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

BACKGROUND: Experimental studies have shown that disinfection byproducts (DBPs) induce coagulotoxicity, but human evidence is scarce. OBJECTIVE: This study aimed to explore the relationships of DBP exposures with blood coagulation parameters. METHODS: Among 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. RESULTS: Elevated 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). CONCLUSION: Higher levels of urinary DCAA and TCAA are associated with prolonged clotting time among women.

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

BACKGROUND: Disinfection byproducts (DBPs), the ubiquitous contaminants in drinking water, have been shown to impair renal function in experimental studies. However, epidemiological evidence is sparse. OBJECTIVE: To investigate exposures to DBPs in associations with renal function among women. METHODS: A 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. RESULTS: We found null evidence of urinary TCAA in associations with renal function indicators. However, elevated urinary DCAA tertiles were related to decreased eGFR (ß = -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). CONCLUSION: Urinary DCAA but not TCAA was associated with impaired renal function among women undergoing assisted reproductive technology.

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

BACKGROUND: Disinfection by-products (DBPs) have been shown to impair female reproductive function. However, epidemiological evidence on reproductive hormones is scarce. OBJECTIVE: To investigate the associations between DBP exposures and reproductive hormones among women undergoing assisted reproductive technology. METHODS: 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 (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. RESULTS: 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. CONCLUSION: Urinary DCAA but not TCAA was associated with altered serum PRGE and PRL levels among women undergoing assisted reproductive technology.

Maternal urinary levels of trichloroacetic acid and association with adverse pregnancy outcomes.

The current study aimed to determine the association between trichloroacetic acid (TCAA) levels and adverse pregnancy outcomes among third-trimester pregnant women who were exposed to chlorinated drinking water. A total of 205 pregnant women who participated in the disinfection by-products exposure and adverse pregnancy outcome study in South Africa were randomly asked to participate in this study by providing their morning urine sample voids. Samples were analysed for urinary creatinine and TCAA. Furthermore, participants gave individual data using a structured questionnaire. The mean (median) concentration of creatinine-adjusted urinary TCAA was 2.34 (1.95) µg/g creatinine. Elevated levels of creatinine-adjusted TCAA concentrations showed an increased risk of premature birth, small for gestational age (SGA) and low birth weight. There was no significant statistical correlation observed between creatinine-adjusted TCAA concentrations and the total volume of cold water ingested among the study population. No statistically significant association was observed between creatinine-adjusted urinary TCAA and premature birth, SGA and low birth weight newborns among the study subjects. However, the urinary TCAA concentrations identified in this study suggest potential health risks towards women and foetus. Therefore, further studies are warranted to prevent further adverse pregnancy outcomes.

Urinary trichloroacetic acid and high blood pressure: A cross-sectional study of general adults in Shijiazhuang, China.

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.

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.

Urinary biomarker of late pregnancy exposure to drinking water disinfection by-products and ultrasound measures of fetal growth in Wuhan, China.

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.

Utilizing two detectors in the measurement of trichloroacetic acid in human urine by reaction headspace gas chromatography.

A reaction headspace gas chromatography (HS-GC) technique was investigated for quantitatively analyzing trichloroacetic acid in human urine. This method is based on the decomposition reaction of trichloroacetic acid under high-temperature conditions. The carbon dioxide and chloroform formed from the decomposition reaction can be respectively detected by the thermal conductivity detection HS-GC and flame ionization detection HS-GC. The reaction can be completed in 60 min at 90°C. This method was used to quantify 25 different human urine samples, which had a range of trichloroacetic acid from 0.52 to 3.47 mg/L. It also utilized two different detectors, the thermal conductivity detector and the flame ionization detector. The present reaction HS-GC method is accurate, reliable and well suitable for batch detection of trichloroacetic acid in human urine.

Exposure reconstruction of trichloroethylene among patients with occupational trichloroethylene hypersensitivity syndrome.

Occupational trichloroethylene (TCE) exposure can induce life-threatening generalized dermatitis accompanied by hepatitis: TCE hypersensitivity syndrome (HS). Since the patients' exposure levels have not been fully clarified, this study estimated end-of-shift urinary concentrations of trichloroacetic acid (TCA) and their lower limit below which the disease occurrence was rare. TCA concentration was measured in 78 TCE HS patients whose urine was collected at admission between 2nd and 14th d after their last shift. Then a linear regression model was used to calculate the mean TCA concentration with 95% confidence interval (95% CI) and 95% prediction interval (95% PI) in the end-of-shift urine. The estimated mean concentration was 83 (95% CI, 49-140) mg/l with 95% PI 9.6-720 mg/l. TCA concentrations were also measured in the end-of-shift urine of 38 healthy workers involved in the same job as were the patients. The geometric mean and its 95% CI were 127 mg/l and 16-984 mg/l, respectively. The exposure levels in HS patients might have thus overlapped with those in workers without HS. Accordingly, it was suggested that HS occurred in the environment where the workers were exposed to the TCE concentration corresponding to the urinary TCA concentration as low as 10 mg/l.

Prenatal exposure to drinking water disinfection by-products and DNA methylation in cord blood.

Maternal exposure to drinking water disinfection by-products (DBPs) during pregnancy has been related to adverse birth outcomes. While experimental studies have shown that exposure to DBPs induce DNA hypomethylation, evidence from humans is limited. This study aimed to examine whether prenatal exposure to drinking water DBPs was associated with DNA methylation in cord blood. Maternal biomarkers of exposure to drinking water DBPs including blood trihalomethanes [THMs, including chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and urinary trichloroacetic acid (TCAA) were measured during late pregnancy. DNA methylation in Alu and long interspersed nucleotide element-1 (LINE-1) repetitive elements from cord blood samples (n=115) was measured by pyrosequencing. We used multivariable linear regression to estimate the associations of DNA methylation in cord blood with maternal blood THMs and urinary TCAA. We found no statistically significant association between urinary TCAA and DNA methylation. However, we found that blood TBM was associated with decreased Alu methylation (-0.39%; 95% CI: -0.83%, 0.05% for the highest versus lowest exposure group; p for trend=0.08) and decreased LINE-1 methylation (-1.27%; 95% CI: -2.91%, 0.36% for the highest versus lowest exposure group; p for trend=0.06). Our results suggest that prenatal exposure to drinking water TBM is associated with DNA hypomethylation in cord blood. However, further studies are needed to confirm our findings.

Environmental and personal determinants of the uptake of disinfection by-products during swimming.

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 40min 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 14.4µg/m(3) and from 2.5 to 5.8µmol/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.

In vivo effects of naproxen, salicylic acid, and valproic acid on the pharmacokinetics of trichloroethylene and metabolites in rats.

It was recently demonstrated that some drugs modulate in vitro metabolism of trichloroethylene (TCE) in humans and rats. The objective was to assess in vivo interactions between TCE and three drugs: naproxen (NA), valproic acid (VA), and salicylic acid (SA). Animals were exposed to TCE by inhalation (50 ppm for 6 h) and administered a bolus dose of drug by gavage, equivalent to 10-fold greater than the recommended daily dose. Samples of blood, urine, and collected tissues were analyzed by headspace gas chromatography coupled to an electron capture detector for TCE and metabolites (trichloroethanol [TCOH] and trichloroacetate [TCA]) levels. Coexposure to NA and TCE significantly increased (up to 50%) total and free TCOH (TCOHtotal and TCOHfree, respectively) in blood. This modulation may be explained by an inhibition of glucuronidation. VA significantly elevated TCE levels in blood (up to 50%) with a marked effect on TCOHtotal excretion in urine but not in blood. In contrast, SA produced an increase in TCOHtotal levels in blood at 30, 60, and 90 min and urine after coexposure. Data confirm in vitro observations that NA, VA, and SA affect in vivo TCE kinetics. Future efforts need to be directed to evaluate whether populations chronically medicated with the considered drugs display greater health risks related to TCE exposure.

Use of urinary trichloroacetic acid as an exposure biomarker of disinfection by-products in cancer studies.

Urinary trichloroacetic acid (TCAA) has been proposed as a valid exposure biomarker for ingested disinfection by-products (DBP) for reproductive studies. However, it has never been used in epidemiologic studies on cancer. We investigate the performance of urinary TCAA as a biomarker of DBP exposure in the framework of an epidemiologic study on cancer. We conducted home visits to collect tap water, first morning void urine, and a 48h fluid intake diary among 120 controls from a case-control study of colorectal cancer in Barcelona, Spain. We measured urine TCAA and creatinine, and 9 haloacetic acids and 4 trihalomethanes (THM) in tap water. Lifetime THM exposure was estimated based on residential history since age 18 plus routine monitoring data. Robust linear regressions were used to estimate mean change in urinary TCAA adjusted by covariates. Among the studied group, mean age was 74 years (range 63-85) and 41 (34%) were females. Mean total tap water consumption was 2.2l/48h (standard error, 0.1l/48h). Geometric mean urine TCAA excretion rate was 17.3pmol/min [95%CI: 14.0-21.3], which increased 2% for a 10% increase in TCAA ingestion and decreased with total tap water consumption (-17%/l), water intake outside home (-32%), plasmatic volume (-64%/l), in smokers (-79%), and in users of non-steroidal anti-inflammatory drugs (-50%). Urinary TCAA levels were not associated with lifetime THM exposure. In conclusion, our findings support that urine TCAA is not a valid biomarker in case-control studies of adult cancer given that advanced age, comorbidites and medication use are prevalent and are determinants of urine TCAA levels, apart from ingested TCAA levels. In addition, low TCAA concentrations in drinking water limit the validity of urine TCAA as an exposure biomarker.

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.

Predictors of urinary trichloroacetic acid and baseline blood trihalomethanes concentrations among men in China.

Urinary trichloroacetic acid (TCAA) and baseline blood trihalomethanes (THMs) have been measured as biomarkers of exposure to drinking water disinfection by-products (DBPs) that have been associated with increased risk of cancers and adverse reproductive outcomes. This study aimed to identify predictors of urinary TCAA and baseline blood THMs among men in China. Urine samples, blood samples, and information on socio-demographic factors and water-use activities were collected from 2216 men who participated in a cross-sectional study of exposure to drinking water DBPs and reproductive health during 2011 to 2012. Urinary TCAA and baseline blood THMs including chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) were analyzed. Multivariable linear regression was used to evaluate predictors of urinary TCAA and baseline blood THM concentrations. Tap water consumption was significantly associated with creatinine-adjusted urinary TCAA concentration (ß = 0.23 µg/g creatinine per log10 unit; 95% CI: 0.12, 0.35). Men with surface water source had 0.13 (95% CI: 0.00, 0.27) higher mean creatinine-adjusted urinary TCAA concentrations than those with ground water source. Smoking was associated with lower concentration of creatinine-adjusted urinary TCAA. Age was significantly associated with baseline blood Br-THM (sum of BDCM, DBCM, and TBM) concentration (ß = 0.01 ng/L per unit; 95% CI: 0.00, 0.02). Increased household income was associated with decreased concentrations of baseline blood BDCM and Br-THMs. Our results suggest that tap water consumption, water source, smoking, age, and household income as the primary determinants of exposure to drinking water DBPs should be considered in exposure assessment.

Drinking-water disinfection by-products and semen quality: a cross-sectional study in China.

BACKGROUND: Exposure to disinfection by-products (DBPs) has been demonstrated to impair male reproductive health in animals, but human evidence is limited and inconsistent. OBJECTIVE: We examined the association between exposure to drinking-water DBPs and semen quality in a Chinese population. METHODS: We recruited 2,009 men seeking semen analysis from the Reproductive Center of Tongji Hospital in Wuhan, China, between April 2011 and May 2012. Each man provided a semen sample and a urine sample. Semen samples were analyzed for sperm concentration, sperm motility, and sperm count. As a biomarker of exposure to drinking-water DBPs, trichloroacetic acid (TCAA) was measured in the urine samples. RESULTS: The mean (median) urinary TCAA concentration was 9.58 (7.97) µg/L (interquartile range, 6.01-10.96 µg/L). Compared with men with urine TCAA in the lowest quartile, increased adjusted odds ratios (ORs) were estimated for below-reference sperm concentration in men with TCAA in the second and fourth quartiles (OR = 1.79; 95% CI: 1.19, 2.69 and OR = 1.51; 95% CI: 0.98, 2.31, respectively), for below-reference sperm motility in men with TCAA in the second and third quartiles (OR = 1.46; 95% CI: 1.12, 1.90 and OR = 1.30; 95% CI: 1.00, 1.70, respectively), and for below-reference sperm count in men with TCAA in the second quartile (OR 1.62; 95% CI: 1.04, 2.55). Nonmonotonic associations with TCAA quartiles were also estimated for semen parameters modeled as continuous outcomes, although significant negative associations were estimated for all quartiles above the reference level for sperm motility. CONCLUSION: Our findings suggest that exposure to drinking-water DBPs may contribute to decreased semen quality in humans.

Sex differences in metabolism of trichloroethylene and trichloroethanol in guinea pigs.

OBJECTIVES: Trichloroethylene (TRI) has the potential to cause generalized dermatitis complicated with hepatitis. The guinea pig maximization test (GPMT) also suggests that both TRI and its metabolite trichloroethanol (TCE) exhibit immunogenicity and possible sex differences in guinea pigs. However, TRI and TCE metabolisms in guinea pigs have not been elucidated in detail. The first issue to clarify may be the sex differences in relation to the immunogenicity. METHODS: We collected urine from Hartley male and female guinea pigs 24 hours after intracutaneous injection of TRI, TCE or trichloroacetic acid (TCA) during a GPMT and measured the urinary metabolites by gas chromatography-mass spectrometry. RESULTS: After TRI treatment, the amount of TCA was significantly greater in females than males, while there was no sex difference in the total amount (TCA + TCE). TCA was only detected in urine after TCA treatment. Interestingly, not only TCE but also TCA was detected in urine of both sexes after TCE treatment, and the amount of TCA was also greater in females than males. An additional experiment showed that TCE treatment did not result in the detection of urinary TCA in cytochrome P450 (CYP)2E1-null mice TCEbut did in wild-type mice, suggesting the involvement of CYP2E1 in the metabolism from TCE to TCA. The constitutive expression of CYP2E1 in the liver of guinea pigs was greater in females than males. CONCLUSIONS: The sex difference in urinary TCA excretion after TRI and TCE treatments may be due to variation of the constitutive expression of CYP2E1.

Assessment of serum S100B and neuron specific enolase levels to evaluate the neurotoxic effects of organic solvent exposure.

OBJECTIVES: Long-term organic solvent exposure may cause toxic effects in central nervous system . Trichloroethylene (TCE) is known to be one of the neurotoxic chlorinated organic solvents. Trichloroacetic acid (TCA) is an oxidative pathway metabolite of TCE. S100B, a calcium-binding protein in glial cells, and neuron specific enolase (NSE) in neuron cytoplasma are protein markers of astrocyte and neuron damage, respectively. MATERIALS AND METHODS: Clinical and laboratory assesments were performed in 25 participants with organic solvent exposure history. Control group included 25 healthy age and sex-matched individuals. Measurements of serum S100B and NSE were performed using Roche Cobas E 601 compatible kits and elechtrochemiluminescence immunoassay. The levels of TCA in urine were measured by the headspace GC technique, after methyl esterification by methanol. RESULTS: Median value of urine TCA in solvent-exposed group was 12.30 mg/L with 10.20 mg/L and 35.00 mg/L minimum and maximum values, respectively. The difference between serum S100B levels of solvent-exposed group (0.064 µg/L) and control group (0.049 µg/L) was statistically significant (p < 0.05). Serum NSE levels of control group (15.61 ng/ml) were higher than solvent-exposed group (13.90 ng/ml) but difference was not statistically significant (p > 0.05). CONCLUSIONS: Serum S100B levels were found to be higher in solvent-exposed group when compared with control group. NSE levels were comparable between two groups. Increased Serum S100B levels in organic solvent exposure may indicate a preventive response to neuronal damage caused by reactive oxygen species (ROS) produced through oxidative metabolic pathways of organic solvents.

Risk of cancer among workers exposed to trichloroethylene: analysis of three Nordic cohort studies.

BACKGROUND: Trichloroethylene (TCE) is a widely used chlorinated solvent with demonstrated carcinogenicity in animal assays. Some epidemiologic studies have reported increased risk of cancer of the kidney, cervix, liver and biliary passages, non-Hodgkin lymphoma, and esophageal adenocarcinoma. METHODS: We established a pooled cohort, including 5553 workers with individual documented exposure to TCE in Finland, Sweden, and Denmark. Study participants were monitored for the urinary TCE metabolite trichloroacetic acid from 1947 to 1989 and followed for cancer. Standardized incidence ratios (SIRs) were calculated based on cancer incidence rates in the three national populations. Cox proportionate hazard analyses were used for internal comparisons. Tests of statistical significance are two-sided. RESULTS: Overall, 997 cases of cancer (n = 683 in men; n = 314 in women) were identified during 154 778 person-years of follow-up. We observed statistically significant elevated standardized incidence ratios for primary liver cancer (1.93; 95% confidence interval [CI] = 1.19 to 2.95) and cervical cancer (2.31; 95% CI = 1.32 to 3.75). The standardized incidence ratio for kidney cancer was 1.01 (95% CI = 0.70 to 1.42) based on 32 cases; we did not observe a statistically significant increased risk of non-Hodgkin's lymphoma (SIR = 1.26; 95% CI = 0.89 to 1.73) or esophageal adenocarcinoma (SIR = 1.84; 95% CI = 0.65 to 4.65). Tobacco- and alcohol-associated cancers were not statistically significantly increased. CONCLUSIONS: Our results suggest TCE exposure is possibly associated with an increased risk for liver cancer. The relationship between TCE exposure and risks of cancers of low incidence and those with confounding by lifestyle and other factors not known in our cohort require further study.

Validation of trichloroacetic acid exposure via drinking water during pregnancy using a urinary TCAA biomarker.

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.