Exposure to haloacetic acid disinfection by-products and male steroid hormones: An epidemiological and in vitro study.

Haloacetic acids (HAAs) are ubiquitous in drinking water and have been associated with impaired male reproductive health. However, epidemiological evidence exploring the associations between HAA exposure and reproductive hormones among males is scarce. In the current study, the urinary concentrations of dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the internal exposure markers of HAAs, as well as sex hormones (testosterone [T], progesterone [P], and estradiol [E2]) were measured among 449 Chinese men. Moreover, in vitro experiments, designed to simulate the real-world scenarios of human exposure, were conducted to assess testosterone synthesis in the Leydig cell line MLTC-1 and testosterone metabolism in the hepatic cell line HepG2 in response to low-dose HAA exposure. The DCAA and TCAA urinary concentrations were found to be positively associated with urinary T, P, and E2 levels (all p < 0.001), but negatively associated with the ratio of urinary T to E2 (p < 0.05). Combined with in vitro experiments, the results suggest that environmentally-relevant doses of HAA stimulate sex hormone synthesis and steroidogenesis pathway gene expression in MLTC-1 cells. In addition, the inhibition of the key gene CYP3A4 involved in the testosterone phase Ⅰ catabolism, and induction of the gene UGT2B15 involved in testosterone phase Ⅱ glucuronide conjugation metabolism along with the ATP-binding cassette (ABC) transport genes (ABCC4 and ABCG2) in HepG2 cells could play a role in elevation of urinary hormone excretion upon low-dose exposure to HAAs. Our novel findings highlight that exposure to HAAs at environmentally-relevant concentrations is associated with increased synthesis and excretion of sex hormones in males, which potentially provides an alternative approach involving urinary hormones for the noninvasive evaluation of male reproductive health following exposure to DBPs.

Dichloroacetic acid and trichloroacetic acid as disinfection by-products in drinking water are endocrine-disrupting chemicals.

Dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) are two typical non-volatile disinfection by-products (DBPs) found in drinking water. Increasing evidence has demonstrated that they show reproductive toxicity. However, whether they might have endocrine disrupting properties remains largely unknown. To discover this, we treated male mice or pregnant mice with 0, 1-, 102-, 103-, 104-, or 5 × 104-fold maximal concentration level (MCL) of DCAA or TCAA in drinking water. In male mice, the levels of testosterone in serum and androgen receptor (AR) in testis were declined with ≥ 103-fold MCL of DCAA (26.4 mg/kg/d) or TCAA (52.7 mg/kg/d). In pregnant mice, miscarriage rates were increased with ≥ 104-fold MCL of DCAA (264 mg/kg/d) or ≥ 103-fold MCL of TCAA. The levels of FSH in serum were increased and those of estradiol and progesterone were reduced with ≥ 103-fold MCL of DCAA or TCAA. The protein levels of estrogen receptors (ERα and ERß) in ovary were reduced with ≥ 102-fold MCL of DCAA (2.64 mg/kg/d) or TCAA (5.27 mg/kg/d). Exposure to some certain fold MCL of DCAA or TCAA also altered the protein levels of ERα and ERß in uterus and placenta. Exposure to 5 × 104-fold MCL of both DCAA and TCAA showed the combined effects. Therefore, both DCAA and TCAA could be considered as novel reproductive endocrine disrupting chemicals, which might be helpful for further assessment of the toxicological effects of DCAA and TCAA and the awareness of reproductive endocrine disrupting properties caused by DCAA and TCAA in drinking water.

Phytotoxicity of trihalomethanes and trichloroacetic acid on Vigna radiata and Allium cepa plant models.

Disinfection by-products (DBPs) are a concern due to their presence in chlorinated wastewater, sewage treatment plant discharge, and surface water, and their potential for environmental toxicity. Despite some attention to their ecotoxicity, little is known about the phytotoxicity of DBPs. This study aimed to evaluate the individual and combined phytotoxicity of four trihalomethanes (THMs: trichloromethane (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and tribromomethane (TBM) and their mixture (THM4)), and trichloroacetic acid (TCAA) using genotoxic and cytotoxic assays. The analysis included seed germination tests using Vigna radiata and root growth tests, mitosis studies, oxidative stress response, chromosomal aberrations (CA), and DNA laddering using Allium cepa. The results showed a progressive increase in root growth inhibition for both plant species as the concentration of DBPs increased. High concentrations of mixtures of four THMs resulted in significant (p < 0.05) antagonistic interactions. The effective concentration (EC50) value for V. radiata was 5655, 3145, 2690, 1465, 3570, and 725 mg/L for TCM, BDCM, DBCM, TBM, THM4, and TCAA, respectively. For A. cepa, the EC50 for the same contaminants was 700, 400, 350, 250, 450, and 105 mg/L, respectively. DBP cytotoxicity was observed through CAs, including C-metaphase, unseparated anaphase, lagging chromosome, sticky metaphase, and bridging. Mitotic depression (MD) increased with dose, reaching up to 54.4% for TCAA (50-500 mg/L). The electrophoresis assay showed DNA fragmentation and shearing, suggesting genotoxicity for some DBPs. The order of phytotoxicity for the tested DBPs was TCAA > TBM > DBCM > BDCM > THM4 > TCM. These findings underscore the need for further research on the phytotoxicity of DBPs, especially given their common use in agricultural practices such as irrigation and the use of sludge as manure.

Sub-lethal toxicity of five disinfection by-products on microalgae determined by flow cytometry - Lines of evidence for adverse outcome pathways.

Standardised tests are often used to determine the ecotoxicity of chemicals and focus mainly on one or a few generic endpoints (e.g. mortality, growth), but information on the sub-cellular processes leading to these effects remain usually partial or missing. Flow cytometry (FCM) can be a practical tool to study the physiological responses of individual cells (such as microalgae) exposed to a stress via the use of fluorochromes and their morphology and natural autofluorescence. This work aimed to assess the effects of five chlorine-based disinfection by-products (DBPs) taken individually on growth and sub-cellular endpoints of the green microalgae Raphidocelis subcapitata. These five DBPs, characteristic of a chlorinated effluent, are the following monochloroacetic acid (MCAA), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), bromochloroacetic acid (BCAA) and 1,1-dichloropropan-2-one (1,1-DCP). Results showed that 1,1-DCP had the strongest effect on growth inhibition (EC50 = 1.8 mg.L-1), followed by MCAA, TCAA, BCAA and DCAA (EC50 of 10.1, 15.7, 27.3 and 64.5 mg.L-1 respectively). Neutral lipid content, reactive oxygen species (ROS) formation, red autofluorescence, green autofluorescence, size and intracellular complexity were significantly affected by the exposure to the five DBPs. Only mitochondrial membrane potential did not show any variation. Important cellular damages (>10%) were observed for only two of the chemicals (BCAA and 1,1-DCP) and were probably due to ROS formation. The most sensitive and informative sub-lethal parameter studied was metabolic activity (esterase activity), for which three types of response were observed. Combining all this information, an adverse outcome pathways framework was proposed to explain the effect of the targeted chemicals on R. subcapitata. Based on these results, both FCM sub-cellular analysis and conventional endpoint of algal toxicity were found to be complementary approaches.

Innovative electrochemical biosensor with nitrifying biofilm and nitrite oxidation signal for comprehensive toxicity detection in Tuojiang River.

Water toxicity detection, as a valuable supplement to conventional water quality measurement, is an important method for evaluating water environmental quality standards. However, the toxicity of composite pollutants is more complicated due to their mixture effects. This study developed a novel, rapid and interference-resistant detection method for water toxicity based on an electrochemical biosensor using peak current from nitrite oxidation as a signal. Toxicants could weaken the characteristic peak current of nitrite to indicate the magnitude of toxicity. The proof-of-concept study was first conducted using a synthetic water sample containing trichloroacetic acid (TCAA), and then the results were compared with those of the traditional toxicity colorimetric method (CCK-8 kit) and laser confocal microscopy (CLSM). The accuracy of the biosensor was further verified with water samples containing individual pollutants such as Cd2+ (50-150 µg/L), Cr6+ (20-80 µg/L) mixture, triclosan (TCS; 0.1-1.0 µg/L) and TCAA (10-80 µg/L), or a mixture of the above. The viability of the sensor was further validated with the actual water sample from the Tuojiang River. The results demonstrated that although the concentration of a single conventional pollutant in water did not exceed the discharge standard for surface water, the comprehensive toxicity of natural water should not be ignored. This method could be a beneficial supplement to conventional water quality detection to understand the characteristics of the water, and thus contribute to the next stage of water treatment.

Oxidative Damage to BV2 Cells by Trichloroacetic Acid: Protective Role of Boron via the p53 Pathway.

This study aimed to investigate the neurotoxicity induced by trichloroacetic acid (TCA) and the possible protective mechanisms of boron (B). Mouse BV2 cells were treated with TCA (0, 0.39, 0.78, 1.56, 3.12, 6.25, or 12.5 mmol/L) and B (0, 7.8, 15.6, 31.25, 62.5, 125, 500, or 1,000 mmol/L) for 3 h and 24 h, respectively. Then, reactive oxygen species, and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure. Beyond the dose-dependent decrease in the cellular viability, it clearly increased after B supplementation ( P < 0.05). Moreover, B decreased oxidative damage, and significantly down-regulated IL-6 levels and up-regulated TNF-ß production ( P < 0.05). B also decreased apoptosis via the p53 pathway. The present findings indicated that TCA may induce oxidative damage, whereas B mitigates these adverse effects by decreasing cell apoptosis.

Time-concentration-dependent profile of histone modifications on human hepatocytes treated by trichloroacetic acid.

Trichloroacetic acid (TCA) is a common non-volatile by-product of chlorination disinfection for drinking water. It is necessary to know the epigenetic toxicity and mechanisms for establishing safe exposure limit for environmental TCA exposure. This study explored the histone modification variations of TCA-treated human hepatocytes L-02 at different time and concentrations. TCA (0.1 mM, 0.3 mM and 0.9 mM) had an inhibitory effect on the growth of L-02 cells, with no significant changes in morphology. Treated with TCA for 24 h and 48 h, L-02 cells showed decreased mRNA and protein level of histone deacetylases (HDACs), but increased after 72 h. The downregulation of HDACs in early stage of TCA exposure might be one of the important reasons for the increase of H3K9ac level. These changes of histone modification may serve as early epigenetic biomarkers for TCA exposure and the related diseases, offering the safe environmental exposure concentration reference.

Oxidative Damage to BV2 Cells by Trichloroacetic Acid: Protective Role of Boron via the p53 Pathway / 生物医学与环境科学（英文）

This study aimed to investigate the neurotoxicity induced by trichloroacetic acid (TCA) and the possible protective mechanisms of boron (B). Mouse BV2 cells were treated with TCA (0, 0.39, 0.78, 1.56, 3.12, 6.25, or 12.5 mmol/L) and B (0, 7.8, 15.6, 31.25, 62.5, 125, 500, or 1,000 mmol/L) for 3 h and 24 h, respectively. Then, reactive oxygen species, and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure. Beyond the dose-dependent decrease in the cellular viability, it clearly increased after B supplementation ( P < 0.05). Moreover, B decreased oxidative damage, and significantly down-regulated IL-6 levels and up-regulated TNF-β production ( P < 0.05). B also decreased apoptosis via the p53 pathway. The present findings indicated that TCA may induce oxidative damage, whereas B mitigates these adverse effects by decreasing cell apoptosis.

Molecular mechanisms underlying the effect of diacerein on trichloroacetic acid-induced hepatic pre-neoplastic lesions in rats.

CONCLUSION: IL-1ß mediates angiogenesis indirectly, as it has been shown to induce hypoxia-inducible factor-1α (HIF-1α) which upregulates VEGF.

Associations of urinary dichloroacetic acid and trichloroacetic acid exposure with platelet indices: Exploring the mediating role of blood pressure in the general population.

Human exposure to drinking water disinfection by-products (DBPs) is potentially linked to high blood pressure (BP), which may be associated with abnormal platelet activation. This study investigated whether the relationship between DBP exposure with platelet change was mediated by BP. DBP biomarkers, such as urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), BP and platelet indices from 505 adults from a hospital in Shijiazhuang, China were measured. The cross-sectional associations among DCAA and TCAA exposure, BP and platelet indices were explored through multivariable linear regressions, and the mediation effect of BP was evaluated using the Sobel-Goodman test. We observed that DCAA and TCAA were positively associated with systolic BP (all p for trends < 0.01), which was positively associated with platelet count (PLC) (p for trend < 0.05). Mediation analysis indicated that systolic BP fully mediated the associations of DCAA and TCAA with PLC. When BP was controlled, a previously inverse significant relation between DCAA and platelet distribution width (PDW) remained significant (p < 0.05). Obtained results suggested that exposure to DCAA may contribute to decreased PDW in humans. Systolic BP is a possible mediator of the association between DCAA exposure and PLC. TCAA may indirectly positively affect PLC by increasing systolic BP.

Trichloroethylene and trichloroethanol induce skin sensitization with focal hepatic necrosis in guinea pigs.

OBJECTIVES: Occupational exposure to trichloroethylene (TCE) induces trichloroethylene hypersensitivity syndrome (TCEHS), which causes hypersensitivity dermatitis and hepatitis. However, whether TCE itself or its two metabolites, trichloroethanol (TCEOH) and trichloroacetic acid (TCA), are involved in TCEHS remains unclear. Therefore, in this study we explored the allergens causing TCEHS and characterized TCEHS-related liver injury in guinea pigs. METHOD: The guinea pig maximization test was performed using TCE, TCEOH, and TCA as candidate allergens. Skin inflammation was scored, and liver function and histopathological changes were evaluated by biochemical tests and hematoxylin and eosin staining, respectively. RESULTS: The sensitization rates for TCE, TCEOH, and TCA were 90.0%, 50.0%, and 0.0%, respectively. In the TCE and TCEOH experimental groups, the skin showed varying degrees of erythema with eosinophil granulocyte infiltration in the dermis. Additionally, serum alanine aminotransferase and γ-glutamyl transpeptidase levels increased significantly, and histological analysis revealed focal hepatocellular necrosis with inflammatory cell infiltration in the liver. CONCLUSIONS: TCE is the main cause of allergy and TCEOH is a secondary factor for allergy in guinea pigs. TCE and TCEOH can cause immune-mediated skin sensitization complicated by focal hepatic necrosis.

The critical role for TAK1 in trichloroethylene-induced contact hypersensitivity in vivo and in CD4+ T cell function alteration by trichloroethylene and its metabolites in vitro.

Occupational exposure to trichloroethylene (TCE) has been associated with severe, generalized contact hypersensitivity (CHS) skin disorder, which is considered a delayed-type hypersensitivity reaction mediated by antigen-specific T cells. Transforming growth factor-ß activated kinase-1 (TAK1) is essential for regulating the development and effector function of T cells. We hypothesized that disrupting TAK1 activity might inhibit TCE-induced CHS response. In this study, a local lymph node assay was employed to build a CHS model induced by TCE combined with the inducible-TAK1 deletion system to study the effect of TAK1 on it. It was observed that TAK1 deficiency ameliorated the TCE-induced CHS response and was associated with defective T cell expansion and activation and IFN-γ production in vivo. Furthermore, we investigated the effects of TCE and its metabolites trichloroacetic acid (TCA) and dichloroacetic acid (DCA) on CD4+ T cell function and the effect of TAK1 on it in vitro. The results showed that TCE, TCA and DCA augmented the proliferation, activation and differentiation of CD4+ T cells through Jnk MAPK and NF-κB pathways. TAK1 deletion significantly attenuated these effects induced by TCE, TCA or DCA on CD4+ T cells. In conclusion, it is suggested that TAK1 plays a critical role both in TCE-induced CHS response in vivo and in TCE and its metabolite-induced CD4+ T cell activation in vitro. Local inhibition of TAK1 might offer a promising alternative feasible strategy for TCE-induced CHS.

Degradation of haloacetic acids with the Fenton-like and analysis by GC-MS: use of bioassays for monitoring of genotoxic, mutagenic and cytotoxic effects.

In this study, a method was developed to evaluate the degradation of haloacetic acids (HAAs) in water by a heterogenous Fenton-like process catalyzed by cobalt-doped magnetite nanoparticles (Fe3 - xCoxO4), extraction of the contaminants by liquid-liquid extraction (LLE), and analysis by gas chromatography-mass spectrometry (GC-MS). The developed method was efficient in the degradation of HAAs, with the following degradation values: 63%, 62%, 30%, 39%, 37%, 50%, 84%, 41%, and 79% for monochloroacetic acid, monobromoacetic acid, dichloroacetic acid, trichloroacetic acid, bromochloroacetic acid, dibromoacetic acid, bromodichloroacetic acid, dibromochloroacetic acid, and tribromoacetic acid compounds, respectively. Through the application of the Allium cepa test, the cytotoxicity, genotoxicity, and mutagenicity of HAAs were evaluated. The results confirm its genotoxic and mutagenic effects on Allium cepa meristematic cells. Through this study, it was possible to verify the effectiveness of the developed method and its potential as a proposal for environmental remediation.

DNA methyltransferase expression and DNA hypomethylation status in human hepatocytes following trichloroacetic acid exposure.

Trichloroacetic acid (TCA) is one of the major metabolites of trichloroethylene (TCE) as the significant factor of environmental and occupational pollution. TCA has been shown to induce a series of epigenetic mutation in mouse liver. However, the epigenetic cytotoxicity of TCA is still in infancy. In this study, we explored the cellular biological characteristics, the genome DNA methylation status and the expression profile of DNA methyltransferases in human hepatic L-02 cells treated with TCA with certain time and dose effects. The cell cycle measured by flow cytometry revealed an increasing S + G2 (M) phase of TCA (0.9 mM 24 h, 48 h and 72 h) treated cells after a recovery day, and sub-G1 phase was not appeared. The levels of 5 -mC were decreased in TCA (0.9 mM 24 h and 72 h) treated cells by 5-mC immunolocalization process and HPCE (decreased from 27.2% to 50.1% respectively). Meanwhile, the mCpG% in normal L-02 cells and TCA (0.9 mM 48 h) treated cells was 79.6% ± 6.5% and 50.8% ± 3.8%, respectively (P < 0.05). It also revealed that treatment of L-02 cells with TCA induced decreased in DNMT1 and DNMT3a mRNA and protein levels with a time-dependent manner and a dose-response relationship, while DNMT3b had no obvious change. These results establish a link between DNA methyltransferases and Genome DNA hypomethylation, which is associated with TCA exposure.

Environmental risk appraisement of disinfection by-products (DBPs) in plant model system: Allium cepa.

The organic toxicants formed in chlorinated water cause potential harm to human beings, and it is extensively concentrated all over the world. Various disinfection by-products (DBPs) occur in chlorinated water are genotoxic and carcinogenic. The toxicity is major concern for chlorinated DBPs which has been present more in potable water. The purpose of the work was to evaluate genotoxic properties of DBPs in Allium cepa as a plant model system. The chromosomal aberration and DNA laddering assays were performed to examine the genotoxic effect of trichloroacetic acid (TCAA), trichloromethane (TCM), and tribromomethane (TBM) in a plant system with distinct concentrations, using ethyl methanesulfonate (EMS) as positive control and tap water as negative control. In Allium cepa root growth inhibition test, the inhibition was concentration dependent, and EC50 values for trichloroacetic acid (TCAA), trichloromethane (TCM), and tribromomethane (TBM) were 100 mg/L, 160 mg/L, and 120 mg/L respectively. In the chromosome aberration assay, root tip cells were investigated after 120 h exposure. The bridge formation, sticky chromosomes, vagrant chromosomes, fragmented chromosome, c-anaphase, and multipolarity chromosomal aberrations were seen in anaphase-telophase cells. It was noticed that with enhanced concentrations of DBPs, the total chromosomal aberrations were more frequent. The DNA damage was analyzed in roots of Allium cepa exposed with DBPs (TCAA, TCM, TBM) by DNA laddering. The biochemical assays such as lipid peroxidation, H2O2 content, ascorbate peroxidase, guaiacol peroxidase, and catalase were concentration dependent. The DNA interaction studies were performed to examine binding mode of TCAA, TCM, and TBM with DNAs. The DNA interaction was evaluated by spectrophotometric and spectrofluorometric studies which revealed that TCAA, TCM, and TBM might interact with Calf thymus DNA (CT- DNA) by non-traditional intercalation manner.

Topical Corticosteroid Pretreatment Mitigates Cellular Damage After Caustic Injury to the Nasal Upper Airway Epithelium.

BACKGROUND: Topical corticosteroids are currently employed to reduce established airway inflammation; their prophylactic use might help limit cellular damage against harmful stimuli. OBJECTIVES: To determine the effects of a prophylactic topical application of budesonide (BD) on an in vivo nasal epithelium injury model induced by trichloroacetic acid (TCA). METHODS: C57Bl/6 mice were exposed to intranasal TCA topical application. Three groups received topical intranasal BD, saline solution, or no intervention prior to a single topical exposure to TCA. Controls were not exposed to TCA. Whole nasal cavity coronal sections were analyzed at 1, 3, and 6 days postinjury at tissue and cellular levels using histopathological analysis, immunofluorescent staining, and fresh tissue RNA microarray analysis. RESULTS: Prophylactic topical corticosteroid exposure protected the nasal epithelium from acute damage, maintaining epithelial thickness and cell survival. Six days following TCA exposure, epithelial and cellular changes were less pronounced on the BD-treated group compared to all exposure groups. The microarray analysis was used to evaluate the gene transcripts in all treatment groups. Ciliary tip protein, Sentan, and submucosal protein S100b were identified as potential factors in epithelial airway protection; immunofluorescent staining corroborated their presence and location within the respiratory epithelium. CONCLUSION: Topical corticosteroid treatment to the nasal epithelium can mitigate several of the early deleterious effects of acute epithelial damage in experimental airway injuries caused by TCA. These findings suggest a novel, direct cytoprotective effect of corticosteroids on the nasal epithelium, and the potential of expanding the use of prophylactic periprocedural topical corticosteroids for respiratory epithelial tissues.

Developmental effects of trichloroacetate in Zebrafish embryos: Association with the production of superoxide anion.

To assess the developmental toxicity of trichloroacetate (TCA), zebrafish embryos were exposed to 8 to 48 mM of TCA and evaluated for developmental milestones from 8- to 144-hour postfertilization (hpf). All developmental toxicities are reported in this paper. Embryos were found to have developed edema in response to 16 to 48 mM of TCA exposure at 32- to 80-hpf, experienced delay in hatching success in response to 24 to 48 mM at 80-hpf. Lordosis was observed in developing embryos exposed to 40 to 48 mM at 55- to 144-hpf. The observed toxic effects of TCA exposure were found to be concentration and exposure period independent. Effects were found to be associated with increases in superoxide anion production, but these increases were also found to be concentration and time independent. TCA resulted in concentration-dependent increases in embryonic lethality at 144-hpf, with an LC50 determined to be 29.7 mM.

Effect modification of CPY2E1 and GSTZ1 genetic polymorphisms on associations between prenatal disinfection by-products exposure and birth outcomes.

BACKGROUND: Prenatal disinfection by-products (DBPs) exposure is linked with adverse birth outcomes. Genetic susceptibility to DBP metabolism may modify the exposure-outcome associations. OBJECT: To investigate whether CYP2E1 and GSTZ1 genetic polymorphisms modified the associations of prenatal DBP exposures with adverse birth outcomes. METHODS: Two biomarkers of DBP exposures including trihalomethanes (THMs) in blood and trichloroacetic acid (TCAA) in urine were determined among 426 pregnant women from a Chinese cohort study. CYP2E1 (rs2031920, rs3813867, and rs915906) and GSTZ1 (rs7975) polymorphisms in cord blood were genotyped. Statistical interactions between prenatal DBP exposures and newborns CYP2E1 and GSTZ1 polymorphisms on birth outcomes (birth weight, birth length, and gestational age) were examined by multivariable linear regression with adjustment for potential confounders. RESULTS: We found that newborns CYP2E1 genetic polymorphisms (rs2031920 and rs3813867) modified the associations of maternal blood THMs or urinary TCAA levels with birth outcomes. However, these interactions were nonsignificant after Bonferroni correction for multiple comparisons, except for the interaction between maternal blood BrTHMs [sum of dibromochloromethane (DBCM), bromodichloromethane (BDCM), and bromoform (TBM)] and newborns CYP2E1 gene rs2031920 polymorphisms on birth weight (P for interaction = 0.003). CONCLUSION: Newborns genetic variations of CYP2E1 rs2031920 may modify the impacts of prenatal BrTHM exposure on birth weight. This finding needs to be further confirmed.

Detection of genotoxic effects of drinking water disinfection by-products using Vicia faba bioassay.

Plant-based bioassays have gained wide use among the toxicological and/or ecotoxicological assessment procedures because of their simplicity, sensitivity, low cost, and reliability. The present study describes the use of Vicia faba (V. faba) micronucleus (MN) test and V. faba comet assay in the evaluation of the genotoxic potential of disinfection by-products (DBPs) commonly found in chlorine-disinfected drinking water. Five haloacetic acids and three halogenated acetonitriles were chosen as representatives of DBPs in this study because they are of potentially great public health risk. Results of the MN test indicated that monochloroacetic acid (MCA), monobromoacetic acid (MBA), dichloroacetic acid (DCA), dibromoacetic acid (DBA), trichloroacetic acid (TCA), and trichloroacetonitrile (TCAN) caused a statistically significant increase in MN frequency in V. faba root tip cells. However, no genotoxic response was observed for dichloroacetonitrile (DCAN) and dibromoacetonitrile (DBAN). Results of the comet assay showed that all tested DBPs induced a statistically significant increase in genomic DNA damage to V. faba root tip cells. On considering the capacity to detect genomic damage of a different nature, we suggest that a combination of V. faba MN test and V. faba comet assay is a useful tool for the detection of genotoxic effects of DBPs. It is worthy of assessing the feasibility of using V. faba comet assay combined with V. faba MN test to screen for the genotoxic activity of chlorinated drinking water in future work.

Joint effects of trihalomethanes and trichloroacetic acid on semen quality: A population-based cross-sectional study in China.

Exposure to trihalomethanes (THMs) and haloacetic acids (HAAs) has been individually associated with adverse male reproductive effects; however, their joint male reproductive toxicity is largely unknown. This study aimed to explore the joint effects of THMs and trichloroacetic acid (TCAA) on semen quality in a Chinese population. A total of 337 men presenting to the Reproductive Center of Tongjing Hospital, in Wuhan, China to seek semen analysis were included this study. Baseline blood THMs [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and urinary TCAA were analyzed and dichotomized at their median levels. The joint effects of THMs and TCAA on below-reference semen quality parameters were evaluated by calculating the relative excess risk due to interaction (RERI). After adjusting for potential confounders, we found a suggestive synergistic effect between Br-THMs (sum of BDCM, DBCM, and TBM) and TCAA for below-reference sperm count (RERI = 2.14, 95% CI: -0.37, 4.91) (P = 0.076); men with high Br-THMs and TCAA levels (above the median) had 3.31 times (95% CI: 1.21, 9.07) elevated risk of having below-reference sperm count than men with low Br-THMs and TCAA levels (below the median). No apparent joint effects were observed between THMs and TCAA for other semen quality parameters. Our results suggest that co-exposure to Br-THMs and TCAA is associated with additive effects on decreased semen quality. However, further studies in a larger sample size and mechanistic studies are needed to confirm the findings.