The application of in vitro data in the derivation of the acceptable dailyintake of food additives

The acceptable daily intake (ADI) for food additives is commonly derived fr om the NOAEL (no-observed-adverse-effect level) in long-term animal in vivo studies. To derive an ADI a safety or uncertainty factor (commonly 100) is applied to the NOAEL in the most sensitive test species. The 100-fold safe ty factor is considered to be the product of both species and inter-individ ual differences in toxicokinetics and toxicodynamics. Although in vitro dat a have previously been considered during the risk assessment of food additi ves, they have generally had no direct influence on the calculation of ADI values. In this review 18 food additives are evaluated for the availability of in vitro toxicity data which might be used for the derivation of a spec ific data-derived uncertainty factor. For the majority of the food additive s reviewed, additional in vitro eats have been conducted which supplement a nd support the short- and long-term in vivo toxicity studies. However, it w as recognized that these in vitro studies could not be used in isolation to derive an ADI; only when sufficient in vivo mechanistic data are available can such information be used in a regulatory context. Additional short-ter m studies are proposed for the food additives which, if conducted, would pr ovide data that could then be used for the calculation of data-derived unce rtainty factors. (C) 2000 Published by Elsevier Science Ltd. All rights res erved.