2021 FDA Science Forum
Evaluation of the Medical Device Chemical Space in the ToxCast/Tox21 High-Throughput Screening (HTS) Program
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Contributing OfficeCenter for Devices and Radiological Health
Abstract
ToxCast/Tox21 high-throughput screening (HTS) in vitro assays constitute a rapid and cost-effective platform for identifying chemical hazards by screening large chemical libraries for effects on biochemical endpoints, cellular processes, and phenotypes. The ToxCast/Tox21 HTS program covers a broad spectrum of chemical-induced biological effects on over 1,000 assay endpoints, including interaction with receptors, transporters, ion channels, enzyme inhibition, induction of cell stress pathways, and cytotoxicity. Analysis of the bioactivity profile of medical device relevant chemicals in ToxCast/Tox21 assays has not been performed yet. The purpose of this project is to evaluate the medical device chemical space across the ToxCast/Tox21 HTS program, focusing on chemicals, which includes tentatively identified substances, reported to be present in polymers/plastics. A total of 1,226 chemicals associated with polymers/plastics were tested in ToxCast/Tox21 assays. These chemicals were cross-referenced against the CDRH’s Image2000 database to evaluate potential relevance for the medical device space. A total of 1,118 chemicals were reported in medical device submissions captured in the Image2000 database. Chemical bioactivity was evaluated across tested assay endpoints in the ToxCast/Tox21 platform and major biological targets were identified. This effort using chemical screening data from ToxCast/Tox21 assays will help identify potential hazards for chemicals suspected to leach from medical devices, and may be an additional source of information for sponsors and regulators in the evaluation of medical device biocompatibility.
