Division II.6.6.2.3.2

Human exposure to such substances may be expected to come from both exogenous (treatment related residues plus natural levels in food of animal origin) and endogenous (human physiological) origin. The risk assessment of the residues is complicated by the difficulty in assessing the likely response of ingestion of low exogenous levels when humans are constantly exposed to relatively high and fluctuating levels of endogenously produced substance and fluctuating dietary levels. In addition, for many active substances (like hormones, corticosteroids) exogenous exposure may lead to regulation of the endogenous production that, in turn, may change the endogenous hormone levels and the overall response. This complicates the interpretation of conventional toxicology studies and the derivation of an ADI. In addition, findings in laboratory animals may be difficult to extrapolate to the situation in humans owing to complex specific differences in biochemical/pharmacodynamic regulatory mechanisms.