Mixtures research at NIEHS: An evolving program

Abstract

The National Institute of Environmental Health Sciences (NIEHS) has a rich history in evaluating the toxicity of mixtures. The types of mixtures assessed by the Division of the National Toxicology Program (DNTP) and the extramural community (through the Division of Extramural Research and Training (DERT)) have included a broad range of chemicals and toxicants, with each study having a unique set of questions and design considerations. Some examples of the types of mixtures studied include: groundwater contaminants, pesticides/fertilizers, dioxin-like chemicals (assessing the toxic equivalency approach), drug combinations, air pollution, metals, polycyclic aromatic hydrocarbons, technical mixtures (e.g. pentachlorophenol, flame retardants), and mixed entities (e.g. herbals, asbestos). These endeavors have provided excellent data on the toxicity of specific mixtures and have been informative to the human health risk assessment process in general (e.g. providing data on low dose exposures to environmental chemicals). However, the mixtures research effort at NIEHS, to date, has been driven by test article nominations to the DNTP or by investigator-initiated research through DERT. Recently, the NIEHS has embarked upon an effort to coordinate mixtures research across both intramural and extramural divisions in order to maximize mixtures research results. A path forward for NIEHS mixtures research will be based on feedback from a Request for Information (RFI) designed to gather up-to-date views on the knowledge gaps and roadblocks to evaluating mixtures and performing cumulative risk assessment, and a workshop organized to bring together mixtures experts from risk assessment, exposure science, biology, epidemiology, and statistics. The future of mixtures research at NIEHS will include projects from nominations to DNTP, studies by extramural investigators, and collaborations across government agencies that address high-priority questions in the field of mixtures research.

Residential proximity to agricultural fumigant use and IQ, attention and hyperactivity in 7-year old children

“…These fumigant exposure models could be used in larger epidemiological studies that combine cohorts or use available data to assess the relationship between agricultural fumigant use and neurodevelopment in children. There is also a need for further development of statistical methods for analyzing environmental exposures to highly correlated chemical mixtures (Rider et al, 2013). …”

Sequential assessment via daphnia and zebrafish for systematic toxicity screening of heterogeneous substances

“…The misunderstanding can underestimate the mixtures' toxic effects, which can pose a threat to public health. Most evaluation methods are based on an individual substance's toxicity rather than on a whole mixture of various substances (Abdelraheem et al, 2015;Backhaus and Faust, 2012;Buckley and Farraj, 2015;Herzog et al, 2013;Marcone et al, 2012;Nabeshi et al, 2011;Nazarenko et al, 2012;Rider et al, 2013). Pesticides for agriculture (Bussy et al, 2015;Jang et al, 2014b;Seiber et al, 2014), industrial products for consumers ( Alvarez et al, 2009;El-Didamony et al, 2013;Mastella et al, 2014;Misik et al, 2014), and by-products from the automobile and electronic industries (Feng et al, 2015;Snow et al, 2014) are introduced into ecosystems in mixture forms.…”

Evaluation of time-dependent toxicity and combined effects for a series of mono-halogenated acetonitrile-containing binary mixtures

“…Via exposure profiling of reactive mixtures [1], docking-based receptor library [2] or toxicogenomics [3] studies, or examining aquatic toxicity [4], mammalian reproductive effects [5] or endocrine disruptors [6] such research efforts can improve the ability to predict mixture toxicity. Assessments of toxicity in binary [7], ternary [8] or complex chemical mixtures [9] have been common, with such toxicity having been evaluated for metals [10], pesticides [11], polycyclic aromatic hydrocarbons [12], [13], and micropollutants [14].…”