Feed Additives

IRTA – Centre de Mas Bové

Symposium on Food Safety and Animal Feeding 3th October 2003

Jürgen M. Gropp

Present and Future Strategies

in Assessing

Feed Additives

Present and Future Strategies

in Assessing

Feed Additives

Preliminary remark Present strategies

describes the well known past

¾

¾¾

¾ with the Standing Committee on Feedingstuffs

¾ with the SCAN

under governance of DG VI/EU-Commission

Future strategies

describes presence with (unknown) further development

¾ with the Committee on the Food Chain and Animal Health

¾

¾¾

¾ with EFSA and FEEDAP (and some other panels)

Legislation

Completely harmonized within members states The famous Directive 70/524 EEC

A new Directive for feed additives

Council Directive 87/153 EEC

amended by Commission Directive 2001/79 EC future Directive Part II ....

Assessment

Regulation (EC) No 178/2002

laying down the general principles and requirements

Feed Additive

The new Directive for feed additives defines

Feed additives means substances, micro-organisms or

preparations, other than feed material and premixtures, which are intentionally added to feed or water

in order to perform, in particular, one or more of the functions mentioned in Article 5(3).

Appendix I defines 4 additive groups:

Technological additives (e.g. preservatives, antioxidants)

Sensory additives (e.g. colorants, flavouring compounds)

Nutritional additives (e.g. vitamins, trace elements)

Zootechnical additives (e.g. enzymes, micro-organisms)

Application to the Commission Past

Presence: a transitional stage Future

¾ to the Commission

¾ to the Standing Committee for Feedingstuffs

¾Whenever it suited to SCAN

¾ to the Commission

¾ without delay to the members states and to the Authority (EFSA)

Assessment

Risk* assessment

¾

¾¾

¾ Scientific procedure

¾

¾¾

¾ EFSA -FEEDAP

Risk* management

¾¾

¾¾ Administrative procedure

¾¾

¾¾ Commission – DG IV – the Committee

* Risk: Function of the probability of an adverse effect and the severity of that effect, consequential to a hazard

Criteria

Efficacy

Safety for the target animal Safety for the consumer

Safety for the worker

Safety for the environment

PAST

Criteria

Efficacy

Safety for the target animal,

Safety for the consumer

Safety for the worker

Safety for the environment,

PRESENCE

ADI - MRL

Efficacy

The European parliament ?

Studies on the effect of zootechnical additives

Now: zootechnical, nutritional and flavouring additives Negative and positive control groups,

healthy animals, 3 independent trials, 2 locations, animal species/category, significance (!),

Analysis of relevant nutrients and of the active substance !

Dose titration studies, Interactions and incompatibilities.

Studies on the quality of animal produce.

Whatever is claimed, efficacy has to be demonstrated

Safety for the target species

Tolerance tests

Microbiological safety

selection of resistant strains, effect on opportunistic Pathogens, shedding)

In cases of an antimicrobial action, field studies to monitor for bacterial resistance.

Toxins from micro-organisms

Safety for the consumer Metabolism and residues

The aim of the studies is

¾¾

¾¾ to establish the metabolic pathways,

¾¾

¾¾ to identify residues and establish their kinetics

¾

¾

¾

¾ to identify the excreted substances (environment)

Pharmacokinetics

Identification of those residues, which represent More than 10 % of the total residue (except..) Steady state, target tissue, marker residue

Depletion study (at least 4 animals per point)

Safety for the consumer

Toxicity studies –

Acute toxicity – 2 mammalian species

Genotoxicity studies including mutagenicity Subchronic (90-day) oral toxicity studies

Chronic oral toxicity studies

Reproduction toxicity studies

Metabolism and disposition studies

Bioavailability NOEL

Safety for the consumer ADI and MRL

The ADI (mg additive/person and day) is derived by dividing the NOEL (mg/kg bw) by an

appropriate safety factor and multiplying by a mean human body weight of 60 kg.

The chemical nature of the drug-related material must be defined (marker residue). The ratios of the marker residue/total residue in connection with the ADI should be established at all time points during the depletion studies (withdrawal period).

A suitable analytical method for this marker residue must be available.

Safety for the consumer

The food basket – realistic (?)

Mammals Birds Fish

Muscle 300 g 300 g 300 g^*

Liver 100 g 100 g

Kidney 50 g 10 g

Fat 50 g^** 90 g^***

-Milk 1,500 g

-Egg 100 g

* Muscle and skin in natural proportions

** For pigs 50 g of fat and skin in natural proportions

*** Fat and skin in natural proportions

Safety for the worker

Workers can be exposed mainly by inhalation or topical exposure while manufacturing or handling or using the additive.

Toxicological risk assessment

¾¾¾

¾ Effects on the respiratory system

¾¾¾

¾ Effects on the eyes and skin

¾¾¾

¾ Systemic toxicity Exposure assessment

¾

¾¾

¾ Measures to control exposure

Use of personal protective devices should only be regarded as measure of last resort to protect against any residual risk

Safety for the environment

Phase I assessment – phase II assessment

PEC PNEC

PNEC

- PNEC

“This assessment does not cover the uses of groundwater, and in particular, the use of groundwater as drinking water that must be addressed in the human health risk assessment”

Phase II not necessary “for physiological/natural substances (e.g. a vitamin or a mineral .. unless there is evident reason for concern (e.g. copper)”.

Assessment at the request

Of the Commission

On its own initiative (self tasking) Of the European Parliament

Of member states

EFSA has a (limited) right to refuse

Assessment to be done in a limited period,

EFSA is obliged to – with honorary panel members (?)

Herbal compounds

Which assessing procedure ?

Flavouring compounds: substances the inclusion of which in feedingstuffs increases smell or palatability.

The European Parliament voted against labelling:

Mixtures and premixtures containing flavourings and appetite stimulants shall be exempt from labelling requirements for each additive. This shall not apply to flavourings and appetite

stimulants subject to a quantitative limitation when used in feed and drinking water.

Reason: Protection of corporate know-how.

Presence ?

Herbal compounds used as flavourings ?

Carvacrol(5-isopropyl-2-methyl- phenol) Finishing pigs (66 – 105

kg bw)

850 900 950 1000 1050 1100

280 300 320 340 360 380

g gain/day g gain/kg feed

Schuhmacher et al., 2003

Future needs

More flexibility in the assessment

procedure – but without any potential harm to the consumer

Better communication between

the stakeholders

IRTA – Centre de Mas Bové

Symposium on Food Safety and Animal Feeding 3th October 2003

Present and future strategies in assessing feed additives

New guidelines will have

to be prepared in accordance with the new

Feed Additive Directive

Improvements by experience New guidelines will have

to be prepared in accordance with the new

Feed Additive Directive

Improvements by experience