Disinfection By-products In Drinking Water Research Articles

The alternation of halobenzoquinone disinfection byproduct on toxicogenomics of DNA damage and repair in uroepithelial cells

Halobenzoquinones (HBQs) were recently discovered as an emerging class of drinking water disinfection byproducts with carcinogenic concern. However, the molecular mechanism underlying HBQs-induced DNA damage is not clear. In this study, we integrated in vitro genotoxicity, computational toxicology, and the quantitative toxicogenomic analysis of HBQs on DNA damage/repair pathways in human bladder epithelial cells SV-HUC-1. The results showed that HBQs could induce cytotoxicity with the descending order as 2,6-DIBQ > 2,6-DCBQ ≈ 2,6-DBBQ. Also, HBQs can increase DNA damage in SV-HUC-1 cells and thus generate genotoxicity. However, there is no significant difference in genotoxicity among the three HBQs. The results of molecular docking and molecular dynamics simulation further confirmed that HBQs had high binding fractions and stability to DNA. Toxicogenomic analysis indicated that HBQs interfered with DNA repair pathways, mainly affecting base excision repair, nucleotide excision repair and homologous recombination repair. These results have provided new insights into the underlying molecular mechanisms of HBQs-induced DNA damage, and contributed to the understanding of the relationship between exposure to DBPs and risks of developing bladder cancer.

Exposures to drinking water disinfection byproducts and kidney function in Chinese women

BackgroundDisinfection byproducts (DBPs), the ubiquitous contaminants in drinking water, have been shown to impair renal function in experimental studies. However, epidemiological evidence is sparse. ObjectiveTo investigate exposures to DBPs in associations with renal function among women. MethodsA total of 920 women from December 2018 to January 2020 were abstracted from the Tongji Reproductive and Environmental (TREE) Study, an ongoing cohort study in Wuhan, China. Urine samples were gathered at baseline recruitment and analyzed for dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) as biomarkers of DBP exposures. Serum uric acid (UA), creatinine, and estimated glomerular filtration rate (eGFR) were measured as indicators of renal function. Multivariate linear regression and restricted cubic spline (RCS) models were conducted to assess urinary DCAA and TCAA concentrations in associations with renal function indicators. Stratified analyses by age and body mass index (BMI) were also performed. ResultsWe found null evidence of urinary TCAA in associations with renal function indicators. However, elevated urinary DCAA tertiles were related to decreased eGFR (β = −1.78%, 95% CI: 3.21%, −0.36%, comparing the upper vs. lower tertile; P for trend = 0.01). This inverse association still existed when urinary DCAA concentration was treated as a continuous variable, and the dose-response relationship was linear based on the RCS model (P for overall association = 0.002 and P for non-linear associations = 0.44). In the stratified analyses, we found an association of urinary DCAA concentration with decreased UA level among women <30 years but an association with increased UA level among women ≥30 years (P for interaction = 0.04). ConclusionUrinary DCAA but not TCAA was associated with impaired renal function among women undergoing assisted reproductive technology.

Urinary biomarkers of drinking-water disinfection byproducts in relation to diminished ovarian reserve risk: A case-control study from the TREE cohort

BackgroundDisinfection byproducts (DBPs) as ovarian toxicants have been documented in toxicological studies. However, no human studies have explored the effects of exposure to DBPs on diminished ovarian reserve (DOR). ObjectiveTo assess whether urinary biomarkers of exposure to drinking-water DBPs were associated with DOR risk. MethodsA total of 311 women undergoing assisted reproductive technology were diagnosed with DOR in the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. The cases were matched to the controls with normal ovarian reserve function by age in a ratio of 1:1. Urinary trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) were quantified as biomarkers of drinking-water DBP exposures. The conditional logistic regression and restricted cubic spline (RCS) were used to explore urinary biomarkers of drinking-water DBP exposures in associations with the risk of DOR. ResultsElevated urinary DCAA levels were associated with higher DOR risk [adjusted odds ratio (OR) = 1.87; 95 % confidence interval (CI): 1.16, 3.03 for the highest vs. lowest quartiles; P for trend = 0.016]. The association was confirmed in the RCS model, with a linear dose-response curve (P for overall association = 0.029 and P for non-linear association = 0.708). The subgroup analysis by age and body mass index (BMI) showed that urinary DCAA in association with DOR risk was observed among women ≥35 years old and leaner women (BMI < 24 kg/m2), but the group differences were not statistically significant. Moreover, a U-shaped dose-response curve between urinary TCAA and DOR risk was estimated in the RCS model (P for overall association = 0.011 and P for non-linear association = 0.004). ConclusionsExposure to drinking-water DBPs may contribute to the risk of DOR among women undergoing assisted reproductive technology.

Disinfection by-products in drinking water and risk of colorectal cancer: a population-based cohort study.

Colorectal cancer is the third most common malignancy worldwide and is strongly linked to lifestyle and environmental risk factors. Although several drinking-water disinfection by-products are confirmed rodent carcinogens, the evidence in humans for carcinogenicity associated with these by-products, including colorectal cancer, is still inconclusive. We assessed the association of long-term exposure to trihalomethanes (THMs), the most prevalent disinfection by-products in chlorinated drinking water, with incidence of colorectal cancer in 58 672 men and women in 2 population-based cohorts. Exposure was assessed by combining long-term information of residential history with drinking water-monitoring data. Participants were categorized according to no exposure, low exposure (<15µg/L), and high exposure (≥15µg/L). Incident cases of colorectal cancer were ascertained by use of the Swedish National Cancer Register. During an average follow-up of 16.8years (988 144 person-years), 1913 cases of colorectal cancer were ascertained (1176 cases in men and 746 in women, respectively). High THM concentrations in drinking water (≥15 µg/L) were associated with increased risk of colorectal cancer in men (hazard ratio = 1.26, 95% confidence interval = 1.05-1.51) compared with no exposure. When subsites were assessed, the association was statistically significant for proximal colon cancer (hazard ratio = 1.59, 95% confidence interval = 1.11 to 2.27) but not for distal colon cancer or rectal cancer. In women, we observed overall no association of THMs with colorectal cancer. These results add further evidence that disinfection by-products in drinking water may be a possible risk factor for proximal colon cancer in men. This observation was made at THM concentrations lower than those in most previous studies.

Genotoxicity Induced by Low Dose and Mixed Exposure to Haloacetaldehydes, an Emerging Class of Drinking Water Disinfection By-products

Genotoxicity Induced by Low Dose and Mixed Exposure to Haloacetaldehydes, an Emerging Class of Drinking Water Disinfection By-products

Effect of spray aeration on unregulated drinking water disinfection byproducts

AbstractSpray aeration is a comparatively low‐cost option to reduce trihalomethane (THM) concentrations in distribution system storage. The effect of spray aeration on unregulated, toxic disinfection by‐products was investigated in a bench‐scale apparatus in closed‐tank and open‐tank experiments. In the closed‐tank experiments, initially over 90% of THMs, trichloroacetonitrile, and chloropicrin were removed, while 36% of dihaloacetonitriles were removed. However, due to the buildup of concentrations in the tank headspace, removal rates for all compounds decreased significantly with time, falling to 44% removal of THMs, 76% removal of trichloroacetonitrile, and 58% removal of chloropicrin. Removal of dihaloacetonitriles decreased to zero. In the open‐tank experiments, THM removal rates were high and did not decrease with time. Considering the results with open and closed tanks as approximate bounds for performance expected under real‐world conditions in storage tanks, the findings suggest that spray aeration may not significantly reduce haloacetonitrile‐related toxicity while halonitromethane‐related toxicity may be reduced.

Drinking water disinfection byproduct iodoacetic acid affects thyroid hormone synthesis in Nthy-ori 3–1 cells

Iodoacetic acid (IAA) is an emerging and the most genotoxic iodinated disinfection byproduct to date. IAA can disrupt the thyroid endocrine function in vivo and in vitro, but the underlying mechanisms remain unclear. In this work, transcriptome sequencing was used to investigate the effect of IAA on the cellular pathways of human thyroid follicular epithelial cell line Nthy-ori 3–1 and determine the mechanism of IAA on the synthesis and secretion of thyroid hormone (TH) in Nthy-ori 3–1 cells. Results of transcriptome sequencing indicated that IAA affected the TH synthesis pathway in Nthy-ori 3–1 cells. IAA reduced the mRNA expression of thyroid stimulating hormone receptor, sodium iodide symporter, thyroid peroxidase, thyroglobulin, paired box 8 and thyroid transcription factor-2, inhibited the cAMP/PKA pathway and Na+-K+-ATPase, and decreased the iodine intake. The results were confirmed by our previous findings in vivo. Additionally, IAA downregulated glutathione and the mRNA expression of glutathione peroxidase 1, leading to increased reactive oxygen species production. This study is the first to elucidate the mechanisms of IAA on TH synthesis in vitro. The mechanisms are associated with down-regulating the expression of genes related to TH synthesis, inhibiting iodine uptake, and inducing oxidative stress. These findings may improve future health risk assessment of IAA on thyroid in human.

Thiol Reactome: A Nontargeted Strategy to Precisely Identify Thiol Reactive Drinking Water Disinfection Byproducts.

The precise identification of predominant toxic disinfection byproducts (DBPs) from disinfected water is a longstanding challenge. We propose a new acellular analytical strategy, the 'Thiol Reactome', to identify thiol-reactive DBPs by employing a thiol probe and nontargeted mass spectrometry (MS) analysis. Disinfected/oxidized water samples had reduced cellular oxidative stress responses of 46 ± 23% in Nrf2 reporter cells when preincubated with glutathione (GSH). This supports thiol-reactive DBPs as the predominant drivers of oxidative stress. This method was benchmarked using seven classes of DBPs including haloacetonitriles, which preferentially reacted with GSH via substitution or addition depending on the number of halogens present. The method was then applied to chemically disinfected/oxidized waters, and 181 tentative DBP-GSH reaction products were detected. The formulas of 24 high abundance DBP-GSH adducts were predicted, among which nitrogenous-DBPs (11) and unsaturated carbonyls (4) were the predominant compound classes. Two major unsaturated carbonyl-GSH adducts, GSH-acrolein and GSH-acrylic acid, were confirmed by their authentic standards. These two adducts were unexpectedly formed from larger native DBPs when reacting with GSH. This study demonstrated the "Thiol Reactome" as an effective acellular assay to precisely identify and broadly capture toxic DBPs from water mixtures.

Methods and Software to Analyze Gene-Environment Interactions under a Case-Mother-Control-Mother Design with Partially Missing Child Genotype

Introduction: The case-mother-control-mother design allows to study fetal and maternal genetic factors together with environmental exposures on early life outcomes. Mendelian constraints and conditional independence between child genotype and environmental factors enabled semiparametric likelihood methods to estimate logistic models with greater efficiency than standard logistic regression. Difficulties in child genotype collection require methods handling missing child genotype. Methods: We review a stratified retrospective likelihood and two semiparametric likelihood approaches: a prospective one and a modified retrospective one, the latter either modeling the maternal genotype as a function of covariates or leaving their joint distribution unspecified (robust version). We also review software implementing these modeling alternatives, compare their statistical properties in a simulation study, and illustrate their application, focusing on gene-environment interactions and partially missing child genotype. Results: The robust retrospective likelihood provides generally unbiased estimates, with standard errors only slightly larger than when modeling maternal genotype based on exposure. The prospective likelihood encounters maximization problems. In the application to the association of small-for-gestational-age babies with CYP2E1 and drinking water disinfection by-products, the retrospective likelihood allowed a full array of covariates, while the prospective likelihood was limited to few covariates. Conclusion: We recommend the robust version of the modified retrospective likelihood.

СОДЕРЖАНИЕ ХЛОРОФОРМА В КРОВИ НАСЕЛЕНИЯ КАК БИОМАРКЕР ЭКСПОЗИЦИИ ПОБОЧНЫМИ ПРОДУКТАМИ ДЕЗ-ИНФЕКЦИИ ПИТЬЕВОЙ ВОДЫ

The modern methodological approaches, such as biomonitoring, could be used to improve the evidence base reliability and reduce uncertainty under chemicals health risk assessments and hygienic rationing. The aim of the study was to substantiate using the results of chloroform determination in human blood as a biomarker of exposure to drinking water disinfection byproducts under republican conditions. A gas chromatography-mass spectrometry meth-od for determination of chloroform in whole blood based on the use of acetoni-trile as solvent and additional extraction of chloroform from acetonitrile su-pernatant by small amounts of hexane was developed. Chloroform concentra-tions in the blood of population at the territories supplied with chlorinated drinking water are significantly higher than that of population at the territories supplied with water without chlorination (0.03–0.54 ng/ml, P95 0.27 ng/ml versus 0.00–0.37 ng/ml, P95 0.13 ng/ml respectively). A proposed linear de-pendence model enables to predict the chloroform blood level in the exposed population based on water concentrations and vice versa. We recommend the determination of chloroform in the whole blood of the population as an in-formative biomarker of cumulative exposure, reflecting real exposure scenarios for the preceding period of time, based on identified trends.

Quantitative structure-toxicity relationships of halobenzoquinone isomers on DNA reactivity and genotoxicity

Halobenzoquinones (HBQs) are an emerging class of drinking water disinfection byproducts that have been predicted as bladder carcinogens. However, data on the genotoxicity of HBQs are still scarce. This study performed a quantitative structure-toxicity relationship (QSTR) analysis of HBQ isomers on DNA reactivity and genotoxicity. The interaction of HBQs with calf thymus DNA (ct-DNA) was studied using multi-spectroscopic and molecular docking techniques. UV–Vis absorption spectra observed a significant hyperchromic effect with the increase of HBQ concentration. The fluorescence intensity of both probe-ct-DNA decreased with the increasing concentration of HBQs, indicating that the interaction mode between each HBQs and DNA was quite complicated, and there were both minor groove binding and intercalation binding. Molecular docking showed that HBQs interacted with DNA predominantly via hydrogen bond at guanine-rich areas in the minor groove of DNA. The genotoxicity of HBQs on human hepatocytes (L-02) was evaluated by micronucleus test, and the results showed that HBQs could cause significant chromosomal damage. The rank order of HBQ isomers on DNA reactivity and genotoxicity was 2,5-HBQs > their corresponding 2,6-HBQs. QSTR analysis found that dipole moment is the key structural descriptor influencing both DNA reactivity and genotoxicity of HBQ isomers. This study suggested that HBQs have caused genotoxicity which was influenced by their isomeric effects, warranting a comprehensive understanding of the genotoxic and carcinogenic risks associated with HBQs exposure.

Bromoacetic acid impairs mouse oocyte in vitro maturation through affecting cytoskeleton architecture and epigenetic modification

As a major public health achievement, disinfection of drinking water significantly decreases outbreaks of waterborne disease, but produces drinking water disinfection by-products (DBPs) unfortunately. The haloacetic acids (HAAs) including bromoacetic acid (BAA), the second major class of DBPs, are considered as a global public health concern. BAA has been identified as cytotoxic, genotoxic, mutagenic, carcinogenic, and teratogenic in somatic cells. However, the toxic effects of BAA on oocyte maturation remain obscure. Herein, we documented that exposure to BAA compromised mouse oocyte maturation in vitro, causing blocked polar body extrusion (PBE). Meiotic progression analysis demonstrated that exposure to BAA induced the activated spindle assembly checkpoint (SAC) mediated metaphase I (MI) arrest in oocytes. Further study revealed that exposure to BAA resulted in the hyperacetylation of α-tubulin, disrupting spindle assembly and chromosome alignment, which is responsible for the activation of SAC. Besides, the organization of actin, the other major component of cytoskeleton in oocytes, was disturbed after BAA exposure. In addition, exposure to BAA altered the status of histone H3 methylation and 5 mC, indicative of the damaged epigenetic modifications. Moreover, we found that exposure to BAA induced DNA damage in a dose-dependent manner in oocytes. Collectively, our study evidenced that exposure to BAA intervened mouse oocyte maturation via disrupting cytoskeletal dynamics, damaging epigenetic modifications and inducing accumulation of DNA damage.

Oxidative injury induced by drinking water disinfection by-products dibromoacetonitrile and dichloroacetonitrile in mouse hippocampal neuronal cells: The protective effect of N-acetyl-L-cysteine

Dibromoacetonitrile (DBAN) and dichloroacetonitrile (DCAN) are haloacetonitriles (HANs) produced as by-products of chloramine disinfection of drinking water and can cause neurotoxicity. The molecular pathways leading to HAN-induced neuronal cell death remain unclear. The nuclear factor erythroid 2–related factor 2 (Nrf2) is an important regulator of oxidation reactions. We explored the role of the sequestosome 1 (p62)–Kelch-like ECH-associated protein 1 (Keap1)–Nrf2 pathway in DBAN- and DCAN-induced mouse hippocampal neuronal (HT22) cell injury. DBAN and DCAN reduced cell viability, increased lactate dehydrogenase release rate, and promoted apoptosis. Over the same treatment time, DBAN at lower concentrations caused cell injury, suggesting that DBAN is more cytotoxic than DCAN. DBAN and DCAN triggered oxidative stress by reducing intracellular glutathione and increasing reactive oxygen species concentrations. DBAN and DCAN activated the Nrf2 pathway. Furthermore, Nrf2 inhibitors (all-trans retinoic acid) attenuated DBAN- and DCAN-induced toxicity, whereas Nrf2 activators (tert-Butylhydroquinone) achieved the opposite effect. This indicates that activation of the Nrf2 pathway mediates DBAN- and DCAN-induced cell injury. Notably, the expression of p62, a noncanonical pathway that mediates Nrf2 activation, increased, whereas the expression of Keap1, another regulator of Nrf2, decreased. We noted that high p62 expression activated the Nrf2 pathway, and p62 was regulated through Nrf2, forming a positive feedback loop. N-acetyl-L-cysteine, a mercaptan substance, protected against DBAN- and DCAN-induced toxicity and inhibited the Nrf2 pathway. In summary, Nrf2 pathway inhibition and mercaptan supplementation prevent DBAN- and DCAN-induced HT22 cell injury, accordingly, targeting them is a potential approach to preventing HAN-induced neurotoxicity.

Drinking Water Disinfection Byproducts, Ingested Nitrate, and Risk of Endometrial Cancer in Postmenopausal Women.

Background:Disinfection byproducts (DBPs) and N-nitroso compounds (NOC), formed endogenously after nitrate ingestion, are suspected endometrial carcinogens, but epidemiological studies are limited.Objectives:We investigated the relationship of these exposures with endometrial cancer risk in a large prospective cohort.Methods:Among postmenopausal women in the Iowa Women’s Health Study cohort, we evaluated two major classes of DBPs, total trihalomethanes (TTHM) and five haloacetic acids (HAA5), and nitrate-nitrogen () in public water supplies (PWS) in relation to incident primary endometrial cancer (1986–2014). For women using their PWS at enrollment (; ), we computed historical averages of annual concentrations; exposures were categorized into quantiles and when possible percentile. We also computed years of PWS use above one-half the U.S. maximum contaminant level (; TTHM; HAA5; ). Dietary nitrate/nitrite intakes were estimated from a food frequency questionnaire. We estimated hazard ratios (HR) and 95% confidence intervals (CI) via Cox models adjusted for age, endometrial cancer risk factors [e.g., body mass index, hormone replacement therapy (HRT)], and mutually adjusted for . We evaluated associations for low-grade () vs. high-grade () type I tumors. We assessed interactions between exposures and endometrial cancer risk factors and dietary factors influencing NOC formation.Results:Higher average concentrations of DBPs (95th percentile: TTHM , HAA5 ) were associated with endometrial cancer risk (TTHM: , 95% CI: 1.41, 3.40; HAA5: , 95% CI: 1.19, 2.83; ). Associations were similarly observed for women greater than median years of PWS use with levels , in comparison with zero years (TTHM: , 95% CI: 1.18, 2.21; HAA5: , 95% CI: 1.31, 2.62). Associations with DBPs appeared stronger for low-grade tumors (TTHM: , 95% CI: 1.17, 3.83; ) than for high-grade tumors (TTHM: , 95% CI: 0.80, 2.44; ), but differences were not statistically significant (). Associations with TTHM were stronger among ever HRT users than non-HRT users (). We observed no associations with in drinking water or diet.Discussion:We report novel associations between the highest DBP levels and endometrial cancer for our Iowa cohort that warrant future evaluation. https://doi.org/10.1289/EHP10207

Associations between drinking water disinfection byproducts and menstrual cycle characteristics: A cross-sectional study among women attending an infertility clinic.

Disinfection byproducts (DBPs) have been shown to alter ovarian steroidogenesis and cause estrous cyclicity disturbance and prolongation in experimental studies, however human studies are lacking. We aimed to evaluate the cross-sectional associations between drinking water DBPs and menstrual cycle characteristics. A total of 1078 women attending an infertility clinic in Wuhan, China were included between December 2018 and January 2020. Characteristics of menstrual cycle were collected by questionnaires. Concentrations of dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were measured in urine as biomarkers of drinking water DBPs. Multivariate logistic and linear regression models were used to evaluate the associations between urinary DCAA and TCAA concentrations and menstrual cycle characteristics. Higher urinary DCAA concentrations were associated with increased odds ratios (ORs) of irregular menstrual cycle (OR=1.80; 95% CI: 0.97, 3.33 for the highest vs. lowest quartile; P for trend=0.05) and long menstrual cycle (OR=1.62; 95% CI: 0.97, 2.70 for the highest vs. lowest quartile; P for trend=0.06), as well as prolonged variation in cycle length (β=1.27 days; 95% CI: -0.11, 2.66 for the highest vs. lowest quartile; P for trend=0.04). Higher urinary TCAA concentrations were associated with prolonged bleeding duration (β=0.23 days; 95% CI: -0.06, 0.51 for the highest vs. lowest quartile; P for trend=0.07). These results suggest that exposure to drinking water DBPs is associated with menstrual cycle disturbances. These findings are warranted to confirm in other studies.

Effects of iodoacetic acid drinking water disinfection byproduct on the gut microbiota and its metabolism in rats

Iodoacetic acid (IAA) is an unregulated disinfection byproduct in drinking water and has been shown to exert cytotoxicity, genotoxicity, tumorigenicity, and reproductive and developmental toxicity. However, the effects of IAA on gut microbiota and its metabolism are still unknown, especially the association between gut microbiota and the metabolism and toxicity of IAA. In this study, female and male Sprague–Dawley rats were exposed to IAA at 0 and 16 mg/kg bw/day daily for 8 weeks by oral gavage. Results of 16S rRNA gene sequencing showed that IAA could alter the diversity, relative abundance and function of gut microbiota in female and male rats. IAA also increased the abundance of genes related to steroid hormone biosynthesis in the gut microbiota of male rats. Moreover, metabolomics profiling revealed that IAA could significantly disturb 6 and 13 metabolites in the feces of female and male rats, respectively. In female rats, the level of androstanediol increased in the IAA treatment group. These results were consistent with our previous findings, where IAA was identified as an androgen disruptor. Additionally, the perturbed gut microbiota and altered metabolites were correlated with each other. The results of this study indicated that IAA could disturb gut microbiota and its metabolism. These changes in gut microbiota and its metabolism were associated with the reproductive and developmental toxicity of IAA.

Drinking Water Disinfection by-Products and Congenital Malformations: A Nationwide Register-Based Prospective Study.

Background:Drinking water chlorination by-products have been associated with adverse reproductive outcomes, although the findings for congenital malformations are still inconclusive.Objective:We conducted a nationwide register-based prospective study to assess whether first trimester maternal exposure to the four most common trihalomethanes [total trihalomethanes (TTHM)] via municipal drinking water was associated with risk of congenital malformation among newborns.Methods:We included all births during 2005–2015 (live and stillbirths) of mothers residing in Swedish localities having inhabitants, two or fewer operating water works, and sufficient municipal TTHM monitoring data. Individual maternal first trimester exposure was obtained by linking TTHM measurements to residential information, categorized into no chlorination and , 5–15, and TTHM/L. We also made chlorination treatment-specific analyses (exclusive use of chloramine or hypochlorite). Outcomes and covariates were obtained via linkage to health care and administrative registers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression.Results:Based on 623,468 births and a prevalence of congenital malformation of cases/100 births, we observed associations between TTHM exposure in areas using chloramine and malformations of the nervous system (; 95% CI: 1.07, 3.12), urinary system (; 95% CI: 1.53, 2.78), genitals (; 95% CI: 1.38, 2.26), and limbs (; 95% CI: 1.10, 1.64), comparing the highest exposed category with the unexposed. No associations were observed in areas using exclusively hypochlorite as the primary water treatment method. By contrast, for malformations of the heart, a significant inverse association was observed only in areas using hypochlorite.Discussion:TTHM exposure was associated with the increased risk of malformations of the nervous system, urinary system, genitals, and limbs in areas exclusively using chloramine. An association between chloramine-related chlorination by-products and congenital malformations has not previously been highlighted and needs further attention. https://doi.org/10.1289/EHP9122

Drinking water disinfection byproducts and ingested nitrate with the risk of endometrial cancer in postmenopausal women

BACKGROUND AND AIM: Disinfection by-products (DBPs) and {N}-nitroso compounds, formed endogenously after nitrate/nitrite ingestion, are suspected endometrial carcinogens but epidemiologic studies are limited. We investigated their relationship with endometrial cancer risk in a large prospective cohort. METHODS: Among postmenopausal women in the Iowa Women’s Health Study cohort, we evaluated ingestion of total trihalomethanes (TTHM), the sum of five haloacetic acids (HAA5), and nitrate-nitrogen (NO₃-N) in public water supplies (PWS), and dietary nitrate/nitrite in relation to incident primary endometrial cancer (1986-2014). For women using their PWS ≥10 years at enrollment (N=10,501; cases=261), we computed historical averages of annual concentrations based on years of use. We assessed dietary nitrate/nitrite intakes with a food frequency questionnaire (N=22,897; cases=566). We estimated hazard ratios (HR) and 95% confidence intervals (CI) via Cox models adjusted for age, endometrial cancer risk factors (e.g., body mass index, hormone therapy), and mutually adjusted for DBPs or NO₃-N. We used a competing risk model to evaluate associations with low-grade (cases=99) versus high-grade (cases=114) type I tumors. We evaluated joint effects between drinking water exposures and risk factors. RESULTS:Average DBPs ≥95th percentile (TTHM ≥93; HAA5 ≥49 µg/L) were associated with endometrial cancer risk (TTHM HR95vsQ1=2.22;CI=1.43–3.46; HAA5 HR95vsQ1=1.87;CI=1.21–2.88; {p}trends 0.01). Associations with TTHM exposure at the fourth quartile remained significant for low-grade (HRQ4vsQ1=2.11;CI=1.16-3.85) but not high-grade tumors (HRQ4vsQ1=1.39;CI=0.79-2.43; {p}heterogeneity=0.44). For women who ever used estrogen therapy compared to never users, we observed a greater than additive risk at the highest quartile of TTHM (relative excess risk due to interaction, RERI=1.74;CI=0.16-3.33). Associations with NO₃-N in drinking water and dietary nitrate/nitrite were null. CONCLUSIONS:We report the first epidemiologic analysis to demonstrate an association between relatively high DBP levels and endometrial cancer. This observation warrants future evaluation. KEYWORDS: Environmental epidemiology, Cancer and cancer precursors, Female, Water quality

Urinary biomarkers of exposure to drinking water disinfection byproducts and ovarian reserve: A cross-sectional study in China

Experimental studies have demonstrated that disinfection byproducts (DBPs) can cause ovarian toxicity including inhibition of antral follicle growth and disruption of steroidogenesis, but there is a paucity of human evidence. We aimed to investigate whether urinary biomarkers of exposure to drinking water DBPs were associated with ovarian reserve. The present study included 956 women attending an infertility clinic in Wuhan, China from December 2018 to January 2020. Antral follicle count (AFC), ovarian volume (OV), anti-Mullerian hormone (AMH), and follicle-stimulating hormone (FSH) were measured as indicators of ovarian reserve. Urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were assessed as potential biomarkers of drinking water DBP exposures. Multivariate linear and Poisson regression models were applied to estimate the associations of urinary DCAA and TCAA concentrations with indicators of ovarian reserve. Elevated urinary DCAA and TCAA levels were monotonically associated with reduced total AFC (− 5.98%; 95% CI: − 10.30%, − 1.44% in DCAA and − 12.98%; 95% CI: − 17.00%, − 8.76% in TCAA comparing the extreme tertiles; both P for trends ≤ 0.01), and the former was only observed in right AFC but not in left AFC, whereas the latter was estimated for both right and left AFC. Moreover, elevated urinary TCAA levels were monotonically associated with decreased AMH (− 14.09%; 95% CI: − 24.79%, − 1.86% comparing the extreme tertiles; P for trend = 0.03). These negative associations were still observed for the exposure biomarkers modeled as continuous variables. Our findings suggest that exposure to drinking water DBPs may be associated with decreased ovarian reserve.

UPLC-ESI/MS analysis of disinfection by-products (perchlorate, bromate, nitrate, nitrite and sulfite) in micro-filtered drinking water obtained from spring, well and tap water (desalinated) sources

ObjectivesIn the current study, an analytical technique has been optimized for the analysis of disinfection by-products (perchlorate (ClO4−), bromate (BrO3−), nitrate (NO3−), nitrite and sulfite (SO32–) in drinking water obtained from spring, well and tap water (desalinated) sources. MethodsThe ultra-performance liquid chromatography-electrospray ionization mass spectrometry (UPLC-ESI/MS) conditions have been optimized for oxyhalides ClO4− (isotopes, 37ClO4− and 35ClO4−) and BrO3− (isotopes, 81BrO3− and 79BrO3−), and inorganic anions NO3−, NO2− and SO32–. Separation was achieved by BEH C18 column with methanol (75%) and water (24.99%, HCOOH 0.01%) mobile phase at flow rate 0.2 mL/min. ResultsThe analysis was carried out in <1 min with excellent coefficient of determination, (R2 > 0.995–0.999), limit of detection (0.016–0.043 µg/L), limit of quantification (0.051–0.104 µg/L) and precision (repeatability, 1.54–2.28% and reproducibility, 3.13–4.08%) in terms of RSD%. The method was successfully applied, and the amounts of 35ClO4− (5.33–22.64 µg/L), 81BrO3− (7.52–16.73 µg/L), NO3− (5.42–12.14 mg/L), NO2− (1.08–4.37 mg/L) and SO32– (6.84–32.45 mg/L) were identified in spring water, whereas well and tap water contained 35ClO4− (4.20–21.33 µg/L), 81BrO3− (8.05–15.13 µg/L), NO3− (1.27–16.11 mg/L), NO2− (0.43–10.77 mg/L) and SO32– (7.14–36.10 mg/L), and 35ClO4− (0.89–7.37 µg/L), 81BrO3− (5.15–14.68 µg/L), NO3− (1.12–6.33 mg/L), NO2− (0.67–3.95 mg/L) and SO32– (5.40–23.26 mg/L), respectively. ConclusionsThe levels of 35ClO4−, 81BrO3−, NO3−, NO2− and SO32– were found beyond the maximum contaminant levels and drinking water equivalent levels regulated by the Environmental Protection Agency, respectively. The outcomes also revealed that comparatively tap water produced lower levels of these contaminants especially in the cities with low population densities. In addition, the geographical site would be helpful to categorize the tap water samples.