Disinfection By-products In Drinking Water Research Articles

Human cell toxicogenomic analysis of bromoacetic acid: A regulated drinking water disinfection by‐product

The disinfection of drinking water is a major achievement in protecting the public health. However, current disinfection methods also generate disinfection by-products (DBPs). Many DBPs are cytotoxic, genotoxic, teratogenic, and carcinogenic and represent an important class of environmentally hazardous chemicals that may carry long-term human health implications. The objective of this research was to integrate in vitro toxicology with focused toxicogenomic analysis of the regulated DBP, bromoacetic acid (BAA) and to evaluate modulation of gene expression involved in DNA damage/repair and toxic responses, with nontransformed human cells. We generated transcriptome profiles for 168 genes with 30 min and 4 hr exposure times that did not induce acute cytotoxicity. Using qRT-PCR gene arrays, the levels of 25 transcripts were modulated to a statistically significant degree in response to a 30 min treatment with BAA (16 transcripts upregulated and nine downregulated). The largest changes were observed for RAD9A and BRCA1. The majority of the altered transcript profiles are genes involved in DNA repair, especially the repair of double strand DNA breaks, and in cell cycle regulation. With 4 hr of treatment the expression of 28 genes was modulated (12 upregulated and 16 downregulated); the largest fold changes were in HMOX1 and FMO1. This work represents the first nontransformed human cell toxicogenomic study with a regulated drinking water disinfection by-product. These data implicate double strand DNA breaks as a feature of BAA exposure. Future toxicogenomic studies of DBPs will further strengthen our limited knowledge in this growing area of drinking water research.

Reliability of using urinary and blood trichloroacetic acid as a biomarker of exposure to chlorinated drinking water disinfection byproducts

This study was designed to analyse the reliability of using urinary and blood trichloroacetic acid (TCAA) as a biomarker of exposure. A total of 46 healthy women consumed supplied TCAA-containing tap water for 15 days and provided urine and blood samples for TCAA measurements. The findings revealed that the reliability of measurements was excellent by using measures of TCAA ingestion, blood concentration and urinary excretion (intraclass correlation coefficients (ICC) > 0.75, p < 0.001). Volume of tap water consumption (ICC = 0.69) and creatinine-adjusted urinary concentration (ICC = 0.72) were less reliable. This indicated that the intraindividual variability was small and the interindividual reliability was high by using these measures in this cohort study. Laboratory variability did not significantly contribute to total variance (ICC > 0.95, p < 0.001). Other possible sources of variation such as bathing, showering, dishwashing and physical activities were unlikely to contribute significantly to total variance. For sampling strategies, 1-day blood sampling and 2-day urine sampling are sufficient to achieve reliability for an epidemiological study if a quasi-steady-state TCAA level in the body is reached. The results suggest that TCAA ingestion, TCAA loading in blood and urinary TCAA excretion are reliable measures for use as biomarkers in epidemiological studies.

Multivariate distributions of disinfection by-products in chlorinated drinking water

Drinking water disinfection by-product (DBP) occurrence research is important in supporting risk assessment and regulatory performance assessment. Recent DBP occurrence surveys have expanded their scope to include non-regulated priority DBPs as well as regulated DBPs. This study applies a Box–Cox transformed multivariate normal model and data augmentation methods for left-censored and missing observations to US EPA Information Collection Rule (ICR) drinking water data to describe the variability in the trihalomethane (THM4), trihaloacetic acid (THAA), dihaloacetic acid (DHAA), and dihaloacetonitrile (DHAN) DBP classes, the relationship between class-sum and the occurrence of individual DBPs within these classes. Inferences about bromine incorporation in these classes are then compared to those made by Obolensky and Singer (2005). Results reported herein show that class-based and individual DBP concentrations are strongly related to bromine substitution, and that speciation and bromine substitution patterns are consistent across DBP classes. In addition, the multiple imputation approach employed reveals that uncertainties related to missing and left-censored DBPs have important implications for understanding bromine substitution in the THAA class. These concerns should be considered through alternative approaches to DBP regulation in subsequent Stage II D/DBP assessment and revisions, where appropriate.

Validation of urinary trichloroacetic acid as a biomarker of exposure to drinking water disinfection by-products

Disinfection by-products (DBPs) in drinking water represent a public health issue and a challenge for epidemiology to provide evidence towards the causation of various hypothesized health effects. Validation of a biomarker of exposure to DBPs is a strategy to achieve progress which has been advocated. The objective of this study was to validate urinary trichloroacetic acid (TCAA) excretion as a biomarker of exposure to DBPs in an experimental exposure cohort. A total of 52 healthy women participated in the study. Participants consumed supplied tap water for 15 d and provided urine and blood samples for TCAA measurements. The findings revealed that (1) background levels of TCAA in urine and blood were readily detectable, (2) TCAA levels in blood and urine increased with increased amounts of TCAA ingested, (3) the correlations between measurements of TCAA ingestion and urinary excretion were modest (r=0.66, p<0.001) based on one days' sampling and high (r=0.77-0.83, p<0.001) based on two to four days' sampling, (4) the correlations between measurements of TCAA ingestion and blood TCAA concentration were high (r=0.80, p<0.001) and (5) multiple days' urinary TCAA measures improved the prediction of TCAA ingestion through urinary TCAA excretion. TCAA can be a valid biomarker of exposure for DBPs in drinking water.

Evaluating the Similarity of Complex Drinking-Water Disinfection By-Product Mixtures: Overview of the Issues

Humans are exposed daily to complex mixtures of environmental chemical contaminants, which arise as releases from sources such as engineering procedures, degradation processes, and emissions from mobile or stationary sources. When dose-response data are available for the actual environmental mixture to which individuals are exposed (i.e., the mixture of concern), these data provide the best information for dose-response assessment of the mixture. When suitable data on the mixture itself are not available, surrogate data might be used from a sufficiently similar mixture or a group of similar mixtures. Consequently, the determination of whether the mixture of concern is “sufficiently similar” to a tested mixture or a group of tested mixtures is central to the use of whole mixture methods. This article provides an overview for a series of companion articles whose purpose is to develop a set of biostatistical, chemical, and toxicological criteria and approaches for evaluating the similarity of drinking-water disinfection by-product (DBPs) complex mixtures. Together, the five articles in this series serve as a case study whose techniques will be relevant to assessing similarity for other classes of complex mixtures of environmental chemicals. Schenck et al. (2009) describe the chemistry and mutagenicity of a set of DBP mixtures concentrated from five different drinking-water treatment plants. Bull et al. (2009a, 2009b) describe how the variables that impact the formation of DBP affect the chemical composition and, subsequently, the expected toxicity of the mixture. Feder et al. (2009a, 2009b) evaluate the similarity of DBP mixture concentrates by applying two biostatistical approaches, principal components analysis, and a nonparametric “bootstrap” analysis. Important factors for determining sufficient similarity of DBP mixtures found in this research include disinfectant used; source water characteristics, including the concentrations of bromide and total organic carbon; concentrations and proportions of individual DBPs with known toxicity data on the same endpoint; magnitude of the unidentified fraction of total organic halides; similar toxicity outcomes for whole mixture testing (e.g., mutagenicity); and summary chemical measures such as total trihalomethanes, total haloacetic acids, total haloacetonitriles, and the levels of bromide incorporation in the DBP classes.

Evaluating Sufficient Similarity for Drinking-Water Disinfection By-Product (DBP) Mixtures with Bootstrap Hypothesis Test Procedures

In chemical mixtures risk assessment, the use of dose-response data developed for one mixture to estimate risk posed by a second mixture depends on whether the two mixtures are sufficiently similar. While evaluations of similarity may be made using qualitative judgments, this article uses nonparametric statistical methods based on the “bootstrap” resampling technique to address the question of similarity among mixtures of chemical disinfectant by-products (DBP) in drinking water. The bootstrap resampling technique is a general-purpose, computer-intensive approach to statistical inference that substitutes empirical sampling for theoretically based parametric mathematical modeling. Nonparametric, bootstrap-based inference involves fewer assumptions than parametric normal theory based inference. The bootstrap procedure is appropriate, at least in an asymptotic sense, whether or not the parametric, distributional assumptions hold, even approximately. The statistical analysis procedures in this article are initially illustrated with data from 5 water treatment plants (Schenck et al., 2009), and then extended using data developed from a study of 35 drinking-water utilities (U.S. EPA/AMWA, 1989), which permits inclusion of a greater number of water constituents and increased structure in the statistical models.

Evaluating Sufficient Similarity for Disinfection By-Product (DBP) Mixtures: Multivariate Statistical Procedures

For evaluation of the adverse health effects associated with exposures to complex chemical mixtures in the environment, the U.S. Environmental Protection Agency (EPA) (2000) states, “if no data are available on the mixture of concern, but health effects data are available on a similar mixture … a decision must be made whether the mixture on which health effects are available is ‘sufficiently’ similar to the mixture of concern to permit a risk assessment.” This article provides a detailed discussion of statistical considerations for evaluation of the similarity of mixtures. Multivariate statistical procedures are suggested to determine whether individual samples of drinking-water disinfection by-products (DBPs) vary significantly from a group of samples that are considered to be similar. The application of principal components analysis to (1) reduce the dimensionality of the vectors of water samples and (2) permit visualization and statistical comparisons in lower dimensional space is suggested. Formal analysis of variance tests of homogeneity are illustrated. These multivariate statistical procedures are applied to a data set describing samples from multiple water treatment plants. Essential data required for carrying out sensitive analyses include (1) identification and measurement of toxicologically sensitive process input and output characteristics, and (2) estimates of variability within the data to construct statistically efficient estimates and tests.

Morphological alterations of neuronal dendrites in developmental disorder model

Disinfection of surface water for human consumption results in the generation of a complex mixture of chemicals in potable water. Cancer risk assessment methodology assumes additivity of carcinogenic effects in the regulation of mixtures. A rodent model of hereditary renal cancer was used to investigate the carcinogenic response to a mixture of drinking water disinfection by-products (DBPs). Rats carrying a mutation in the Tsc2 tumor suppressor gene (Eker rats) readily develop renal preneoplastic and neoplastic lesions, and are highly susceptible to the effects of renal carcinogens. Male and female Eker rats were exposed via drinking water to individual or a mixture of DBPs for 4 or 10 months. Potassium bromate, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), chloroform, and bromodichloromethane were administered at low concentrations of 0.02, 0.005, 0.4 and 0.07 g/l, respectively, and high concentrations of 0.4, 0.07, 1.8 and 0.7 g/l, respectively. Low and high dose mixture solutions were comprised of all four chemicals at either low concentrations or high concentrations, respectively, Following necropsy, each kidney was examined microscopically for preneoplastic lesions (atypical tubules and hyperplasias) and tumors. While some of the mixture responses observed in male rats did fall within the range expected for an additive response, especially at the high dose, predominantly antagonistic effects on renal lesions were observed in response to the low dose mixture in male rats and the high dose mixture in female rats. These data suggest that current default risk assessments assuming additivity may overstate the cancer risk associated with exposure to mixtures of DBPs at low concentrations.

Developing a Conceptual Model for Risk-Benefit Analysis of Disinfection Byproducts and Microbes in Drinking Water

Developing a Conceptual Model for Risk-Benefit Analysis of Disinfection Byproducts and Microbes in Drinking Water

Fate and toxicity of emerging pollutants, their metabolites and transformation products in the aquatic environment

There has been a great effort to study the fate, the occurrence and the ecotoxicology of emerging pollutants in the aquatic environment. Recently, several articles have focused on degradation products of emerging pollutants and the study of their toxicological effects. We review the fate and the ecotoxicology of emerging pollutants, especially focusing on their metabolites and transformation products (TPs) in the aquatic environment, including pharmaceuticals, hormones, perfluorinated compounds, by-products of drinking-water disinfection, sunscreens or UV filters, benzotriazoles and naphthalenic acids. We describe analytical methodologies for the quantitative analysis of emerging pollutants, their metabolites, and their TPs in sewage and surface waters, and we give the results of monitoring surveys obtained from the application of these analytical methodologies.

Drinking Water Disinfection By-Product Exposure and Duration of Gestation

Recent studies suggest elevated exposure to drinking water disinfection by-products (DBPs) may be associated with decreased risk of preterm birth. We examined this association for exposure to total trihalomethanes (TTHMs), 5 haloacetic acids (HAA5), and total organic halides. Analysis included 2039 women in a prospective pregnancy study conducted from 2000 through 2004 in 3 study sites. Water samples were collected and analyzed for DBP concentrations. Participant data were collected through interviews, an early ultrasound, and birth records. We assessed the associations between DBPs and preterm birth (<37-weeks' gestation) using log-binomial regression. Discrete-time hazard analysis was used to model the conditional odds of delivery each week in relation to DBP exposure. Average second trimester DBP levels were associated with lower risk of preterm birth. Adjusted risk ratios for TTHM levels of 33.1-55.0, 55.1-66.3, 66.4-74.8, and 74.9-108.8 microg/L versus 2.2-4.6 microg/L were 0.8 (95% confidence intervals = 0.5-1.3), 0.9 (0.6-1.4), 0.7 (0.4-1.1), and 0.5 (0.3-0.9), respectively. Risk ratios for HAA5 levels of 17.9-22.0, 22.1-31.5, 31.6-40.4, and 40.5-52.8 microg/L versus 0-0.9 microg/L were 1.1 (0.8-1.7), 0.8 (0.5-1.2), 0.5 (0.3-0.8), and 0.7 (0.4-1.1), respectively. The conditional odds of delivery each week were decreased for the highest TTHM and HAA5 exposure groups versus the low exposure group for gestational weeks 33-40. The probability of preterm birth was not increased with high DBP exposure.

Drinking Water Disinfection By-Product Exposure and Fetal Growth

Previous studies suggest that elevated exposure to drinking water disinfection by-products (DBPs)--in particular, total trihalomethanes (TTHMs)--may lead to fetal growth restriction. We examined the effects of exposure to TTHMs, haloacetic acids, and total organic halide on the probability of delivering a small-for-gestational-age (SGA) infant and on birth weight at term. Women early in pregnancy (< or =12 weeks' gestation) or planning a pregnancy were enrolled in a prospective pregnancy study conducted in 3 US communities from 2000 through 2004. Weekly (or biweekly) water samples were collected at each site as well as individual-level participant data. Associations between DBP exposures (TTHMs, haloacetic acids, total organic halide) and fetal growth were assessed using log-binomial regression for SGA (n = 1958) and linear regression for term birth weight (n = 1854). We conducted a Bayesian analysis to examine associations between individual DBP species and fetal growth. Haloacetic acids and total organic halide were not associated with SGA or term birth weight. The probability of delivering an SGA infant was elevated when comparing women with an average third-trimester residential TTHM concentration > or =80 microg/L to women with exposure <80 microg/L (risk ratio = 2.0 [95% confidence interval = 1.1-3.6]), but not when examining other exposure contrasts. Bayesian analyses did not support a consistent association between any DBP species and fetal growth, although these analyses were based on small sample sizes. Our results do not suggest an adverse effect of haloacetic acid or total organic halide exposure on fetal growth. An association of TTHM with SGA was seen only for average residential concentrations above the current regulatory standard.

Evaluation of associations between lifetime exposure to drinking water disinfection by-products and bladder cancer in dogs

To assess the risk of bladder cancer in dogs from exposure to drinking water disinfection by-products and determine whether dogs could serve as sentinels for human bladder cancer associated with such exposures. Case-control study. 100 dogs with cancer of the urinary bladder and 100 control dogs. Case and control dogs were frequency-matched by age (within 2 years) and sex. Owners of dogs enrolled provided verbal informed consent and were interviewed by telephone. The telephone questionnaire included a complete residence history for each dog. Each dog's total exposure history to trihalomethanes was reconstructed from its residence history and corresponding drinking water utility company data. No association was detected between increasing years of exposure to chlorinated drinking water and risk of bladder cancer. Dogs with bladder cancer were exposed to higher total trihalomethanes concentrations than control dogs; however, the difference was not significant. Although humans and their dogs live in the same household, the activity patterns of dogs may lead to lower exposures to household tap water. Thus, although exposure to disinfection by-products in tap water may be a risk factor for human bladder cancer, this may not be true for canine bladder cancer at the concentrations at which dogs are exposed.

Drinking Water Disinfection By-Products and Time to Pregnancy

Laboratory evidence suggests tap water disinfection by-products (DBPs) could have an effect very early in pregnancy, typically before clinical detectability. Undetected early losses would be expected to increase the reported number of cycles to clinical pregnancy. We investigated the association between specific DBPs (trihalomethanes, haloacetic acids, brominated-trihalomethanes, brominated-haloacetic acids, total organic halides, and bromodichloromethane) and time to pregnancy among women who enrolled in a study of drinking water and reproductive outcomes. We quantified exposure to DBPs through concentrations in tap water, quantity ingested through drinking, quantity inhaled or absorbed while showering or bathing, and total integrated exposure. The effect of DBPs on time to pregnancy was estimated using a discrete time hazard model. Overall, we found no evidence of an increased time to pregnancy among women who were exposed to higher levels of DBPs. A modestly decreased time to pregnancy (ie, increased fecundability) was seen among those exposed to the highest level of ingested DBPs, but not for tap water concentration, the amount absorbed while showering or bathing, or the integrated exposure. Our findings extend those of a recently published study suggesting a lack of association between DBPs and pregnancy loss.

Occurrence, Synthesis, and Mammalian Cell Cytotoxicity and Genotoxicity of Haloacetamides: An Emerging Class of Nitrogenous Drinking Water Disinfection Byproducts

The haloacetamides, a class of emerging nitrogenous drinking water disinfection byproduct (DBPs), were analyzed for their chronic cytotoxicity and for the induction of genomic DNA damage in Chinese hamster ovary cells. The rank order for cytotoxicity of 13 haloacetamides was DIAcAm > IAcAm > BAcAm > TBAcAm > BIAcAm > DBCAcAm > CIAcAm > BDCAcAm > DBAcAm > BCAcAm > CAcAm > DCAcAm > TCAcAm. The rank order of their genotoxicity was TBAcAm > DIAcAm approximately equal to IAcAm > BAcAm > DBCAcAm > BIAcAm > BDCAcAm > CIAcAm > BCAcAm > DBAcAm > CAcAm > TCAcAm. DCAcAm was not genotoxic. Cytotoxicity and genotoxicity were primarily determined by the leaving tendency of the halogens and followed the order I > Br > > Cl. With the exception of brominated trihaloacetamides, most of the toxicity rank order was consistent with structure-activity relationship expectations. For di- and trihaloacetamides, the presence of at least one good leaving halogen group (I or Br but not Cl) appears to be critical for significant toxic activity. Log P was not a factor for monohaloacetamides but may play a role in the genotoxicity of trihaloacetamides and possible activation of dihaloacetamides by intracellular GSH and -SH compounds.

Organic Carbon and Disinfection Byproduct Precursor Loads from a Constructed, Non-Tidal Wetland in California's Sacramento-San Joaquin Delta

Wetland restoration on peat islands in the Sacramento-San Joaquin Delta will change the quality of island drainage waters entering the Delta, a primary source of drinking water in California. Peat island drainage waters contain high concentrations of dissolved and particulate organic carbon (DOC and POC) and organic precursors to drinking water disinfection byproducts, such as trihalomethanes (THMs). We quantified the net loads of DOC, POC, and THM-precursors from a constructed subsidence mitigation wetland on Twitchell Island in the Delta to determine the change in drainage water quality that may be caused by conversion of agricultural land on peat islands to permanently flooded, non-tidal wetlands. Creation of permanently flooded wetlands halts oxidative loss of the peat soils and thereby may mitigate the extensive land-surface subsidence of the islands that threatens levee stability in the Delta. Net loads from the wetland were dominated by DOC flushed from the oxidized shallow peat soil layer by seepage flow out of the wetland. The permanently flooded conditions in the overlying wetland resulted in a gradual evolution to anaerobic conditions in the shallow soil layer and a concomitant decrease in the flow could be minimized by reducing the hydraulic gradient between the wetland and the adjacent drainage ditch. Estimates of net loads from the wetland assuming efflux of surface water only were comparable in magnitude to net loads from nearby agricultural fields, but the wetland and agricultural net loads had opposite seasonal variations. Wetland surface water net loads of DOC, POC, and THM-precursors were lower during the winter months when the greatest amounts of water are available for diversion from the Delta to drinking water reservoirs.

Chemicals causing mammary gland tumors in animals signal new directions for epidemiology, chemicals testing, and risk assessment for breast cancer prevention

Identifying chemical carcinogens in animal studies is currently the primary means of anticipating cancer effects in humans. Animal studies to evaluate potential chemical carcinogenicity are particularly important for breast cancer because environmental and occupational epidemiologic research is sparse. Chemicals that increased mammary gland tumors in animal studies were compiled from the International Agency for Research on Cancer (IARC), the U.S. National Toxicology Program (NTP), and other sources. Summary assessments of the carcinogenic potential for each chemical and potentially exposed populations were also compiled. In all, 216 chemicals were identified that have been associated with increases in mammary gland tumors in at least 1 study. These include industrial chemicals, chlorinated solvents, products of combustion, pesticides, dyes, radiation, drinking water disinfection byproducts, pharmaceuticals and hormones, natural products, and research chemicals. Twenty-nine are produced in the U.S. at >1 million pounds/year; 35 are air pollutants, 25 have involved occupational exposures to >5000 women, and 73 have been present in consumer products or as contaminants of food. Thus, exposure is widespread. Nearly all of the chemicals were mutagenic and most caused tumors in multiple organs and species; these characteristics are generally believed to indicate likely carcinogenicity in humans. To our knowledge, this is the most comprehensive list developed of animal mammary gland carcinogens and, along with associated data, is publicly available at URL: www.silentspring.org/sciencereview and at URL: www.komen.org/environment. Valuable information from cancer bioassays is not well utilized in risk assessment and regulatory processes, suggesting a need to strengthen chemicals testing and risk assessment as tools for breast cancer prevention.

Effects of bromodichloromethane on ex vivo and in vitro luteal function and bromodichloromethane tissue dosimetry in the pregnant F344 rat

Bromodichloromethane (BDCM), a drinking water disinfection by-product, causes pregnancy loss, i.e. full-litter resorption, in F344 rats when treated during the luteinizing hormone (LH)-dependent period. This effect is associated with reduced maternal serum progesterone (P) and LH levels, suggesting that BDCM disrupts secretion of LH. To test the hypothesis that BDCM also affects luteal responsiveness to LH, we used ex vivo and in vitro approaches. For the ex vivo study (i.e., in vivo exposure followed by in vitro assessment), dams were dosed by gavage on gestation days (GD) 6–9 (plug day = GD 0) at 0 or 100 mg/kg/d. One hour after the GD-9 dose, rats were killed, blood was collected, and tissue concentrations of BDCM were assessed. Corpora lutea (CL) were incubated with or without hCG, an LH agonist, to stimulate P secretion. For the in vitro study, CL were pooled from untreated F344 rats on GD 9 and cultured with BDCM at 0, 0.01, 0.10 or 3.0 mM. BDCM was found at highest concentrations in adrenal, ovarian, adipose, and hypothalamic tissues. BDCM treatment decreased serum P and LH levels in vivo. Ex vivo, however, BDCM-exposed CL showed >2-fold increases in P secretion relative to controls. Both control and BDCM-exposed CL displayed a 2.4-fold increase in P secretion in response to hCG challenge. In contrast, in vitro exposures reduced CL responsiveness in a dose-related fashion while baseline levels were unaffected. It is unclear if the ex vivo ‘rebound’ reflects the removal of the CL from a possible direct inhibitory influence of BDCM, or a response to diminished LH stimulation in vivo. Thus, these data suggest that BDCM disrupts pregnancy in F344 rats via two modes: disruption of LH secretion, and disruption of the CL’s ability to respond to LH.

Haloacetonitriles vs. Regulated Haloacetic Acids: Are Nitrogen-Containing DBPs More Toxic?

Haloacetonitriles (HANs) are toxic nitrogenous drinking water disinfection byproducts (N-DBPs) and are observed with chlorine, chloramine, or chlorine dioxide disinfection. Using microplate-based Chinese hamster ovary (CHO) cell assays for chronic cytotoxicity and acute genotoxicity, we analyzed 7 HANs: iodoacetonitrile (IAN), bromoacetonitrile (BAN), dibromoacetonitrile (DBAN), bromochloroacetonitrile (BCAN), chloroacetonitrile (CAN), dichloroacetonitrile (DCAN), and trichloroacetonitrile (TCAN). The cytotoxic potency (%C1/2 values) ranged from 2.8 microM (DBAN) to 0.16 mM (TCAN), with a descending rank order of DBAN > IAN approximately BAN > BCAN > DCAN > CAN > TCAN. HANs induced acute genomic DNA damage; the single cell gel electrophoresis (SCGE) genotoxicity potency ranged from 37 microM (IAN) to 2.7 mM (DCAN). The rank order of declining genotoxicity was IAN > BAN approximately DBAN > BCAN > CAN > TCAN > DCAN. The accompanying structure-activity analysis of these HANs was in general agreement with the genotoxicity rank order. These data were incorporated into our growing quantitative comparative DBP cytotoxicity and genotoxicity databases. As a chemical class, the HANs are more toxic than regulated carbon-based DBPs, such as the haloacetic acids. The toxicity of N-DBPs may become a health concern because of the increased use of alternative disinfectants, such as chloramines, which may enhance the formation of N-DBPs, including HANs.

The healthy men study: design and recruitment considerations for environmental epidemiologic studies in male reproductive health

To describe study design, conduct and response, and participant characteristics. Prospective cohort study. Participants were male partners of women who were enrolled in a community-based prospective cohort study of drinking water disinfection by-products and pregnancy health. Two hundred thirty presumed fertile men recruited from 3 study sites in the United States. Men completed a telephone interview about demographics, health history, and exposures and provided a semen sample that was express mailed to the study laboratory. Response and participation rates, participant demographics, and lifestyle exposures. We obtained a high participation rate (84%) among men who were located, but a low overall response rate (25%). Participants were more likely to be white, more highly educated, be married, and have a higher household income than the underlying study cohort. Our multisite study design may be applicable to the study of community environmental factors and reproductive health of men. Our design was efficient in that men from geographically disparate sites could be recruited, a semen sample was collected at home, and a telephone interview was conducted from a central study site. Despite these design features, the low response rates may suggest selection bias that can be addressed partially in the analysis.