# 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), Division 4.2.3.1: Studies concerning the safety of use of the additive for the target animals

Extent: E+W+S+N.I.

The whole of subsection 3.1.1 of Annex II applies.
Applicants are encouraged to use, wherever possible, at least a 100-fold overdose in the experimental group and consequently reduce the number of end-points required. A concentrated form of the additive can be used for this purpose. Concentration shall be adjusted by reducing the amount of carrier present but the ratio of active agent(s)/substance(s) to the other fermentation products must remain the same as in the final product. For enzymes, the diet shall provide the appropriate substrate(s).
The whole of subsection 3.1.2 of Annex II applies for all micro-organisms and for those enzymes with a direct catalytic effect on elements of the microbiota or which otherwise are claimed to affect the gut microbiota.
Where there is novel exposure or a substantial increase in the extent of exposure to micro-organisms, additional studies may be necessary to demonstrate the absence of adverse effects on the commensal microbiota of the digestive tract. For ruminants, direct counts of the microbiota will be necessary only if indicted by evidence of an adverse change to rumen function (measured in vitro as a change in volatile fatty acid concentrations, reduction in propionate concentration or reduced cellulolysis).

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Source: https://www.legislation.gov.uk/eur/2008/429/annex/III/division/4/division/4.2/division/4.2.3/division/4.2.3.1 (the official version)
Page: https://openlegislation.uk/eu-regulation-2008-429/annex-III/division-4/division-4.2/division-4.2.3/division-4.2.3.1
Contains public sector information licensed under the Open Government Licence v3.0. Source: legislation.gov.uk, The National Archives.