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Examining the Utility of In Vitro Bioactivity as a Conservative Point of Departure: A Case Study (APCRA)
Citation:
Paul-Friedman, K. AND R. Thomas. Examining the Utility of In Vitro Bioactivity as a Conservative Point of Departure: A Case Study (APCRA). Advancing the Pace of Chemical Risk Assessment (APCRA) team meeting, OttawaC, October 09 - 12, 2018. https://doi.org/10.23645/epacomptox.7243346
Impact/Purpose:
The primary objective of this work is to elucidate whether a POD derived from in vitro bioactivity would be a conservative estimate of traditional POD estimates, using 448 chemicals in a case study comparison of high-throughput predictions of bioactivity, reverse dosimetry, and exposure, as well as traditional hazard information.
Description:
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 by prioritizing chemicals for further evaluation. Advancement toward this goal requires confidence that in vitro bioactivity data, in conjunction with high-throughput toxicokinetic information, can be used to estimate administered equivalent doses at or below the PODs derived from traditional animal studies. The primary objective of this work is to elucidate whether a POD derived from in vitro bioactivity would be a conservative estimate of traditional POD estimates, using 448 chemicals in a case study comparison of high-throughput predictions of bioactivity, reverse dosimetry, and exposure, as well as traditional hazard information. For 92% of these chemicals, a POD derived from new approach methodologies (PODNAM) was a conservative prediction for the traditional POD (PODtraditional) value. For instances when the PODtraditional was less than the PODNAM, there was an enrichment of structural features associated with organophosphate and carbamate insecticides. No particular study type, such as developmental, reproductive, or chronic studies, defined the PODtraditional more frequently when the PODNAM > PODtraditional. High-throughput exposure predictions were greater than the PODNAM for 26 chemicals in the case study, with bioactivity:exposure ratios (BERs) of less than zero, indicating possible priority chemicals for further investigation. When compared to threshold of toxicological concern (TTC) values, the PODNAM tended to be less conservative than TTC, and it may be that these approaches are complementary in application. This work demonstrates the feasibility, and continuing challenges, of using in vitro bioactivity as a conservative estimate of POD in screening level assessments. This abstract does not necessarily reflect U.S. EPA policy.
URLs/Downloads:
DOI: Examining the Utility of In Vitro Bioactivity as a Conservative Point of Departure: A Case Study (APCRA)
PAULFRIEDMAN_APCRA3_RETROSPECTIVE_CASE_STUDY_10OCT2018_V2.PDF (PDF, NA pp, 4595.388 KB, about PDF)