You are here:
Examining the Utility of In Vitro Bioactivity as a Conservative Point of Departure: A Case Study
Citation:
Paul-Friedman, K. Examining the Utility of In Vitro Bioactivity as a Conservative Point of Departure: A Case Study. Presented at Advancing the Pace of Chemical Risk Assessment, Helsinki, FINLAND, October 10 - 11, 2017.
Impact/Purpose:
Use of high-throughput, in vitro bioactivity data in setting a conservative point-of-departure (POD) has the potential to accelerate the pace of human health risk assessments. Advancement toward this goal will require greater confidence that in vitro bioactivity data, in concert with high-throughput toxicokinetic information and reverse dosimetry, can be used to estimate administered dose equivalents (ADEs) at or below the PODs derived from traditional animal studies. The primary goal of this case study is to elucidate whether a “region of safety” (ROS), i.e. a threshold below which no bioactivity or toxicity would be anticipated, can be identified for a list of chemicals with existing human health evaluations. Further, if there are instances for which ADEs do not approximate a conservative POD from these existing assessments, specific uncertainties in the in vitro bioactivity approach will be identified to enable progress on high-throughput human hazard characterization and chemical evaluation.
Description:
The defined objectives for the case study include: (1) Compare in vitro bioactivity-derived administered dose equivalents (ADEs) and publicly available PODs from traditional chemical assessments (PODtraditional) to determine whether ADEs provide a conservative estimate of PODtraditional. (2) Calculate the bioactivity-exposure ratio (BER) based on the ADE distribution for high-throughput bioactivity compared with both high-throughput exposure estimates (e.g., ExpoCast) and exposure estimates from traditional chemical assessments; (3) Determine whether these BERs provide a robust means to prioritize chemicals for additional study and/or to serve as a low tier risk assessment approach; and, (4) Characterize the strengths and possible areas for improvement of NAM-derived PODs (PODNAM) for use in screening-level human hazard characterization and risk evaluations. For 87% of the 379 chemicals evaluated in this case study, PODNAMs were conservatively predictive of POD-traditional. This presentation preliminarily examines the possible reasons why PODNAMs were not conservative for the remaining 48 chemicals.