Taking advantage of the opportunity to implement e-waste control in the Guiyu ER since 2015, we investigated the temporal variations in levels of oxidative DNA damage, 25 volatile organic compound metabolites (VOCs), and 16 metals/metalloids (MeTs) in urine in 918 children between 2016 and 2021 to demonstrate the effectiveness of e-waste control in reducing population exposure risks. The hazard quotients of most MeTs and levels of 8-hydroxy-2'-deoxyguanosine in children decreased significantly during this time, indicating that e-waste control effectively reduces the noncarcinogenic risks of MeT exposure and levels of oxidative DNA damage. Using mVOC-derived indexes as a feature, a bagging-support vector machine algorithm-based machine learning model was constructed to predict the extent of e-waste pollution (EWP). The model exhibited excellent performance with accuracies >97.0% in differentiating between slight and severe EWP. Five simple functions established using mVOC-derived indexes also had high accuracy in predicting the presence of EWP. These models and functions provide a novel human exposure monitoring-based approach for assessing e-waste governance or the presence of EWP in other ERs.

Why Do People Gain Belly Fat in Rural Areas? A Study of Urinary Metal(loid)s and Abdominal Obesity in China.

Obesity is prevalent in rural areas of China, and there are inconsistent findings regarding the association between metal(loid) exposure and the risk of obesity. Abdominal obesity (AOB), which reflects visceral fat abnormity, is a crucial factor in studying obesity-related diseases. We conducted a study measuring 20 urinary metal(loid)s, 13 health indicators, and the waist circumference (WC) in 1849 participants from 10 rural areas of China to investigate their relationships. In the single exposure models, we found that urinary chromium (Cr) was significantly associated with the odds of having AOB [adjusted odds ratio (OR) = 1.81 (95% confidence interval (CI): 1.24, 2.60)]. In the mixture exposure models, urinary Cr consistently emerged as the top contributor to AOB, while the overall effect of mixed metal(loid)s was positive toward the odds of having AOB [adjusted OR: 1.33 (95% CI: 1.00, 1.77)], as revealed from the quantile g-computation model. After adjusting for the effects of other metal(loid)s, we found that the elevation of apolipoprotein B and systolic blood pressure significantly mediated the association between urinary Cr and the odds of having AOB by 9.7 and 19.4%, respectively. Our results suggest that exposure to metal(loid)s is a key factor contributing to the prevalence of AOB and WC gain in rural areas of China.

Volatile organic compounds and metals/metalloids exposure in children after e-waste control: Implications for priority control pollutants and exposure mitigation measures.

The decade-long effort to control e-waste in China has made significant progress from haphazard disposal to organized recycling, but environmental research suggests that exposure to volatile organic compounds (VOCs) and metals/metalloids (MeTs) still poses plausible health risks. To investigate the exposure risk faced by children and identify corresponding priority control chemicals, we evaluated the carcinogenic risk (CR), non-CR, and oxidative DNA damage risks of VOCs and MeTs exposure in 673 children from an e-waste recycling area (ER) by measuring urinary exposure biomarker levels. The ER children were generally exposed to high levels of VOCs and MeTs. We observed distinctive VOCs exposure profiles in ER children. In particular, the 1,2-dichloroethane/ethylbenzene ratio and 1,2-dichloroethane were promising diagnostic indexes for identifying e-waste pollution due to their high accuracy (91.4%) in predicting e-waste exposure. Exposure to acrolein, benzene, 1,3-butadiene, 1,2-dichloroethane, acrylamide, acrylonitrile, arsenic, vanadium, copper, and lead posed considerable CR or/and non-CR and oxidative DNA damage risks to children, while changing personal lifestyles, especially enhancing daily physical exercise, may facilitate mitigating these chemical exposure risks. These findings highlight that the exposure risk of some VOCs and MeTs is still non-negligible in regulated ER, and these hazardous chemicals should be controlled as priorities.

Co-exposure levels of volatile organic compounds and metals/metalloids in children: Implications for E-waste recycling activity prediction.

Identifying informal e-waste recycling activity is crucial for preventing health hazards caused by e-waste pollution. This study attempted to build a prediction model for e-waste recycling activity based on the differential exposure biomarkers of the populations between the e-waste recycling area (ER) and non-ER. This study recruited children in ER and non-ER and conducted a quasi-experiment among the adult investigators to screen differential exposure or effect biomarkers by measuring urinary 25 volatile organic compound (VOC) metabolites, 18 metals/metalloids, and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Compared with children of the non-ER, the ER children had higher metal/metalloid (e.g., manganese [Mn], lead [Pb], antimony [Sb], tin [Sn], and copper [Cu]) and VOC exposure (e.g., carbon-disulfide, acrolein, and 1-bromopropane) levels, oxidative DNA damage, and non-carcinogenic risks. Individually added 8-OHdG, VOC metabolites, and metals/metalloids to the support vector machine (SVM) classifier could obtain similar classification effects, with the area under curve (AUC) ranging from 0.741 to 0.819. The combined inclusion of 8-OHdG and differential VOC metabolites, metals/metalloids, and mixed indexes (e.g., product items or ratios of different metals/metalloids) in the SVM classifier showed the highest performance in predicting e-waste recycling activity, with an AUC of 0.914 and prediction accuracy of 83.3 %. "Sb × Mn", followed by "Sn × Pb/Cu", "Sb × Mn/Cu", and "Sn × Pb", were the top four important features in the models. Compared with non-ER children, the levels of urinary Mn, Pb, Sb, Sn, and Cu in ER children were 1.2 to 2.4 times higher, while the levels of "Sb × Mn", "Sn × Pb/Cu", "Sb × Mn/Cu", and "Sn × Pb" were 3.5 to 4.7 times higher, suggesting that these mixed indexes could amplify the differences between e-waste exposed and non-e-waste exposed populations. With the continued inclusion of new biomarkers of e-waste pollution in the future, our prediction model is promising for screening informal e-waste recycling sites.

Associations between trace level thallium and multiple health effects in rural areas: Chinese Exposure and Response Mapping Program (CERMP).

Thallium (Tl) is a cumulative high toxicant in the environment, but few studies have investigated the comprehensive health effects underlying chronic Tl exposure at trace levels. This study aims to evaluate the liver, kidney, lung and other potential health effects associated with chronic Tl exposure at trace levels in rural areas of China. Urinary Tl concentrations of 2883 adults from rural areas of 12 provinces in China were measured and 2363 participants were involved in the final analysis. Indicators of liver and kidney functions in the serum, as well as the lung function indicators, were determined in the participants. General linear regression and restricted cubic spline regression were combined to study the associations between urinary Tl and health indicators or outcomes. In this study, the detected rate of Tl in the urine of the participants was 97.28 %. When the urinary Tl concentration was ranged at the fourth quintile, the risk of having liver function disorder was 70 % higher [Odds ratio (OR) = 1.70 (95 % confidence intervals (CI): 1.30, 2.22)] in all the participants, whereas the farmers were more likely to have the disorder [OR = 2.08 (95 % CI: 1.49, 2.92)] than the non-farmers [OR = 1.20 (95 % CI: 0.77, 1.88)]. Nonlinear associations between most of the liver health indicators and urinary Tl were identified, of which serum bilirubin was strongly associated with the elevation of urinary Tl when its concentration was >0.40 µg/g creatinine. Besides, urinary Tl was negatively associated with lung health indicators. Our study proposes the safety re-assessment of the current exposure level of Tl in the environment, especially in rural areas of China.