Incidence and severity in relation to magnitude of intake above the ADI orTDI: Use of critical effect data

Noncancer effects are considered to show thresholds, such that no effect wo uld be produced when the intake is below the threshold. Application of a 10 0-fold uncertainty factor to the no-observed-adverse-effect level (NOAEL) f or the critical effect in animal studies provides an estimate of an intake for sensitive humans (the acceptable daily intake or ADI) without significa nt adverse health effects. The risks of intakes by humans above the ADI the oretically move the most sensitive subjects from negligible risk to possibl e risk. An increase in intake above the ADI would move the population distr ibution of internal dose toward the dose-response curve for sensitive subje cts. The proportion of a population affected depends on the magnitude of th e excess intake, the relationship of the NOAEL and the biological threshold in animals, and the coefficient of variation for the kinetic parameters (e .g., clearance and bioavailability) which determine the internal dose in hu mans. The severity of any effect in sensitive and high-intake individuals d epends on the magnitude of the excess intake, the nature of the critical ef fect, and the slope of the dose-response relationship.