There is increasing interest in the use of tiered approaches in risk assessment of mixtures or co-exposures to chemicals for prioritization. One possible screening-level risk assessment approach is the threshold of toxicological concern (TTC). To date, default assumptions of dose or response additivity have been used to characterize the toxicity of chemical mixtures. Before a screening-level approach could be used, it is essential to know whether synergistic interactions can occur at low, environmentally relevant exposure levels. Studies demonstrating synergism in mammalian test systems were identified from the literature, with emphasis on studies performed at doses close to the points of departure (PODs) for individual chemicals. This search identified 90 studies on mixtures. Few included quantitative estimates of low-dose synergy; calculations of the magnitude of interaction were included in only 11 papers. Quantitative methodology varied across studies in terms of the null hypothesis, response measured, POD used to test for synergy, and consideration of the slope of the dose-response curve. It was concluded that consistent approaches should be applied for quantification of synergy, including that synergy be defined in terms of departure from dose additivity; uniform procedures be developed for assessing synergy at low exposures; and the method for determining the POD for calculating synergy be standardized. After evaluation of the six studies that provided useful quantitative estimates of synergy, the magnitude of synergy at low doses did not exceed the levels predicted by additive models by more than a factor of 4.

Background: There is a recognized need to improve the application of epidemiologic data in human health risk assessment especially for understanding and characterizing risks from environmental and occupational exposures. Although there is uncertainty associated with the results of most epidemiologic studies, techniques exist to characterize uncertainty that can be applied to improve weight-of-evidence evaluations and risk characterization efforts.Methods: This report derives from a Health and Environmental Sciences Institute (HESI) workshop held in Research Triangle Park, North Carolina, to discuss the utility of using epidemiologic data in risk assessments, including the use of advanced analytic methods to address sources of uncertainty. Epidemiologists, toxicologists, and risk assessors from academia, government, and industry convened to discuss uncertainty, exposure assessment, and application of analytic methods to address these challenges.Synthesis: Several recommendations emerged to help improve the utility of epidemiologic data in risk assessment. For example, improved characterization of uncertainty is needed to allow risk assessors to quantitatively assess potential sources of bias. Data are needed to facilitate this quantitative analysis, and interdisciplinary approaches will help ensure that sufficient information is collected for a thorough uncertainty evaluation. Advanced analytic methods and tools such as directed acyclic graphs (DAGs) and Bayesian statistical techniques can provide important insights and support interpretation of epidemiologic data.Conclusions: The discussions and recommendations from this workshop demonstrate that there are practical steps that the scientific community can adopt to strengthen epidemiologic data for decision making.Citation: Burns CJ, Wright JM, Pierson JB, Bateson TF, Burstyn I, Goldstein DA, Klaunig JE, Luben TJ, Mihlan G, Ritter L, Schnatter AR, Symons JM, Yi KD. 2014. Evaluating uncertainty to strengthen epidemiologic data for use in human health risk assessments. Environ Health Perspect 122:1160–1165; http://dx.doi.org/10.1289/ehp.1308062

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A total of 10,000 U.S. households in 25 standard metropolitan statistical areas and 25 counties were included in the United States. More than 8,200 households granted an interview. Nine of every ten households in the United States used some types of pesticide in their house, garden, or yard. Households in the southeastern United States used the most pesticides. Although more than 500 different pesticide formulations were used by the sampled households, 15 pesticides accounted for 65.5% of all pesticides reported in this study. Thirteen of these 15 pesticides were insecticides, one was a herbicide, and one was a rodenticide.

Workers employed in jobs with routine potential for plutonium exposure have low mortality rates compared to other Hanford workers even with adjustment for demographic, socioeconomic, and employment factors. This may be due, in part, to medical screening. Associations between duration of employment in jobs with routine potential for plutonium exposure and mortality may indicate occupational exposure effects.