An exposome atlas of serum reveals the risk of chronic diseases in the Chinese population.

Although adverse environmental exposures are considered a major cause of chronic diseases, current studies provide limited information on real-world chemical exposures and related risks. For this study, we collected serum samples from 5696 healthy people and patients, including those with 12 chronic diseases, in China and completed serum biomonitoring including 267 chemicals via gas and liquid chromatography-tandem mass spectrometry. Seventy-four highly frequently detected exposures were used for exposure characterization and risk analysis. The results show that region is the most critical factor influencing human exposure levels, followed by age. Organochlorine pesticides and perfluoroalkyl substances are associated with multiple chronic diseases, and some of them exceed safe ranges. Multi-exposure models reveal significant risk effects of exposure on hyperlipidemia, metabolic syndrome and hyperuricemia. Overall, this study provides a comprehensive human serum exposome atlas and disease risk information, which can guide subsequent in-depth cause-and-effect studies between environmental exposures and human health.

[Exposure characteristics and health risk assessment of 97 typical chemical pollutants in human serum].

Rapid industrial and agricultural developments in China have led to the wide use and discharge of chemical products and pesticides, resulting in extensive residues in environmental media. These residues can enter the human body through various pathways, leading to high exposure risks and health hazards. Because the human body is exposed to a variety of chemical pollutants, accurately quantifying the exposure levels of these pollutants in the human body and evaluating their health risks are of great importance. In this study, the serum concentrations of 97 typical chemical pollutants of 60 adults in central China were simultaneously determined using solid-phase extraction coupled with gas chromatography-tandem mass spectrometry (SPE-GC-MS/MS). In this method, 200 µL of a serum sample was mixed with 10 µL of an isotope-labeled internal standard solution. The sample was vortexed and refrigerated overnight at 4 ℃. Each sample was then deproteinized by the addition of 200 µL of 15% formic acid aqueous solution and vortexed. The serum sample was loaded into a preconditioned Oasis® PRiME HLB SPE cartridge and rinsed with 3 mL of methanol-water (6∶1, v/v). The SPE cartridge was subsequently vacuumed. The analytes were eluted with 3 mL of dichloromethane followed by 3 mL of n-hexane. The eluent was concentrated to near dryness under a gentle nitrogen stream and reconstituted with 100 µL of acetone. The samples were determined by GC-MS/MS and separated on a DB-5MS capillary column (30 m×0.25 mm×0.25 µm) with temperature programming. The column temperature was maintained at 70 ℃ for 2 min, increased at a rate of 25 ℃/min to 150 ℃, increased at a rate of 3 ℃/min to 200 ℃, and then held for 2 min. Finally, the column temperature was increased at a rate of 8 ℃/min to 300 ℃ and maintained at this temperature for 8 min. The samples were detected in multiple-reaction monitoring (MRM) mode and quantitatively analyzed using the internal standard method. Multiple linear regression models were used to analyze the effects of demographic characteristics, lifestyle habits, and diet on the concentrations of the chemical pollutants in the serum samples, and known biomonitoring equivalents (BEs) and human biomonitoring (HBM) values were combined to compute hazard quotients (HQs) and hazard indices (HIs) and evaluate the health risks of single and cumulative exposures to the chemical pollutants. The results showed that the main pollutants detected in human serum were organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). The detection rates of eight pollutants, including hexachlorobenzene (HCB) (100%), pentachlorophenol (PCP) (100%), p,p'-dichlorodiphenylene (p,p'-DDE) (100%), PCB-138 (100%), PCB-153 (98.3%), ß-hexachlorocyclohexane (ß-HCH) (91.7%), fluorene (Flu) (85.0%), and anthracene (Ant) (75.0%), were greater than 70%. The serum levels of ß-HCH were higher in females than in males, and age was positively correlated with exposure to p,p'-DDE, PCB-138, PCB-153, and ß-HCH. Increased exposure levels to p,p'-DDE and ß-HCH may be associated with a high frequency of meat intake, whereas increased exposure level to PCP may be associated with a high frequency of vegetable intake. The serum HQ of PCP was greater than 1 in 6.7% of the samples, and no risk was observed for HCB and p,p'-DDE exposure in the study population. Approximately 28.3% of the study subjects had HI values greater than 1. Overall, the general adult population in this region is widely exposed to a wide range of chemical pollutants, and gender, age, and diet are likely to be the main factors influencing the concentration of chemical pollutants. The health risk of single and compound exposures to chemical pollutants should not be ignored.

Prenatal exposure to organophosphate esters and growth trajectory in early childhood.

Maternal exposure to organophosphate esters (OPEs) has been linked to an increased risk of adverse birth outcomes. However, the impact of OPEs on childhood growth remains uncertain. This study assessed the associations between prenatal concentrations of OPE metabolites and the growth trajectory in early childhood. 212 singleton pregnant women were included in this study, and they were recruited between August 2014 and August 2016 in Wuhan, China. We measured the urinary concentrations of OPE metabolites during the 1st, 2nd, and 3rd trimesters. Standard deviation scores for weight and length were calculated for children at birth, 1, 6, 12, and 24 months. Trajectories of weight-for-age z-score (WAZ) and weight-for-length z-score (WLZ) were classified into four groups using group-based trajectory modeling. Trajectories of length-for-age z-score (LAZ) were classified into three groups with the same model. Then, we calculated odds ratios (ORs) and 95 % confidence interval (95%CI) using multinomial logistic regression to estimate increases in odds of different growth trajectories per doubling in OPE concentrations compared with moderate-stable trajectory. For average concentrations of OPE metabolites and growth trajectory, our results indicated that higher bis(2-butoxyethyl) phosphate, total aromatic OPE metabolites, and total OPE metabolites during pregnancy were associated with a higher likelihood of children falling into the low-stable and low-rising WAZ trajectory. Furthermore, compared to the moderate-stable LAZ trajectory, increased concentrations of 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate were linked to an elevated risk of a low-stable LAZ trajectory. Additionally, the 1st and 2nd trimesters may represent critical windows of heightened vulnerability to the effects of OPE metabolites on childhood growth. In conclusion, our study proves that prenatal exposure to OPE metabolites is inversely related to childhood growth. It is essential to conduct further research involving larger populations and to consider other compounds with known developmental toxicity to obtain more reliable and comprehensive results.

Associations of polychlorinated biphenyl and organochlorine pesticide exposure with hyperuricemia: modification by lifestyle factors.

Recent research has reported positive associations of exposure to polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) with hyperuricemia. However, most of these studies have primarily focused on the individual effects of PCB/OCP exposure. We aimed to explore the associations of both individual and combined PCB/OCP exposure with hyperuricemia and examine whether such associations could be modified by lifestyle factors. The cross-sectional study recruited 2032 adults between March and May 2019 in Wuhan, China. Logistic regression and weighted quantile sum (WQS) regression were applied to explore the relationship of individual and combined PCB/OCP exposure with hyperuricemia, while considering the modified effects of lifestyle factors. Of the 2032 participants, 522 (25.7%) had hyperuricemia. Compared with the non-detected group, the detected groups of PCB153 and PCB180 exhibited a positive association with hyperuricemia, with OR (95% CIs) of 1.52 (1.22, 1.91) and 1.51 (1.20, 1.90), respectively. WQS regression showed that PCB/OCP mixture was positively associated with hyperuricemia (OR: 1.31, 95% CI: 1.08, 1.58). PCB153/PCB180 exposure, combined with an unhealthy lifestyle, has a significant additive effect on hyperuricemia. Overall, PCB/OCP mixture and individual PCB153/PCB180 exposure were positively associated with hyperuricemia. Adherence to a healthy lifestyle may modify the potential negative impact of PCBs/OCPs on hyperuricemia.

Crosstalk between Breast Milk N-Acetylneuraminic Acid and Infant Growth in a Gut Microbiota-Dependent Manner.

The healthy growth of infants during early life is associated with lifelong consequences. Breastfeeding has positive impacts on reducing obesity risk, which is likely due to the varied components of breast milk, such as N-acetylneuraminic acid (Neu5Ac). However, the effect of breast milk Neu5Ac on infant growth has not been well studied. In this study, targeted metabolomic and metagenomic analyses were performed to illustrate the association between breast milk Neu5Ac and infant growth. Results demonstrated that Neu5Ac was significantly abundant in breast milk from infants with low obesity risk in two independent Chinese cohorts. Neu5Ac from breast milk altered infant gut microbiota and bile acid metabolism, resulting in a distinct fecal bile acid profile in the high-Neu5Ac group, which was characterized by reduced levels of primary bile acids and elevated levels of secondary bile acids. Taurodeoxycholic acid 3-sulfate and taurochenodeoxycholic acid 3-sulfate were correlated with high breast milk Neu5Ac and low obesity risk in infants, and their associations with healthy growth were reproduced in mice colonized with infant-derived microbiota. Parabacteroides might be linked to bile acid metabolism and act as a mediator between Neu5Ac and infant growth. These results showed the gut microbiota-dependent crosstalk between breast milk Neu5Ac and infant growth.

Individual and mixtures of polychlorinated biphenyls and organochlorine pesticides exposure in relation to metabolic syndrome among Chinese adults.

Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) are commonly detected in humans due to their persistence and bioaccumulation, and are suspected risk factors for metabolic syndrome (MetS). However, most studies have focused on individual rather than combined exposure. We explored the associations between individual and combined PCBs/OCPs exposure and MetS to better assess the health effects of PCBs and OCPs. This cross-sectional study included 1996 adults from Wuhan, China. A total of 338 participants fulfilled criteria for MetS. Eight PCBs and OCPs were detected in >50 % of the samples. Most of the hexachlorocyclohexanes (HCHs) in the serum were derived from the recent environmental input of lindane, while the high levels of dichlorodiphenyltrichloroethane (DDTs) were mainly due to historical use. Multivariate linear regression analyses revealed that ß-HCH, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), PCB-52, PCB-153, and PCB-180 were positively correlated with increased odds of MetS. The profiles of the PCBs and OCPs associated with the different components of MetS were distinct. Furthermore, quantile-based g computation (qgcomp) analyses showed that PCB and OCP mixtures were positively associated with the risk of MetS, and p,p'-DDE was the largest contributor to our model. These findings suggest that PCB and OCP concentrations, both individually and as mixtures, are associated with MetS risk. Prospective studies are needed to confirm these results.

The association between organophosphate esters exposure and body mass index in children and adolescents: The mediating effect of sex hormones.

Organophosphate esters (OPEs), used as flame retardants and plasticizers, have been indicated to impair growth and development in toxicological studies, but current epidemiological data on their associations with body mass index (BMI) are limited and the underlying biological mechanisms remain unclear. In this study, we aim to explore the association of OPE metabolites with BMI z-score, and assess whether sex hormones mediate the relationships between OPE exposure and BMI z-score. We measured weight and height, and determined OPE metabolites in spot urine samples and sex hormones in serum samples among 1156 children and adolescents aged 6-18 years in Liuzhou city, China. The results showed that di-o-cresyl phosphate and di-pcresyl phosphate (DoCP & DpCP) levels were associated with lower BMI z-score of all participants and a similar pattern of associations were presented in prepubertal boys stratified by sex-puberty groups and male children stratified by sex-age groups. In addition, sex hormone binding globulin (SHBG) were related to reduced BMI z-score among all subgroups including prepubertal boys, prepubertal girls, pubertal boys, and pubertal girls (all Ptrend<0.05). We also found that DoCP & DpCP showed positive associations with SHBG among prepubertal boys. Mediation analysis further showed that SHBG mediated 35.0% of the association between DoCP & DpCP and reduced BMI z-score in prepubertal boys. Our results indicated that OPEs may impair growth and development by disrupting the sex hormones in prepubertal boys.

Independent and combined effects of exposure to organophosphate esters on thyroid hormones in children and adolescents.

Toxicological studies suggest that organophosphate esters (OPEs) may impair thyroid function. Epidemiological evidence, related to children and adolescents, has not been reported, and little is known about the combined effects of exposure to OPE mixtures. In this study, we collected information of 1156 children and adolescents (aged 6-18 years, 48.4% males) from a cross-sectional study in Liuzhou, China, and measured the levels of 15 urinary OPE metabolites and 5 serum thyroid hormones. Multivariate linear regression and quantile g-computation (QGC) approach were used to examine the associations which adjusted for demographic and lifestyle characteristics. Few participants had levels of triiodothyronine (T3) and free thyroxine (FT4) outside age-specific pediatric ranges. QGC analyses showed that individuals in the second, third, and fourth quartiles (Q2-Q4) of exposure had 3.93% (2.14%, 5.75%), 8.01% (4.32%, 11.8%), and 12.3% (6.54%, 18.3%) higher T3 than those in the first quartile (Q1), with similar pattern for free triiodothyronine (FT3). Individuals in Q2 and Q3 had higher thyroid-stimulating hormone (TSH) than those in Q1, but no differences were observed in TSH between Q1-Q4. In contrast, compared to the lowest quartile, FT4 was lower for those in Q2 (- 1.54%; 95% CI: - 3.02%, -0.04%), Q3 (-3.07%; 95% CI: -5.95%, -0.09%), and Q4 (-4.56%; 95% CI: - 8.80%, - 0.13%). These associations were consistent with the results from multivariate linear regression. When stratified by sex, OPE exposure (individual or mixtures) was associated with increased T3 and FT3 in males and decreased FT4 in females. This study provides the first evidence to characterize the thyroid-disrupting effects of OPE exposure in children and adolescents.

Urinary concentrations of organophosphate esters in relation to semen quality: A cross-sectional study.

Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers in consumer products. Toxicological studies have indicated that OPEs may affect male reproductive health, but human evidence is inconclusive. In this study, we explored associations of individual and mixtures of OPE exposure with semen quality among 1015 Chinese men from an infertility clinic. After adjusting for potential confounders, we observed that higher diphenyl phosphate (DPHP) and [Bis(2-methylphenyl) phosphate (BMPP)] exposure was associated with increased odds ratios (ORs) of having below-reference total sperm count. Higher bis (2-butoxyethyl) phosphate (BBOEP) exposure was associated with increased ORs of having below-reference progressive motility and total motility. For semen quality parameters modeled as continuous outcomes, inverse associations with individual OPE were still observed. In addition, urinary 1-hydroxy-2-propyl bis (1-chloro-2-propyl) phosphate (BCIPHIPP) concentrations were inversely associated with the percentage of normal morphology while positively associated with the percentage of abnormal heads. Quantile g-computation regression analyses showed that exposure to higher OPE mixtures was associated with lower total sperm motility and normal morphology. Our results indicated that both individual and mixtures of OPE exposure were associated with reduced semen quality.

Effect of Breastmilk Microbiota and Sialylated Oligosaccharides on the Colonization of Infant Gut Microbial Community and Fecal Metabolome.

The complex microbiota and sialylated oligosaccharides in breastmilk are important bioactive components that affect the gut microbiota. However, the effect of breastmilk microbiota and sialylated oligosaccharides on the gut microbiota during the neonatal period has been largely overlooked. Here, 16S rRNA gene sequencing and metabolomics analysis were applied to the breastmilk and feces of 69 newborns to clarify the link between breastmilk components and the newborn gut. Results showed that Staphylococcus, Enterococcus, and Bacteroides were commonly shared and positively correlated between breastmilk and the neonatal intestine and they were the main bacteria of breastmilk that interacted with the newborn fecal metabolome. Breastmilk Staphylococcus mainly interacted with amino acids, whereas Bacteroides was involved in the tryptophan, nucleotide, and vitamin metabolism. Breastmilk sialylated oligosaccharides were related to Bacteroides and amino acids of the newborn fecal metabolites. Moreover, Bacteroides was related to the interaction between breastmilk 3'-sialyllactose and newborn fecal metabolites in the mediation effect models. Finally, we pointed out that breastmilk Bacteroides was important in the milk-gut interaction, and it was negatively associated with waist circumference in infants aged 1 year. Our study provides a scientific basis for understanding the role of breastmilk in the development of newborn gut microbiota and metabolome.

Accumulative levels, temporal and spatial distribution of common chemical pollutants in the blood of Chinese adults.

China has been in a rapid development period in recent decades, the mass production and use of chemical industrial products and pesticides have resulted in a large amount of pollutants in the environment. These pollutants enter the human body through environmental exposure and dietary intake, causing adverse health effects. Although many of them have been banned and restricted in the production and use in China, these pollutants still remain in the human body due to their high persistence and strong bioaccumulation. In this review, we aim to reveal the accumulation levels and profiles, as well as the temporal and spatial distribution of common chemical pollutants including chlorinated paraffins (CPs), polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers, organophosphorus flame retardants (OPFRs), new halogenated flame retardants (NHFRs), polychlorinated biphenyls, phthalic acid esters, perfluorinated compounds, bisphenols, organophosphorus pesticides and pyrethroid insecticides in the blood (including whole blood, serum and plasma) of Chinese adults by extracting 93 related studies published from 1990 to 2021. Results have shown that CPs, OCPs and PAHs were the main pollutants in China, the levels of short-chain chlorinated paraffin, p,p'-DDE and phenanthrene in blood even reached 11,060.58, 740.41 and 498.28 ng/g lipid respectively. Under the strict control of pollutants in China, the levels of most pollutants have been on a downward trend except for perfluoro octanoate and perfluoro nonanoate. Besides, OPFRs, NHFRs and PAHs may have a potential upward trend, requiring further research and observation. As for spatial distribution, East China (Bohai Bay and Yangtze River Delta) and South China (Pearl River Delta) were the major polluted regions due to their fast development of industry and agriculture.

Development of magnetic molecularly imprinted solid-phase extraction and ultra-high performance liquid chromatography tandem mass spectrometry for rapid and selective determination of urinary diphenyl phosphate of college students.

Organophosphate esters (OPEs), known as novel alternative flame retardants, are a class of environmental endocrine disruptors. Long-term exposure to OPEs may bring a non-negligible health risk to human. Urinary OPE metabolites (mOPEs) are generally used as biomarkers to evaluate the internal exposure to OPEs. Diphenyl phosphate (DPHP), the main metabolite of aryl-OPEs, exhibited high detection rates and concentrations in urine samples. To establish a selective and simple analytical method for biomonitoring urinary DPHP, a specific magnetic molecular imprinted polymer (MMIP) was fabricated via a sol-gel method. Under optimum magnetic solid-phase extraction (MSPE) conditions, the resultant MMIP exhibited selective recognition ability, ideal adsorption capacity and good reusability on urinary DPHP enrichment. The developed MSPE method coupled with ultra-high performance liquid chromatography tandem mass spectrometry (U-HPLC-MS/MS) exhibited good precision and accuracy (spiked recoveries of 85.8%-109% with relative standard deviations (RSDs) ranged from 5.1%-13%), low detection limit of 0.035 ng/mL, and negligible matrix inhibition. Then we used this proposed method to detect urinary DPHP levels of recruited 30 college students and investigate the time variability and potential determinants. All urine samples revealed the presence of DPHP at a median concentration of 0.56 µg/g Creatinine (Cr). Moderate reproducibility of DPHP level was observed in first morning urine samples (ICC>0.40). Significant correlations were found between urinary DPHP levels and gender (ß=0.72; 95% CI: 0.48∼0.96), sampling time (ß=0.36; 95% CI: 0.08∼0.65) as well as the frequency for take-out food (ß=0.45; 95% CI: 0.07∼0.74) (p< 0.05). Hence, a fast and sensitive MSPE-U-HPLC-MS/MS method was successfully built to quantify urinary DPHP.

[Simultaneous determination of 35 organochlorine pesticides and polychlorinated biphenyls in the serum of the general population in Wuhan by solid phase extraction-gas chromatography-tandem mass spectrometry].

Owing to their persistence, ease of accumulation in organisms, and high toxicity, the use of persistent organic pollutants (POPs) has been limited ever since the Stockholm Convention on Persistent Organic Pollutants was signed in 2001 by the United Nations Environment Programme (UNEP). As typical POPs, organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) can persist in the environment for long periods. They can enter human bodies through many pathways and pose a high exposure risk to humans. OCPs and PCBs can lead to endocrine disruption, neurotoxicity, immunotoxicity, reproductive toxicity, and cancer in human beings. Accurate quantification of pollutant load levels in vivo is crucial for the evaluation of health effects. In this study, a rapid and sensitive method based on solid phase extraction-gas chromatography-tandem mass spectrometry (SPE-GC-MS/MS) was developed for the simultaneous determination of 35 OCPs and PCBs in serum. Accordingly, 100 µL of the serum sample was gently mixed with the isotope-labeled internal standard solution (10 µL) to obtain a final mass concentration of 10 ng/mL for each internal standard. After incubation overnight, the samples were mixed with 100 µL purified water for dilution. After protein precipitation with 100 mg urea, the serum samples were passed through preconditioned Oasis® HLB cartridges, washed with 6 mL purified water, and eluted with 5 mL hexane-dichloromethane (1∶1, v/v). The SPE eluant was collected, evaporated to near dryness under a gentle nitrogen stream, and dissolved in 100 µL n-hexane. The reconstitution in the vial insert was injected into the GC-MS/MS instrument for analysis. The analytes were separated on an Agilent J&W DB-5MS capillary column (30 m×0.25 mm×0.25 µm) with temperature programming. The mass spectrometer was operated in the electron ionization (EI) mode. The optimal mass spectrometry conditions were realized by optimizing the instrument parameters such as ion pairs and collision energies. The analytes were detected in the multiple reaction monitoring (MRM) mode, and the internal standard method was used for quantitative analysis. The OCPs and PCBs had good linearities in the range of 0.05-50.0 ng/mL. The limits of detection (LODs, S/N=3) ranged from 1.2 to 71.4 ng/L. The recoveries of the 35 compounds were 72.6%-142% with relative standard deviations (RSDs) of less than 25% at the three spiked levels. The developed SPE-GC-MS/MS method was successfully applied to the simultaneous analysis of OCPs and PCBs in serum samples obtained from the general population in Wuhan. The results showed that the general population in Wuhan was widely exposed to OCPs and PCBs, especially the former. The detection frequencies of eight OCPs and seven PCBs were greater than 50%, and p,p'-DDE, p,p'-DDD, and methoxychlor were detected in all serum sample pools. Non-dioxin-like PCBs (NDL-PCBs) were the dominant PCB congeners, while PCB-28, PCB-153, and PCB-52 were the dominant PCBs in the general population of Wuhan. The concentration of OCPs increased with age. Moreover, the concentration of OCPs in individuals who were more than 66 years old was significantly higher as compared to that in younger individuals. The positive association differing by gender was significant in individuals over 60 years of age. There were no significant differences in PCB concentrations according to gender or age. There were no seasonal differences in the residue levels of OCPs and PCBs in the general population of Wuhan. The developed method is rapid and sensitive; it has the advantages of low limits of detection, satisfactory recoveries, accurate precision, and microsample volume, thus allowing for the simultaneous analysis of trace OCPs and PCBs in microserum samples in epidemiological studies. This robust analytical method also provides a powerful tool for the health risk assessment of OCP and PCB exposure.

Organophosphate esters in children and adolescents in Liuzhou city, China: concentrations, exposure assessment, and predictors.

Dermal contact with dust is commonly considered an important pathway of exposure to organophosphate esters (OPEs), but the importance of OPE uptake from diet is unclear. Herein, we used hand wipes to estimate OPE exposure from indoor dust and examined whether urinary OPE metabolite concentrations were influenced by sociodemographic characteristics, OPE amount in hand wipes, and dietary factors. OPEs were measured in urine and hand wipes from 6 to 18-year-old children and adolescents (n=929) in Liuzhou, China. Sociodemographic and dietary factors were obtained from questionnaire. Six OPE metabolites were detected in >70% of the urine samples, and seven OPEs were detected in >50% of the hand wipes. Estimated daily intakes (EDIs) were calculated using urinary OPE metabolites to investigate the total daily intake of OPEs, in which 0.36-10.1% of the total intake was attributed to the exposure from dermal absorption. In multivariate linear regression models, sex, age, and maternal education were significant predictors of urinary OPE metabolite concentrations. Urinary diphenyl phosphate (DPHP) is positively associated with its parent compounds 2-ethylhexyl-diphenyl phosphate (EHDPP) and triphenyl phosphate (TPHP) in hand wipes. High versus low vegetable intake was associated with a 23.7% higher DPHP (95% confidence interval (CI): 0.51%, 52.1%). Barreled water drinking was associated with a 30.4% (95% CI: 11.8%, 52.0%) increase in bis(1-chloro-2-propyl) 1-hydroxy-2-propyl phosphate (BCIPHIPP) compared to tap water drinking. Our results suggested the widespread exposure to OPEs in children and adolescents. In addition to dermal absorption, dietary intake may be an important exposure source of certain OPEs.

Association of exposure to organophosphate esters with increased blood pressure in children and adolescents.

Organophosphate esters (OPEs) are widely added to various industrial and consumer products, and are mainly used as flame retardants and plasticizers. Existing epidemiological studies suggest that OPE exposure may be linked to increased blood pressure (BP) and hypertension risk in adults. However, it remains unclear whether OPE exposure is associated with increased BP in children and adolescents. Here, we investigated the associations between OPE exposure and BP levels in 6-18-year-old children and adolescents from a cross-sectional study in Liuzhou, China. OPE metabolites were determined in spot urine samples (n = 1194) collected between April and May 2018. Three measurements of systolic and diastolic BP for each participant were averaged as study outcomes. Associations of OPE exposure with age-, sex- and height-standardized BP were assessed using linear regression models. We found that each natural log unit increment of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) was associated with a 0.06 standard deviation unit (95% confidant interval (CI): 0.01, 0.11) increase in systolic BP z-score. When conducting stratified analysis based on sex, age, and BMI category, BDCIPP was shown to be positively associated with systolic/diastolic BP z-score in females, but not in males. The associations between bis(2-butoxyethyl) phosphate (BBOEP) and systolic/diastolic BP z-score were pronounced in adolescents, but not in children. Moreover, a significant positive association between 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) and diastolic BP z-score was observed in obese subjects. The present study provides the first evidence that OPE exposure was related to increased BP in children and adolescents. Given the scarcity of high-quality evidence supporting these results, the health effects of OPEs are warrant investigation in well-designed prospective studies.

Biological monitoring and health assessment of 21 metal(loid)s in children and adolescents in Liuzhou City, Southwest China.

Exposure to metal(loid)s is associated with adverse effects on human health, especially for children and adolescents. This study was designed to evaluate metal(loid)s exposure in 2050 children and adolescents aged 6-18 years from Liuzhou City, Southwest China. The detection rates of 21 elements were all above 99%. We found that age was an important predictor for most elements, and that children exhibited more exposure than adolescents, expect for strontium (p < 0.05). Interestingly, urinary levels were higher in girls for 13 of our study elements. Multiple regression models also showed that dietary habits also affected the distribution of elements. Moreover, we estimated exposure risk by generating the hazard quotient (HQ) for single metal and the hazard index (HI) for the co-occurrence of metals. The HQ of cadmium was > 1 at the P95 value and that the risk of the mixed effect of cadmium, mercury, and thallium was not negligible, and indicated that the associated risk was of concern. Our results provide basic data on the reference values of urinary metal(loid) levels and an assessment of health risks for children and adolescents that reside in industrial areas.

Metabolome-wide association study of serum exogenous chemical residues in a cohort with 5 major chronic diseases.

BACKGROUND: Chronic diseases have become main killers affecting the health of human, and environmental pollution is a major health risk factor that cannot be ignored. It has been reported that exogenous chemical residues including pesticides, herbicides, fungicides, veterinary drugs and persistent organic pollutants are associated with chronic diseases. However, the evidence for their relationship is equivocal and the underlying mechanisms are unclear. OBJECTIVES: We aim to investigate the linkages between serum exogenous chemical residues and 5 main chronic diseases including obesity, hyperuricemia, hypertension, diabetes and dyslipidemia, and further reveal the metabolic perturbations of chronic diseases related to exogenous chemical residue exposure, then gain potential mechanism insight at the metabolic level. METHODS: LC-MS-based targeted and nontargeted methods were respectively performed to quantify exogenous chemical residues and acquire metabolic profiling of 496 serum samples from chronic disease patients. Non-parametric test, correlation and regression analyses were carried out to investigate the association between exogenous chemical residues and chronic diseases. Metabolome-wide association study combined with the meeting-in-the-middle strategy and mediation analysis was performed to reveal and explain exposure-related metabolic disturbances and their risk to chronic diseases. RESULTS: In the association analysis of 106 serum exogenous chemical residues and 5 chronic diseases, positive associations of serum perfluoroalkyl substances (PFASs) with hyperuricemia were discovered while other associations were not significant. 240 exposure markers of PFASs and 84 disease markers of hyperuricemia were found, and 47 of them were overlapped and considered as putative effective markers. Serum uric acid, amino acids, cholesterol, carnitines, fatty acids, glycerides, glycerophospholipids, ceramides, and a part of sphingolipids were positively correlated with PFASs and associated with increased risk for hyperuricemia. Creatine, creatinine, glyceryl monooleate, phosphatidylcholine 36:6, phosphatidylethanolamine 40:6, cholesterol and sphingolipid 36:1;2O were significant markers which mediated the associations of the residues with hyperuricemia. CONCLUSIONS: Our study demonstrated a significantly positive association between PFASs exposure and hyperuricemia. The most significant metabolic abnormality was lipid metabolism which not only was positively associated with PFASs, but also increased the risk of hyperuricemia.

Individual and joint effects of metal exposure on metabolic syndrome among Chinese adults.

Growing evidence suggests that metal exposure contributes to metabolic syndrome (MetS), but little is known about the effects of combined exposure to metal mixtures. This cross-sectional study included 3748 adults who were recruited from the Medical Physical Examination Center of Tongji Hospital, Wuhan, China. The levels of 21 metal(loid)s in urine were measured by inductively coupled plasma mass spectrometry. MetS was diagnosed according to National Cholesterol Education Program's Adult Treatment Panel III recommendations. Multivariate logistic regression model was uesd to explore the effects of single-metal and multi-metal exposures. The elastic net (ENET) regularization with an environmental risk score (ERS) was performed to estimate the joint effects of exposure to metal mixtures. A total of 636 participants (17%) were diagnosed with MetS. In single metal models, MetS was positively associated with zinc (Zn) and negatively associated with nickel (Ni). In multiple metal models, the associations remained significant after adjusting for the other metals. In the joint association analysis, the ENET models selected Zn as the strongest predictor of MetS. Compared to the lowest quartile, the highest quartile of ERS was associated with an elevated risk of MetS (OR = 3.72; 95% CI: 2.77, 5.91; P-trend < 0.001). Overall, we identified that the combined effect of multiple metals was related to an increased MetS risk, with Zn being the major contributor. These findings need further validation in prospective studies.

Serum concentrations of organochlorine pesticides, biomarkers of oxidative stress, and risk of breast cancer.

Studies have documented that exposure to organochlorine pesticides (OCPs) is linked with breast cancer, but the underlying biological mechanisms are still unknown. This study included 313 women diagnosed with breast cancer and 313 controls in Wuhan, China, and measured 18 OCPs in serum and 3 oxidative stress biomarkers in urine. Multivariable adjusted regression models were used to evaluate the associations among OCPs, oxidative stress biomarkers, and breast cancer. The mediating effect of oxidative stress was assessed by mediation analysis. We observed that most OCPs were positively associated with risk of breast cancer (all FDR-P values < 0.05 or 0.10). Moreover, we found that p,p'-DDT, p,p'-DDD, dieldrin, heptachlor, and heptachlor epoxide were positively associated with 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) and 8-iso-prostaglandin F2α (8-isoPGF2α), which in turn were positively associated with risk of breast cancer. Mediation analysis indicated that HNE-MA and 8-isoPGF2ɑ mediated the positive associations between these OCPs and risk of breast cancer, with mediating proportion ranging from 6.23% to 19.9%. Our results suggest that lipid peroxidation may mediate the positive associations between OCP exposures and risk of breast cancer.