Table 3.

Cross-cutting themes that emerged from the NIEHS mixtures workshop.

In vitro versus in vivo approaches -A combination of in vitro and in vivo approaches are required to move forward on mixtures questions -Mixtures projects that include both in vitro and in vivo endpoints are needed Cross-disciplinary effort -Better coordination between epidemiology and toxicology is recommended -Specific areas that require attention include: ▪Different mixtures terminology in epidemiology and toxicology ▪More use of potency data from toxicology in epidemiology studies ▪Development of better statistical methods for assessing multi-chemical associations to disease Systems-based approaches for studying mixtures -Better understanding of biological pathways is required to develop mixtures hypotheses -Innovative bioinformatics approaches for managing “data-rich” mixtures experiments are needed Sufficient similarity as a key approach -Whole mixtures approaches are preferred by risk assessors and require fewer assumptions -Sufficient similarity methods require development/validation and more case studies Need for both bottom-up and top-down approaches -Both component-based and whole-mixtures approaches will be required in the future Federated databases should be developed to manage mixtures data, including exposure, in vitro, animal, and human data -Searchable, user-friendly database that integrates across data types would be an invaluable resource Prioritization of chemicals/mixtures is needed -Examples of suggested approaches included: ▪NHANES data to identify combinations with high exposure potential ▪Environment-wide Association Studies (EWAS) to develop testable hypotheses ▪Maximum cumulative ratio to prioritize mixtures for cumulative risk assessments