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

Abstract

The use of a safety factor specifically for nature of toxicity by different advisory and regulatory bodies has been reviewed. The main reasons for the application of such a factor were the detection of carcinogenicity 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 applied specifically to the no-observed-adverse-effect-level (NOAEL) for the toxicity endpoint which triggered the use of the extra factor. However, in many cases the extra factor was applied when the NOAEL used to calculate the tolerable daily intake (TDI) was for an unrelated toxicity, 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 NOAEL for the toxicity which resulted in its use; the TDI should be calculated for different toxicity endpoints using the total safety/uncertainty factor appropriate for each endpoint. The TDI adopted would then be the lowest of those calculated for different endpoints.