Division 3.2.2 Toxicological studies

The safety of the additive is assessed on the basis of the toxicological studies performed in vitro and in vivo on laboratory animals. They generally include measurements of:

1. (1)

   acute toxicity;

2. (2)

   genotoxicity (mutagenicity, clastogenicity);

3. (3)

   sub-chronic oral toxicity;

4. (4)

   chronic oral toxicity/carcinogenicity;

5. (5)

   reproduction toxicity including teratogenicity; and

6. (6)

   other studies.

Further studies providing additional information necessary for the assessment of the safety of the active substance and its residues shall be conducted if there is any reason for concern.

On the basis of the results of these studies a toxicological NOAEL must be established.

Additional studies on particular metabolites may be necessary if these metabolites are produced by target species and are not formed to a significant extent in the laboratory test species. If metabolic studies are available in humans, data shall be taken into consideration in deciding the nature of eventual additional studies.

Toxicological studies must be carried out with the active substance. If the active substance is present in a fermentation product, the fermentation product shall be tested. The fermentation product tested must be identical to that to be used in the commercial product.

Studies must be carried out using internationally validated test methods and shall be performed in accordance with F1F2assimilated law in force or OECD Guidelines for methodological details and according to the principles of GLP. The studies involving laboratory animals shall respect the rules on animal welfare laid down by assimilated law and they shall not be repeated if not necessary.