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

1.3. Section III: studies concerning the safety of the additive

Subsections 3.1, 3.2 and 3.4 of Annex II do not apply to silage additives where it can be demonstrated that:

• no detectable amounts of the active substance(s) or relevant metabolites or the active agent(s) survive in the final feed; or

• the active substance(s) and agent(s) occur as normal constituents of silage and use of the additive does not substantially increase their concentration compared to silage prepared without use of the additive (i.e. where there is no substantial change in exposure).

In the other cases the whole of Section 3 of Annex II applies.

1.3.1. Studies concerning the safety of use of the additive to the target animals

For xenobiotic(1) substances: the full subsection 3.1 of Annex II applies.

1.3.1.1. Tolerance studies for the target species

For silage additives:

• the product shall be added to a basal diet and results compared to a negative control with the same diet. The basal diet may contain a single source of silage prepared without the use of an additive.

• the dose selected for the tolerance studies shall be a multiple of the concentration present in the ensiled material at the time of normal use where this can be conclusively established. Particular consideration shall be given to product containing viable micro-organisms and their capacity for survival and multiplication during ensiling.

Tolerance studies can usually be limited to a ruminant species, normally the dairy cows. Studies involving other species are required only when the nature of the ensiled material makes it more appropriate for use with non-ruminants.

Other substances:

for the other substances requesting authorisation as technological additives not already authorised for feed use the absence of harm to animals at the highest proposed level shall be demonstrated. This demonstration may be limited to one experiment in one of the most sensitive target species or in one laboratory animal species.

1.3.1.2. Microbial studies

The whole of subsection 3.1.2 of Annex II applies.

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

1.3.2.1. Metabolic and residue studies

Metabolic and residue studies are not required if:

(1)

the substance or its metabolites are not present in the feedingstuff at time of feeding; or

(2)

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

(3)

the substance is absorbed in the form of physiological compounds; or

(4)

the active component(s) of the additive consists only of micro-organisms or enzymes).

Metabolic studies also are not required if the substance is naturally present in significant amounts in food or feedingstuffs or 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 the comparison of the tissues/products levels in an untreated group and in the group supplemented with the highest recommended dose.

1.3.2.2. Toxicological studies

Toxicological studies are not required if:

(1)

the substance or its metabolites are not present in the feedingstuff at time of feeding; or

(2)

the substance is absorbed in the form of physiological compound(s); or

(3)

the product consists of micro-organisms commonly encountered in ensiled materials or those already used in food; or

(4)

the product consists of enzymes with a high degree of purity arising from micro-organisms with a history of documented safe use.

For micro-organisms and enzymes not excluded above, genotoxicity studies (including mutagenicity) and a subchronic oral toxicity study are required. Genotoxicity studies shall not be made in the presence of living cells.

For xenobiotic substances, not exempted above, the whole of subsection 3.2.2 Annex II applies.

For other substances a case by case approach shall be taken, taking into account the level and means of exposure.

1.3.2.3. Assessment of consumer safety

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

1.3.3. Studies concerning the safety of use of the additive for users/workers

The whole of subsection 3.3 of Annex II applies. Additives containing enzymes and micro-organisms are assumed to be respiratory sensitisers unless convincing evidence to the contrary is provided.

1.3.4. Studies concerning the safety of use of the additive for the environment

The whole of subsection 3.4 of Annex II applies. For silage additives, the effects of the additive on the production of effluent from clamp or silo during ensiling shall be considered.

(1)

A xenobiotic is a chemical substance which is not a natural component of the organism exposed to it. It can also cover substances which are present in much higher concentrations than are usual.