Commission Regulation (EC) No 429/2008 of 25 April 2008 on detailed rules for the implementation of Regulation (EC) No 1831/2003 of the European Parliament and of the Council as regards the preparation and the presentation of applications and the assessment and the authorisation of feed additives (Text with EEA relevance) (c. 429)

ANNEX II GENERAL REQUIREMENTS TO BE SATISFIED BY THE DOSSIER PROVIDED FOR IN ARTICLE 3

3. SECTION III: STUDIES CONCERNING SAFETY OF THE ADDITIVE

3.2. Studies concerning the safety of use of the additive for consumers

3.2.2. Toxicological studies

3.2.2.4. Chronic oral toxicity studies (including carcinogenicity studies)

To investigate the chronic toxic potential and carcinogenic potential, a chronic oral toxicity study must be carried out in at least one species, and shall be of at least 12 months' duration. The species chosen shall be the most appropriate on the basis of all available scientific data, including the results of the 90-day studies. The default species is the rat. If a second study is requested, a rodent or a non-rodent mammalian species shall be used. The test item must be administered orally with at least three levels in addition to a control group to obtain a dose response.

If the chronic toxicity study is combined with an examination of carcinogenicity, then the duration shall be extended to 18 months for mice and hamsters, and to 24 months for rats.

Carcinogenicity studies may not be necessary if the active substance and its metabolites:

(1)

give consistently negative results in the genotoxicity tests;

(2)

are not structurally related to known carcinogens; and

(3)

give no effects indicative of potential (pre)neoplasia in chronic toxicity assays.

Protocols should be in line with OECD Guideline 452 (chronic toxicity study) or 453 (combined chronic toxicity/carcinogenicity study).