THE USE OF AN ADDITIONAL SAFETY OR UNCERTAINTY FACTOR FOR NATURE OF TOXICITY IN THE ESTIMATION OF ACCEPTABLE DAILY INTAKE AND TOLERABLE DAILY INTAKE VALUES

The use of a safety factor specifically for nature of toxicity by diff erent advisory and regulatory bodes has been reviewed. The main reason s for the application of such a factor were the detection of carcinoge nicity for nongenotoxic chemicals and teratogenicity. Inconsistencies and discrepancies were found between different advisory bodies and by the same body when considering the databases for different chemicals. In some cases the extra safety factor for nature of toxicity was appli ed specifically to the no-observed-adverse-effect-level (NOAEL) for th e toxicity endpoint which triggered the use of the extra factor. Howev er, in many cases the extra factor was applied when the NOAEL used to calculate the tolerable daily intake (TDI) was for an unrelated toxici ty, sometimes in a different species. If a safety factor for nature of toxicity is to be used, then logically it should be applied to the NO AEL for the toxicity which resulted in its use; the TDI should be calc ulated for different toxicity endpoints using the total safety/uncerta inty factor appropriate for each endpoint, The TDI adopted would then be the lowest of those calculated for different endpoints. (C) 1995 Ac ademic Press,Inc.