Commission Regulation (EC) No 429/2008Show full title

4. ZOOTECHNICAL ADDITIVES

4.1. Zootechnical additives other than enzymes and micro-organisms

4.1.1. Section I: summary of the dossier.

The whole of Section I of Annex II applies.

4.1.2. Section II: identity, characterisation and conditions of use of the additive; methods of analysis

The whole of Section II of Annex II applies.

4.1.3. Section III: studies concerning the safety of the additives

4.1.3.1. Studies concerning the safety of use of the additive for target animals

The whole of subsection 3.1 of Annex II applies.

4.1.3.2. Studies concerning the safety of use of the additive for consumer

(1)

Metabolic and residue studies

These studies are not required if:

• the substance or its metabolites can be demonstrated to be excreted unchanged and essentially to be not absorbed; or

• the substance is absorbed in physiological form and physiological level of compound(s).

No metabolic studies are needed if the substance is naturally present in significant amounts in food or feedingstuffs or if the substance is a normal constituent of body fluids or tissues. However, in these cases, there is a requirement for residue studies which can be limited to a comparison of the levels in the tissues or products in an untreated group to the levels found in the group supplemented with the highest recommended dose.

In all other cases the whole of subsection 3.2.1 of Annex II applies.

(2)

Toxicological studies

Toxicological studies are not required if the substance is absorbed in the form of physiological compound(s).

For xenobiotic substances the whole of subsection 3.2.2 of Annex II applies.

For other substances, a case by case approach shall be used, taking into account the level and means of exposure, and any omission of data prescribed in this section must be fully justified.

(3)

Assessment of consumer safety

The whole of subsection 3.2.3 of Annex II applies for food producing animals.

4.1.3.3. Studies concerning the safety of the additive for users/workers

The whole of subsection 3.3 of Annex II applies.

4.1.3.4. Studies concerning the safety of the additive for the environment

The whole of subsection 3.4 of Annex II applies

4.1.4. Section IV: studies concerning the efficacy of the additive

The whole of Section IV of Annex II applies.

(1)

Additives favourably affecting animal production, performance or welfare and for the functional group ‘other zootechnical additives’.

The effects can only be demonstrated in relation to each target animal species or category. Depending on the properties of the additive, outcome measures may be based either on performance characteristics (e.g. feed efficiency, average daily gain, increasing of animal products), carcass composition, herd performance, reproduction parameters or animal welfare. Evidence of the mode of action can be provided by short term efficacy studies or laboratory studies measuring relevant end-point.

(2)

Additives favourably affecting the environmental consequences of animal production

For these additives which favourably affect the environment (e.g. reduced nitrogen or phosphorus excretion or reduced methane production, off-flavours), evidence of efficacy for the target species can be given by three short term efficacy studies with animals showing significant beneficial effects. The studies shall take into consideration the possibility of an adaptive response to the additive.

4.1.5. Section V: post-market monitoring plan

This section shall apply under provision of Article 7(3)(g) of Regulation (EC) No 1831/2003.

4.2. Zootechnical additives: enzymes and micro-organisms

4.2.1. Section I: summary of the dossier

The whole of Section I of Annex II applies.

4.2.2. Section II: identity, characterisation and conditions of use of the additive; methods of analysis

The whole of Section II of Annex II applies.

4.2.3. Section III: studies concerning the safety of the additives

4.2.3.1. Studies concerning the safety of use of the additive for the target animals

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).

4.2.3.2. Studies concerning the safety of the additive use for consumer

(1)

Metabolic and residue studies are not required.

(2)

Toxicological studies, according to subsection 3.2.2 of Annex II.

Enzymes and micro-organisms form only a part of the whole additive which, in most cases, can include other components originated from the fermentation process. Consequently, it is necessary to test the additive to ensure it does not contain mutagenic or otherwise materials that can harm human consumers of food derived from animals feed with feedingstuffs or water treated with these additives.

However, most viable bacteria intended for direct or indirect ingestion by mammals (including humans) are selected from groups of organisms with a history of apparent safe use or from groups where the toxic hazards are well defined. Similarly, the hazards associated with micro-organisms currently used for the production of enzymes generally are well recognised and substantially reduced by modern production methods. Therefore, for enzymes from microbial sources and for micro-organisms with a history of apparent safe use and where the components of fermentation process are well defined and know, toxicity tests (e.g. oral toxicity or genotoxicity testing) are not considered necessary. However, for both live organisms and those used for the production of enzymes, the specific concerns in section 2.2.2.2 of Annex II shall always be addressed.

When the organism or its application is novel and insufficient is known about the biology of the (production) organism to exclude a potential for the production of toxic metabolites, genotoxicity and oral toxicity studies made with additives containing viable micro-organisms or enzymes shall be introduced. In this case, they shall take the form of genotoxicity studies including mutagenicity and a subchronic oral toxicity study. It is recommended that such studies are performed with the cell-free fermentation broth or in the case of a solid state fermentation, an appropriate extract.

4.2.3.3. Studies concerning the safety of the additive for users/workers

The whole of subsection 3.3 of Annex II applies except:

• enzymes and micro-organisms, as proteinaceous substances, are assumed to be respiratory sensitisers unless convincing evidence to the contrary is provided. Therefore, no direct testing is required.

• the formulation of the product (e.g. micro-encapsulation) may obviate the need for some or all tests. In such cases, appropriate justification shall be provided.

4.2.3.4. Studies concerning the safety of the additive for the environment

The whole of subsection 3.4 of Annex II fully applies for micro-organisms which are not of gut origin or are not ubiquitous in the environment.

4.2.4. Section IV: studies concerning the efficacy of the additives

The whole of Section IV of Annex II applies.

(1)

Additives favourably affecting animal production, performance or welfare and for the functional group ‘other zootechnical additives’.

The effects can only be demonstrated in relation to each target animal species or category. Depending on the properties of the additive, outcome measures may be based either on performance characteristics (e.g. feed efficiency, average daily gain, increasing of animal products), carcass composition, herd performance, reproduction parameters or animal welfare. Evidence of the mode of action can be provided by short term efficacy studies or laboratory studies measuring relevant end-point.

(2)

Additives favourably affecting the environmental consequences of animal production.

For these additives which favourably affect the environment (e.g. reduced nitrogen or phosphorus excretion or reduced methane production, off-flavours), evidence of efficacy for the target species can be given by three short term efficacy studies with animals showing significant beneficial effects. The studies shall take into consideration the possibility of an adaptive response to the additive.

4.2.5. Section V: post-market monitoring plan

This section shall apply under provision of Article 7(3)(g) of Regulation (EC) No 1831/2003.