5 - Tolerable intake values for leachables: Practical use of ISO 10993-17 standard

Abstract

This chapter describes an approach for setting tolerable intake (TI) values for chemical compounds released from medical device materials based on the method described in the ISO 10993-17 standard (Biological evaluation of medical devices—Part 17: Establishment of allowable limits for leachable substances). Practical advice is provided on how to derive both non-cancer and cancer-based TI values and recommendations are offered on how to account for potential toxicological interactions among the chemical constituents of an extract, how to derive a TI from an LD50 value (i.e., a dose associated with 50% death in exposed animals), how to conduct route-to-route extrapolation of dose, and how to apply the threshold of toxicological concern (TTC) approach) to derive a default TI in the absence of the toxicity data needed to derive a TI. The chapter also explores how the approach outlined in the ISO 10993-17 standard for derivation of TI values compares with methods developed by other groups for the establishment of safe exposure levels for environmental pollutants and impurities in drug substances and how to identify a key toxicity study to serve as the basis for the TI value.