Division 3.2.3.1 Proposal of the acceptable daily intake (ADI) for the active substance(s)

The acceptable daily intake (ADI) (expressed as mg of additive or additive related material per person per day) is derived by dividing the lowest NOAEL (mg per kg body weight) by an appropriate safety factor and multiplying by the average human body weight of 60 kg.

An ADI shall, where appropriate, be proposed. An ADI can also be ‘not specified’ because of low toxicity in animal tests. An ADI shall not be proposed if the substance shows genotoxic or carcinogenic properties relevant to humans.

The setting of an ADI normally requires the similarity of metabolic fate of the active substance in the target animals and laboratory animals (see 3.2.1.4 Bioavailability of residues) which ensures that consumers are exposed to the same residues as the laboratory animals used in toxicological studies. If not, additional studies in a second laboratory animal species or with the metabolites specific to the target species may still allow an ADI to be set.

The safety factor used to determine the ADI for a particular additive will take into consideration the nature of the biological effects and the quality of the data used to identify the NOAEL, the relevance of these effects to man and their reversibility and any knowledge of the direct effect(s) of the residues in human.

A safety factor of at least 100 in calculating the ADI (if a full toxicological package has been provided) shall be employed. Where data on the active substance are available for human, a lower safety factor may be acceptable. Higher safety factors might be applied to account for additional sources of uncertainty in data or where the NOAEL is set on the basis of a particular critical endpoint, such as teratogenicity.