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While it is known that exposure to disinfection by-products (DBPs), including trihalomethanes (THMs), impairs liver function, few epidemiological studies have explored this association. Here, we determined the concentrations of four urinary trihalomethanes (chloroform [TCM], and three Br-THMs, bromodichloromethane [BDCM], dibromochloromethane [DBCM], and bromoform [TBM]), and nine serum liver function indicators in 182 adults ≥ 18 years of age, examined at a medical examination center in Wuxi, China, in 2020 and 2021. Generalized linear model analysis revealed positive associations between urinary DBCM and alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), total protein (TP), and albumin (ALB). Urinary Br-THMs and total THMs (TTHMs) were positively associated with ALT, AST, TBIL, indirect bilirubin (IBIL), TP, and ALB (all P < 0.05). Urinary THMs were not associated with alkaline phosphatase (ALP) or glutamine transaminase (GGT) (all P > 0.05). Generalized additive model–based penalized regression splines were used to confirm these associations. In conclusion, THM exposure was associated with altered serum biomarkers of liver function. [ABSTRACT FROM AUTHOR]

Humans are exposed to disinfection by-products (DBPs) mainly through drinking water ingestion and dermal contact. As an emerging class of nitrogenous DBPs (N-DBPs), haloacetamides (HAcAms) have been found to have significantly higher cytotoxicity than regulated DBPs. In this study, we investigated the cytotoxicity of HAcAms on two exposure pathway-related cell lines: human gastric epithelial GES-1 cells and immortalized keratinocytes HaCaT. Our results showed that the ranking order of cytotoxicity of 13 HAcAms was different between HaCaT and GES-1 cells. In addition, the 50% inhibitive concentration in HaCaT was 1.01–3.29 times that in GES-1. Further comparison among GES-1, HaCaT and CHO cell lines confirmed that different cell lines exhibited different sensitivity to the same compound. Importantly, HAcAms showed 5.83–7.13 × 104 times higher toxicity than the well-clarified DBP chloroform, clearly demonstrating the increased toxicity of HAcAms. Finally, using a novel high-content screening (HCS) analysis, we found that 39.29% of chlorinated HAcAms, 42.86% of brominated HAcAms and 16.07% of iodinated HAcAms significantly affected at least one of the cell-health parameters, such as nuclear size, membrane permeability, mitochondrial membrane potential, or cytochrome c release, in GES-1 or HaCaT cells. Thus, brominated HAcAms appear to have stronger effects under the sublethal exposure dose, possibly causing cytotoxicity via apoptosis. Together, our study provides new insights to the toxicity of HAcAms and a comprehensive toxicology dataset for health risk assessment. Unlabelled Image • Haloacetamides (HAcAms) showed higher cytotoxicity to GES-1 cells than HaCaT cells • Different cell lines exhibited different sensitivity to the same compound of HAcAms • HAcAms showed thousands times higher toxicity than the well-clarified DBP chloroform • Sublethal dosed Brominated HAcAms have stronger effects on cell health • HAcAms possibly cause cytotoxicity via apoptosis. [ABSTRACT FROM AUTHOR]

As an emerging class of nitrogenous disinfection by-products (N-DBPs), haloacetamides (HAcAms) have been widely detected in drinking water. Limited toxicity studies have shown an inconsistent toxicity of monoHAcAms, including CAcAm, BAcAm and IAcAm. In this study, the developmental toxicity of monoHAcAms was evaluated in embryo-larval stage of zebrafish. Embryos were exposed to one concentration of 2.50, 5.00, 10.0, 20.0, 40.0 and 80.0 mg/L monoHAcAms from 4 h post-fertilization (hpf) to 120 hpf. Multiple endpoints, including hatching rate, morphological abnormalities, mortality as well as locomotor behavior were assessed at specified stages (24, 48, 72, 96 and 120 hpf). Results showed that 80 mg/L CAcAm and 40 mg/L BAcAm significantly decreased the hatching rate, IAcAm decreased the hatching rate and delayed the hatching process in a concentration-dependent manner with an EC 50 of 16.37 mg/L at 72 hpf. The frequency and severity order of morphological abnormalities increased with the raised exposure concentrations and prolonged exposure time, and the corresponding EC 50 at 96 hpf were 21.10, 9.77 and 16.60 mg/L for CAcAm, BAcAm and IAcAm, respectively. MonoHAcAms exposure resulted in a time- and dose-dependent response in mortality and the calculated LC 50 at 72 hpf were 38.44, 17.74 and 28.82 mg/L for CAcAm, BAcAm and IAcAm, respectively. Based on EC 50 for morphological abnormalities and LC 50 , a toxicity rank order of BAcAm > IAcAm > CAcAm was observed. Different degrees of hyperactivity and hypoactivity were observed from locomotor behavior analysis in larvae from ≤10.0 mg/L monoHAcAms exposure groups. The light-dark periodic change was disappeared in larvae of 10.0 mg/L BAcAm exposure group. In summary, our study showed that monoHAcAms were developmentally toxic to zebrafish even at very low concentrations and BAcAm exerted higher toxicity than IAcAm and CAcAm. These results will further our understanding of the toxicity of HAcAms and its potential toxicological impact on human and ecological environment. Image 1 • Monohaloacetamides (monoHAcAms) is an emerging class of nitrogenous DBPs. • MonoHAcAms disturbed the hatching process of embryos. • MonoHAcAms induced curved body axis, pericardial and yolk sac oedema of zebrafish. • MonoHAcAms affected the mortality and locomotor behavior of zebrafish. • Bromoacetamide exerted higher toxicity than iodoacetamide and chloroacetamide. [ABSTRACT FROM AUTHOR]

Chlorination is widely used to disinfect drinking water to keep humans safe from microorganisms. During chlorination, chlorine and its compounds react with contaminants to form disinfection by-products (DBPs). Toxicological and epidemiological studies have demonstrated that trihalomethanes (THMs) are the most widely investigated DBPs in drinking water, and their exposure has been associated with some adverse health effects. However, studies about risk characteristics in this field are limited. We estimated the health risks of THMs exposure in drinking water through multi-pathways, and systematically analyzed the factors influencing health risks of THMs in Wuxi, China. A total of 488 drinking water samples were collected and analyzed for THMs from four water treatment utilities from 2008 to 2016 in Wuxi. And water exposure parameters were obtained from 602 participants by structured questionnaires. The median concentration of THMs ranged from 6.71 μg/L to 9.18 μg/L. The cumulative cancer risk of THMs exposure through multi-pathways was 1.26 × 10−4, and CHBr 2 Cl made the largest contribution to the total cancer risk (48.25%). The non-cancer risk of THMs exposure was 2.02 × 10−1. Health risks of the exposure to THMs in drinking water in summer were significantly higher than that in winter (P = 0.0003 for cancer risk, and P = 5.95 × 10−7 for non-cancer risk). In our study, the average individual disability-adjusted life years (DALYs) lost was 1.27 × 10−4 per person-year (ppy). This study attempted to use DALYs for risk assessment of THMs, which will provide useful information for risk comparison and prioritization of hazards in drinking water. This suggested that potential higher risk might exist, and possible measures could be considered to decrease the health risks. [Display omitted] • Cumulative cancer risk of trihalomethanes exposure was 1.26 × 10−4. • Non-carcinogenic risk of trihalomethanes in drinking water was lower than 1. • CHBr 2 Cl made the largest contribution to the cancer and non-cancer risk. • Average individual trihalomethane cancer risk was 1.27 × 10−4 DALYs per person-year. • Inhalation exposure was the most important pathway for total risk. [ABSTRACT FROM AUTHOR]

• An auto-SPE-GC-ECD method was developed for quantification of ten HAcAms in drinking water. • The solvent-, sample-, labor-saving method was fully optimized and validated. • Sixteen water samples from four WTPs were analyzed by SPE-GC-ECD. Drinking water disinfection may result in the formation of different classes of toxic disinfection by-products (DBPs). Haloacetamides (HAcAms) are an emerging class of nitrogenous DBPs (N-DBPs), which are generally more prevalent at lower concentrations in disinfected water than carbonaceous DBPs. Herein a fast, convenient, and effective method of analyzing 10 HAcAms in drinking water samples was demonstrated. This method was developed using gas chromatography /electron capture detection (GC/ECD) supplemented with automated solid phase extraction (auto-SPE). The variables for automated SPE procedures were further optimized, including the selection of SPE sorbents, types and volumes of extraction solvents, SPE washing solvents and wash times. Under optimized conditions, the instrumental linearity range was 0.5–150 μg L-1 with correlation coefficients>0.9975. The limits of detection and quantification of this method were 0.002–0.003 μg L-1 and 0.005–0.010 μg L-1, respectively. The recovery values ranged from 72.4% to 108.5%, and the relative standard deviations ranged from 3.3% to 9.1%. Therefore, the auto-SPE-GC-ECD method showed acceptable linearity and repeatability and was subsequently validated and applied to analyze 10 HAcAms in drinking water. [ABSTRACT FROM AUTHOR]