Setting of acute reference doses for pesticides based on existing regulatory requirements and regulatory test guidelines

Reference doses (RfD) for the definition of tolerable food residues have tr aditionally been based on the lowest no observed adverse effect level (NOAE L), which usually comes from chronic toxicity studies. While this is genera lly agreed to be a safe approach to evaluate the overall significance of ex pected consumption it is clear that it is not appropriate for evaluation of the toxicological significance of residues in a single meal. Standard acut e toxicity tests are not designed to generate an NOAEL, from which an RfD c an be derived. They are more appropriate to evaluating risk following accid ental high exposure to the product itself rather than to food residues. A t ypical toxicological database for a pesticide active substance contains stu dies which may be appropriate, on a case-by- case basis, to evaluate shorte r term endpoints of interest for specific molecules, such as developmental or acute neurotoxicity studies. However, their specificity limits their sco pe of application. General toxicological endpoints are well covered by shor t-term, 28- or 90-day, guideline studies. However, neither of these studies is ideal for setting of an acute RfD (ARfD) as the treatment period is sig nificantly longer than the duration of consumer exposure. This could be bal anced by applying a reduced safety factor to the NOAEL to set the ARfD. Alt ernatively, a test guideline could be designed to generate a relevant acute NOAEL but the time necessary for development, validation and acceptance of such a guideline means that an interim approach is, in any case, necessary .