Toxicity testing and derivation of the ADI.

The ADI is an estimate of the amount of a chemical that can be ingested daily over a lifetime without appreciable health risk. It is derived from No-Observed-Adverse-Effect-Levels (NOAELs) determined in a battery of toxicity tests in animals and augmented by human data where available. The toxicity tests are intended (with a few exceptions) to embrace all the circumstances of human exposure to dietary chemicals. Hence these tests include chronic studies, sometimes with prior exposure in utero, and reproduction tests covering the reproductive phase including effects on the parental animals and the offspring. The tests should also cover the rapid growth phase from weaning to maturing. The ADI is calculated from the lowest NOAEL in the most sensitive test and the most sensitive species, unless other data indicate otherwise, and if the reproductive, neonatal or rapid growth phases indicate particular periods of sensitivity this should drive the numerical derivation of the ADI. In calculating the ADI, the NOAEL is divided by appropriate arbitrary or data-derived safety or uncertainty factors. Care in selecting the pivotal test, the NOAEL and the safety factors should ensure that the ADI does apply to children (or other age groups). However, because of the higher food intake of children on a body weight basis, specific risk management measures may be needed to ensure that the ADI is not exceeded.