Associations of Trimester-Specific Exposure to Perchlorate, Thiocyanate, and Nitrate with Childhood Neurodevelopment: A Birth Cohort Study in China.

Studies about the impacts of maternal exposure to perchlorate, thiocyanate, and nitrate on offspring neurodevelopment are scarce. Based on a birth cohort in China, 1,028 mothers provided urine samples at three trimesters for determination of the three target analytes, and their offspring neurodevelopment was evaluated at 2 years old. Associations of maternal exposure to the three chemicals with offspring neurodevelopment were estimated using three statistical methods. Trimester-specific analyses using generalized estimating equation models showed that double increment of thiocyanate and nitrate during the first trimester was associated with 1.56 (95% CI: -2.82, -0.30) and 1.22 (-2.40, -0.03) point decreases in the offspring mental development index (MDI), respectively. Weighted quantile sum (WQS) regression analyses showed that the mixture exposure at the first and second trimesters was negatively associated with the offspring MDI (ß = -2.39, 95% CI: -3.85, -0.93; ß = -1.75, 95% CI: -3.04, -0.47, respectively) and thiocyanate contributed the most to the association (65.0 and 91.6%, respectively). Bayesian kernel machine regression analyses suggested an inverted U-shape relationship of maternal urinary thiocyanate with the offspring MDI. These findings suggested that prenatal exposure to the three chemicals (at current levels), especially thiocyanate and nitrate, may impair neurodevelopment. Early pregnancy seems to be the sensitive window.

Association between urinary parabens and gestational diabetes mellitus across prepregnancy body mass index categories.

Increasing evidence suggests a potential role of endocrine disrupting chemicals (EDCs) in inducing gestational diabetes mellitus (GDM). However, as far as we know, no study has examined the associations between GDM and exposure to parabens, a kind of EDCs. In this study, we explored the association between urinary parabens of pregnant women and GDM and studied the modification effect of prepregnancy body mass index (BMI). Urine samples were collected from 696 pregnant women and parabens were measured, including four alkyl side chain substituted para-hydroxybenzoic acid ester, substituents varying from methyl to butyl (abbreviates as MeP, EtP, PrP and BuP), and benzyl substituted para-hydroxybenzoic acid ester (BzP). Logistic regression models adjusting for potential confounders were used to study the association of parabens and GDM in the overall population, and further stratified analysis by prepregnancy BMI categories was also performed. The detection rates for the five parabens in the urine samples were 97.70% (MeP), 71.26% (EtP), 96.55% (PrP), 15.80% (BuP) and 2.73% (BzP). No significant association was found between parabens and GDM among the overall population. However, significant non-linear associations of PrP and the summed estrogenic activity of parabens with GDM were found in the stratified analysis by prepregnancy BMI in the overweight/obese population, with adjusted odds ratios (aORs) of 3.47 (95% CI: 1.28, 9.42) and 2.87 (95% CI: 1.07, 7.73) for GDM in the second tertile of urinary PrP and the summed estrogen activity, respectively, when compared to the first tertile. Although no statistically significant association between parabens and GDM was found in the overall population, we found that among the overweight/obese pregnant women, who represent a subgroup more prone to GDM, moderately higher levels of PrP and summed estrogenic activity of parabens were significantly associated with an increasing GDM prevalence.

Ultrahigh pressure filtration dewatering of municipal sludge based on microwave pretreatment.

Municipal sludge is difficult to treat and dispose of because of its high moisture content (MC) and volume. In this study, a novel dewatering method that utilizes ultrahigh pressure filtration (UHPF) and thin-cake-press (TCP) coupled with microwave pretreatment was proposed to reduce the MC of sludge cake. The influence of microwave contact time (MCT), microwave intensity (MI), initial MC of sludge, dewatering time, applied pressure and sludge weight (Ws) on the MC of a sludge cake was investigated by the single-factor experiment. Moreover, a water discharge path model was developed to understand the dewatering mechanism and explain the relationship between thickness and MC of the cake. The key factors affecting the MC of the cake were explored by the orthogonal experiment. The experimental results showed that microwave irradiation could effectively improve the dewatering performance and reduce the MC of the sludge cake. The MC of the cake reached its lowest value of 28% at MCT of 120 s and MI of 400 W, which is much lower than the value obtained by the traditional dewatering method. Among the parameters mentioned above, Ws has the most significant influence on MC because a large amount of sludge leads to a thicker cake, which seriously hampers the flow of filtrate and inevitably increases the MC of the cake.

Low-level perfluorooctanoic acid enhances 3 T3-L1 preadipocyte differentiation via altering peroxisome proliferator activated receptor gamma expression and its promoter DNA methylation.

Recent studies suggest that perfluorooctanoic acid (PFOA) can play a role in the development of obesity; however, the associated mechanisms are poorly understood. We investigated how PFOA exposure affected the differentiation of 3 T3-L1 preadipocytes and the associated transcriptional and epigenetic mechanisms. Cells treated with different doses of PFOA (ranging from 0.01 to 100 µg ml-1 ) were assessed for proliferation, differentiation and triglyceride accumulation. The gene expression levels of peroxisome proliferator activated receptor gamma (PPARγ) and its target genes were measured. DNA methylation levels of PPARγ promoter and global DNA methylation levels were also tested. We found a concentration-dependent enhancement of adipocyte proliferation and differentiation following PFOA exposure. PFOA also induced a significant concentration-dependent increase in the accumulation of lipid and triglyceride. Increased gene expression was also observed for PPARγ, CCAAT/enhancer binding proteins α, fatty acid binding protein 2 and lipoprotein lipase in differentiated cells after PFOA exposure. The ability of PFOA to induce adipogenesis was blocked by GW9662, a known PPARγ antagonist. In addition, significant demethylation of the cytosine-phosphate-guanine sites in the PPARγ promoter was observed after exposure to PFOA. In addition, PFOA exposure resulted in decreased global DNA methylation and increased expression levels of DNA methyltransferases genes. We found that treatment with low levels of PFOA can induce adipogenic differentiation in preadipocytes, and the underlying mechanisms probably involve the activation of PPARγ transcription and demethylation of PPARγ promoter.

Maternal urinary manganese and risk of low birth weight: a case-control study.

BACKGROUND: Manganese (Mn) is an essential element for humans, but exposure to high levels has been associated with adverse developmental outcomes. Early epidemiological studies evaluating the effect of Mn on fetal growth are inconsistent. METHODS: We investigated the association between maternal urinary Mn during pregnancy and the risk of low birth weight (LBW). Mn concentrations in maternal urine samples collected before delivery were measured in 816 subjects (204 LBW cases and 612 matched controls) recruited between 2012 and 2014 in Hubei Province, China. RESULTS: The median Mn concentration in maternal urine was 0.69 µg/g creatinine. Compared to the medium tertile of Mn levels, an increased risk of LBW was observed for the lowest tertile (≤0.30 µg/g creatinine) [adjusted odds ratio (OR) = 1.28; 95 % confidence interval (CI) = 0.67, 2.45], and a significantly increased risk of LBW was observed for the highest tertile (≥1.16 µg/g creatinine) [adjusted OR = 2.04; 95 % CI = 1.12, 3.72]. A curvilinear relationship between maternal urinary Mn and risk of LBW was observed, showing that the concentration at 0.43 µg/g creatinine was the point of inflection. Similar associations were observed among the mothers with female infants and among the younger mothers < 28 years old. However, among the mothers with male infants or the older mothers ≥ 28 years old, only higher levels of Mn were positively associated with LBW. CONCLUSIONS: Lower or higher levels of maternal urinary Mn are associated with LBW, though only the association of LBW risk and higher levels of Mn was statistically significant. The findings also show that the associations may vary by maternal age and infant sex, but require confirmation in other populations.

Occurrence of pentachlorophenol in surface water from the upper to lower reaches of the Yangtze River and treated water in Wuhan, China.

Pentachlorophenol (PCP), a persistent organic pollutant, has been banned in many countries, but it is still used in China as a wood preservative, molluscicide, or reagent for fish-pond cleaning, which may pose risks to the ecosystem and humans. However, data on the occurrence of PCP in the environment are scarce in the recent decade. The Yangtze River was regarded as a priority area of PCP pollution according to previous documents. This study aimed to examine the spatial distribution of PCP in the Yangtze River water, the differences in dry and wet seasons, the ecological risk for aquatic organisms, and its removal efficiency in tap water treatment plants. The river water samples (n = 144) were collected from the upper, middle, and lower reaches across ten provinces (or municipalities) in December 2020 and June 2021, respectively. PCP was detected in 88.9% of all the samples, ranging from

Urinary polycyclic aromatic hydrocarbon metabolites in Chinese pregnant women: Concentrations, variability, predictors, and association with oxidative stress biomarkers.

Polycyclic aromatic hydrocarbons (PAHs) are a class of pervasive contaminants having adverse health effects. Urinary monohydroxylated PAHs (OH-PAHs) are commonly employed as biomarkers to estimate PAH exposure levels in humans. However, little is understood about the variability in OH-PAHs among pregnant women across trimesters and their relationship with oxidative stress biomarkers (OSBs). Based on a prospective birth cohort study conducted in Wuhan, China, we selected 644 women who donated (spot) urine samples across different trimesters and measured the urinary concentrations of eight OH-PAHs and three selected OSBs (8-OHG, 8-OHdG, and HNEMA) to explore the relationship between the OH-PAHs and OSBs. Pregnant women were found to be ubiquitously exposed to the PAHs, with detection rates of the OH-PAHs ranging from 86.3% to 100%. 2-Hydroxynaphthalene (2-OH-Nap) had the highest urinary concentrations among the OH-PAHs during the three trimesters (specific gravity-adjusted median values for the first, second, and third trimesters: 1.86, 2.39, and 2.20 ng/mL, respectively). However, low reproducibility of the OH-PAHs was observed across the three trimesters with intraclass correlation coefficients ranged between 0.02 and 0.22. Most urinary OH-PAHs had the highest concentrations at the first trimester and the lowest at the third trimester. Some OH-PAH concentrations were higher in pregnant women with lower educational level [2-hydroxyphenanthrene (2-OH-Phen) and 3-hydroxyphenanthrene (3-OH-Phen)], those who were overweight [2-OH-Nap, 2/3-hydroxyfluorene (2/3-OH-Fluo), 2-OH-Phen, and 4-hydroxyphenanthrene (4-OH-Phen)], those who were unemployed during pregnancy [1-hydroxynaphthalene, 1/9-hydroxyphenanthrene, and 4-OH-Phen], and the samples donated in summer (most OH-PAHs, except for 2-OH-Nap). In multivariable linear mixed-effects model analyses, every OH-PAH was found to be significantly associated with increased levels of the three OSBs. For example, each interquartile range-fold increase in 2/3-OH-Fluo concentration was associated with the largest increase in 8-OHdG (65.4%) and 8-OHG (49.1%), while each interquartile range-fold increase in 3-OH-Phen concentration was associated with the largest increase in HNEMA (76.3%). Weighted quantile sum regression models, which were used to examine the joint effect of OH-PAH mixture on the OSBs, revealed positive associations between the OH-PAH mixture exposure and the OSBs. Specifically, 2/3-OH-Fluo and 2-OH-Nap were the major contributors in the association with oxidative damage of nucleic acids (8-OHdG and 8-OHG), while hydroxyphenanthrenes and 1-hydroxypyrene were the major contributors in the association with oxidative damage of lipid (HNEMA). Further work is required to examine the potential mediating role of oxidative stress in the relationship of adverse health outcomes with elevated PAH exposure among pregnant women.

Associations of pentachlorophenol exposure during pregnancy with maternal and infant reproductive hormones based on a birth cohort.

Pentachlorophenol (PCP), a typical environmental endocrine disruptor and a new persistent organic pollutant, has been extensively used as a pesticide worldwide. Although its use has been restricted for decades, PCP remains prevalent in both the environment and human bodies. Despite the known endocrine-disrupting and exogenous hormonal effects of PCP, few epidemiological studies examined such impact, especially among sensitive populations and during critical periods. Based on a prospective birth cohort in Wuhan, China, we collected maternal (first trimester; 13.0 ± 1.02 gestational weeks) and infant urine samples (1.16 ± 0.22 months postpartum) from 720 mother-infant pairs. We aimed to examine the association of PCP exposure during early pregnancy with maternal and infant urinary sex steroid hormones, including estrogens (estrone, E1; estradiol, E2; estriol, E3), progestogens (progesterone, P4; pregnenolone, P5; 17α-OH-Progesterone, 17OHP4; 17α-OH-Pregnenolone, 17OHP5), and androgens (testosterone, Testo; dihydrotestosterone, DHT; dehydroepiandrosterone, DHEA; androstenedione, A4). Additionally, gonadotropins [follicle-stimulating hormone (FSH) and luteinizing hormone (LH)] were measured in infant urine. Detection frequencies of all the sex steroid hormones in the maternal urine samples (>99 %) were higher than those in the infants' [most ≥80 %, except for E1 (3.36 %) and E2 (21.4 %)]. Maternal urinary PCP concentration was found to be significantly related with increased maternal sex steroid hormone concentrations; each interquartile increase in PCP concentration was positively related with percent change of the hormones (%Δ) ranging from 26.6 % to 48.5 %. On the other hand, maternal PCP exposure was associated with significantly increased P4 in male infants [%Δ (95 % confidence interval): 10.5 (0.56, 21.4)] but slightly decreased P4 in female infants [-11.9 (-21.8, 0.68)]. In addition, maternal PCP exposure was significantly associated with decreased FSH [%Δ (95 % CI): -9.90 (-17.0, -2.18)] and LH [-8.44 (-16.0, -0.19)] in the female infants, but not in the male infants. Sensitivity analyses, excluding infertility related treatment, pregnancy complications, preterm birth, or low birth weight, showed generally consistent results. Our findings implied that maternal/prenatal PCP exposure might disrupt the homeostasis of maternal and infant reproductive hormones. However, further studies are needed to confirm the findings.

Dyslexia is associated with urinary polycyclic aromatic hydrocarbon metabolite concentrations of children from China: Data from the READ program.

It has been found that exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the risk of certain childhood neurodevelopmental disorders. However, no research has investigated the relationship between exposure to PAHs and children's dyslexia odds. The objective of this research was to investigate whether urinary mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) are associated with increased dyslexia odds in Chinese children. We recruited 1,089 children (542 dyslexic children and 547 non-dyslexic children) for this case-control study. Ten OH-PAHs were measured in the participants' urine samples, which were collected between November 2017 and March 2023. Odds ratios (ORs) of the associations between the OH-PAHs and dyslexia were calculated using logistic regression models, after adjustment for the potential confounding factors. A significant association was found between urinary concentrations of 2-hydroxynaphthalene (2-OHNap) and the elevated odds of dyslexia. The children in the highest quartile of 2-OHNap had a higher OR of dyslexia (1.87, 95% CI: 1.07-3.27) than those in the lowest quartile (P-trend = 0.02) after adjustment for the covariates. After excluding children with maternal disorders during pregnancy, logistic regression analyses showed similar results. Our results suggested a possible association between PAH exposure and the elevated odds of dyslexia.

Exposure to organophosphate, pyrethroid, and neonicotinoid insecticides and dyslexia: Association with oxidative stress.

Organophosphates (OPPs), pyrethroids (PYRs), and neonicotinoids (NNIs) are three major classes of insecticides used worldwide. They might compromise child neurodevelopment. However, few studies have explored the association between exposure to them and dyslexia. The present study aimed to investigate the association between dyslexia and exposure to the three classes of insecticides, as well as explore the potential role of oxidative stress in the association. A total of 355 dyslexic children and 390 controls were included in this study. The exposure biomarkers were determined by liquid chromatography-tandem mass spectrometry. Specifically, the exposure biomarkers included three typical metabolites of OPPs, three of PYRs, and nine of NNIs. Additionally, three typical oxidative stress biomarkers, namely, 8-hydroxy-2'-deoxyguanosine (8-OHdG) for DNA damage, 8-hydroxyguanosine (8-OHG) for RNA damage, and 4-hydroxy-2-nonenal-mercapturic acid (HNEMA) for lipid peroxidation were measured. The detection frequencies of the urinary biomarkers ranged from 83.9% to 100%. Among the target metabolites of the insecticides, a significant association was observed between urinary 3,5,6-trichloro-2-pyridinol (TCPy, the metabolite of chlorpyrifos, an OPP insecticide) and dyslexia. After adjusting for potential confounding variables, children in the highest quartile of TCPy levels had an increased odds of dyslexia (odds ratio [OR], 1.68; 95% confidence interval [CI]: 1.03, 2.75] in comparison to those in the lowest quartile. Among the three oxidative stress biomarkers, urinary HNEMA concentration showed a significant relationship with dyslexia. Children in the highest quartile of HNEMA levels demonstrated an increased dyslexic odds in comparison to those in the lowest quartile after multiple adjustments (OR, 1.64; 95% CI: 1.01, 2.65). Mediation analysis indicated a significant effect of HNEMA in the association between urinary TCPy and dyslexia, with an estimate of 17.2% (P < 0.01). In conclusion, this study suggested the association between urinary TCPy and dyslexia. The association could be attributed to lipid peroxidation partially.

Urinary biomarkers of exposure to organophosphate, pyrethroid, neonicotinoid insecticides and oxidative stress: A repeated measurement analysis among pregnant women.

Exposure to insecticides may be associated with increased oxidative stress (OS), but few studies have assessed the associations of OS biomarkers (OSBs) with exposure to multiple insecticides and their mixture, especially in pregnant women who are a vulnerable population. In the present study, 1,094 Chinese pregnant women were recruited and a total of 3,282 urine samples were collected at their three trimesters to measure eight metabolites of organophosphates, three metabolites of pyrethroids, nine typical neonicotinoids/their metabolites, and three OSBs of DNA damage (8-OHdG), RNA damage (8-OHG), and lipid peroxidation (HNE-MA). Among the twenty target insecticide metabolites, sixteen of them were frequently detected; thirteen of them were detected in over 86% of all the urine samples except for imidacloprid (IMI, detection frequency: 72.9%), desnitro-imidacloprid (DN-IMI, 70.0%), and clothianidin (CLO, 79.6%). The reproducibility of their concentrations across the three trimesters was poor to fair (intraclass correlation coefficients <0.50). Multiparity and warm season were related to higher urinary levels of some insecticide metabolites, while higher education level and inadequate weight gain during pregnancy were significantly associated with lower concentrations of certain insecticide metabolites. Linear mixed model analyses suggested that almost all the frequently detected insecticide metabolites [other than 3-phenoxybenzoic acid (3-PBA)] were significantly associated with elevated levels of the three OSBs (8-OHdG, 8-OHG, and HNE-MA), where the percent change (Δ%) ranged 8.10-36.0% for 8-OHdG, 8.49-34.7% for 8-OHG, and 5.92-182% for HNE-MA, respectively, with each interquartile ratio (IQR)-fold increase in the concentrations of the individual exposure biomarkers. Weighted quantile sum models demonstrated that the insecticide metabolite mixture was positively associated with the three OSBs. Overall, urinary desmethyl-clothianidin (DM-CLO) and 3,5,6-trichloro-2-pyridinol (TCPy) were the top insecticide exposure biomarkers contributing to the association with 8-OHdG and 8-OHG levels, while PNP contributed the most to the association with HNE-MA levels. These findings suggested that gestational exposure to organophosphates, pyrethroids, neonicotinoids, their transformation products, and their mixture may increase oxidative damage to lipids, RNA, and DNA during pregnancy.

Association between urinary BTEX metabolites and dyslexic odds among school-aged children.

Benzene, toluene, ethylbenzene, and xylene (BTEX) are ubiquitous in the environment, and all of them can cause neurotoxicity. However, the association between BTEX exposure and dyslexia, a disorder with language network-related regions in left hemisphere affected, remains unclear. We aimed to assess the relationship between BTEX exposure and dyslexic odds among school-aged children. A case-control study, including 355 dyslexics and 390 controls from three cities in China, was conducted. Six BTEX metabolites were measured in their urine samples. Logistic regression model was used to explore the association between the BTEX metabolites and the dyslexic odds. Urinary trans,trans-muconic acid (MU: a metabolite of benzene) was significantly associated with an increased dyslexic odds [odds ratio (OR) = 1.23, 95% confidence interval (CI): 1.01, 1.50], and the adjusted OR of the dyslexic odds in the third tertile was 1.72 (95% CI: 1.06, 2.77) compared to that in the lowest tertile regarding urinary MU concentration. Furthermore, the association between urinary MU level and the dyslexic odds was more pronounced among children from low-income families based on stratified analyses. Urinary metabolite levels of toluene, ethylbenzene, and xylene were not found to be associated with the dyslexic odds. In summary, elevated MU concentrations may be associated with an increased dyslexic odds. We should take measures to reduce MU related exposure among children, particularly those with low family income.

Association of exposure to phthalates and phthalate alternatives with dyslexia in Chinese primary school children.

Previous studies have shown associations between children's exposure to phthalates and neurodevelopmental disorders. Whereas the impact of exposure to phthalate alternatives is understudied. This study aimed to evaluate the association of exposure to phthalates/their alternatives with the risk of dyslexia. We recruited 745 children (355 dyslexia and 390 non-dyslexia) via the Tongji Reading Environment and Dyslexia Research Project, and their urine samples were collected. A total of 26 metabolites of phthalates/their alternatives were measured. Multivariate logistic regression and quantile-based g-computation were used to estimate the associations of exposure to the phthalates/their alternatives with dyslexia. More than 80% of the children had 17 related metabolites detected in their urine samples. After adjustment, the association between mono-2-(propyl-6-hydroxy-heptyl) phthalate (OH-MPHP) with the risk of dyslexia was observed. Compared with the lowest quartile of OH-MPHP levels, the odds of dyslexia for the third quartile was 1.93 (95% CI 1.06, 3.57). Regarding mixture analyses, it was found that OH-MPHP contributed the most to the association. Further analyses stratified by sex revealed that this association was only observed in boys. Our results suggested a significantly adverse association of di-2-propylheptyl phthalate exposure with children's language abilities. It highlights the necessity to prioritize the protection of children's neurodevelopment by minimizing their exposure to endocrine-disrupting chemicals like di-2-propylheptyl phthalate.

[Determination of volatile nitrosamines in urine through gas chromatography-mass spectrometry].

OBJECTIVE: To establish a detection method based on gas chromatography-mass spectrometry (GC-MS) for concentrations of volatile nitrosamine compounds in urine, and apply it to the test of real samples. METHODS: Target compounds dichloromethane in urine samples was extracted with dichloromethane through liquid-liquid extraction, then the dichloromethane extract was filtrated, evaporated with nitrogen at 40°C to dryness, and the volume was set with 0.2 ml dichloromethane. Analysis of nine volatile nitroso-compounds were performed with GC-MS under selected ion monitoring mode, external reference method was used for quantification, and the detection limit, repeatability and sensitivity were evaluated. In addition, nine volatile nitroso-compounds of 92 urine samples in a town of Anhui province were measured. RESULTS: A good linear range of 2 - 200 ng/ml (with correlation coefficient 0.9985 - 0.9999) were obtained for the above mentioned nine kinds of analyte, and the lowest examination concentration was 0.05 - 0.50 ng/ml. The addition standard recoveries were 68%-102% with the RSD of 0.4% - 5.5% (n = 3). The detection limits were 0.001 - 0.013 ng/ml urine. The detection rate of N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine (NMEA), N-nitrosodiethylamine (NDEA), N-nitrosodi-n-propylamine (NDPA), N-nitrosopyrrolidine (NPYR), N-nitrosomorpholine (NMOR), N-nitrosopiperidine (NPIP), N-nitrosodi-n-butylamine (NDBA) and N-nitrosodiphenylamine (NDPhA) were 71% (65), 74% (68), 65% (60), 80% (73), 92% (85), 78% (72), 76% (70), 87% (80), 98% (90), respectively, with the results (0.27 ± 0.12), (0.75 ± 0.29), (0.06 ± 0.02), (0.16 ± 0.07), (23.66 ± 5.18), (1.01 ± 0.35), (0.38 ± 0.11), (2.47 ± 0.52) and (15.13 ± 3.48) nmol/g creatinine. CONCLUSIONS: A gas chromatography-mass spectrometry detect method was developed for low level volatile nitrosamines in urine samples.

Occurrence, fate, seasonal variability, and risk assessment of twelve triazine herbicides and eight related derivatives in source, treated, and tap water of Wuhan, Central China.

Triazine herbicides have been widely used, are frequently detected in aqueous environments and soils, and can cause acute or chronic toxicity to living organisms. We collected source water samples (n = 20) originating from the Hanshui River and the Yangtze River of Wuhan section, treated water samples (n = 20), and tap water samples (n = 169) in Wuhan, Central China during 2019 for determination of twelve triazine herbicides and their eight derivatives (collectively defined as TZs) and characterizing their fate during water treatment. Eighteen of the twenty TZs were detected in the source water. Atrazine (ATZ) had the highest concentrations (median: 22.4 ng/L) in the source water samples while DACT had the highest concentrations (median: 31.4 ng/L) in the treated water. "Tryns" (ametryn, prometryn, simetryn, terbutryn) were efficiently removed by conventional water treatment, while other target analytes were not; interestingly, hydroxypropazine and prometon increased significantly accompanied by prometryn disappearance, which implicated potential transformation pathways. In addition, "tryns" might be transformed into "tons" (atraton, prometon, secbumeton, terbumeton) by ozonation. In the tap water samples, diaminochlorotriazine had the highest concentrations (median: 34.9 ng/L) among the target analytes, followed by ATZ (18.3 ng/L), hydroxyatrazine (5.17 ng/L), deethylatrazine (5.00 ng/L), hydroxypropazine (3.20 ng/L), deisopropylatrazine (2.05 ng/L), hydroxydesethylatrazine (1.68 ng/L), and others. The TZs had the highest cumulative concentration in July in the tap water samples (median: 89.7 ng/L). This study found that ozonation in combination with activated carbon was more efficient in removing triazine herbicides, although "tryns" could also be transformed during conventional treatment. Ecological risk assessment showed moderate risks posed by hydroxyterbuthylazine, prometryn, and simetryn; the Hanshui River had higher risks than the Yangtze River, and July had higher risks than February. Human exposure to the TZs via water ingestion was low compared to the reference doses. This study characterized the occurrence of some new emerging TZs in the source water, their fate during drinking water treatment, and their seasonal variability in the tap water.

Urinary concentrations of fungicide carbendazim's metabolite and associations with oxidative stress biomarkers in young children.

Carbendazim (CBDZ) is the most widely used fungicide in China. It is ubiquitous in environment and can induce oxidative stress in mammals, while data on occurrence of its metabolite in human urine are scarce, and the relationship between CBDZ and oxidative stress biomarkers (OSBs) in young children has not been examined. The aim of this study was to measure the concentrations of methyl 5-hydroxy-2-benzimidazolecarbamate (5-HBC, the main metabolite of CBDZ in urine) in 390 urine samples collected from 130 healthy young (< 6.6 years old) children from Shenzhen and Wuhan, in south and central China, respectively, and to evaluate the associations of 5-HBC with three selected OSBs (4-HNEMA, 8-OHG, and 8-OHdG, for lipid, RNA, and DNA, respectively). 5-HBC was found in 99.2% of the urine samples at concentrations ranging from below the method detection limit (< 0.005 ng/mL) to 10.9 ng/mL (median: 0.11 ng/mL). Moderate inter-day reproducibility was found for specific gravity-adjusted 5-HBC concentrations (intraclass correlation coefficient: 0.50). The urinary 5-HBC concentrations were significantly and positively associated with 4-HNEMA (p < 0.01). An interquartile range increase in urinary 5-HBC concentrations was associated with a 42.1% increase in 4-HNEMA, which implied that CBDZ exposure might be associated with lipid peroxidation in young children without occupational exposure. As far as we know, this pilot study is the first to report urinary 5-HBC and its associations with OSBs in children.

Fipronil and its transformation products in the Yangtze River: Assessment for ecological risk and human exposure.

Fipronil (FP), a phenylpyrazole insecticide, is widely used in agricultural, residential, and veterinary settings. It is toxic to ecosystems and humans; moreover, some of its transformation products are more toxic than FP. A comprehensive profile of the contamination of the Yangtze River by FP and its transformation products (FPs) is not yet available. This study aims to fill this data gap. A total of 144 water samples were collected from 72 sampling locations along the river during the wet (June 2021) and dry (December 2020) seasons. High detection rates (85.4-91.7%) of FPs were found, with ΣFPs' median concentration of 0.49 ng/L. The parent compound FP was the most abundant (median: 0.13 ng/L), followed by FP-desulfinyl (0.08), FP-sulfone (0.07), FP-detrifluoromethylsulfinyl (DTF, 0.07), FP-sulfide (0.06) and FP-amide (0.06). Their concentrations increased significantly from the upper to the lower reaches; for approximately every 100 km toward the lower reaches, the level of FPs increased by 13-15%. The urban region and wet season had the higher FPs contamination. Through water ingestion, the human exposure risk posed by FPs in the river was acceptable; however, the ecological risk assessment showed a moderate to high risk posed by FPs. Follow-up studies are warranted to establish integrated ecological risk assessment models and conduct epidemiological risk assessments among population groups with high exposure levels of FPs. Given the high ecological risk of FPs, regular monitoring of them in the Yangtze River is necessary. FP-DTF was reported in surface water for the first time.

Urinary pentachlorophenol in general population of central China: reproducibility, predictors, and associations with oxidative stress biomarkers.

Pentachlorophenol (PCP) is a ubiquitous environmental persistent organic pollutant and a Group 1 carcinogen. Human exposure level of PCP was reported to be relatively higher in China than in many other countries, because sodium pentachlorophenate was abused as molluscicide in China. PCP can induce oxidative stress; however, the relationship of PCP exposure with oxidative stress biomarkers (OSBs) in human beings has rarely been documented. In this study, 404 first-morning urine samples (including repeated samples in three days donated by 74 participants) were collected from 128 healthy adults (general population without occupational exposure to PCP) in autumn and winter of 2018, respectively, in Wuhan, central China. Urinary concentrations of PCP and three select OSBs [including 8-OHG (abbreviation of 8-hydroxy-guanosine), 8-OHdG (8-hydroxy-2'-deoxyguanosine), and 4-HNEMA (4-hydroxy-2-nonenal mercapturic acid), which reflect oxidative damage of RNA, DNA, and lipid, respectively] were determined. PCP was detectable in 100% of the urine samples (specific gravity-adjusted median concentration: 0.44 ng/mL; range: 0.02-14.2 ng/mL). Interday reproducibility of urinary PCP concentrations was excellent (intraclass correlation coefficient: 0.88) in three days. Significant differences in PCP concentrations were found among different age groups; the group of participants aged 20-45 y (median: 0.72 ng/mL) had higher concentrations than those in the elders (aged 45-60 y and > 60 y). Spatial disparity was observed in autumn, and urban residents had higher PCP concentrations than rural residents (median: 0.60 vs. 0.31 ng/mL), whereas such disparity was not found in winter. There were no season-, sex-, or BMI-related differences between the corresponding subgroups. The urinary PCP concentrations were found to be associated with increases in 8-OHdG and 8-OHG rather than 4-HNEMA. An interquartile range increase in urinary PCP concentration was associated with a 23.5% (95% CI: 9.18-39.6) increase in 8-OHdG and a 21.3% (95% CI: 9.18-32.4) increase in 8-OHG, implied that PCP exposure at environmental relevant dose might be associated with nucleic acid oxidative damage in the general population. This pilot study reported associations between PCP exposure and OSBs in human beings. Future studies are needed to elucidate the mediating roles of OSBs in the association between PCP exposure and certain adverse health outcomes.

Urinary perchlorate, thiocyanate, and nitrate and their associated risk factors among Chinese pregnant women.

Perchlorate, nitrate, and thiocyanate are well-known inhibitors of iodide uptake and thyroid-disrupting chemicals. Widespread human exposure to them has been identified, whereas studies on their internal exposure levels among Chinese pregnant women are scarce and factors associated with them are not well recognized. The objective of this study is to determine their levels and identify the associated factors among pregnant women (n = 1120), based on a prospective birth cohort in Wuhan, central China, using repeated urine samples of three trimesters. Urinary perchlorate, thiocyanate, and nitrate were 100% detected in the samples, and specific gravity-adjusted median concentrations of them in all the samples were 12.6 ng/mL, 367 ng/mL, and 63.7 µg/mL, respectively. Their concentrations were weakly-to-moderately correlated with each other, with Spearman correlation coefficients ranging from 0.27 to 0.54. Poor reproducibility were observed for the three analytes over the three trimesters, with intraclass correlation coefficient of 0.07, 0.19, 0.04 for perchlorate, thiocyanate, and nitrate, respectively. The women who were overweight or used tap water as drinking water had significantly higher perchlorate concentrations, while those with excessive gestational weight gain had significantly higher thiocyanate concentrations (p < 0.05). The women with a college degree or above had lower nitrate concentrations (p < 0.05). Meanwhile, the median concentration of perchlorate in urine samples collected in spring, thiocyanate in those collected in winter, and nitrate in those collected in autumn, was significantly higher compared to their median concentrations in the samples collected in other three seasons (p < 0.05), respectively. Urinary perchlorate and nitrate concentrations of pregnant women in this study were higher than the concentrations of pregnant women in other countries, while thiocyanate concentrations were lower than that of most other countries. This study suggested potential covariates for future epidemiological analyses.

Association of Prenatal Exposure to Organophosphate, Pyrethroid, and Neonicotinoid Insecticides with Child Neurodevelopment at 2 Years of Age: A Prospective Cohort Study.

BACKGROUND: Widespread insecticide exposure might be a risk factor for neurodevelopment of our children, but few studies examined the mixture effect of maternal coexposure to organophosphate insecticides (OPPs), pyrethroids (PYRs), and neonicotinoid insecticides (NNIs) during pregnancy on child neurodevelopment, and critical windows of exposure are unknown. OBJECTIVES: We aimed to evaluate the association of prenatal exposure to multiple insecticides with children's neurodevelopment and to identify critical windows of the exposure. METHODS: Pregnant women were recruited into a prospective birth cohort study in Wuhan, China, from 2014-2017. Eight metabolites of OPPs (mOPPs), three metabolites of PYRs (mPYRs), and nine metabolites of NNIs (mNNIs) were measured in 3,123 urine samples collected at their first, second, and third trimesters. Children's neurodevelopment [mental development index (MDI) and psychomotor development index (PDI)] was assessed using the Bayley Scales of Infant Development at 2 years of age (N=1,041). Multivariate linear regression models, generalized estimating equation models, and weighted quantile sum (WQS) regression were used to estimate the association between the insecticide metabolites and Bayley scores. Potential sex-specific associations were also examined. RESULTS: Single chemical analysis suggested higher urinary concentrations of some insecticide metabolites at the first trimester were significantly associated with lower MDI and PDI scores, and the associations were more prominent among boys. Each 1-unit increase in ln-transformed urinary concentrations of two mOPPs, 3,5,6-trichloro-2-pyridinol and 4-nitrophenol, was associated with a decrease of 3.16 points [95% confidence interval (CI): -5.59, -0.74] and 3.06 points (95% CI: -5.45, -0.68) respectively in boys' MDI scores. Each 1-unit increase in that of trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid (trans-DCCA; an mPYR) was significantly associated with a decrease of 2.24 points (95% CI: -3.89, -0.58) in boys' MDI scores and 1.90 points (95% CI: -3.16, -0.64) in boys' PDI scores, respectively. Significantly positive associations of maternal urinary biomarker concentrations [e.g., dimethyl phosphate (a nonspecific mOPP) and desmethyl-clothianidin (a relatively specific mNNI)] with child neurodevelopment were also observed. Using repeated holdout validation, a 1-quartile increase in the WQS index of the insecticide mixture (in the negative direction) at the first trimester was significantly associated with a decrease of 3.02 points (95% CI: -5.47, -0.57) in MDI scores among the boys, and trans-DCCA contributed the most to the association (18%). CONCLUSIONS: Prenatal exposure to higher levels of certain insecticides and their mixture were associated with lower Bayley scores in children, particularly in boys. Early pregnancy may be a sensitive window for such an effect. Future studies are needed to confirm our findings. https://doi.org/10.1289/EHP12097.