US EPA

An approach for evaluating and integrating genomic data in chemical risk assessment was developed based on the lessons learned from performing a case study for the chemical dibutyl phthalate. A case study prototype approach was first developed in accordance with EPA guidance and recommendations of the scientific community. Dibutyl phthalate was selected for the case study exercise and the scoping phase of the dibutyl phthalate case study was conducted. The available dibutyl phthalate data was considered for whether these data, taken together, could inform various risk assessment aspects, such as toxicodynamics, toxicokinetics, and dose-response. A description of weighing the available dibutyl phthalate genomic data for utility in risk assessment provides a template for considering genomic data for future chemical assessments. As a result of conducting the scoping process, two questions - Do the DBP toxicogenomic data inform 1) the mechanisms or modes of action?, and 2) the interspecies differences in toxicodynamics? - were selected to focus the case study exercise. Principles of the general approach include considering the genomics data in conjunction with all other data to determine their ability to inform the various quantitative and/or qualitative aspects of risk assessment, and evaluating the relationship between the available genomic and toxicity outcome data with respect to study comparability and phenotypic anchoring. Based on the experience of the DBP case study, recommendations and a general approach for integrating genomic data in chemical assessment were developed to advance the broader effort to utilize 21st century data in risk assessment.

EULING, S., C. M. Thompson, W. CHIU, AND R. Benson. An Approach for Integrating Toxicogenomic Data in Risk Assessment: The Dibutyl Phthalate Case Study. Susan Y. Euling, Chad Thompson, Weihsueh A. Chiu, Robert Benson (ed.), Submitted to: TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 271(3):324-335, (2013).