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 Schenck, K. M. , Sivaganesan, M. and Rice, G. 2009. Correlations of water quality parameters with mutagenicity of chlorinated drinking water samples. J. Toxicol. Environ. Health A., 72: 461–467. [Taylor & Francis Online], [Web of Science ®] [Google Scholar] ) describe the chemistry and mutagenicity of a set of DBP mixtures concentrated from five different drinking-water treatment plants. Bull et al. (2009a Bull, R. J. , Teuschler, L. and Rice, G. 2009a. Determinants of whether or not mixtures of disinfection by-products are similar. J. Toxicol. Environ. Health A., 72: 437–460. [Taylor & Francis Online], [Web of Science ®] [Google Scholar] , 2009b Bull, R. J. , Rice, G. , Teuschler, L. and Feder, P. I. 2009b. Chemical measures of similarity among disinfection by-product mixtures. J. Toxicol. Environ. Health A., 72: 429–436. [Google Scholar] ) 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 Feder, P. I. , Ma, Z. , Bull, R. J. , Teuschler, L. K. , Schenck, K. M. , Simmons, J. E. and Rice, G. E. 2009a. Evaluating sufficient similarity for disinfection by-product (DBP) similar mixtures via multivariate statistical procedures. J. Toxicol. Environ. Health A., 72: 468–481. [Taylor & Francis Online], [Web of Science ®] [Google Scholar] , 2009b Feder, P. I. , Ma, Z. , Bull, R. J. , Teuschler, L. K. and Rice, G. E. 2009b. Evaluating sufficient similarity for drinking water disinfection by-product (DBP) mixtures with bootstrap hypothesis test procedures. J. Toxicol. Environ. Health A., 72: 494–504. [Taylor & Francis Online], [Web of Science ®] [Google Scholar] ) 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.

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 %FEV₁and %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: β = 2.1, 95% CI: 0.1, 3.3; 400 m: β = 1.6, 95% CI: 0.3, 2.9) and %FVC (200 m: β = 1.8, 95% CI: 0.7, 3.0; 400 m: β = 1.6, 95% CI: 0.3, 2.8; 800 m: β = 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 (β = 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.

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.

This article presents a toxicologically-based risk assessment strategy for identifying the individual components or fractions of a complex mixture that are associated with its toxicity. The strategy relies on conventional component-based mixtures risk approaches such as dose addition, response addition, and analyses of interactions. Developmental toxicity data from two drinking-water concentrates containing disinfection by-products (DBP) mixtures were used to illustrate the strategy. The results of this study showed that future studies of DBP concentrates using the Chernoff–Kavlock bioassay need to consider evaluating DBP that are concentrated more than 130-fold and using a rat strain that is more sensitive to chemically-induced pregnancy loss than Sprague-Dawley rats. The results support the planned experimental design of a multigeneration reproductive and developmental study of DBP concentrates. Finally, this article discusses the need for a systematic evaluation of DBP concentrates obtained from multiple source waters and treatment types. The development of such a database could be useful in evaluating whether a specific DBP concentrate is sufficiently similar to tested combinations of source waters and treatment alternatives so that health risks for the former may be estimated using data on the latter.

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.