Residential greenness, asthma, and lung function among children at high risk of allergic sensitization: a prospective cohort study.

BACKGROUND: While benefits of greenness to health have been reported, findings specific to child respiratory health are inconsistent. METHODS: We utilized a prospective birth cohort followed from birth to age 7 years (n = 617). Residential surrounding greenness was quantified via Normalized Difference Vegetation Index (NDVI) within 200, 400, and 800 m distances from geocoded home addresses at birth, age 7 years, and across childhood. Respiratory health outcomes were assessed at age 7 years, including asthma and lung function [percent predicted forced expiratory volume in the first second (%FEV1), percent predicted forced vital capacity (%FVC), and percent predicted ratio of forced expiratory volume in the first second to forced vital capacity (%FEV1/FVC)]. We assessed associations using linear and logistic regression models adjusted for community deprivation, household income, and traffic-related air pollution. We tested for effect measure modification by atopic status. RESULTS: We noted evidence of positive confounding as inverse associations were attenuated upon adjustment in the multivariable models. We found evidence of effect measure modification of NDVI and asthma within 400 m at age 7 years by atopic status (p = 0.04), whereby children sensitized to common allergens were more likely to develop asthma as exposure to greenness increased (OR = 1.3, 95% CI: 0.9, 2.0) versus children not sensitized to common allergens (OR = 0.8, 95% CI: 0.5, 1.2). We found consistently positive associations between NDVI and %FEV1 and %FVC which similarly evidenced positive confounding upon adjustment. In the adjusted regression models, NDVI at 7 years of age was associated with %FEV1 (200 m: ß = 2.1, 95% CI: 0.1, 3.3; 400 m: ß = 1.6, 95% CI: 0.3, 2.9) and %FVC (200 m: ß = 1.8, 95% CI: 0.7, 3.0; 400 m: ß = 1.6, 95% CI: 0.3, 2.8; 800 m: ß = 1.5, 95% CI: 0.1, 2.8). Adjusted results for %FEV1/FVC were non-significant except exposure at birth in the 400 m buffer (ß = 0.81, 95% CI: 0.1, 1.5). We found no evidence of effect measure modification of NDVI by atopic status for objective measures of lung function. CONCLUSION: Sensitivity to allergens may modify the effect of greenness on risk for asthma in children but greenness is likely beneficial for concurrent lung function regardless of allergic status.

Ambient ozone and fine particulate matter exposures and autism spectrum disorder in metropolitan Cincinnati, Ohio.

BACKGROUND: Epidemiological studies report fairly consistent associations between various air pollution metrics and autism spectrum disorder (ASD), with some elevated risks reported for different prenatal and postnatal periods. OBJECTIVES: To examine associations between ASD and ambient fine particulate matter (PM2.5) and ozone concentrations during the prenatal period through the second year of life in a case-control study. METHODS: ASD cases (n = 428) diagnosed at Cincinnati Children's Hospital Medical Center were frequency matched (15:1) to 6420 controls from Ohio birth records. We assigned daily PM2.5 and ozone estimates for 2005-2012 from US EPA's Fused Air Quality Surface Using Downscaling model to each participant for each day based on the mother's census tract of residence at birth. We calculated adjusted odds ratios (aORs) using logistic regression across continuous and categorical exposure window averages (trimesters, first and second postnatal years, and cumulative measure), adjusting for maternal- and birth-related confounders, both air pollutants, and multiple temporal exposure windows. RESULTS: We detected elevated aORs for PM2.5 during the 2nd trimester, 1st year of life, and a cumulative period from pregnancy through the 2nd year (aOR ranges across categories: 1.41-1.44, 1.54-1.84, and 1.41-1.52 respectively), and for ozone in the 2nd year of life (aOR range across categories: 1.29-1.42). Per each change in IQR, we observed elevated aORs for ozone in the 3rd trimester, 1st and 2nd years of life, and the cumulative period (aOR range: 1.19-1.27) and for PM2.5 in the 2nd trimester, 1st year of life, and the cumulative period (aOR range: 1.11-1.17). DISCUSSION: We saw limited evidence of linear exposure-response relationships for ASD with increasing air pollution, but the elevated aORs detected for PM2.5 in upper exposure categories and per IQR unit increases were similar in magnitude to those reported in previous studies, especially for postnatal exposures.

Characterizing Risk for Cumulative Risk Assessments.

In assessing environmental health risks, the risk characterization step synthesizes information gathered in evaluating exposures to stressors together with dose-response relationships, characteristics of the exposed population, and external environmental conditions. This article summarizes key steps of a cumulative risk assessment (CRA) followed by a discussion of considerations for characterizing cumulative risks. Cumulative risk characterizations differ considerably from single chemical- or single source-based risk characterization. CRAs typically focus on a specific population instead of a pollutant or pollutant source and should include an evaluation of all relevant sources contributing to the exposures in the population and other factors that influence dose-response relationships. Second, CRAs may include influential environmental and population-specific conditions, involving multiple chemical and nonchemical stressors. Third, a CRA could examine multiple health effects, reflecting joint toxicity and the potential for toxicological interactions. Fourth, the complexities often necessitate simplifying methods, including judgment-based and semi-quantitative indices that collapse disparate data into numerical scores. Fifth, because of the higher dimensionality and potentially large number of interactions, information needed to quantify risk is typically incomplete, necessitating an uncertainty analysis. Three approaches that could be used for characterizing risks in a CRA are presented: the multiroute hazard index, stressor grouping by exposure and toxicity, and indices for screening multiple factors and conditions. Other key roles of the risk characterization in CRAs are also described, mainly the translational aspect of including a characterization summary for lay readers (in addition to the technical analysis), and placing the results in the context of the likely risk-based decisions.

Swine exposure and methicillin-resistant Staphylococcus aureus infection among hospitalized patients with skin and soft tissue infections in Illinois: A ZIP code-level analysis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA), a bacterial pathogen, is a predominant cause of skin and soft tissue infections (SSTI) in the United States. Swine-production facilities have been recognized as potential environmental reservoirs of MRSA. To better understand how swine production may contribute to MRSA infection, we evaluated the association between MRSA infection among SSTI inpatients and exposure measures derived from national swine inventory data. METHODS: Based on adjusted odds ratios from logistic regression models, we evaluated the association between swine exposure metrics and MRSA infections among all Illinois inpatient hospitalizations for SSTI from January 2008 through July 2011. We also assessed if swine exposures had greater association with suspected community-onset MRSA (CO-MRSA) compared to suspected hospital-onset MRSA (HO-MRSA). Exposures were estimated using the Farm Location and Agricultural Production Simulator, generating the number of farms with greater than 1000 swine per residential ZIP code and the residential ZIP code-level swine density (swine/km2). RESULTS: For every increase in 100 swine/km2 within a residential ZIP code, the adjusted OR (aOR) for MRSA infection was 1.36 (95% CI: 1.28-1.45). For every additional large farm (i.e., >1000 swine) per ZIP code, the aOR for MRSA infection was 1.06 (95% CI: 1.04-1.07). The aOR for ZIP codes with any large farms compared to those with no large farms was 1.24 (95% CI: 1.19-1.29). We saw no evidence of an increased association for CO-MRSA compared to HO-MRSA with either continuous exposure metric (aORs=0.99), and observed inconsistent results across exposure categories. CONCLUSIONS: These publicly-available, ecological exposure data demonstrated positive associations between swine exposure measures and individual-level MRSA infections among SSTI inpatients. Though it is difficult to draw definitive conclusions due to limitations of the data, these findings suggest that the risk of MRSA may increase based on indirect environmental exposure to swine production. Future research can address measurement error related to these data by improving exposure assessment precision, increased specification of MRSA strain, and better characterization of specific environmental exposure pathways.

Method to assess component contribution to toxicity of complex mixtures: Assessment of puberty acquisition in rats exposed to disinfection byproducts.

A method based on regression modeling was developed to discern the contribution of component chemicals to the toxicity of highly complex, environmentally realistic mixtures of disinfection byproducts (DBPs). Chemical disinfection of drinking water forms DBP mixtures. Because of concerns about possible reproductive and developmental toxicity, a whole mixture (WM) of DBPs produced by chlorination of a water concentrate was administered as drinking water to Sprague-Dawley (S-D) rats in a multigenerational study. Age of puberty acquisition, i.e., preputial separation (PPS) and vaginal opening (VO), was examined in male and female offspring, respectively. When compared to controls, a slight, but statistically significant delay in puberty acquisition was observed in females but not in males. WM-induced differences in the age at puberty acquisition were compared to those reported in S-D rats administered either a defined mixture (DM) of nine regulated DBPs or individual DBPs. Regression models were developed using individual animal data on age at PPS or VO from the DM study. Puberty acquisition data reported in the WM and individual DBP studies were then compared with the DM models. The delay in puberty acquisition observed in the WM-treated female rats could not be distinguished from delays predicted by the DM regression model, suggesting that the nine regulated DBPs in the DM might account for much of the delay observed in the WM. This method is applicable to mixtures of other types of chemicals and other endpoints.

Comprehensive assessment of a chlorinated drinking water concentrate in a rat multigenerational reproductive toxicity study.

Some epidemiological studies report associations between drinking water disinfection byproducts (DBPs) and adverse reproductive/developmental effects, e.g., low birth weight, spontaneous abortion, stillbirth, and birth defects. Using a multigenerational rat bioassay, we evaluated an environmentally relevant "whole" mixture of DBPs representative of chlorinated drinking water, including unidentified DBPs as well as realistic proportions of known DBPs at low-toxicity concentrations. Source water from a water utility was concentrated 136-fold, chlorinated, and provided as drinking water to Sprague-Dawley rats. Timed-pregnant females (P0 generation) were exposed during gestation and lactation. Weanlings (F1 generation) continued exposures and were bred to produce an F2 generation. Large sample sizes enhanced statistical power, particularly for pup weight and prenatal loss. No adverse effects were observed for pup weight, prenatal loss, pregnancy rate, gestation length, puberty onset in males, growth, estrous cycles, hormone levels, immunological end points, and most neurobehavioral end points. Significant, albeit slight, effects included delayed puberty for F1 females, reduced caput epidydimal sperm counts in F1 adult males, and increased incidences of thyroid follicular cell hypertrophy in adult females. These results highlight areas for future research, while the largely negative findings, particularly for pup weight and prenatal loss, are notable.

A sensitivity analysis using alternative toxic equivalency factors to estimate U.S. dietary exposures to dioxin-like compounds.

EPA recommends sensitivity analyses when applying the toxic equivalency factor (TEF) method to evaluate exposures to dioxin-like compounds (DLCs). Applying the World Health Organization's (WHO) 2005 TEF values and estimating average U.S. daily dietary intakes of 25 DLCs from eight food categories, we estimate a toxic equivalency (TEQ) intake of 23 pg/day. Among DLCs, PCB 126 (26%) and 1,2,3,7,8-PeCDD (23%) dominate TEQ intakes. Among food categories, milk (14%), other dairy (28%), beef (25%), and seafood (18%) most influenced TEQ intakes. We develop two approaches to estimate alternative TEF values. Based on WHO's assumption regarding TEF uncertainty, Approach1 estimates upper and lower TEFs for each DLC by multiplying and dividing, respectively, its individual TEF by ± half a log. Based on compiled empirical ranges of relative potency estimates, Approach2 uses percentile values for individual TEFs. Total TEQ intake estimates using the lower and upper TEFs based on Approach1 were 8 and 68 pg TEQ/day, respectively. The 25th and 75th percentile TEFs from Approach2 yielded 12 and 28 pg TEQ/day, respectively. The influential DLCs and food categories remained consistent across alternative TEFs, except at the 90th percentile using Approach2. We highlight the need for developing underlying TEF probability distributions.

An empirical approach to sufficient similarity: combining exposure data and mixtures toxicology data.

When assessing risks posed by environmental chemical mixtures, whole mixture approaches are preferred to component approaches. When toxicological data on whole mixtures as they occur in the environment are not available, Environmental Protection Agency guidance states that toxicity data from a mixture considered "sufficiently similar" to the environmental mixture can serve as a surrogate. We propose a novel method to examine whether mixtures are sufficiently similar, when exposure data and mixture toxicity study data from at least one representative mixture are available. We define sufficient similarity using equivalence testing methodology comparing the distance between benchmark dose estimates for mixtures in both data-rich and data-poor cases. We construct a "similar mixtures risk indicator"(SMRI) (analogous to the hazard index) on sufficiently similar mixtures linking exposure data with mixtures toxicology data. The methods are illustrated using pyrethroid mixtures occurrence data collected in child care centers (CCC) and dose-response data examining acute neurobehavioral effects of pyrethroid mixtures in rats. Our method shows that the mixtures from 90% of the CCCs were sufficiently similar to the dose-response study mixture. Using exposure estimates for a hypothetical child, the 95th percentile of the (weighted) SMRI for these sufficiently similar mixtures was 0.20 (i.e., where SMRI <1, less concern; >1, more concern).

Developmental toxicity evaluations of whole mixtures of disinfection by-products using concentrated drinking water in rats: gestational and lactational effects of sulfate and sodium.

A developmental toxicity bioassay was used in three experiments to evaluate water concentrates for suitability in multigenerational studies. First, chlorinated water was concentrated 135-fold by reverse osmosis; select lost disinfection by-products were spiked back. Concentrate was provided as drinking water to Sprague-Dawley and F344 rats from gestation day 6 to postnatal day 6. Maternal serum levels of luteinizing hormone on gestation day 10 were unaffected by treatment for both strains. Treated dams had increased water consumption, and increased incidences of polyuria, diarrhea, and (in Sprague-Dawley rats) red perinasal staining. Pup weights were reduced. An increased incidence of eye defects was seen in F344 litters. Chemical analysis of the concentrate revealed high sodium (6.6 g/l) and sulfate (10.4 g/l) levels. To confirm that these chemicals caused polyuria and osmotic diarrhea, respectively, Na2SO4 (5-20 g/l) or NaCl (16.5 g/l) was provided to rats in drinking water. Water consumption was increased at 5- and 10-g Na2SO4/l and with NaCl. Pup weights were reduced at 20-g Na2SO4/l. Dose-related incidences and severity of polyuria and diarrhea occurred in Na2SO4-treated rats; perinasal staining was seen at 20 g/l. NaCl caused polyuria and perinasal staining, but not diarrhea. Subsequently, water was concentrated ∼120-fold and sulfate levels were reduced by barium hydroxide before chlorination, yielding lower sodium (≤1.5 g/l) and sulfate (≤2.1 g/l) levels. Treatment resulted in increased water consumption, but pup weight and survival were unaffected. There were no treatment-related clinical findings, indicating that mixtures produced by the second method are suitable for multigenerational testing.

Use of systematic evidence maps within the US environmental protection agency (EPA) integrated risk information system (IRIS) program: Advancements to date and looking ahead.

Systematic evidence maps (SEMs) are increasingly used to inform decision-making and risk management priority-setting and to serve as problem formulation tools to refine the focus of questions that get addressed in full systematic reviews. Within the U.S. Environmental Protection Agency (EPA) Office of Research and Development (ORD) Integrated Risk Information System (IRIS), SEMs have been used to inform data gaps, determine the need for updated assessments, inform assessment priorities, and inform development of study evaluation considerations, among other uses. Increased utilization of SEMs across the environmental health field has the potential to increase transparency and efficiency for data gathering, problem formulation, read-across, and evidence surveillance. Use of the SEM templates published in the companion text (Thayer et al.) can promote harmonization in the environmental health community and create more opportunities for sharing extracted content.

Systematic evidence map (SEM) template: Report format and methods used for the US EPA Integrated Risk Information System (IRIS) program, Provisional Peer Reviewed Toxicity Value (PPRTV) program, and other "fit for purpose" literature-based human health analyses.

BACKGROUND: Systematic evidence maps (SEMs) are gaining visibility in environmental health for their utility to serve as problem formulation tools and assist in decision-making, especially for priority setting. SEMs are now routinely prepared as part of the assessment development process for the US Environmental Protection Agency (EPA) Integrated Risk Information System (IRIS) and Provisional Peer Reviewed Toxicity Value (PPRTV) assessments. SEMs can also be prepared to explore the available literature for an individual chemical or groups of chemicals of emerging interest. OBJECTIVES: This document describes the typical methods used to produce SEMs for the IRIS and PPRTV Programs, as well as "fit for purpose" applications using a variety of examples drawn from existing analyses. It is intended to serve as an example base template that can be adapted as needed for the specific SEM. The presented methods include workflows intended to facilitate rapid production. The Populations, Exposures, Comparators and Outcomes (PECO) criteria are typically kept broad to identify mammalian animal bioassay and epidemiological studies that could be informative for human hazard identification. In addition, a variety of supplemental content is tracked, e.g., studies presenting information on in vitro model systems, non-mammalian model systems, exposure-level-only studies in humans, pharmacokinetic models, and absorption, distribution, metabolism, and excretion (ADME). The availability of New Approach Methods (NAMs) evidence is also tracked (e.g., high throughput, transcriptomic, in silico, etc.). Genotoxicity studies may be considered as PECO relevant or supplemental material, depending on the topic and context of the review. Standard systematic review practices (e.g., two independent reviewers per record) and specialized software applications are used to search and screen the literature and may include the use of machine learning software. Mammalian bioassay and epidemiological studies that meet the PECO criteria after full-text review are briefly summarized using structured web-based extraction forms with respect to study design and health system(s) assessed. Extracted data is available in interactive visual formats and can be downloaded in open access formats. Methods for conducting study evaluation are also presented which is conducted on a case-by-case basis, depending on the usage of the SEM.

Identification of developmentally toxic drinking water disinfection byproducts and evaluation of data relevant to mode of action.

Reactions between chemicals used to disinfect drinking water and compounds present in source waters produce chemical mixtures containing hundreds of disinfection byproducts (DBPs). Although the results have been somewhat inconsistent, some epidemiological studies suggest associations may exist between DBP exposures and adverse developmental outcomes. The potencies of individual DBPs in rodent and rabbit developmental bioassays suggest that no individual DBP can account for the relative risk estimates reported in the positive epidemiologic studies, leading to the hypothesis that these outcomes could result from the toxicity of DBP mixtures. As a first step in a mixtures risk assessment for DBP developmental effects, this paper identifies developmentally toxic DBPs and examines data relevant to the mode of action (MOA) for DBP developmental toxicity. We identified 24 developmentally toxic DBPs and four adverse developmental outcomes associated with human DBP exposures: spontaneous abortion, cardiovascular defects, neural tube defects, and low birth weight infancy. A plausible MOA, involving hormonal disruption of pregnancy, is delineated for spontaneous abortion, which some epidemiologic studies associate with total trihalomethane and bromodichloromethane exposures. The DBP data for the other three outcomes were inadequate to define key MOA steps.

Predicting the migration rate of dialkyl organotins from PVC pipe into water.

Organotins (OTs) are additives widely used as thermal and light stabilizers in polyvinyl chloride (PVC) plastics. OTs can leach into water flowing through PVC pipes. This work examines the leaching rates of two potentially neurotoxic OTs, dimethyl tin (DMT) and dibutyl tin (DBT), from PVC pipe. Water was circulated in a closed loop laboratory PVC pipe system. Using a gas chromatograph-pulsed flame photometric detector (GC-PFPD), the change in concentrations of DMT and DBT in the water in the system was monitored over time and allowed to reach equilibrium. OT concentration as a function of time was analyzed using a mechanistic leaching rate model. The diffusion coefficient for OT in the PVC pipe material, the only unknown model parameter, was found to be 9 × 10(-18) m(2)/s. This value falls within with the range of values estimated from the literature (2 × 10(-18) to 2 × 10(-17) m(2)/s) thus increasing confidence in the leaching rate model.

ExpoKids: An R-based tool for characterizing aggregate chemical exposure during childhood.

BACKGROUND: Aggregate exposure, the combined exposures to a single chemical from all pathways, is a critical children's health issue. OBJECTIVE: The primary objective is to develop a tool to illustrate potential differences in aggregate exposure at various childhood lifestages and the adult lifestage. METHODS: We developed ExpoKids (an R-based tool) using oral exposure estimates across lifestages generated by US EPA's Exposure Factors Interactive Resource for Scenarios Tool (ExpoFIRST). RESULTS: ExpoKids is applied to illustrate aggregate oral exposure, for ten media, as average daily doses (ADD) and lifetime average daily doses (LADD) in five graphs organized across seven postnatal childhood lifestages and the adult lifestage. This data visualization tool conveys ExpoFIRST findings, from available exposure data, to highlight the relative contributions of media and lifestages to chemical exposure. To evaluate the effectiveness of ExpoKids, three chemical case examples (di[2-ethylhexyl] phthalate [DEHP], manganese, and endosulfan) were explored. Data available from the published literature and databases for each case example were used to explore research questions regarding media and lifestage contributions to aggregate exposure. SIGNIFICANCE: These illustrative case examples demonstrate ExpoKids' versatile application to explore a diverse set of children's health risk assessment and management questions by visually depicting specific media and lifestage contributions to aggregate exposure.

Using the Key Characteristics of Carcinogens to Develop Research on Chemical Mixtures and Cancer.

BACKGROUND: People are exposed to numerous chemicals throughout their lifetimes. Many of these chemicals display one or more of the key characteristics of carcinogens or interact with processes described in the hallmarks of cancer. Therefore, evaluating the effects of chemical mixtures on cancer development is an important pursuit. Challenges involved in designing research studies to evaluate the joint action of chemicals on cancer risk include the time taken to perform the experiments because of the long latency and choosing an appropriate experimental design. OBJECTIVES: The objectives of this work are to present the case for developing a research program on mixtures of environmental chemicals and cancer risk and describe recommended approaches. METHODS: A working group comprising the coauthors focused attention on the design of mixtures studies to inform cancer risk assessment as part of a larger effort to refine the key characteristics of carcinogens and explore their application. Working group members reviewed the key characteristics of carcinogens, hallmarks of cancer, and mixtures research for other disease end points. The group discussed options for developing tractable projects to evaluate the joint effects of environmental chemicals on cancer development. RESULTS AND DISCUSSION: Three approaches for developing a research program to evaluate the effects of mixtures on cancer development were proposed: a chemical screening approach, a transgenic model-based approach, and a disease-centered approach. Advantages and disadvantages of each are discussed. https://doi.org/10.1289/EHP8525.

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.

A Cumulative Risk Perspective for Occupational Health and Safety (OHS) Professionals.

Cumulative risk assessment (CRA) addresses the combined risk associated with chemical and non-chemical exposures. Although CRA approaches are utilized in environmental and ecological contexts, they are rarely applied in workplaces. In this perspectives article, we strive to raise awareness among occupational health and safety (OHS) professionals and foster the greater adoption of a CRA perspective in practice. Specifically, we provide an overview of CRA literature as well as preliminary guidance on when to consider a CRA approach in occupational settings and how to establish reasonable boundaries. Examples of possible workplace co-exposures and voluntary risk management actions are discussed. We also highlight important implications for workplace CRA research and practice. In particular, future needs include simple tools for identifying combinations of chemical and non-chemical exposures, uniform risk management guidelines, and risk communication materials. Further development of practical CRA methods and tools are essential to meet the needs of complex and changing work environments.

Determinants of whether or not mixtures of disinfection by-products are similar.

Reactive chemicals have been used to disinfect drinking waters for over a century. In the 1970s, it was first observed that the reaction of these chemicals with the natural organic matter (NOM) in source waters results in the production of variable, complex mixtures of disinfection by-products (DBP). Because limited toxicological and epidemiological data are available to assess potential human health risks from complex DBP mixture exposures, methods are needed to determine when health effects data on a specific DBP mixture may be used as a surrogate for evaluating another environmental DBP mixture of interest. Before risk assessors attempt such efforts, a set of criteria needs to be in place to determine whether two or more DBP mixtures are similar in composition and toxicological potential. This study broadly characterizes the chemical and toxicological measures that may be used to evaluate similarities among DBP mixtures. Variables are discussed that affect qualitative and quantitative shifts in the types of DBP that are formed, including disinfectants used, their reactions with NOM and with bromide/iodide, pH, temperature, time, and changes in the water distribution system. The known toxicological activities of DBP mixtures and important single DBPs are also presented in light of their potential for producing similar toxicity. While DBP exposures are associated with a number of health effects, this study focuses on (1) mutagenic activity of DBP mixtures, (2) DBP cancer epidemiology, and (3) toxicology studies to evaluate similarity among DBP mixtures. Data suggest that further chemical characterization of DBP mixtures and more systematic study of DBP toxicology will improve the quality and usefulness of similarity criteria.

Correlations of water quality parameters with mutagenicity of chlorinated drinking water samples.

Adverse health effects that may result from chronic exposure to mixtures of disinfection by-products (DBPs) present in drinking waters may be linked to both the types and concentrations of DBPs present. Depending on the characteristics of the source water and treatment processes used, both types and concentrations of DBPs found in drinking waters vary substantially. The composition of a drinking-water mixture also may change during distribution. This study evaluated the relationships between mutagenicity, using the Ames assay, and water quality parameters. The study included information on treatment, mutagenicity data, and water quality data for source waters, finished waters, and distribution samples collected from five full-scale drinking water treatment plants, which used chlorine exclusively for disinfection. Four of the plants used surface water sources and the fifth plant used groundwater. Correlations between mutagenicity and water quality parameters are presented. The highest correlation was observed between mutagenicity and the total organic halide concentrations in the treated samples.

Chemical measures of similarity among disinfection by-product mixtures.

There are few measures that can be used to distinguish among mixtures of disinfection by-products (DBPs) produced in the chlorination or chloramination of drinking water. Objective measures of similarities among DBP mixtures would greatly simplify judgments about the risk that may be associated with exposure to DBPs in a given water supply. Major by-products of chlorination/chloramination include the trihalomethanes (THMs) and haloacetic acids (HAAs), which are routinely measured for compliance to regulations. A key question is whether measurement of similar amounts of these DBPs is indicative of the myriad other DBPs that are known to be produced. This article utilized data from a survey of 35 utilities in the United States that included several additional parameters, including members of the haloacetonitrile, trihaloacetaldehyde, and halopropanone classes. Based upon the distribution of bromine in the THM class, the concentrations of unmeasured brominated and bromochlorinated compounds could be determined. This allowed determination of whether measures of the THM and/or HAA classes reflected the amounts of these less abundant classes. Variations in relative yields among DBP classes were observed with water source type and with whether chlorine or chloramine was used as the disinfectant. However, most of the variability was attributable to geographic location. The relative abundance of brominated by-products also varied among water sources. Recent documentation that potent by-products, such as nitrosamines, are selectively produced in particular water systems and preferentially with chloramination indicates that more measures of individual DBP are needed to evaluate similarity among DBPs mixtures.