Trihalomethanes in global drinking water: Distributions, risk assessments, and attributable disease burden of bladder cancer.

This study aimed to assess the global spatiotemporal variations of trihalomethanes (THMs) in drinking water, evaluate their cancer and non-cancer risks, and THM-attributable bladder cancer burden. THM concentrations in drinking water around fifty years on a global scale were integrated. Health risks were assessed using Monte Carlo simulations and attributable bladder cancer burden was estimated by comparative risk assessment methodology. The results showed that global mean THM concentrations in drinking water significantly decreased from 78.37 µg/L (1973-1983) to 51.99 µg/L (1984-2004) and to 21.90 µg/L (after 2004). The lifestage-integrative cancer risk and hazard index of THMs through all exposure pathways were acceptable with the average level of 6.45 × 10-5 and 7.63 × 10-2, respectively. The global attributable disability adjusted of life years (DALYs) and the age-standardized DALYs rate (ASDR) dropped by 16% and 56% from 1990-1994 to 2015-2019, respectively. A big decline in the attributable ASDR was observed in the United Kingdom (62%) and the United States (27%), while China experienced a nearly 3-fold increase due to the expanded water supply coverage and increased life expectancy. However, China also benefited from the spread of chlorination, which helped reduce nearly 90% of unsafe-water-caused mortality from 1998 to 2018.

Associations between maternal urinary rare earth elements during pregnancy and birth weight-for-gestational age: Roles of cord blood vitamin D levels.

Prenatal exposure to rare earth elements (REEs) may contribute to adverse birth outcomes in previous studies. Cord blood vitamin D has been suggested to modify or mediate the effects of environmental exposures. However, none has investigated these roles of cord blood vitamin D in the associations of prenatal exposure to REEs with fetal growth. Maternal trimester-specific urinary concentrations of 13 REEs, cord blood total 25-hydroxyvitamin D at delivery, and birth weight (BW)-for-gestational age (GA) were determined in 710 mother-newborn pairs from Wuhan, China. Higher maternal average urinary concentrations of europium (Eu), gadolinium (Gd), dysprosium (Dy), holmium (Ho), erbium (Er), and ytterbium (Yb) across three trimesters, either individually or jointly, were significantly associated with lower BW-for-GA Z-scores and higher odds of small for gestational age (SGA) [ß = -0.092; 95 % confidence interval (CI): -0.149, -0.035 for BW-for-GA Z-scores, and odds ratio = 1.60; 95 % CI: 1.14, 2.24 for SGA involved in each unit increase in weighted quantile sum index of REEs mixture]. When stratified by cord blood vitamin D levels, the associations mentioned above persisted in participants with relatively low vitamin D levels (<13.94 µg/L, the first tertile of distribution), but not among those with relatively high levels (≥13.94 µg/L) (all p-values for interaction < 0.05). The mediation analyses taking account of exposure-mediator interaction showed that the relationships between REEs (as individual and mixture) exposure and lower BW-for-GA were partly mediated through decreasing cord blood vitamin D levels. The proportions mediated by cord blood vitamin D levels were 24.48 % for BW-for-GA Z-scores and 29.05 % for SGA corresponding to the REEs mixture exposure. Conclusively, our study revealed that prenatal exposures to Eu, Gd, Dy, Ho, Er, and Yb were related to fetal growth restriction. Cord blood vitamin D might alleviate toxic effects of these REEs and its reduction might partly mediate REE-induced fetal growth restriction.

Prenatal exposure to benzotriazoles and benzothiazoles and child neurodevelopment: A longitudinal study.

Benzotriazoles (BTRs) and benzothiazoles (BTHs) are emerging benzo-heterocyclic compounds that may induce neurotoxicity. However, the effect of prenatal exposure to BTs (BTRs and BTHs) on child neurodevelopment has not been elucidated. We aimed to explore the associations between maternal urinary concentrations of BTs in single or in mixture with child neurodevelopment at the age of two. This study recruited 513 mother-child pairs based on a birth cohort from 2014 to 2015 in Wuhan. Maternal urinary concentrations of eight BTs (four BTRs and four BTHs) in the first, second, and third trimesters were measured. The mental development index (MDI) and psychomotor development index (PDI) of children, as two indexes of neurodevelopment, were assessed at two years old by the Bayley Scales. In the analyses of single BTs, prenatal average tolyltriazole (TTR) exposure level was associated with decreased boys' MDI scores (ß = -2.84, 95 % CI: -5.11, -0.57) and prenatal average 1-H-benzotriazole (1-H-BTR) exposure level was associated with decreased boys' PDI scores (ß = -1.44, 95 % CI: -2.70, -0.17), respectively. Maternal urinary concentrations of benzothiazole (BTH) in the 1st trimester (ß = -1.79, 95 % CI: -2.78, -0.80), 2nd trimester (ß = -1.14, 95 % CI: -2.19, -0.09), and the prenatal average exposure (ß = -2.15, 95 % CI: -3.69, -0.61) were also negatively associated with boys' PDI scores. However, no significantly negative association was observed among girls. In the further mixture analysis, the quantile g-computation model found a significant negative association between prenatal average concentrations of BTs in mixture and boys' PDI scores [ß = -4.80 (95 % CI: -9.08, -0.52)], and BTH weighted the highest in the negative association. As far as we know, this is the first research to estimate the effect of prenatal exposure to BTs on child neurodevelopment. The findings showed that prenatal exposure to BTs was negatively associated with neurodevelopment among boys, suggesting that the associations may be modified by infant sex.

Phthalate Exposure, PPARα Variants, and Neurocognitive Development of Children at Two Years.

Background: The PPARα gene may be crucial to the neurotoxic effect of phthalates. However, epidemiological studies considering the neurodevelopmental influence of phthalates interacting with genetic susceptibility are limited. We hypothesized phthalates could interact with the PPARα gene, synergistically affecting neurocognitive development. Methods: A total of 961 mother-infant pairs were involved in this study. The concentrations of phthalate metabolites in maternal urine during pregnancy were detected. Children's neurocognitive development was estimated with the Bailey Infant Development Inventory (BSID). Genetic variations in PPARα were genotyped with the Illumina Asian Screening Array. We applied generalized linear regression models to estimate genotypes and phthalate metabolites' association with children's neurocognitive development. Results: After adjusting for potential confounders, the mono-n-butyl phthalate (MnBP) concentration was negatively associated with Psychomotor Development Index (PDI) (ß = -0.86, 95% CI: -1.67, -0.04). The associations between MnBP and neurocognitive development might be modified by PPARα rs1800246. Compared with low-MnBP individuals carrying rs1800246 GG genotypes, high-MnBP individuals with the AG + AA genotype had a higher risk of neurocognitive developmental delay, with the odds ratio of 2.76 (95% CI:1.14, 6.24). Conclusions: Our current study revealed that prenatal exposure to MnBP was negatively correlated with children's neurocognitive development, and PPARα rs1800246 might modify the association.

Associations of urine metals and metal mixtures during pregnancy with cord serum vitamin D Levels: A prospective cohort study with repeated measurements of maternal urinary metal concentrations.

BACKGROUND: Vitamin D deficiency has been associated with the increased risk of many diseases, especially during early life. Exposure to some toxic metals may decrease vitamin D levels in adults and children in previous studies. However, less is known about the associations of maternal metals exposure during pregnancy with newborns' vitamin D status. OBJECTIVE: We conducted a prospective cohort study to investigate the relationships between urine metals and metal mixtures during pregnancy and newborns' vitamin D status. METHODS: Urine samples of 598 pregnant women were collected in each trimester and cord blood samples of newborns were collected at delivery. The concentrations of 20 metals in urine and 25-hydroxyvitamin D [25(OH)D] in cord serum were quantified. Generalized linear models were used to estimate the associations between individual metals and cord serum total 25(OH)D. We applied Bayesian Kernel Machine Regression (BKMR) to evaluate the mixture and interaction effects of urine metals. RESULTS: In individual metals analyses, we reported that a double increase in urine vanadium (V), cobalt (Co), and thallium (Tl) throughout pregnancy was associated with a 9.91% [95% confidence interval (CI): -18.58%, -0.30%], 11.42% (95% CI: -17.73%, -4.63%), and 12.64% (95% CI: -21.44%, -2.86%) decrease in cord serum total 25(OH)D, respectively. Exposures to the three metals during the whole pregnancy were also correlated to increased odds for newborns' vitamin D deficiency (<20 ng/mL) [odds ratio (95% CI): 1.80 (1.05, 3.10) for V, 1.88 (1.25, 2.82) for Co, and 1.90 (1.07, 3.38) for Tl]. BKMR analyses revealed a negative influence of metal mixtures (V+Co+Tl) on neonatal vitamin D status, as well as potential synergism between V and Co and between V and Tl. CONCLUSIONS: Our study provides evidence of negative impacts of maternal exposure to V, Co, and Tl during pregnancy on cord serum vitamin D levels at delivery. Potential synergism between V and Co and between V and Tl existed in their associations with cord serum total 25(OH)D.

Fine particulate matter exposure and perturbation of serum metabolome: A longitudinal study in Baoding, China.

Metabolomics represents a powerful tool for measuring environmental exposures and biological responses to unveil potential mechanisms. Few studies have investigated the effects of exposure to fine particulate matter (PM2.5) longitudinally on serum metabolomics in regions with high-level PM2.5. Therefore, we examined the changes of serum metabolomics corresponding to individual PM2.5 exposure levels in spring and autumn among 63 healthy college students in Baoding city, Hebei, China. The metabolic profiling was determined by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The average level of individual PM2.5 in the spring was 1.82-fold higher than in the autumn (240 µg/m3 vs 132 µg/m3). Males were exposed to a higher level of PM2.5 than females in the spring. Metabolic profiling was clearly separated by orthogonal partial least square-discriminant analysis in males but not in females. In the analysis of the associations between the metabolome and PM2.5 of the two seasons, the changes of 14 serum metabolites were significantly associated with PM2.5 in males. The metabolites related to heme metabolism (bilirubin, biliverdin), energy metabolism and oxidative stress (2-Octenoylcarnitine, N-Heptanoylglycine, and acetylcysteine), phospholipid metabolism (lysophosphatidic acid, phospholipid acid, and lysophosphatidylethanolamine), and tryptophan metabolism (N-Acetylserotonin, indolepyruvate, and melatonin) were decreased in the range of 2.16%-6.80% for each 10 µg/m3 increase of PM2.5, while thyrotropin-releasing hormone, glutathione, and phosphatidylethanolamine related to energy metabolism and oxidative stress, and phospholipid metabolism were increased in the range of 2.95%-4.90% for each 10 µg/m3 increase of PM2.5. This longitudinal study suggests that higher PM2.5 exposure may induce perturbations in serum metabolic signaling related to oxidative stress and inflammation, and males may be more prone to these metabolic perturbations.