Dichloroacetic Acid Concentrations Research Articles

Urinary haloacetic acid concentrations and thyroid function among women: Results from the TREE study

BackgroundDisinfection byproducts (DBPs) have been shown to impair thyroid function in experimental models. However, epidemiological evidence is scarce. MethodsThis study included 1190 women undergoing assisted reproductive technology (ART) treatment from the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. Serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured as indicators of thyroid function. FT4/FT3 and TSH/FT4 ratios were calculated as markers of thyroid hormone homeostasis. Dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the two most abundant HAAs, in urine were detected to assess individual DBP exposures. ResultsAfter adjusting for relevant covariates, positive associations were observed between urinary TCAA concentrations and serum TSH and TSH/FT4 levels (e.g., percent change = 5.82 %, 95 % CI: 0.70 %, 11.21 % for TSH), whereas inverse associations were found for serum FT3 and FT4 (e.g., percent change = −1.29 %, 95 % CI: −2.49 %, −0.07 % for FT3). There also was a negative association between urinary DCAA concentration and serum FT4/FT3 (percent change = −2.49 %, 95 % CI: −4.71 %, −0.23 %). These associations were further confirmed in the restricted cubic spline and generalized additive models with linear or U-shaped dose-response relationships. ConclusionUrinary HAAs were associated with altered thyroid hormone homeostasis among women undergoing ART treatment.

Association between Urinary Haloacetic Acid Concentrations and Liver Injury among Women: Results from the Tongji Reproductive and Environmental (TREE) Study.

Experimental studies have shown that disinfection byproducts (DBPs) including haloacetic acids (HAAs) can cause liver toxicity, but evidence linking this association in humans is sparse. We aimed to explore the associations between HAA exposures and liver injury. We included 922 women between December 2018 and January 2020 from the Tongji Reproductive and Environmental (TREE) cohort study in Wuhan, China. Urinary HAA concentrations including trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) and serum indicators of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) were measured. Liver injury was defined as if any of serum indicator levels were above the 90th percentile. Multivariate logistic and linear regression models were fitted to assess the associations of urinary HAA concentrations with the risk of liver injury and liver function indicators. Stratified analyses by age, body mass index (BMI), alcohol use, and passive smoking were also applied to evaluate the potential effect modifiers. There is little evidence of associations of urinary TCAA concentrations with liver injury risk and liver function indicators. However, urinary DCAA concentrations were associated with a higher risk of liver injury [odds ratios (OR) for 1-interquartile range (IQR) increase in natural log (ln) transformed DCAA concentrations: 1.45; 95% confidence interval (CI): 1.07, 1.98]. This association was observed only among nondrinkers (). We also found that a 1-IQR increase in ln-transformed DCAA concentrations was positively associated with ALT levels (percentage ; 95% CI: 0.48%, 11.95%) and negatively associated with AST/ALT (percentage ; 95% CI: , ). In addition, urinary DCAA concentrations in relation to higher GGT levels was observed only among passive smokers (). Our findings suggest that exposure to DCAA but not TCAA is associated with liver injury among women undergoing assisted reproductive technology. https://doi.org/10.1289/EHP13386.

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.

Associations of exposure to disinfection by-products with blood coagulation parameters among women: Results from the Tongji reproductive and environmental (TREE) study

BackgroundExperimental studies have shown that disinfection byproducts (DBPs) induce coagulotoxicity, but human evidence is scarce. ObjectiveThis study aimed to explore the relationships of DBP exposures with blood coagulation parameters. MethodsAmong 858 women from the Tongji Reproductive and Environmental (TREE) study, urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected as internal biomarkers of DBP exposures. We measured activated partial thromboplastin time (APTT), fibrinogen (Fbg), international normalized ratio (INR), prothrombin time (PT), and thrombin time (TT) as blood coagulation parameters. Multivariable linear regression models were utilized to estimate the relationships between urinary DCAA and TCAA and blood coagulation parameters. The effect modifications by demographic and lifestyle characteristics were further explored. ResultsElevated tertiles of urinary DCAA concentrations were associated with increased PT and INR (11.29%, 95% CI: 1.66%, 20.92% and 0.99%, 95% CI: 0.08%, 1.90% for the third vs. first tertile, respectively; both P for trends < 0.05). Stratification analysis showed that the positive associations were only observed among younger (< 30 years), leaner (body mass index < 24.0 kg/m2), and non-passive smoking women. Moreover, elevated tertiles of urinary TCAA concentrations in positive associations with PT and INR were observed among younger women (17.89%, 95% CI: 2.50%, 33.29% and 1.82%, 95% CI: 0.34%, 3.30% for the third vs. first tertile, respectively; both P for trends < 0.05) but not among older women (both P for interactions < 0.05). ConclusionHigher levels of urinary DCAA and TCAA are associated with prolonged clotting time among women.

Associations between Urinary Concentrations of Disinfection Byproducts and in Vitro Fertilization Outcomes: A Prospective Cohort Study in China.

Experimental studies show that disinfection byproducts (DBPs) can inhibit oocyte maturation, decrease fertilization capacity, and impair embryo development, but human evidence is lacking. We aimed to evaluate the associations between exposure to drinking water DBPs and in vitro fertilization (IVF) outcomes. The study included 1,048 women undergoing assisted reproductive technology (ART) treatment between December 2018 and January 2020 from a prospective cohort study, the Tongji Reproductive and Environmental study in Wuhan, China. Exposure to DBPs was assessed by dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) in up to four urine samples, which were collected on the day of both enrollment and oocyte retrieval. Multivariable generalized linear mixed models, accounting for multiple IVF cycles per woman, were applied to evaluate the associations between urinary biomarkers of DBP exposures and IVF outcomes. Stratified analyses were used to explore the potential effect modifiers. The included 1,048 women underwent 1,136 IVF cycles, with 960 (91.6%), 84 (8.0%), and 4 (0.4%) women contributing one cycle, two cycles, and three cycles, respectively. We found that elevated quartiles of urinary DCAA and TCAA concentrations were associated with reduced numbers of total oocytes and metaphase II oocytes and that urinary DCAA concentrations with a lower proportion of best-quality embryos (all p for ). Moreover, elevated quartiles of urinary DCAA concentrations were associated with decreased proportions of successful implantation, clinical pregnancy, and live birth (14%, 15%, and 15% decreases in adjusted means comparing the extreme quartiles, respectively; all p for ). Stratification analyses showed that the inverse associations of urinary TCAA concentrations with multiple IVF outcomes were stronger among women y of age (p for ). Exposure to drinking water DBPs was inversely associated with some IVF outcomes among women undergoing ART treatment. Further study is necessary to confirm our findings. https://doi.org/10.1289/EHP12447.

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.

Exposure to disinfection by-products and reproductive hormones among women: Results from the Tongji Reproductive and Environmental (TREE) study

BackgroundDisinfection by-products (DBPs) have been shown to impair female reproductive function. However, epidemiological evidence on reproductive hormones is scarce. ObjectiveTo investigate the associations between DBP exposures and reproductive hormones among women undergoing assisted reproductive technology. MethodsWe 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 (E2), 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. ResultsAfter 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. ConclusionUrinary DCAA but not TCAA was associated with altered serum PRGE and PRL levels among women undergoing assisted reproductive technology.

Profiles, variability and predictors of concentrations of blood trihalomethanes and urinary haloacetic acids along pregnancy among 1760 Chinese women

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.

Photocatalysis in an external four-lamp reactor: modelling and validation—dichloroacetic acid photo-oxidation in the presence of TiO2

Monte Carlo (MC) approach has been used to simulate the photocatalysis process in a photoreactor surrounded by four UV-A lamps attached to a cylindrical aluminum-covered surface. The asymmetrical configuration of the experimental setup suggests the use of MC as a suitable mathematical tool to solve the radiation transfer equation (RTE). Reflectance of frontiers in the photocatalytic reactor has been optimized to minimize the differences between the experimental and the theoretical overall volumetric rate of photon absorption (OVRPA). OVRPA increases as the TiO2 concentration is raised up to values in the proximity of 0.1 g L−1; thereafter, this parameter remains constant. The theoretical results have been validated by means of the photocatalysis of dichloroacetic acid (DCA). Validation has been carried out by completing experiments at different initial DCA concentrations and TiO2 doses. MC algorithm facilitates the solution of the RTE in complex photocatalytic systems. The use of imaginary frontiers reduces computational efforts with no loss in model validation. DCA photocatalysis sustains the theoretical results obtained under different experimental conditions.

Dichloroacetic acid upregulates apoptosis of ovarian cancer cells by regulating mitochondrial function.

BackgroundMetabolic reprogramming is a characteristic of tumor cells and is considered a potential therapeutic target. Even under aerobic conditions, tumor cells use glycolysis to produce energy, a phenomenon called the “Warburg effect”. Pyruvate dehydrogenase kinase 1 (PDK1) is a key factor linking glycolysis and the tricarboxylic acid cycle. Dichloroacetic acid (DCA) reverses the Warburg effect by inhibition of PDK1 to switch cytoplasmic glucose metabolism to mitochondrial oxidative phosphorylation (OXPHOS).MethodsCell viability was examined using a standard MTT assay. Glucose consumption and l-lactate production were measured using commercial colorimetric kits, and intracellular lactate dehydrogenase (LDH) activity was evaluated using cell lysates and an LDH Quantification Kit. Real-time PCR was used to detect the expression of related genes. The production of total ROS was evaluated by staining with dichlorofluorescin diacetate.ResultsComparison of various aspects of glucose metabolism, such as expression of key enzymes in glycolysis, lactate production, glucose consumption, mitochondrial oxygen consumption rate, and citric acid production, revealed that A2780/DDP cells were primarily dependent on glycolysis whereas A2780 cells were primarily dependent on mitochondrial OXPHOS. Mitochondrial uncoupling protein 2 (UCP2) protects against mitochondrial ROS while allowing energy metabolism to switch to glycolysis. Treatment of A2780 cells with various concentrations of DCA resulted in decreased expression of UCP2, a metabolic switch from glycolysis to mitochondrial OXPHOS, and an increase in oxidative stress induced by ROS. These effects were not observed in A2780/DDP cells with higher UCP2 expression suggesting that UCP2 might induce changes in mitochondrial functions that result in different sensitivities to DCA.ConclusionOur results show that a drug targeting tumor metabolic changes affects almost the entire process of glucose metabolism. Thus, it is necessary to comprehensively determine tumor metabolic functions to facilitate individualized antitumor therapy.

Genetic damage in young swimmers exposed to pool disinfection by-products

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.

Guidance for the risk assessment of enzyme-containing consumer products

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.

A Mechanism-Based Pharmacokinetic Enzyme Turnover Model for Dichloroacetic Acid Autoinhibition in Rats

Dichloroacetic acid (DCA), a halogenated organic acid, is a pyruvate dehydrogenase kinase inhibitor that has been used to treat congenital or acquired lactic acidosis and is currently in early-phase clinical trials for cancer treatment. DCA was found to inhibit its own metabolism by irreversibly inactivating glutathione transferase zeta 1 (GSTZ1-1), resulting in nonlinear kinetics and abnormally high accumulation ratio after repeated dosing. In this analysis, a semi-mechanistic pharmacokinetic enzyme turnover model was developed for the first time to capture DCA autoinhibition, gastrointestinal region–dependent absorption, and time-dependent change in bioavailability in rats. The maximum rate constant for DCA-induced GSTZ1-1 inactivation is estimated to be 0.96/h, which is 110 times that of the rate constant for GSTZ1-1 natural degradation (0.00875/h). The model-predicted DCA concentration that corresponds to 50% of maximum enzyme inhibition (EC50) is 4.32 mg/L. The constructed pharmacokinetic enzyme turnover model, when applied to human data, could be used to predict the accumulation of DCA after repeated oral dosing, guide selection of dosing regimens in clinical studies, and facilitate clinical development of DCA.

Formation of disinfection by-products during chlorine dioxide pre-oxidation of chironomid larvae metabolites followed by chlorination

AbstractThe objective of this research was to investigate the formation of disinfection by-products (DBPs) during chlorine dioxide pre-oxidation of chironomid larvae metabolites followed by chlorination. The mode of action of chlorine dioxide/chlorine combination was clarified, including the impact of different factors on DBP formation. The results indicated that pre-oxidation suppressed the production of most DBPs such as trihalomethanes, haloacetic acids, haloacetonitriles, and haloketones, compared to when chlorination was used alone. The concentrations of trichloromethane (TCM), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), dichloroacetonitrile (DCAN), and 1,1-dichloro-2-propanone (1,1-DCP) decreased with prolonged pre-oxidation times, with the highest yields observed for DCAA and TCAA. The solution pH had a distinct influence on DBP formation, with the concentrations of DCAA, TCAA, DCAN, 1,1-DCP, and 1,1,1-trichloro-2-propanone (1,1,1-TCP) initially increasing and then decreasing with incr...

Temporal variability in urinary levels of drinking water disinfection byproducts dichloroacetic acid and trichloroacetic acid among men

Urinary haloacetic acids (HAAs), such as dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), have been suggested as potential biomarkers of exposure to drinking water disinfection byproducts (DBPs). However, variable exposure to and the short elimination half-lives of these biomarkers can result in considerable variability in urinary measurements, leading to exposure misclassification. Here we examined the variability of DCAA and TCAA levels in the urine among eleven men who provided urine samples on 8 days over 3 months. The urinary concentrations of DCAA and TCAA were measured by gas chromatography coupled with electron capture detection. We calculated the intraclass correlation coefficients (ICCs) to characterize the within-person and between-person variances and computed the sensitivity and specificity to assess how well single or multiple urine collections accurately determined personal 3-month average DCAA and TCAA levels. The within-person variance was much higher than the between-person variance for all three sample types (spot, first morning, and 24-h urine samples) for DCAA (ICC=0.08–0.37) and TCAA (ICC=0.09–0.23), regardless of the sampling interval. A single-spot urinary sample predicted high (top 33%) 3-month average DCAA and TCAA levels with high specificity (0.79 and 0.78, respectively) but relatively low sensitivity (0.47 and 0.50, respectively). Collecting two or three urine samples from each participant improved the classification. The poor reproducibility of the measured urinary DCAA and TCAA concentrations indicate that a single measurement may not accurately reflect individual long-term exposure. Collection of multiple urine samples from one person is an option for reducing exposure classification errors in studies exploring the effects of DBP exposure on reproductive health.

Disinfection by-product formation from the monochloramination of chironomid larvae

Formation of disinfection by-products (DBPs), including dichloroacetonitrile (DCAN), trichloroacetonitrile (TCAN), chloroform (TCM), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), chloropicrin (TCNM) and chloral hydrate (CH), from monochloramination of chironomid larvae was investigated at different contact times, pH levels and temperatures. Increased monochloramine dosage and prolonged reaction time resulted in an increase in most DBPs. Furthermore, the concentrations of TCAN, DCAN and CH initially increased over time before reaching a plateau. This is because of the hydrolysis of functional groups and the function of NH2Cl. The concentrations of DCAA, TCAA and TCM decreased as pH was increased from 5 to 10, and TCAN, DCAN and CH were not detected when the pH exceeded 8. As for TCNM, their concentration increased as the pH increased from 5 to 7, following a subsequent decrease at higher pH values. High temperatures led to higher DCAN and TCAN concentrations, while low temperatures resulted in higher TCNM and DCAA concentrations. Both high and low temperatures reduced the concentrations of TCAN and CH. Finally, concentrations of the four predominant DBPs (TCM, DCAN of DCAA and TCAA) all decreased as Cl/N ratio declined.

Long-term dietary exposure to low concentration of dichloroacetic acid promoted longevity and attenuated cellular and functional declines in aged Drosophila melanogaster

Dichloroacetic acid (DCA), a water disinfection by-product, has attained emphasis due to its prospect for clinical use against different diseases including cancer along with negative impact on organisms. However, these reports are based on the toxicological as well clinical data using comparatively higher concentrations of DCA without much of environmental relevance. Here, we evaluate cellular as well as organismal effects of DCA at environmentally and mild clinically relevant concentrations (0.02-20.0 μg/ml) using an established model organism, Drosophila melanogaster. Flies were fed on food mixed with test concentrations of DCA for 12-48 h to examine the induction of reactive oxygen species (ROS) generation, oxidative stress (OS), heat shock genes (hsps) and cell death along with organismal responses. We also examined locomotor performance, ROS generation, glutathione (GSH) depletion, expression of GSH-synthesizing genes (gclc and gclm), and hsps at different days (0, 10, 20, 30, 40, 50) of the age in flies after prolonged DCA exposure. We observed mild OS and induction of antioxidant defense system in 20.0 μg/ml DCA-exposed organism after 24 h. After prolonged exposure to DCA, exposed organism exhibited improved survival, elevated expression of hsp27, gclc, and gclm concomitant with lower ROS generation and GSH depletion and improved locomotor performance. Conversely, hsp27 knockdown flies exhibited reversal of the above end points. The study provides evidence for the attenuation of cellular and functional decline in aged Drosophila after prolonged DCA exposure and the effect of hsp27 modulation which further incites studies towards the therapeutic application of DCA.

Dichloroacetic Acid (DCA)-Induced Cytotoxicity in Human Breast Cancer Cells Accompanies Changes in Mitochondrial Membrane Permeability and Production of Reactive Oxygen Species

Cancer cells utilize cytosolic glycolysis for their energy production even in the presence of adequate levels of oxygen (Warbug effect) due to mitochondrial defects. Dichloroacetic acid (DCA) shifts cytosolic glucose metabolism to aerobic oxidation by inhibiting mitochondrial pyruvate dehydrogenase kinase (PDK) and increasing pyruvate uptake. Therefore, DCA has potential in reversing the glycolytic metabolism defect in cancerous cells. DCA is also known to induce apoptosis in a number of cancer cell lines, the mechanism of which is not well understood. In this study, an attempt has been made to investigate the effects of DCA on aggressive human breast cancer (MCF-7) cells as compared with less aggressive mouse osteoblastic (MC3T3) cells. Cell cytotoxicity was determined by MTT, crystal violet and Trypan blue exclusion assays. Western blot was used to detect any changes in the expression of apoptotic markers. Flow cytometry was used to measure apoptotic and necrotic effects of DCA. Mitochondrial integrity was determined by change in mitochondrial membrane potential (Δψm), whereas oxidative damage was determined by production of reactive oxygen species (ROS). DCA caused a concentration-dependent cytotoxicity both in MCF-7 and MC3T3 cell lines. MCF-7 cells were most affected. Flow cytometry results showed a significantly higher apoptosis in MCF-7 even at lower concentrations of DCA. However, higher concentrations of DCA were necrotic. Western blotting showed an increased expression of Mn-SOD-1 upon DCA treatment. Further, DCA decreased Δψm and increased ROS production. The effects of DCA were more pronounced on MCF-7 cells as compared to MC3T3 cells. Our results suggest that DCA-induced cytotoxicity in cancerous cells is mediated via changes in Δψm and production of ROS.

Formation of disinfection by-products from the monochloramination of chironomid larvae metabolite solution

Abstract In this study, the formation of disinfection by-products (DBPs) was investigated during the monochloramination of chironomid larvae metabolite solution under different conditions, to find out how the metabolites produced by organisms to affect the water safety and the production of DBPs. Longer reaction time and higher monochloramine dosage resulted in an increase of the most DBPs in bulk solution, where the concentrations of dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) appeared to be much higher than those of the trichloronitromethane (TCNM) and trichloroacetonitrile (TCAN), and chloral hydrate (CH) formation which exhibited an initial increase with a following stable stage. The pH affected the formation of different DBPs in the distinct manner. The concentrations of TCAN, DCAA, TCAA, and CH became lower gradually as pH increasing from 5 to 10, and TCAN and CH could not be detected when the pH exceeded 8–9. And as to the trichloromethane (TCM), dichloroacetonitrile (DCAN), and TCNM...

A kinetic model for the degradation of dichloroacetic acid and formic acid in water employing the H2O2/UV process

A kinetic model for the simultaneous degradation of dichloroacetic acid (DCAA) and formic acid (FA) has been developed. The oxidation is produced by the combination of hydrogen peroxide (HP) and UV (253.7nm) radiation. A set of four equations, three differentials and one algebraic, represents the time evolution of the concentration of DCAA, FA, HP and hydrochloric acid (HCl), a measurable by-product. The model is based on a complete reaction mechanism, which comprises hydrogen peroxide photolysis and decomposition of dichloroacetic and formic acids. It takes into account the effect of non-uniform distribution of the local rate of absorbed photons. The mathematical model renders simulation results that agree with the experimental data. It was also shown that FA decays much faster than DCAA.