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The removal of algal organic matter (AOM) through water treatment processes is a major approach of reducing the formation of disinfection by-products (DBP). Here, the formation of DBP from AOM in karst water under different combination of potassium permanganate (KMnO 4) and polyaluminium chloride (PACl) was investigated. The effect of divalent ions (Ca2+ and Mg2+) on DBP formation was traced by AOM chemistry variations. For DBP formation after KMnO 4 preoxidation, total carbonaceous DBPs (C-DBPs) decreased by 12.9% but nitrogen-containing DBPs (N-DBPs) increased by 18.8%. Conversely, the C-DBPs further increased by 3.3% but N-DBPs reduced by 10.7% after the addition of PACl besides KMnO 4 preoxidation. The variations of aromatic protein-like, soluble microbial products-like compounds and ultraviolet absorbance at 254 nm (UV 254) were highly correlated with the formation of DBPs, which suggest aromatic substances strongly affect DBP behaviors at different treatment conditions. In the presence of divalent ions (Ca2+ = 135.86 mg/L, Mg2+ = 18.51 mg/L), the combination of KMnO 4 and PACl was more effective in controlling DBP formation compared to the situation without Ca2+ and Mg2+. Specifically, trichloromethane formation was largely inhibited compared to the other tested DBPs, which may refer to complexation of electron-donating groups via divalent ions. While Ca2+ and Mg2+ may not affect the nature of α-carbon and amine groups, so the variation of haloacetonitriles (HANs) was not obvious. The study enhances the understanding of the DBP formation patterns, transformation of carbon and nitrogen by preoxidation-coagulation (KMnO 4 -PACl) treatment in algae-laden karst water. [Display omitted] • DBP formation was investigated by KMnO 4 and PACl in algae-laden karst water • PACl addition after KMnO 4 inhibited N-DBP formation rather than C-DBPs • Aromatic substances in AOM strongly affect DBP behaviors • Ca2+ and Mg2+ inhibited TCM formation by complexing electron-donating groups [ABSTRACT FROM AUTHOR]

Trihalomethanes (THMs) and nitrate are widespread chemicals in drinking water. Chronic exposure has been associated with increased cancer risk despite inconclusive evidence, partly due to the challenges in long-term exposure assessment and potential exposure misclassification. We estimated concentrations of nitrate and THMs in drinking water using a public regulatory monitoring database (SISE-Eaux) for CONSTANCES, a French population-based prospective cohort. We obtained 26,322,366 measurements of drinking water parameters from 2000 to 2020. We excluded missing, implausible and duplicated measurements; we corrected or imputed missing geocodes of sampling locations; we calculated the annual median concentration of nitrate and THMs by surveillance area. To predict missing annual median concentrations, linear mixed models with random intercept using surveillance area as a clustering variable were developed for each region for nitrate and the four THM components (chloroform, chlorodibromomethane, bromodichloromethane and bromoform) separately. Concentrations in the nearest surveillance area from the household were merged per year among 75,462 participants with residential history geocoded for 2000–2020. Estimated concentrations resulting from this approach were compared with measured concentrations in 100 samples collected in Paris, Rennes and Saint-Brieuc in 2021. Median annual concentrations of total THMs and nitrate at study participants' homes for 2000–2020 were, respectively, 15.7 μg/l (IQR: 15.2) and 15.2 mg/l (IQR: 20.8). Among these, 35% were based on measurements for nitrate (16% for THMs), 44% (46%) were predicted using on linear mixed models, and 21% (38%) were based on distribution unit median values. Conditional R2 predictive models ranged from 0.71 to 0.91 (median: 0.85) for nitrate, and from 0.48 to 0.80 for THMs (median: 0.68). These concentrations will allow future association analyses with risk of breast and colorectal cancer. Our cleaning process introduced here could be adapted to other large drinking water monitoring data. • French drinking water parameters are routinely monitored and compiled in SISE-Eaux. • We estimated nitrate and THMs annual median concentrations over France (2000–2020). • The procedure of the database cleaning was described in detail. • We linked these estimates to participants' home address in the CONSTANCES cohort. • These exposure assessments will subsequently be used in epidemiological studies. [ABSTRACT FROM AUTHOR]

In this work, we investigate the photolysis behavior of 2,3-dibromo-5,6-dimethyl-1,4-benzoquinone (DDBQ), the only dibrominated benzoquinone detected in treated water so far. DDBQ solutions prepared in ultra-pure water were exposed to UV radiation centered at 254 nm (UV 254), and the photolysis of the parent compound was monitored together with by-product formation. The DDBQ pseudo-first order photolysis rate constants decreased when increasing the initial DDBQ concentration, and this behavior was caused by saturation of absorption. The photodegradation kinetics was found not to depend on pH and 1-butanol addition, but was affected by humic acids and components that occur in both natural waters and treated wastewater. For the first time with this class of compounds, photolysis studies were also performed using natural and treated wastewater matrices, where photodegradation was always found to proceed significantly slower than in ultra-pure water. The implications for the radiation dose that is required to reach a given treatment target are discussed, and a numerical approach by which to foresee the extent of degradation inhibition is provided that should be taken into account when planning the UV 254 treatment of DDBQ. The phototransformation of DDBQ yielded hydroxyderivatives, most likely via a debromination-hydroxylation pathway. In-silico toxicity screening suggested that the transformation of DDBQ into the detected hydroxyderivatives would not eliminate toxicity. Although the monohydroxylated derivative underwent relatively fast transformation, the dihydroxylated compound was found to accumulate during irradiation. As a compromise, the irradiation conditions that produce over 90% degradation of DDBQ in the studied samples, and at the same time keep by-product formation low are discussed. • UV 254 degradation in aqueous matrices follows pseudo-first-order kinetics. • Photolysis in natural waters and treated wastewaters proceeded slower than in ultra-pure water. • A numerical approach to foresee the extent of degradation inhibition is provided. • Phototranformation proceeds via a debromination-hydroxylation pathway. • In-silico toxicity screening suggests that photolysis will not eliminate toxicity. [ABSTRACT FROM AUTHOR]

Blood trihalomethanes (THMs) and urinary haloacetic acids (HAAs) are the leading candidate biomarkers for disinfection byproduct (DBP) exposure. However, no studies have assessed the exposure profiles, temporal variability, and potential predictors of these biomarkers during pregnancy. Here we collected blood (n = 4304) and urine samples (n = 4165) from 1760 Chinese pregnant women during early, mid-, and late pregnancy, which were separately analyzed for 4 THMs and 2 HAAs. We calculated the intraclass correlation coefficients (ICCs) to assess the variability of these biomarkers and estimated their correlations with sociodemographic, water-use behavioral, dietary and sample collection factors using mixed models. The median concentrations of TCM, BDCM, Br-THMs [sum of BDCM, dibromochloromethane (DBCM), bromoform (TBM)], total THMs (TTHMs, sum of TCM and Br-THMs), DCAA and TCAA in the water distribution system were 4.2 μg/L, 1.7 μg/L, 2.9 μg/L, 7.1 μg/L, 3.4 μg/L and 8.2 μg/L, respectively. Chloroform (TCM), bromodichloromethane (BDCM), dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected in > 75% of the biospecimens. Repeated measurements of blood TCM, BDCM, Br-THMs and TTHMs and urinary DCAA and TCAA uniformly exhibited high variability (ICCs = 0.01–0.13); the use of a single measurement to classify gestational average exposure resulted in a high degree of exposure misclassification. The sampling season was a strong predictor of all analyzed DBPs. Additionally, we detected a positive association of blood TCM and BDCM with household income, urinary DCAA with age, and urinary TCAA with tap water usage, education level and amount of tap water consumed. Inverse associations were found between blood BDCM and vegetable consumption, and between blood Br-THM and TTHM and time interval since the last bathing/showering. Afternoon samples had lower DCAA concentrations than did early morning samples. Our results indicate that blood THM and urinary HAA concentrations vary greatly over the course of pregnancy and are affected by sampling season, time of day of blood/urine collection, sociodemographic factors, recent water-use activities and dietary intake. • Blood (n = 4304) and urine samples (n = 4165) were collected from 1760 pregnant women. • TCM, BDCM, DCAA and TCAA were detected in > 75% of the samples. • Repeated measurements of blood THMs and urinary HAAs all exhibited high variability. • Single specimen may not accurately estimate average DBP exposure during pregnancy. • Sampling season, sociodemographic, behavioral and dietary affect DBP variability. [ABSTRACT FROM AUTHOR]

Abstract Background Disinfection by-products (DBPs) have been shown to be reproductive and developmental toxicity. However, few studies examine the effect of prenatal exposure to DBPs on fetal growth via ultrasound measures. Objective To investigate the associations between maternal exposure to DBPs during late pregnancy and ultrasound measures of fetal growth. Methods We included 332 pregnant women who presented to a hospital to wait for delivery in Wuhan, China. Ultrasound parameters of fetal growth including femur length (FL), head circumference (HC), abdominal circumference (AC) and biparietal diameter (BPD) were assessed. We measured maternal TCAA concentrations in first morning urine collected from late pregnancy as a biomarker of in utero DBP exposure levels. Multivariable linear regression models were used to examine the associations between maternal urinary TCAA concentrations during late pregnancy and ultrasound parameters of fetal growth. Results We found that elevated maternal creatinine (Cr)-adjusted urinary TCAA levels had negative associations with BPD, HC and FL in boys but not in girls (P interaction = 0.04, 0.05 and 0.08, respectively). Male fetal BPD, HC and FL had decreases of 0.21 cm (95% CI: −0.35, −0.07; P for trend = 0.003), 0.46 cm (95% CI: −0.81, −0.10; P for trend = 0.01) and 0.17 cm (95% CI: −0.30, −0.04; P for trend = 0.01) for the highest vs. lowest tertile of Cr-adjusted urinary TCAA, respectively. These negative associations persisted for maternal Cr-adjusted urinary TCAA concentrations modeled as continuous variables. Conclusion The results from our study suggest that maternal exposure to TCAA during late pregnancy may have adverse effects on male fetal growth. Highlights • We used urinary TCAA levels as an internal biomarker to assess DBP exposure. • Ultrasound parameters were used as indicators of fetal growth. • TCAA was associated with decreased BPD, HC and FL in boys but not in girls. [ABSTRACT FROM AUTHOR]

In recent years, pollution caused by disinfection by-products (DBPs) has become a global concern. Initially, there were fewer contaminants, and the mechanism of their generation was unclear; however, the number of contaminants has increased exponentially as a result of rapid industrialization and numerous economic activities (e.q., during the outbreak of COVID-19 a surge in the use of chlorinated disinfectants was observed). DBP toxicity results in various adverse health effects and organ failure in humans. In addition, it profoundly affects other forms of life, including animals, plants, and microorganisms. This review comprehensively discusses the pre-treatment methods of traditional and emerging DBPs and the technologies applied for their detection. Additionally, this paper provides a detailed discussion of the principles, applicability, and characteristics of traditional large-scale instrumentation methods (such as gas/liquid/ion chromatography coupled with mass spectrometry) for detecting DBPs based on their respective detection techniques. At the same time, the design, functionality, classification, and characteristics of rapid detection technologies (such as biosensors) are also detailed and analyzed. [ABSTRACT FROM AUTHOR]

Introduction It has been postulated that swimming in heated indoor swimming pools in the first year of life is associated with the development of spinal deformity in children. We explored in pup mice whether exposure to certain disinfection by-products resulting from chlorination of heated pools would affect the future development of the spinal column. Methods Mice, from birth and for 28 consecutive days, were exposed to chemicals known to be created by disinfection by-products of indoor heated swimming pools. The study made use of a body fluid analogue and a chlorine source to recreate the conditions found in municipal pools. A cohort of 51 wild-type C57B6 mice, male and female, were divided into two groups: experimental (n = 29) and controls (n = 22). 24 mice were observed for 8 months (32 weeks), with 27 culled at 4 months (16 weeks). Serial CT scanning was used to assess the spines. Results Exposure to disinfection by-products resulted in an increase in the normal thoracic kyphotic spinal angle of the mice when compared with their controls at 10 weeks; experimental mice kyphosis range 35–82° versus 29–38° in controls. At 14 weeks the kyphosis of the experimental mice had reduced in size but never to that of the control group. Conclusion We have demonstrated the ability to influence spinal development in pup mice through environmental factors and shown that the developmental deformity became evident only after a significant latent period. [ABSTRACT FROM AUTHOR]

In animal and human studies, exposure to trihalomethanes (THMs) has been associated with reduced semen quality. However, the underlying mechanisms remain poorly understood. To investigate the associations of blood THM concentrations with sperm mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) among healthy men. We recruited 958 men who volunteered as potential sperm donors. A single blood sample was collected from each participant at recruitment and measured for chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) concentrations. Within a 90-day follow-up, the last semen sample provided by each participant was quantified for sperm mtDNAcn and TL. We used multivariable linear regression models to assess the associations between blood THM concentrations and sperm mtDNAcn and TL. We also performed stratified analyses according to the time intervals between baseline blood THM determinations and semen collection (i.e., 0–9, 10–14, 15–69, or >69 days) to explore potential windows of susceptibility. After adjusting for potential confounders, we found inverse associations between quartiles (or categories) of blood TBM, brominated THM (Br-THM, the sum of BDCM, DBCM, and TBM), and total THM (TTHM, the sum of all four THMs) concentrations and sperm mtDNAcn (all P for trend≤0.03). Besides, we found inverse associations between quartiles of blood TCM, Br-THM, chlorinated THM (Cl-THM, the sum of TCM, BDCM, and DBCM), and TTHM concentrations and sperm TL (all P for trend<0.10). Stratified analyses showed stronger associations between Br-THM concentrations and sperm mtDNAcn determined 15–69 days since baseline exposure determinations, and between blood TCM and TTHM concentrations and sperm TL determined >69 days since baseline exposure determinations. Exposure to THMs may be associated with sperm mitochondrial and telomeric dysfunction. [Display omitted] • Blood THMs and sperm mtDNAcn and TL were determined among 958 healthy men. • Blood TBM, Br-THMs, and TTHM were inversely associated with sperm mtDNAcn. • Blood TCM, Br-THMs, Cl-THMs, and TTHMs were inversely associated with sperm TL. • Part of these associations differed across the duration of spermatogenesis. [ABSTRACT FROM AUTHOR]

Background Trihalomethanes (THMs) in exhaled breath and trichloroacetic acid (TCAA) in urine are internal dose biomarkers of exposure to disinfection by-products (DBPs) in swimming pools. Objective We assessed how these biomarkers reflect the levels of a battery of DBPs in pool water and trichloramine in air, and evaluated personal determinants. Methods A total of 116 adults swam during 40 min in a chlorinated indoor pool. We measured chloroform, bromodichloromethane, dibromochloromethane and bromoform in exhaled breath and TCAA in urine before and after swimming, trichloramine in air and several DBPs in water. Personal determinants included sex, age, body mass index (BMI), distance swum, energy expenditure, heart rate and 12 polymorphisms in GSTT1 , GSTZ1 and CYP2E1 genes. Results Median level of exhaled total THMs and creatinine adjusted urine TCAA increased from 0.5 to 14.4 µg/m 3 and from 2.5 to 5.8 µmol/mol after swimming, respectively. The increase in exhaled brominated THMs was correlated with brominated THMs, haloacetic acids, haloacetonitriles, haloketones, chloramines, total organic carbon and total organic halogen in water and trichloramine in air. Such correlations were not detected for exhaled chloroform, total THMs or urine TCAA. Exhaled THM increased more in men, urine TCAA increased more in women, and both were affected by exercise intensity. Genetic variants were associated with differential increases in exposure biomarkers. Conclusion Our findings suggest that, although affected by sex, physical activity and polymorphisms in key metabolizing enzymes, brominated THMs in exhaled breath could be used as a non-invasive DBP exposure biomarker in swimming pools with bromide-containing source waters. This warrants confirmation with new studies. [ABSTRACT FROM AUTHOR]

Trihalomethanes (THMs) have been reported to be associated with altered semen quality, and this association may be modified by inherited differences in cytochrome P450 (CYP2E1) and glutathione S-transferase (GSTZ1 and GSTT1), which metabolize THMs. We conducted a cross-sectional study to examine the interactions between CYP2E1, GSTZ1 and GSTT1 polymorphisms and exposure to THMs on semen quality among 401 men from the Reproductive Center of Tongji Hospital in Wuhan China. The baseline blood concentrations of four individual THMs, chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM) and bromoform (TBM), were measured as biomarkers of exposure to drinking water THMs. Genotypes were determined by real-time PCR, and semen-quality parameters were evaluated according to the World Health Organization guidelines. GSTT1 genotype significantly modified the association between exposure to Br-THMs (sum of BDCM, DBCM and TBM) and below-reference sperm motility (Pint=0.02). Men with above-median blood Br-THM levels had an increased odds ratio (OR) of below-reference sperm compared to men with below-median blood Br-THM levels (OR=2.15, 95% CI: 1.11, 4.19) in the GSTT1 null genotype only. In addition, we found that men with a TT of CYP2E1 rs 915,906 had higher blood TCM and TTHM (sum of TCM, BDCM, DBCM and TBM) concentrations than men with a CT/CC of CYP2E1 rs 915,906. Our results suggest that GSTT1 polymorphisms modify Br-THM exposure relation with semen quality, and CYP2E1 polymorphisms are associated with internal levels of exposure to THMs. [ABSTRACT FROM AUTHOR]

Background Impaired postnatal growth after chloroform exposure in utero has been observed in rodents without an effect on birth weight. We aimed to study the relationship between exposure to trihalomethanes (THMs) during pregnancy and postnatal weight growth during infancy. Methods We analysed 2216 mother–child pairs recruited in Gipuzkoa, Sabadell, Valencia (Spain, INMA Project, enrolment: 2003–2008) and Crete (Greece, RHEA Study, enrolment: 2007–2008). Drinking water habits and water-related activities ascertained through personal interviews were combined with THM measurements in drinking water to estimate THM exposure through different exposure routes during pregnancy. Weight measurements during the first year of life were used to fit postnatal weight growth curves from birth to one year and to predict weight at six months. Multiple linear regression was used to evaluate the relationship between six months weight gain and interquartile range (IQR) increase in THM exposure adjusting for confounders. Results Average weight gain at six months ranged from 4325 g (Gipuzkoa) to 4668 g (Crete). Median residential THM levels ranged from 1 μg/l (Crete) to 117 μg/l (Sabadell). No significant association was observed overall (−24.4 g [95% CI −78.8, 30.0] for an IQR increase in total residential uptake). A negative relationship was observed in Sabadell (−148 g [95% CI −282, −13.7]) for an IQR increase in ingestion THM uptake. Conclusions No consistent evidence of an association between THM exposure during pregnancy and postnatal growth was observed. The novelty of the hypothesis and the negative trend observed in the region with the highest levels warrants the replication in future studies. [ABSTRACT FROM AUTHOR]

Disinfection by-products (DBPs) have been shown to impair female reproductive function. However, epidemiological evidence on reproductive hormones is scarce. To investigate the associations between DBP exposures and reproductive hormones among women undergoing assisted reproductive technology. We included 725 women from the Tongji Reproductive and Environmental (TREE) Study, an ongoing cohort conducted in Wuhan, China during December 2018 and January 2020. Urine samples collected at recruitment were quantified for dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) as biomarkers of DBP exposures. At day 2–5 of menstruation, serum reproductive hormones including luteinizing hormone (LH), estradiol (E 2), total testosterone (T), progesterone (PRGE), and prolactin (PRL) were determined. Multivariate linear regression models were performed to assess the associations of urinary DCAA and TCAA concentrations with reproductive hormone levels. Dose-response relationships were investigated using natural cubic spline (NCS) and restricted cubic spline (RCS) models. After adjusting for relevant confounders, we observed that higher urinary DCAA levels were associated with increased serum PRGE (9.2%; 95% CI: −0.55%, 19.8% for the highest vs. lowest tertile; P for trend = 0.06). Based on NCS models, we observed U-shaped associations of urinary DCAA with serum PRGE and PRL; each ln-unit increment in urinary DCAA concentrations above 3.61 μg/L and 6.30 μg/L was associated with 18.9% (95% CI: 4.8%, 34.7%) and 23.3% (95% CI: −0.92%, 53.5%) increase in serum PRGE and PRL, respectively. The U-shaped associations were further confirmed in RCS models (P for overall association ≤0.01 and P for non-linear associations ≤0.04). We did not observe evidence of associations between urinary TCAA and reproductive hormones. Urinary DCAA but not TCAA was associated with altered serum PRGE and PRL levels among women undergoing assisted reproductive technology. • We included 725 women from the TREE cohort. • Urinary TCAA and DCAA were used as disinfection by-product exposure biomarkers. • Serum reproductive hormones were determined on day 2–5 of menstruation. • We found U-shaped associations between DCAA and serum progesterone and prolactin. • The threshold DCAA concentrations were 3.61 μg/L and 6.30 μg/L, respectively. [ABSTRACT FROM AUTHOR]

The present study aims to assess the probable lifetime cancer and non-cancer risks of exposure to the trihalomethanes in Egypt's drinking water through ingestion, dermal contact, and inhalation. A total of 1667 drinking water samples were collected from twenty-three Egyptian governorates over a three-years period. The concentrations of total trihalomethanes ranged between 29.07 and 86.01 μg/L and were always below the maximum contamination level recommended by the Egyptian standards (100 μg/L). Chloroform was the most prominent trihalomethanes species, while bromoform was rarely detected. The cancer risk study revealed that, among the investigated paths, inhalation poses the greatest risk. And bromodichloromethane had the highest impact to cancer (69%), followed by chlorodibromomethane (28%). Geographically, the highest cancer risk value was found in Matruh governorate (42.2 × 10−6) and the lowest was in Minya governorate (1.0 × 10−6). The cancer risk for the studied governorates, except Minya governorate, was higher than the level recommended by the USEPA (1.0 × 10−6). Hazard index (HI) study revealed that the ingestion pathway caused higher HI values than the dermal pathway and that chloroform had the highest contribution to HI value. However, the values of HI were below unity in all studied governorates demonstrating that there would be negligible non-cancer risk. • First nationwide large-scale trihalomethanes (THMs) monitoring study. • The average total THMs was always below the maximum contamination level of Egypt. • Cancer risk exceeded the value recommended by the USEPA. • Bromodichloromethane and chlorodibromomethane played key role in cancer risk. • Non-cancer risk was negligible. [ABSTRACT FROM AUTHOR]

Abstract: Disinfection by-product (DBP) exposure during pregnancy may be related to reduced fetal growth, but the evidence is inconclusive and improved DBP exposure assessment is required. The authors conducted a nested exposure study on a subset (n=39) of pregnant women in the Born in Bradford cohort to assess validity of TCAA exposure assessment based on tap water sampling and self-reported water-use; water-use questionnaire validity; and use of a one-time urinary TCAA biomarker. TCAA levels in urine and home tap water supply were quantified, and water use was measured via a questionnaire and 7-day diary, at 28 weeks gestation. Diary and urine measures were repeated later in pregnancy (n=14). TCAA level in home tap water supply was not correlated with urinary TCAA (0.18, P=0.29). Cold unfiltered tap water intake at home measured by questionnaire was correlated with urinary TCAA (0.44, P=0.007), but correlation was stronger still for cold unfiltered tap water intake reported over the 3 days prior to urine sampling (0.60, P<0.001). For unemployed women TCAA ingestion at home, derived from tap water sampling and self-reported water-use, correlated strongly with urinary TCAA (0.78, P<0.001), but for employed women the correlation was weak (0.31, P=0.20). Results suggest individual tap water intake is most influential in determining TCAA exposure variability in this cohort, and that TCAA ingestion at home is a valid proxy for TCAA exposure for unemployed women but less satisfactory for employed women. [Copyright &y& Elsevier]

Background: Epidemiological evidence of an association between disinfection by-products (DBPs) exposure via drinking water and reproductive outcomes is still inconclusive. Objective: The aim of this study was to investigate the association between trihalomethanes (THMs), chlorite and chlorate exposure and congenital anomalies. Methods: A case-control study was carried out in Emilia-Romagna Region (Italy). Data on 1917 different congenital anomalies (neural tube, cardiac, diaphragm and abdominal wall, oesophagus, cleft lip and palate, respiratory, urinary tract and chromosomal anomalies) observed in the period 2002–2005 were extracted from the Regional Malformation Registry. Four controls (newborns without anomalies) were randomly selected form the Regional Birth Register and frequency matched to cases according to pregnancy period. The network supplying water during the first trimester of pregnancy was identified on the basis of mother's address: DBPs data, technical and structural information were linked to each subject. Results: Overall, THMs exposure was very low (mean: 3.8±3.6μg/l), and no risk excess was observed. Chlorite and chlorate values were fairly high (mean: 427±184μg/l and 283±79μg/l, respectively). Women exposed to chlorite level >700μg/l were at higher risk of newborns with renal defects (OR: 3.30; 95% IC: 1.35–8.09), abdominal wall defects (OR: 6.88; 95% IC: 1.67–28.33) and cleft palate (OR: 4.1; 95% IC: 0.98–16.8); women exposed to chlorate level >200μg/l were at higher risk of newborns with obstructive urinary defects (OR: 2.88; 95% IC: 1.09–7.63), cleft palate (OR: 9.60; 95% IC:1.04–88.9) and spina bifida (OR: 4.94; 95% IC:1.10–22). Conclusions: This was the first study showing an excess risk of different congenital anomalies related to chlorite and chlorate exposure via drinking water: further research is needed to confirm the observed relationships in large datasets, specifically for chlorate, an unregulated DBP. [Copyright &y& Elsevier]

Abstract: Previous epidemiological studies in Massachusetts have reported a risk of adverse health outcomes in relation to disinfection by-product (DBP) exposures. Measurement error due to the use of indirect exposure surrogates can lead to misclassification bias in epidemiological studies; therefore, it is important to characterize exposure variability in these populations to assess the potential for exposure misclassification. We used 19,944 trihalomethane (THM) samples and 9291 haloacetic acid (HAA) samples collected in 201 public water systems (PWSs) in Massachusetts to examine temporal variability under different drinking water sources and disinfection types. Annual and seasonal variability was also examined in 46 PWSs with complete quarterly THM4 (i.e., the sum of 4 individual THMs) data from 1995 to 2004 and 19 PWSs with complete HAA5 (i.e., the sum of 5 individual HAAs) data from 2001 to 2004. The quarterly ratio of THM4 and HAA5 and correlations between THM4, HAA5 and individual DBP species were examined to determine the adequacy of using different exposure surrogates in epidemiological studies. Individual PWSs were used to examine monthly variability in relation to quarterly averages. Based on all available matched samples (n=9003) from 1995 to 2004 data, we found a correlation of 0.52 for THM4 and HAA5. The correlation was stronger among the 62 ground water systems (r s =0.62) compared to the 81 surface water (r s =0.45) and 40 mixed water (r s =0.39) systems. Mean THM4 levels were fairly stable over the 10-year study period for 46 PWSs including 39 PWSs that did not change disinfection. Large reductions (∼40μg/L) in mean THM4 data were found among seven systems that switched from chlorination to alternative disinfectants. As expected, the highest mean THM4 values were detected for Quarter 3, while the lowest values were found in Quarter 1. The highest HAA5 values were detected in Quarters 2 and 3 and the lowest was found in Quarter 4. Data from four systems showed mean differences up to 66μg/L (67% change) in successive months and by 46μg/L compared to quarterly mean concentrations. Although longer-term disinfection by-product temporality may be minimal in this study population, the use of monthly average concentrations for exposure assessment may be needed for some PWSs to minimize misclassification of narrow critical periods of exposure in epidemiological studies. [Copyright &y& Elsevier]

Abstract: Background: Previous epidemiologic studies of preterm birth and drinking water disinfection by-products (DBP) reported inconsistent results especially for third trimester exposures. These inconsistencies may have been due to differences in the underlying causal model assumed and methodological issues, including the method of analysis (cumulative vs. density-sampling of controls and matching on gestational age) and appropriate control of confounding. Methods: We use data from previously published research to illustrate how different causal models, methods of analysis, and the choice of covariates to control impact results. Results: Exposure at high measured TTHM levels (≥60μg/l) during the last trimester – with cumulatively sampled controls – corresponded to negative effect estimates when comparing preterm to term births and averaging exposure over different length periods. In contrast, density-sampling of controls with an exposure truncated at 36 weeks gestation and adjustment for possible confounding by exposures experienced in prior trimesters led to moderate changes in risk at the highest level of exposure averaged over the four weeks prior to birth. Conclusions: We recommend that future research on an exposure to DBPs and risk of preterm birth explore the sensitivity of their findings to different model specifications, specifically: (1) cumulative vs. density-sampling of controls when evaluating third trimester or whole pregnancy exposures, taking into account exposure-averaging length; (2) short-term peak exposures vs. long-term exposures; and (3) adjustment for exposure during prior pregnancy periods when evaluating later trimester exposures to account for possible ‘priming’ effects of early exposures. [Copyright &y& Elsevier]

Abstract: Toxicological studies indicate an association between exposure to disinfection by-products (DBPs) and impaired male reproductive health in animals. However, epidemiological evidence in humans is still limited. We conducted a hospital-based cross-sectional study to investigate the effect of exposure to DBPs on semen quality in humans. Between May 2008 and July 2008, we recruited 418 male partners in sub-fertile couples seeking infertility medical instruction or assisted reproduction services from the Tongji Hospital in Wuhan, China. Major semen parameters analyzed included sperm concentration, motility, and morphology. Exposure to DBPs was estimated by their urinary creatinine-adjusted trichloroacetic (TCAA) concentrations that were measured with the gas chromatography/electron capture detection method. We used linear regression to assess the relationship between exposure to DBPs and semen quality. According to the World Health Organization criteria (<20million/mL for sperm concentration and <50% motile for sperm motility) and threshold value recommended by Guzick (<9% for sperm morphology), there were 265 men with all parameters at or above the reference values, 33 men below the reference sperm concentration, 151 men below the reference sperm motility, and 6 men below the reference sperm morphology. The mean (median) urinary creatinine-adjusted TCAA concentration was 9.2 (5.1)μg/g creatinine. Linear regression analyses indicated no significant association of sperm concentration, sperm count, and sperm morphology with urinary TCAA levels. Compared with those in the lowest quartile of creatinine-adjusted urinary TCAA concentrations, subjects in the second and third quartiles had a decrease of 5.1% (95% CI: 0.6%, 9.7%) and 4.7% (95% CI: 0.2%, 9.2%) in percent motility, respectively. However, these associations were not significant after adjustment for age, abstinence time, and smoking status. The present study provides suggestive but inconclusive evidence of the relationship between decreased sperm motility and increased urinary TCAA levels. The effect of exposure to DBPs on human male reproductive health in Chinese populations still warrants further investigations. [Copyright &y& Elsevier]

Abstract: The objective of this study was to examine the relationship between total trihalomethanes (TTHM) levels in public water supplies and risk of pancreatic cancer and to determine whether calcium (Ca) and magnesium (Mg) levels in drinking water modify the effects of TTHM on risk to develop pancreatic cancer. A matched case-control study was used to investigate the relationship between the risk of death attributed to pancreatic cancer and exposure to TTHM in drinking water in 53 municipalities in Taiwan. All pancreatic cancer deaths in the 53 municipalities from 1998 through 2007 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels in drinking water were collected from Taiwan Environmental Protection Administration. Information on the levels of Ca and Mg in drinking water was obtained from the Taiwan Water Supply Corporation. The municipality of residence for cancer cases and controls was presumed to be the source of the subject''s TTHM, Ca, and Mg exposure via drinking water. Relative to individuals whose TTHM exposure level<4.9ppb, the adjusted OR (95% CI) for pancreatic cancer was 1.01 (0.85–1.21) for individuals who resided in municipalities served by drinking water with a TTHM exposure>4.9ppb. There was no evidence of an interaction of drinking water TTHM levels with low Ca intake via drinking water. However, we observed evidence of an interaction between drinking water TTHM concentrations and Mg intake via drinking water. Our findings showed that the correlation between TTHM exposure and risk of pancreatic cancer is influenced by Mg in drinking water. Increased knowledge of the interaction between Mg and TTHM in reducing pancreatic cancer risk will aid in public policy making and standard setting. [Copyright &y& Elsevier]

Halonitromethanes (HNMs) constitute an emerging class of disinfection by-products (DBPs) produced when chlorine and/or ozone are used for water treatment. The HNMs are structurally similar to halomethanes, but have a nitro-group in place of hydrogen bonded to the central carbon atom. Since little information exists on the genotoxic potential of HNMs, a study has been carried out with two HNM compounds, namely trichloronitromethane (TCNM) and bromonitromethane (BNM) by using human cells. Primary damage induction has been measured with the Comet assay, which is used to determine both the repair kinetics of the induced damage and the proportion of induced oxidative damage. In addition, the fixed DNA damage has been evaluated by using the micronucleus (MN) assay. The results obtained indicate that both compounds are genotoxic, inducing high levels of DNA breaks in the Comet assay, and that this DNA damage repairs well over time. In addition, oxidized bases constitute a high proportion of DNA-induced damage (50–75%). Contrarily, no positive effects were observed in the frequency of micronucleus, which measures both clastogenic and aneugenic effects, neither using TK6 cells nor peripheral blood lymphocytes. This lack of fixed genetic damage would minimize the potential mutagenic risk associated with HNMs exposure. [Copyright &y& Elsevier]

This cross-sectional study aimed to examine the concentration of the by-products of chlorination in the swimming pool and estimate human health risk for the swimmers of Shiraz University of Medical Sciences. In this study, the chloroform concentrations of 16 samples were measured using Gas Chromatography (GC). All the measured concentrations were less than the allowed amount announced by the World Health Organization (WHO). The results of the cancer risk (CR) and hazard index (HI) showed that the major exposure routes were found to be dermal during swimming and the 95 percentile of estimated CR and HI for the male group were 1.38 × 10−10 and 1.82 × 10−5 respectively, which is higher than the values of 5.48 × 10−10 and 2.25 × 10−5 respectively, for the women group. Sensitivity analyses indicated that the swimming exposure time (ET), and chloroform concentration were the most relevant variables in the health risk model. Therefore, knowledge about the sources of micro-pollutants in swimming pools might help promote the health methods of the pool environment. • Two main exposure pathways to the Chloroform in the swimming pool: Unwanted ingestion of water and skin absorption. • Exposure risk assessment of Chloroform on health in swimming time by USEPA SWIMODEL. • Higher concentration of chloroform in the swimming pool water in winter due to higher temperature of the water. [ABSTRACT FROM AUTHOR]

In the framework of a cohort study of pregnant women conducted in Brittany (France), we assessed the exposure to trihalomethanes (THM) during pregnancy in a subset by evaluating (1) potential sources of variability in household THM levels; (2) the between-and within-subject variability in THM levels; (3) THM levels in swimming pools; and (4) the role of water-related habits on total THM uptake. We visited 109 women from the ongoing cohort study at home for an interview and collection of tap water from October to December 2004. Forty-three of them were re-contacted to obtain a second tap water sample in April–May 2005. We designed a questionnaire to collect individual information on source and amount of drinking water, frequency of showering, bathing, and swimming pool attendance, and household characteristics. We obtained 282 THM measurements, 152 specifically for the study and 130 from a regulatory agency. Personal information and environmental data were combined using two methodologies (method 1 using regulatory data and method 2 using our THM measurements) with a different set of assumptions. We calculated ingestion, showering, bathing, and swimming pool THM uptakes and added up those uptakes to calculate total THM uptake. Average THM levels from our measurements in October, November–December, and April–May were 61. 3, 45. 1, and 54. 5μg/l, respectively. Geographical variability was low and characteristics of the household did not influence THM levels. Within-subject variability in THM levels was three times higher than between-subject variability. Average THM level in swimming pools was 80. 4μg/l. Average water consumption during pregnancy was 1. 9l/day. The source of the household drinking water was 90% bottled, 8% municipal, and 2% from other sources. Forty-seven per cent attended swimming pools during pregnancy. Using method 1, the geometric mean of total THM uptake was 0. 93μg/day. Showering contributed 64%, swimming in pools 23%, bathing 12%, and drinking water 1% to the total THM uptake. In a setting with low geographical variability and limited environmental measurements, individual data is highly relevant to determine personal THM exposure and uptake. In a population that mainly drinks bottled water (e. G. , pregnant women), individual THM uptakes are dominated by inhalation and dermal absorption during, showering, swimming in pools, and bathing. [Copyright &y& Elsevier]

The occurrence of trihalomethanes (THMs) in the water supply in the Ankara, Turkey was investigated. Total THMs and total organic carbon measurements were carried seasonally in the samples collected form 22 different districts along with the samples taken from the Ivedik Water Treatment Plant serving 90% of the city. The average summer nonpurgeable organic carbon (NPOC) concentration in the raw water was 4.2 mg/L, and the NPOC removal achieved in the treatment plant was 31%. The concentration of total THMs ranged from 25 to 74 μg/L, from 28 to 73 μg/L, and from 25 to 110 μg/L in winter, spring, and summer, respectively. In all of the samples chloroform existed at the highest concentrations, while bromoform was almost absent. The total THM concentrations were highest in summer for all districts. However, none of the concentrations detected exceeded the USEPA''s Stage I limit of 80 μg/L and the EU''s limit of 100 μg/L. However, the total THM level in 64% of the districts exceeded the USEPA''s Stage II limit of 40 μg/L. The risk estimations carried out indicated that each year 1 of the 5 million Ankara residents could get cancer from the daily intake of water, mainly because of exposure to chloroform through oral ingestion. [Copyright &y& Elsevier]

Brain tumours (BTs) are one of the most frequent tumour types in young people. We explored the association between tap water, exposure to trihalomethanes (THM) and nitrate and neuroepithelial BT risk in young people. Analysis of tap water consumption were based on 321 cases and 919 appendicitis controls (10–24 years old) from 6 of the 14 participating countries in the international MOBI-Kids case-control study (2010–2016). Available historical residential tap water concentrations of THMs and nitrate, available from 3 countries for 86 cases and 352 controls and 85 cases and 343 for nitrate, respectively, were modelled and combined with the study subjects' personal consumption patterns to estimate ingestion and residential exposure levels in the study population (both pre- and postnatal). The mean age of participants was 16.6 years old and 56% were male. The highest levels and widest ranges for THMs were found in Spain (residential and ingested) and Italy and in Korea for nitrate. There was no association between BT and the amount of tap water consumed and the showering/bathing frequency. Odds Ratios (ORs) for BT in relation to both pre- and postnatal residential and ingestion levels of THMs were systematically below 1 (OR = 0.37 (0.08–1.73)) for postnatal average residential THMs higher than 66 μg/L. For nitrate, all ORs were above 1 (OR = 1.80 (0.91–3.55)) for postnatal average residential nitrate levels higher than 8.5 mg/L, with a suggestion of a trend of increased risk of neuroepithelial BTs with increasing residential nitrate levels in tap water, which appeared stronger in early in life. This, to our knowledge, is the first study on this topic in young people. Further research is required to clarify the observed associations. • Brain tumours are one of the most frequent tumour types in young people. • Trihalomethanes and nitrate are possible carcinogens. • To our knowledge, this is the first study focusing on this topic in young people. • We found a possible increased risk for nitrate, and no association for trihalomethanes. [ABSTRACT FROM AUTHOR]

High levels of disinfection by-products (DBPs) are constantly found in drinking water distributed in Sardinia, an Italian island with a tourist vocation and critical issues related to the drinking water supply. To reduce the concentration of trihalomethanes the disinfectant in use was changed – chlorine dioxide was adopted instead of hypochlorite. However, this caused the appearance of other DBPs (e.g. , chlorites) in water distributed to the population. Thus, the use of monochloramine as a secondary disinfectant (associated with chlorine dioxide as the primary disinfectant) was evaluated in four drinking water treatment plants supplied by artificial basins located in the central-northern part of Sardinia. Raw, disinfected and distributed waters were studied for genotoxicity using a battery of in vitro tests on different cells (bacteria, plant and mammalian cells) to detect different genetic endpoints (i.e. , point and chromosome mutations and DNA damage). Moreover, a chemical and microbiological characterisation of water samples was performed. All samples of water distributed to the people showed mutagenic or genotoxic effects in different cells/organisms. In particular, chromosome aberrations in plant cells and DNA damage in human cells were observed. In this study, the use of chloramines associated with other disinfectants did not eliminate the mutagenicity present in the raw water and when the raw water was not mutagenic it introduced mutagenic/genotoxic substances. A careful management of drinking water is needed to reduce health hazards associated with the mutagenicity of drinking water. • Raw, treated and distributed water from four artificial basins were collected. • Genotoxicity of drinking water was evaluated using various in vitro tests. • Disinfection treatment induced genotoxic by-products. • Chloramines treatment in secondary disinfection did not reduce genotoxicity. • All distributed waters showed genotoxicity in plant and human cells. [ABSTRACT FROM AUTHOR]

The gradual updating of the water supply network is one of the crucial ways to ensure the safety of drinking water all over the world. The phenomenon and regularity of the biological risk and chemical risk of biofilms of the new pipes in drinking water distribution system (DWDS) is inadequate researched by now. In order to explore the biochemical risks of biofilms after new pipes are used, this paper studied the growth of biofilms, the content of disinfection by-products (DBPs) and the potential for disinfection by-products (DBPsFP) after 2-year use by establishing a pilot test platform at both ends of the DWDS in City S. The results showed that the total bacterial count in new pipelines was between 1.38 × 108–9.97 × 108/cm2; the DBPsFP at the front end and at the back end was subtly different. The overall DBPsFP of biofilms was the highest, followed by the ductile cast iron pipe and the galvanized pipe whereas the stainless steel pipe was the lowest. The HPC content of the 2-year-old pipe (1.68 × 105–7.09 × 106 CFU/cm2) was remarkably higher than that of the 1-year-old pipe (1.04 × 105–8.76 × 105 CFU/cm2), and the generation DBPsFP was about 50% higher. When a new pipeline was put into use in the urban drinking water distribution system, biofilms with certain biological hazards and risks of DBPs disinfection by-products would form in a short period of time. Image 1 • Pilot experimental platform was located in a real drinking water distribution system. • The potential biochemical risks caused by the renewal of pipelines was explored. • The growth status of the biofilm of the pipeline was investigated. • The content of DBPs and the formation of potential DBPs was investigated. [ABSTRACT FROM AUTHOR]

Exposure to trichloroacetic acid (TCAA) and its parent chemicals potentially linked to cardiovascular disease. However, the association between TCAA and blood pressure (BP) has not been studied to date. The purpose of this study was to examine the potential association between urinary TCAA levels and BP in a Chinese population. We measured BP parameters (including systolic BP, diastolic BP and pulse pressure) and TCAA concentrations in the urine of 569 adults from a primary health care clinic in Shijiazhuang, China. Logistic and linear regressions were used to investigate the relationships between the urinary TCAA levels and BP parameters. To evaluate the robustness of the results, we conducted sensitivity analyses by re-analysing data after excluding urine samples with extreme specific creatinine values. We found that urine TCAA levels were positively associated with systolic BP and pulse pressure based on trend tests after adjusting for potential confounders (both p for trend < 0.05). Finally, only the association of TCAA with systolic BP remained significant in the sensitivity analyses (p < 0.05). Our results suggested that TCAA exposure was associated with increased BP in adults. Because urinary TCAA has been proposed as a valid biomarker of disinfection by-product (DBP) ingestion through disinfected drinking water, our results further suggest that exposure to drinking water DBPs may contribute to high BP in humans. Additional research is needed to confirm these findings and to evaluate opportunities for intervention. • The association between TCAA exposure and human blood pressure change was examined for the first time. • Urinary TCAA was measured as an exposure biomarker in a general population. • A positive dose–response relationship was observed for urinary TCAA with systolic blood pressure. [ABSTRACT FROM AUTHOR]