Grouping Extractable and Leachable (E&L) Compounds with a Common Mechanism of Action for Toxicological Risk Assessment

The toxicological risk assessment of E&L compounds is typically conducted on a compound-by-compound basis; however, for compounds that lack toxicity data, it may be useful to group compounds together that have similar structural and physical-chemical properties, as well as a similar toxicological mechanism of action, to derive a class-specific Tolerable Intake (TI) or Permitted Daily Exposure (PDE) that is applicable for all compounds in that group. This talk explores ways to group compounds based on their structural and toxicological similarity and how to use computational models to identify a proposed toxicological mechanism of action for compounds in a group. The presentation will also review methods to conduct a cumulative risk assessment of the compounds in the assembled group. This approach of first assembling a group of compounds with a common toxicological mechanism, then conducting a risk toxicological assessment of the compounds in the group, has the potential to streamline the toxicological risk assessment process when large numbers of extractable or leachable compounds are released from a polymeric material and provides a science-based method for setting TI/PDE values that is presumably less conservative than the use of Threshold of Toxicological Concern (TTC) values as default TI/PDE values for the individual compounds