Disinfection Byproducts Bind Human Estrogen Receptor-α.

Disinfection byproducts are formed during most drinking water treatment and presently number >800, some of which are implicated in human health outcomes including bladder cancer and infertility, with unknown mechanisms of action. In particular, it is not yet understood whether these compounds can disrupt the estrogen-signaling pathway through binding to the human estrogen receptor (ER). In the present study, 21 disinfection byproducts, selected for their predicted involvement in endocrine-related diseases and their structural diversity, were individually evaluated for their binding affinity to the human ER and in silico, and then a subset of these chemicals was studied in binary mixtures with the known weak estrogen, 4-n-nonylphenol. Individually, 9 of the 21 disinfection byproducts were able to weakly bind to the ER, with affinities ranging from log median inhibitory concentration values of -3.83 to -2.19 M. In binary mixtures, the chemicals followed concentration addition, with their weak binding affinities having little contribution to the overall mixture affinity. These results demonstrate the variety of small-molecule disinfection byproduct structures that are capable of binding to the ER, and that their weak binding can still be of importance when overall human exposure to mixtures of disinfection byproducts in disinfected drinking water is considered. Environ Toxicol Chem 2019;9999:1-9. © 2019 SETAC.

Identification of endocrine active disinfection by-products (DBPs) that bind to the androgen receptor.

The formation of disinfection by-products (DBPs) in drinking water occurs when chemical disinfectants such as chlorine and chloramine react with natural organic matter and anthropogenic pollutants. Some DBPs have been linked to bladder cancer and infertility; however, the underlying mechanism of action is unknown. One possibility is disruption of the endocrine system, with DBPs binding to the androgen receptor and subsequently altering gene expression. Using the androgen receptor-binding assay and in silico molecular docking, the binding affinity of 21 suspected and known DBPs were tested individually at concentrations over the range 0.1 nM-2 mM. 14 DBPs were found to bind at IC50 values ranging from 1.86 mM for 2,3-dichloropropionamide to 13.5 µM for 3,4,5,6-tetrachloro-benzoquinone as compared to the positive control, 4-n-nonylphenol which bound at 31.6 µM. Since DBPs are present in drinking waters as mixtures, the question of how IC50 values for individual DBPs might be affected by the presence of other chemicals is addressed. Seven of the chemicals with the strongest binding affinities and one chemical with no binding affinity were tested in binary mixtures with 4-n-nonylphenol, a known androgenic chemical found in some surface waters. In these binary mixtures, concentration additive binding was observed. While typical levels of individual androgenic DBPs in drinking water are below their measured IC50 values, their combined binding abilities in mixtures could be a source of androgen disruption.

Asymmetric flow field flow fractionation with light scattering detection - an orthogonal sensitivity analysis.

Asymmetric flow field flow fractionation (AF4) has several instrumental factors that may have a direct effect on separation performance. A sensitivity analysis was applied to ascertain the relative importance of AF4 primary instrument factor settings for the separation of a complex environmental sample. The analysis evaluated the impact of instrumental factors namely, cross flow, ramp time, focus flow, injection volume, and run buffer concentration on the multi-angle light scattering measurement of natural organic matter (NOM) molar mass (MM). A 2(5-1) orthogonal fractional factorial design was used to minimize analysis time while preserving the accuracy and robustness in the determination of the main effects and interactions between any two instrumental factors. By assuming that separations resulting in smaller MM measurements would be more accurate, the analysis produced a ranked list of effects estimates for factors and interactions of factors based on their relative importance in minimizing the MM. The most important and statistically significant AF4 instrumental factors were buffer concentration and cross flow. The least important was ramp time. A parallel 2(5-2) orthogonal fractional factorial design was also employed on five environmental factors for synthetic natural water samples containing silver nanoparticles (NPs), namely: NP concentration, NP size, NOM concentration, specific conductance, and pH. None of the water quality characteristic effects or interactions were found to be significant in minimizing the measured MM; however, the interaction between NP concentration and NP size was an important effect when considering NOM recovery. This work presents a structured approach for the rigorous assessment of AF4 instrument factors and optimal settings for the separation of complex samples utilizing efficient orthogonal factional factorial design and appropriate graphical analysis.

Towards reducing DBP formation potential of drinking water by favouring direct ozone over hydroxyl radical reactions during ozonation.

When ozonation is employed in advanced water treatment plants to produce drinking water, dissolved organic matter reacts with ozone (O3) and/or hydroxyl radicals (OH) affecting disinfection byproduct (DBP) formation with subsequently used chlorine-based disinfectants. This study presents the effects of varying exposures of O3 and •OH on DBP concentrations and their associated toxicity generated after subsequent chlorination. DBP formation potential tests and in vitro bioassays were conducted after batch ozonation experiments of coagulated surface water with and without addition of tertiary butanol (t-BuOH, 10 mM) and hydrogen peroxide (H2O2, 1 mg/mg O3), and at different pH (6-8) and transferred ozone doses (0-1 mg/mg TOC). Although ozonation led to a 24-37% decrease in formation of total trihalomethanes, haloacetic acids, haloacetonitriles, and trihaloacetamides, an increase in formation of total trihalonitromethanes, chloral hydrate, and haloketones was observed. This effect however was less pronounced for samples ozonated at conditions favoring molecular ozone (e.g., pH 6 and in the presence of t-BuOH) over •OH reactions (e.g., pH 8 and in the presence of H2O2). Compared to ozonation only, addition of H2O2 consistently enhanced formation of all DBP groups (20-61%) except trihalonitromethanes. This proves that •OH-transformed organic matter is more susceptible to halogen incorporation. Analogously, adsorbable organic halogen (AOX) concentrations increased under conditions that favor •OH reactions. The ratio of unknown to known AOX, however, was greater at conditions that promote direct O3 reactions. Although significant correlation was found between AOX and genotoxicity with the p53 bioassay, toxicity tests using 4 in vitro bioassays showed relatively low absolute differences between various ozonation conditions.

Using light scattering to evaluate the separation of polydisperse nanoparticles.

The analysis of natural and otherwise complex samples is challenging and yields uncertainty about the accuracy and precision of measurements. Here we present a practical tool to assess relative accuracy among separation protocols for techniques using light scattering detection. Due to the highly non-linear relationship between particle size and the intensity of scattered light, a few large particles may obfuscate greater numbers of small particles. Therefore, insufficiently separated mixtures may result in an overestimate of the average measured particle size. Complete separation of complex samples is needed to mitigate this challenge. A separation protocol can be considered improved if the average measured size is smaller than a previous separation protocol. Further, the protocol resulting in the smallest average measured particle size yields the best separation among those explored. If the differential in average measured size between protocols is less than the measurement uncertainty, then the selected protocols are of equivalent precision. As a demonstration, this assessment metric is applied to optimization of cross flow (V(x)) protocols in asymmetric flow field flow fractionation (AF(4)) separation interfaced with online quasi-elastic light scattering (QELS) detection using mixtures of polystyrene beads spanning a large size range. Using this assessment metric, the V(x) parameter was modulated to improve separation until the average measured size of the mixture was in statistical agreement with the calculated average size of particles in the mixture. While we demonstrate this metric by improving AF(4) V(x) protocols, it can be applied to any given separation parameters for separation techniques that employ dynamic light scattering detectors.

Integrated chemical and toxicological investigation of UV-chlorine/chloramine drinking water treatment.

As the use of alternative drinking water treatment increases, it is important to understand potential public health implications associated with these processes. The objective of this study was to evaluate the formation of disinfection byproducts (DBPs) and cytotoxicity of natural organic matter (NOM) concentrates treated with chlorine, chloramine, and medium pressure ultraviolet (UV) irradiation followed by chlorine or chloramine, with and without nitrate or iodide spiking. The use of concentrated NOM conserved volatile DBPs and allowed for direct analysis of the treated water. Treatment with UV prior to chlorine in ambient (unspiked) samples did not affect cytotoxicity as measured using an in vitro normal human colon cell (NCM460) assay, compared to chlorination alone when toxicity is expressed on the basis of dissolved organic carbon (DOC). Nitrate-spiked UV+chlorine treatment produced greater cytotoxicity than nitrate-spiked chlorine alone or ambient UV+chlorine samples, on both a DOC and total organic halogen basis. Samples treated with UV+chloramine were more cytotoxic than those treated with only chloramine using either dose metric. This study demonstrated the combination of cytotoxicity and DBP measurements for process evaluation in drinking water treatment. The results highlight the importance of dose metric when considering the relative toxicity of complex DBP mixtures formed under different disinfection scenarios.

Factors affecting the formation of disinfection by-products during chlorination and chloramination of secondary effluent for the production of high quality recycled water.

During the production of high quality recycled water by reverse osmosis membrane filtration secondary effluent must be disinfected to limit biofouling on the membrane surface. Advanced Water Treatment Plants in South East Queensland, Australia use disinfectant contact times ranging from 30 min up to 24 h. Disinfectants such as chlorine and chloramines react with effluent organic matter to generate disinfection by-products (DBPs) which could be potentially hazardous to human health if the water is destined for supplementing public water supplies. In this context, secondary effluents are of concern because of their high total organic carbon content which can act as DBP precursors. Also, effluent organic matter may form different DBPs to those formed from natural organic matter during conventional drinking water treatment, either in quantity, identity or simply in the abundance of different DBPs relative to each other. It cannot be assumed per se with certainty that DBP formation will be affected in the same way by operational changes as in drinking water production. Response surface modelling has been employed in this study at the bench scale to investigate the effect of reaction time (0-24 h), pH (5.5-8.5), temperature (23-35 °C), disinfection strategy (chlorine vs chloramines used prior to membrane treatment) and the interaction between these different parameters on DBP formation during disinfection of secondary effluent. The concentration of halogenated DBPs formed during the first 24 h of reaction with the different disinfectants followed the order chlorination >> in line-formed monochloramine > pre-formed monochloramine. Contact time with chlorine was the major influencing factor on DBP formation during chlorination, except for the bromine-containing trihalomethanes and dibromoacetonitrile for which pH was more significant. Chlorination at high pH led to an increased formation of chloral hydrate, trichloronitromethane, dibromoacetonitrile and the four trihalomethanes while the opposite effect was observed for the other targeted DBPs. Temperature was identified as the least influencing parameter compared to pH and reaction time for all DBPs in all the disinfection strategies, except for the formation of chloral hydrate where pH and temperature had a similar significance and bromoform that was similarly affected by temperature and reaction time. Chloramines employed at pH 8.5 reduced the concentration of all studied DBPs compared to pH 5.5. Furthermore, reaction time was the most significant factor for trichloronitromethane, chloroform, trichloroacetonitrile, dichloroacetonitrile and bromochloroacetonitrile formation while pH was the most influencing factor affecting the formation of the remaining DBPs.

Changes in dissolved organic matter fluorescence and disinfection byproduct formation from UV and subsequent chlorination/chloramination.

Ultraviolet (UV) irradiation is being increasingly used to help drinking water utilities meet finished water quality regulations, but its influence on disinfection byproduct (DBP) precursors and DBP formation is not completely understood. This study investigated the effect of medium pressure (MP) UV combined with chlorination/chloramination on the fluorescent fraction of dissolved organic matter (DOM) isolated from a United States surface water with median total organic carbon content. Parallel factor analysis was used to understand how UV may alter the capacity of DOM to form DBPs of potential human health concern. The production of chloral hydrate and cyanogen chloride from MP UV followed by chlorine or chloramine, respectively, correlated with a decrease in fluorescence intensity of a protein/tryptophan-like component (R(2)=0.79-0.99) and a humic-like component (R(2)=0.91-1.00). This suggests that the UV-induced precursors to these compounds originated from DOM with similar characteristics to these components. The fluorescent DOM components identified in this study are similar to reoccurring components that have been previously identified in a range of raw and treated waters, and this work demonstrates the value of using fluorescence analysis of DOM to understand the relationships between DOM source and DBP formation under a range of treatment conditions.

The effect of inorganic precursors on disinfection byproduct formation during UV-chlorine/chloramine drinking water treatment.

Ultraviolet (UV) disinfection is being increasingly used in drinking water treatment. It is important to understand how its application to different types of water may influence finished water quality, particularly as anthropogenic activity continues to impact the quality of source waters. The objective of this study was to evaluate the effect of inorganic precursors on the formation of regulated and unregulated disinfection byproducts (DBPs) during UV irradiation of surface waters when combined with chlorination or chloramination. Samples were collected from three drinking water utilities supplied by source waters with varying organic and inorganic precursor content. The filtered samples were treated in the laboratory with a range of UV doses delivered from low pressure (LP, UV output at 253.7 nm) and medium pressure (MP, polychromatic UV output 200-400 nm) mercury lamps followed by chlorination or chloramination, in the presence and absence of additional bromide and nitrate. The regulated trihalomethanes and haloacetic acids were not affected by UV pretreatment at disinfection doses (40-186 mJ/cm²). With higher doses (1000 mJ/cm²), trihalomethane formation was increased 30-40%. While most effects on DBPs were only observed with doses much higher than typically used for UV disinfection, there were some effects on unregulated DBPs at lower doses. In nitrate-spiked samples (1-10 mg N/L), chloropicrin formation doubled and increased three- to six-fold with 40 mJ/cm² MP UV followed by chloramination and chlorination, respectively. Bromopicrin formation was increased in samples containing bromide (0.5-1 mg/L) and nitrate (1-10 mg N/L) when pretreated with LP or MP UV (30-60% with 40 mJ/cm² LP UV and four- to ten-fold increase with 40 mJ/cm² MP UV, after subsequent chlorination). The formation of cyanogen chloride doubled and increased three-fold with MP UV doses of 186 and 1000 mJ/cm², respectively, when followed by chloramination in nitrate-spiked samples but remained below the World Health Organization guideline value of 70 µg/L in all cases. MP UV and high LP UV doses (1000 mJ/cm²) increased chloral hydrate formation after subsequent chlorination (20-40% increase for 40 mJ/cm² MP UV). These results indicate the importance of bench-testing DBP implications of UV applications in combination with post-disinfectants as part of the engineering assessment of a UV-chlorine/chloramine multi-barrier disinfection design for drinking water treatment.

The effect of water disinfection by-products on pregnancy outcomes in two southeastern US communities.

OBJECTIVE: To determine if exposure to disinfection by-products (DBPs) during gestation increases the risk of adverse birth outcomes, specifically term small for gestational age (SGA) birth, preterm birth (PTB), and very PTB (<32 weeks' gestation). METHODS: We used weekly measurements total trihalomethanes (TTHMs), five haloacetic acids (HAA5), and total organic halides (TOX) collected from two distribution systems to evaluate the associations between DBP concentrations and term SGA, PTB, and very PTB using logistic regression. RESULTS: We found no associations between DBPs and term-SGA. In the site with higher concentrations of bromine-containing DBPs, we found an association between TOX and PTB; this association was larger, though less precise, for very PTB. CONCLUSIONS: Our results do not support an association between TTHMs or HAA5 and the birth outcomes investigated, but an association was found between increased TOX and PTB.

Occurrence and removal of pharmaceuticals and personal care products (PPCPs) in an advanced wastewater reclamation plant.

The occurrence of nineteen pharmaceutically active compounds and personal care products was followed monthly for 12 months after various stages of treatment in an advanced wastewater reclamation plant in Gwinnett County, GA, U.S.A. Twenty-four hour composite samples were collected after primary clarification, activated sludge biological treatment, membrane filtration, granular media filtration, granular activated carbon (GAC) adsorption, and ozonation in the wastewater reclamation plant. Compounds were identified and quantified using high performance liquid chromatography/tandem mass spectrometry (LC-MS/MS) and gas chromatography/mass spectrometry (GC-MS) after solid-phase extraction. Standard addition methods were employed to compensate for matrix effects. Sixteen of the targeted compounds were detected in the primary effluent; sulfadimethoxine, doxycycline, and iopromide were not found. Caffeine and acetaminophen were found at the highest concentrations (∼10(5) ng/L), followed by ibuprofen (∼10(4) ng/L), sulfamethoxazole and DEET (∼10(3) ng/L). Most of the other compounds were found at concentrations on the order of hundreds of ng/L. After activated sludge treatment and membrane filtration, the concentrations of caffeine, acetaminophen, ibuprofen, DEET, tetracycline, and 17α-ethynylestradiol (EE2) had decreased by more than 90%. Erythromycin and carbamazepine, which were resistant to biological treatment, were eliminated by 74 and 88%, on average, by GAC. Primidone, DEET, and caffeine were not amenable to adsorption by GAC. Ozonation oxidized most of the remaining compounds by >60%, except for primidone and DEET. Of the initial 16 compounds identified in the primary effluent, only sulfamethoxazole, primidone, caffeine and DEET were frequently detected in the final effluent, but at concentrations on the order of 10-100 ng/L. Removal of the different agents by the various treatment processes was related to the physical-chemical properties of the compounds.

Concentration, chlorination, and chemical analysis of drinking water for disinfection byproduct mixtures health effects research: U.S. EPA's Four Lab Study.

The U.S. Environmental Protection Agency's "Four Lab Study" involved participation of researchers from four national Laboratories and Centers of the Office of Research and Development along with collaborators from the water industry and academia. The study evaluated toxicological effects of complex disinfection byproduct (DBP) mixtures, with an emphasis on reproductive and developmental effects that have been associated with DBP exposures in some human epidemiologic studies. This paper describes a new procedure for producing chlorinated drinking water concentrate for animal toxicology experiments, comprehensive identification of >100 DBPs, and quantification of 75 priority and regulated DBPs. In the research reported herein, complex mixtures of DBPs were produced by concentrating a natural source water with reverse osmosis membranes, followed by addition of bromide and treatment with chlorine. By concentrating natural organic matter in the source water first and disinfecting with chlorine afterward, DBPs (including volatiles and semivolatiles) were formed and maintained in a water matrix suitable for animal studies. DBP levels in the chlorinated concentrate compared well to those from EPA's Information Collection Rule (ICR) and a nationwide study of priority unregulated DBPs when normalized by total organic carbon (TOC). DBPs were relatively stable over the course of the animal studies (125 days) with multiple chlorination events (every 5-14 days), and a significant portion of total organic halogen was accounted for through a comprehensive identification approach. DBPs quantified included regulated DBPs, priority unregulated DBPs, and additional DBPs targeted by the ICR. Many DBPs are reported for the first time, including previously undetected and unreported haloacids and haloamides. The new concentration procedure not only produced a concentrated drinking water suitable for animal experiments, but also provided a greater TOC concentration factor (136×), enhancing the detection of trace DBPs that are often below detection using conventional approaches.

Evaluation of on-site wastewater treatment technology to remove estrogens, nonylphenols, and estrogenic activity from wastewater.

A series of five on-site wastewater treatment systems were monitored for the removal of steroid estrogens, nonylphenols, and total estrogenic activity through several stages of pretreatment including aerobic and anaerobic sand filters. The objectives of this study were (1) to examine the ability of traditional septic systems and different types of pretreatment add-ons to remove nonylphenols (NPs) and the steroid estrogens estrone (E1), 17beta- estradiol (E2), estriol (E3), and 17alpha- ethinylestradiol (EE2) from the final effluent prior to discharge into the environment and (2) to examine the ability of each system and each stage of treatment within the system to remove total estrogenic activity as measured by a yeast estrogen screen (YES) assay. YES data and instrumental data are compared in the context of analyte recovery and estradiol equivalents. Results indicate excellent removal of NPs and total estrogenic activity to near or below detection limits when multiple stages of pretreatment including aerobic sand filters are used. However, only moderate removal of the steroid estrogens was observed through the anaerobic sand filters.

Meeting report: pharmaceuticals in water-an interdisciplinary approach to a public health challenge.

BACKGROUND: The presence of pharmaceuticals in aquatic environments and in drinking water has prompted significant public interest regarding potential adverse ecological effects and risks to human health. OBJECTIVES: The Environmental Health Summit held in North Carolina, 10-11 November 2008, explored the issues associated with the presence and relative risk of trace levels of pharmaceuticals in water. More than 150 participants from government organizations and institutions, academia, industry, water utilities, and public interest groups participated in discussions aimed at evaluating the current knowledge on this issue and at identifying research gaps and innovative solution-oriented recommendations. DISCUSSION: We present different aspects related to the subject that were discussed at the summit, including the source, fate, and transport of pharmaceuticals, their exposure effects and potential risks to human and ecosystems, and the best management practices to address these issues. Recommendations placed emphasis on research needs as well as education, communication, prevention, and intervention programs, and other public health solutions and actions. CONCLUSIONS: Despite rising concerns about the presence of trace amounts of pharmaceuticals in drinking water, little evidence is currently available that associates these chemicals with adverse human health risks. In order to prioritize which pharmaceutical chemicals could potentially pose the highest risk to consumers and the environment, the summit participants concluded that more studies are needed to generate meaningful and accurate data.

The impact of co-contaminants and septic system effluent quality on the transport of estrogens and nonylphenols through soil.

The impact that varying qualities of wastewater may have on the movement of steroid estrogens through soils into groundwater is little understood. In this study, the steroid estrogens 17beta-estradiol (E2) and estrone (E1) were followed through batch and column studies to examine the impact that organic wastewater constituents from on-site wastewater treatment systems (i.e., septic systems or decentralized systems) may have on influencing the rate of transport of estrogens through soils. Total organic carbon (TOC) content (as a surrogate indicator of overall wastewater quality) and the presence of nonyl-phenol polyethoxylate surfactants (NPEO) at concentrations well below the critical micelle concentration were independently shown to be indicative of earlier breakthrough and less partitioning to soil in batch and column experiments. Both NPEO and wastewater with increasing TOC concentrations led to shifts in the equilibrium of E1 and E2 towards the aqueous phase and caused the analytes to have an earlier breakthrough than in control experiments. The presence of nonylphenols, on the other hand, did not appreciably impact partitioning of E1 or E2. Biodegradation of the steroids in soil was also lower in the presence of septic tank effluents than in an organic-free control water. Furthermore, the data indicate that the rate of movement of E1 and E2 present in septic tank effluent through soils and into groundwater can be decreased by removing the NPEOs and TOC through wastewater treatment prior to sub-surface disposal. This study offers some insights into mechanisms which impact degradation, transformation, and retardation, and shows that TOC and NPEO surfactants play a role in estrogen transport.

Modern approaches to the analysis of disinfection by-products in drinking water.

The discovery and study of disinfection by-products (DBPs) of health and regulatory concern in drinking water have often been hampered by the lack of appropriate analytical methods, but, with the new tools and expertise now available to the drinking water industry, there is an opportunity to plug a major gap in our knowledge of the nature and identity of these chemicals. The challenge is that less than half of the halogenated by-products resulting from the chlorination of drinking water have been identified, and even less is known about those produced in waters treated with ozone, chloramines or chlorine dioxide. For the DBPs that have been identified, very little or no occurrence data exist for the unregulated chemicals to document how often a particular DBP is formed and in what quantity. The elucidation of the nature and identity of these by-products is hindered by two complicating factors. The first is the inherent aqueous solubility of many of these compounds, which renders their efficient extraction from water difficult to achieve. The second is the lack of established identity of specific potential by-products, which complicates targeted analytical approaches. This paper reviews existing and new methodologies that attempt to overcome some of these challenges.

Integrated disinfection by-products mixtures research: disinfection of drinking waters by chlorination and ozonation/postchlorination treatment scenarios.

This article describes disinfection of the same source water by two commonly used disinfection treatment scenarios for purposes of subsequent concentration, chemical analysis, and toxicological evaluation. Accompanying articles in this issue of the Journal of Toxicology and Environmental Health describe concentration of these finished waters by reverse osmosis techniques, chemical characterization of the resulting disinfection by-product (DBP) concentrates, in vivo and in vitro toxicological results, and risk assessment methods developed to analyze data from this project. This project, called the "Four Lab Study," involved participation of scientists from four laboratories/centers of the U.S. Environmental Protection Agency Office of Research and Development as well as extramural collaborators from the water industry and academia. One of the two finished waters was prepared by conventional treatment and disinfected by chlorination. The other finished water was also prepared by conventional treatment and disinfected by ozonation followed by chlorination (ozonation/postchlorination). Chlorination conditions of dose, time and temperature were similar for both treatment scenarios, allowing for a comparison. Both finished waters had acceptably low levels of particulates and bacteria, representative pH and chlorine levels, and contained numerous DBP. Known effects of ozonation were observed in that, relative to the water that was chlorinated only, the ozonated/postchlorinated water had lower concentrations of total organic halogen, trihalomethanes (THM), haloacetic acids (HAA), and higher concentrations of bromate, and aldehydes.

Integrated disinfection by-products mixtures research: comprehensive characterization of water concentrates prepared from chlorinated and ozonated/postchlorinated drinking water.

This article describes the disinfection by-product (DBP) characterization portion of a series of experiments designed for comprehensive chemical and toxicological evaluation of two drinking-water concentrates containing highly complex mixtures of DBPs. This project, called the Four Lab Study, involved the participation of scientists from four laboratories and centers of the U.S. Environmental Protection Agency (EPA) Office of Research and Development, along with collaborators from the water industry and academia, and addressed toxicologic effects of complex DBP mixtures, with an emphasis on reproductive and developmental effects that are associated with DBP exposures in epidemiologic studies. Complex mixtures of DBPs from two different disinfection schemes (chlorination and ozonation/postchlorination) were concentrated successfully, while maintaining a water matrix suitable for animal studies. An array of chlorinated/brominated/iodinated DBPs was created. The DBPs were relatively stable over the course of the animal experiments, and a significant portion of the halogenated DBPs formed in the drinking water was accounted for through a comprehensive qualitative and quantitative identification approach. DBPs quantified included priority DBPs that are not regulated but have been predicted to produce adverse health effects, as well as those currently regulated in the United States and those targeted during implementation of the Information Collection Rule. New by-products were also reported for the first time. These included previously undetected and unreported bromo- and chloroacids, iodinated compounds, bromo- and iodophenols, and bromoalkyltins.

Drinking water disinfection by-product exposure and fetal growth.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Drinking water disinfection by-product exposure and duration of gestation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The probability of preterm birth was not increased with high DBP exposure.