Proposal for a Council Regulation amending Annex I of Regulation (EEC) No 2377/90 laying down a Community procedure for the establishment of maximum residue limits of veterinary medicinal products in foodstuffs of animal origin
Date: 2001-10-26
Institutions: European Commission
Subjects: animal product, health control, public health, veterinary drug, waste

COMMISSION OF THE EUROPEAN COMMUNITIES

Brussels, 26.10.2001
COM(2001) 627 final

Proposal for a

COUNCIL REGULATION

amending Annex I of Regulation (EEC) No 2377/90 laying down a Community
procedure for the establishment of maximum residue limits of veterinary medicinal
products in foodstuffs of animal origin

Proposal for a

COUNCIL REGULATION

amending Annexes I and III of Regulation (EEC) No 2377/90 laying down a Community
procedure for the establishment of maximum residue limits of veterinary medicinal
products in foodstuffs of animal origin

(presented by the Commission)

EXPLANATORY MEMORANDUM

I.

REGULATORY FRAMEWORK

Pursuant to Council Regulation (EEC) No 2377/90 of 26 June 1990 1, binding maximum
residue limits for veterinary medicinal products in foodstuffs of animal origin are established
at a Community level. These limits (hereinafter MRL) are established in accordance with the
regulatory committee procedure, laid down in article 8, following scientific evaluation by the
Committee for Veterinary Medicinal Products (CVMP) of
the European Medicines
Evaluation Agency (EMEA). The pharmacologically active substances are then classified in
one of the four annexes to the Regulation:

–

–

–

–

II.

1.

Annex I: reserved for substances for which a MRL can be set following evaluation of
the toxicological risk they pose to human health;

Annex II: substances for which there is no need to set a MRL;

Annex III: substances for which, given the lack of scientific data, a MRL cannot be
set definitively but which, without compromising consumer health, may be given a
provisional MRL for a defined period calculated according to the time needed to
complete the scientific studies. This period may be extended once only in exceptional
cases;

Annex IV: substances for which it appears no MRL can be set because they pose a
risk to human health in whatever quantity.

REGULATORY PROCEDURE AND REFERRAL TO THE COUNCIL

steroid

The two proposals of Council Regulations concern the establishment of MRLs for
acetate,
(altrenogest,
hormones
certain
the uses of which are regulated through Council
norgestomet, progesterone),
Directive 96/22/EC. The Commission decided on 25 July 2001 to adopt
two
proposals of Commission Regulations to be presented to the Standing Committee for
Veterinary Medicinal Products. The Standing Committee expressed an unfavourable
opinion on the draft Commission Regulations on 12 September 2001 in plenary
session. The votes cast were as follows:

chlormadinone,

flugestone

Draft Regulation concerning progesterone and norgestomet: 18 votes in favour
in favour (Belgium, Denmark, Finland, France,
(Spain and Italy), 55 votes not
Germany, The Netherlands, Portugal, Sweden and United Kingdom)
and
14 abstaining votes (Austria, Greece, Ireland and Luxembourg).

Draft Regulation concerning altrenogest, chlormadinon and flugestone acetate:
61 votes in favour (Belgium, Denmark, Finland, France, Greece, Ireland, Italy,
Spain, Sweden and United Kingdom) and 26 abstaining votes (Austria, Germany,
Luxembourg, The Netherlands and Portugal).

1

OJ L 224, 18.8.1990, p. 1.

2

2.

According to Article 8 of Council Regulation (EEC) n° 2377/90, in cases where the
the Standing
measures proposed are not
Committee, the Commission shall without delay submit to the Council the measures
to be adopted.

in accordance with the opinion of

III.

THE DIFFERENT SUBSTANCES

1.

2.

3.

The steroid hormones have been subject to discussions for a considerable time both
within the Community and in international fora (WTO, Codex). These steroid
hormones are either endogenous or synthetic derivatives with the same hormonal
actions (mainly regulating reproductive functions). The CVMP proposed quantitative
values for some of the hormonal substances (altrenogest, chlormadinone and
flugestone acetate) and for others (norgestomet and progesterone) no values were
proposed. The opinion of the SCVPH (Scientific Committee on Veterinary measures
relating to Public Health) on the potential risks for human health from hormone
residues in bovine meat and meat products, when used as growth promotors, in
bovine animals was not endorsed by CVMP, even after a re-evaluation asked for by
the Commission services. The SCVPH concluded that a risk to consumers, i.e.
possible endocrine, developmental, immunological, neurobiological, immunotoxic,
genotoxic and carcinogenic effects, has been identified with differing levels of
conclusive evidence for each of the substances, but
the current state of
that
knowledge does not allow a quantitative estimate of the risks.

However, the overall evaluation of the available risk assessments of these substances
and of the entire body of available scientific information and data indicate that, as
concerns the excessive intake of hormones residues and their metabolites, and in
view of the intrinsic properties of hormones and epidemiological findings, a risk to
the consumer has been identified.

Taking into account the risk to human health from the administration of these
hormones to farm animals and after consideration of the current need to continue to
make available on the Community market some of these substances that are used for
therapeutic or zootechnical treatment of farm animals, it is appropriate to proceed
with the consideration of these substances under Regulation (EEC) No 2377/90 for
the purpose of setting MRL.

III.1.

Progesterone and Norgestomet

1.

2.

These hormones are endogenous substances i.e. produced naturally by animal and
human glands. As mentioned above, the CVMP opinion concludes that no MRLs
need to be established as the use of these substances in veterinary medicine - and in
accordance with Council Directive 96/22/EC - would leave no residues or residues of
no risk to the consumer.

However, the Commission considers as necessary to fix “quantitative safe limits” in
view of the identified scientific uncertainty and for the purposes of controlling the
illegal use of such substances. In such a context, Council Regulation (EEC)
No 2377/90 should be used in the absence of any other available Community legal
instrument.

3

3.

4.

The Commission considers, however, this proposal as exceptional, due to the scope
and the overall implementation of Regulation (EEC) No 2377/90, as it departs from
the opinions adopted by the CVMP on these substances.

The representatives of certain Member States in the Standing Committee questioned
the reasoning behind the proposal presented by the Commission, both with reference
to the values themselves particularly for progesterone, which were considered too
low to encompass all possible physiological levels in animal food stuffs in particular
rendering Directive 96/22/EC
from pregnant cows, and the possible risk of
ineffective should such values be established. It was also stressed by certain Member
States that Regulation (EEC) No 2377/90 should only regulate the legal use of
veterinary medicinal products. It should be pointed out, however, that the MRL
values proposed are indicative only and, when found to be exceeded, this should
normally trigger further investigations and research in the farms concerned by the
competent authorities of the Member States in order to identify the true origin of
such high residue values (e.g. pregnant cows, illegal use, etc.) and, consequently,
take the appropriate action.

III.2. Altrenogest, Chlormadinone and Flugestone acetate

1.

2.

These substances are not endogenous. In its related opinions,
the CVMP has
proposed to include altrenogest, chlormadinone and flugestone acetate in Annexes I
or III of Regulation (EEC) No 2377/90 with MRLs quantitative values depending on
the species or on the tissues considered. Therefore, the proposal is to follow these
scientific opinions of the CVMP and include the three hormones in one Regulation
with due reference to Directive 96/22/EC in the recitals.

Representatives of certain Member States in the Standing Committee were
questioning the reasoning behind the proposal adopted by the Commission,
particularly with regard to the mentioning of illegal use of hormones in the recitals.
it was stressed again by Member States that Regulation (EEC)
In particular,
No 2377/90 should only regulate the legal use of veterinary medicinal products.

IV.

ACTION REQUIRED

As the proposed measures are not in accordance with the opinion of the Standing Committee,
the Commission is sending to the Council a proposal for a regulation to be adopted under the
procedure laid down in Article 8 of Regulation (EEC) No 2377/90.

By virtue of the same Article, the Council is invited to adopt the proposed measures within
three months of the date of referral.

4

Proposal for a

COUNCIL REGULATION

amending Annex I of Regulation (EEC) No 2377/90 laying down a Community
procedure for the establishment of maximum residue limits of veterinary medicinal
products in foodstuffs of animal origin

(Text with EEA relevance)

THE COUNCIL OF THE EUROPEAN UNION,

Having regard to the Treaty establishing the European Community,

Having regard to Council Regulation (EEC) No 2377/90 of 26 June 1990 laying down a
Community procedure for the establishment of maximum residue limits of veterinary
medicinal products in foodstuffs of animal origin 2, as last amended by Commission
Regulation (EC) No 1879/20013 and in particular Articles 7 and 8 thereof,

Having regard to the proposal from the Commission,

Whereas:

(1)

(2)

(3)

In accordance with Regulation (EEC) No 2377/90, maximum residue limits should be
established for all pharmacologically active substances that are used within the
Community in veterinary medicinal products intended for administration to food-
producing animals.

Maximum residue limits should be established after examination, within the
Committee for Veterinary Medicinal Products (CVMP), of all the relevant information
provided by applicants in accordance with the provisions of Regulation (EEC)
2377/90 and taking into account all publicly available relevant scientific information
concerning the safety of residues of the substance concerned for the consumer of
foodstuffs of animal origin,
the Scientific
Committee on Veterinary Measures Relating to Public Health, reports from the Joint
FAO/WHO Expert Committee on Food Additives (JECFA) or
reports from
internationally renowned research organisations.

including for example opinions of

In establishing maximum residue limits for residues of veterinary medicinal products
in foodstuffs of animal origin, it is necessary to specify the animal species in which the
residues may be present, the levels at which they may be present in each of the
relevant tissues obtained from the treated animal (target tissue) as well as the nature of
the residue that is relevant for the monitoring of residues (marker residue). In the case
of veterinary medicinal products intended for use in lactating animals maximum
residue limits must be established for milk.

2

3

OJ L 224, 18.8.1990, p. 1.
OJ L 258, 27.9.2001, p. 11.

5

(4)

(5)

(6)

(7)

(8)

(9)

Regulation (EEC) No 2377/90 provides that the establishment of maximum residue
relevant Community
limits shall
legislation.

in no way prejudice the application of other

For the purpose of monitoring residues, as provided for in appropriate Community
legislation, maximum residue limits should usually be established for the target tissues
of liver or kidney. However, as the liver and kidney are frequently removed from
carcasses moving in international trade, maximum residue limits should consequently
be established always for muscle or fat tissues.

The substances Progesterone and Norgestomet are progestagen hormones, and
therefore are subject to restrictions and control of use as provided for in Council
Directive 96/22/EC of 29 April 1996 concerning the prohibition on the use in
stockfarming of certain substances having a hormonal or thyrostatic action and of b -
agonists, and repealing Directives 81/602/EEC, 88/146/EEC and 88/299/EEC. 4 Under
these hormones may be administered to farm animals for
certain conditions,
therapeutic or zootechnical purposes only. In particular, these conditions require the
administration of these substances by a veterinarian or under his direct responsibility.
In addition, the type of treatment, the types of products authorised,
the date of
treatment and the identity of the animals treated must be officially recorded by the
veterinarian.

the conditions

laid down in Directive 96/22/EC prohibit

Furthermore,
the
administration of hormones for therapeutic or zootechnical purposes to breeding
animals during the fattening period at the end of their reproductive life. Moreover,
they provide that meat or products from animals to which hormones have been
administered for therapeutic or zootechnical treatment should not be placed on the
market for human consumption unless they have been treated in accordance with the
provisions of Directive 96/22/EC and in so far as the withdrawal period laid down was
observed before the animals were slaughtered.

Following its evaluation, the CVMP considered that it was not necessary, for the
protection of public health, to establish maximum residues limits for Progesterone and
Norgestomet when used in authorised veterinary medicinal products in accordance
with Community legislation in force, notably Directive 96/22/EC. The substances
were therefore proposed to be included in the list in Annex II of Regulation (EEC)
No 2377/90.

However, the overall evaluation of the available risk assessments of these substances
and of the entire body of available scientific information and data indicate that, as
concerns the excess intake of hormone residues and their metabolites, and in view of
the intrinsic properties of hormones and epidemiological findings, a risk to the
consumer has been identified.

4

OJ L 125, 23.5.1996, p. 3.

6

(10)

(11)

(12)

(13)

(14)

(15)

Furthermore, given the intrinsic properties of sexual hormones and as it is not possible
to exclude that good veterinary practice is not systematically applied, and that
therefore the authorities should be provided with means of control of illegal use of
these hormones, Council Directive 96/23/EC of 29 April 1996 on measures to monitor
certain substances and residues thereof in live animals and animal products and
repealing Directives 85/358/EEC and 86/469/EEC and Decisions 89/187/EEC and
91/664/EEC5, requires the authorities to carry out
investigations in the case of
suspected animals or positive laboratory results.

Therefore, as only national tolerances are currently used for triggering the control and
investigation procedure laid down in Directive 96/23/EC, it is considered appropriate
to set harmonised levels for Progesterone and Norgestomet in the Community.

Taking into account the identified potential adverse effects to human health from the
administration of these hormones to farm animals for any purpose and after
consideration of the current need to continue to make available on the Community
market some of these substances that are currently used for therapeutic or zootechnical
treatment of farm animals and, taking also into account the strict conditions under
which Directive 96/22/EC authorises the use of these substances for therapeutic or
zootechnical purposes, it is appropriate to proceed with the consideration of these
substances under Regulation (EEC) No 2377/90 for the purpose of setting up
maximum residue limits.

Provided that there are no grounds for supposing that residues of the substance
concerned at the level proposed present a hazard for the health of the consumer,
maximum residue limits should be established in Annex I of Regulation (EEC)
No 2377/90. However, given the overall evaluation on the risk assessments of sexual
hormones, as concerns possible excess intake of hormone residues and their
metabolites, a possible risk to the consumer needs to be regularly reviewed on the
basis of any new scientific evidence.

Progesterone is a natural endogenously produced hormone. The level of natural
hormones in animals is variable, depending notably on gender, age, breed and sexual
cycle of the animals. There are currently no methods available to distinguish between
residues of the naturally occurring hormones and of residues of the natural hormones
that are exogenously administered to animals.

For Progesterone, maximum residues limits cannot be established for the purpose of
residue monitoring, as is normally the case for determination of violative residue
levels. It
indicative concentration values on the basis of the
physiological naturally levels occurring in food of animal origin. Such values are
mentioned, in particular in the CVMP and in the JECFA reports on Progesterone.

is necessary to set

(16)

It is thus considered appropriate to place Progesterone and Norgestomet in Annex I of
Council Regulation (EEC) No 2377/90, in accordance with the conditions and the
limits specified for each of these substances in the Annexes to the present Regulation.

5

OJ L 125, 23.5.1996, p. 10.

7

(17) However, it has to be stressed that, as a result of new information or a re-assessment of
existing information, Regulation (EEC) No 2377/90 can be amended in order to
protect human or animal health, in accordance with the procedures provided for in this
Regulation.

(18)

The Standing Committee on Veterinary Medicinal Products referred to in Article 8 of
Regulation (EEC) No 2377/90 has not delivered a favourable opinion on the
Commission proposed measures,

HAS ADOPTED THIS REGULATION:

Annex I of Regulation (EEC) No 2377/90 is hereby amended as set out in the Annex to this
Regulation.

Article 1

Article 2

This Regulation shall enter into force on the third day following that of its publication in the
Official Journal of the European Communities.

It shall apply from the 60th day following its publication.

This Regulation shall be binding in its entirety and directly applicable in all Member States.

Done at Brussels, […]

For the Council
The President

8

ANNEX

The following substances are inserted in Annex I (List of pharmacologically active substances for which maximum residue limits have been fixed).

6. Agents acting on the reproductive system
6.1 Progestogens

Pharmacologicallyactive
substance(s)
Norgestomet

Markerresidue
Norgestomet

Animalspecies
Bovine

MRLs Targettissues

0,07 µg/kg Muscle

Otherprovisions
For therapeutic or zootechnical
use only

Progesterone

Progesterone

Bovine

0,07 µg/kg Fat
0,03 µg/kg
0,07 µg/kg Kidney

Liver

0,008 µg/kg Milk

0,25 µg/kg Muscle

2,5 µg/kg Fat

Liver

0,25 µg/kg
0,25 µg/kg Kidney
37,5 µg/kg Milk

For therapeutic or zootechnical
use only

9

Proposal for a

COUNCIL REGULATION

amending Annexes I and III of Regulation (EEC) No 2377/90 laying down a Community
procedure for the establishment of maximum residue limits of veterinary medicinal
products in foodstuffs of animal origin

(Text with EEA relevance)

THE COUNCIL OF THE EUROPEAN UNION,

Having regard to the Treaty establishing the European Community,

Having regard to Council Regulation (EEC) No 2377/90 of 26 June 1990 laying down a
Community procedure for the establishment of maximum residue limits of veterinary
medicinal products in foodstuffs of animal origin 6, as last amended by Commission
Regulation (EC) No 1879/20017 and in particular Articles 7 and 8 thereof,

Having regard to the proposal from the Commission,

Whereas:

(1)

(2)

(3)

In accordance with Regulation (EEC) No 2377/90, maximum residue limits must be
established progressively for all pharmacologically active substances which are used
within the Community in veterinary medicinal products intended for administration to
food-producing animals.

Maximum residue limits should be established only after the examination within the
Committee for Veterinary Medicinal Products of all
information
concerning the safety of residues of the substance concerned for the consumer of
foodstuffs of animal origin and the impact of residues on the industrial processing of
foodstuffs and taking into account all publicly available relevant scientific information
concerning the safety of residues of the substance concerned for the consumer of
the Scientific
foodstuffs of animal origin,
Committee on Veterinary Measures Relating to Public Health, reports from the Joint
FAO/WHO Expert Committee on Food Additives (JECFA) or
reports from
internationally renowned research organisations..

including for example opinions of

the relevant

In establishing maximum residue limits for residues of veterinary medicinal products
in foodstuffs of animal origin, it is necessary to specify the animal species in which
residues may be present, the levels at which they may be present in each of the
relevant tissues obtained from the treated animal (target tissue) and the nature of the
residue which is relevant for the monitoring of residues (marker residue). In the case

6

7

OJ L 224, 18.8.1990, p. 1.
OJ L 258, 27.9.2001, p. 11.

10

(4)

(5)

(6)

(7)

(8)

(9)

of veterinary medicinal products intended for use in lactating animals maximum
residue limits shall be established for milk.

Regulation (EEC) No 2377/90 provides that the establishment of maximum residue
relevant Community
limits shall
legislation.

in no way prejudice the application of other

For the purpose of monitoring residues, as provided for in appropriate Community
legislation, maximum residue limits should usually be established for the target tissues
of liver or kidney. However, as the liver and kidney are frequently removed from
carcasses moving in international trade, maximum residue limits should consequently
be established always for muscle or fat tissues.

The substances Chlormadinone, Flugestone acetate and Altrenogest are hormones, and
therefore are subject to restrictions and control of use as provided for in Council
Directive 96/22/EC of 29 April 1996 concerning the prohibition on the use in
stockfarming of certain substances having a hormonal or thyrostatic action and of b -
agonists, and repealing Directives 81/602/EEC, 88/146/EEC and 88/299/EEC 8. Under
certain conditions,
these hormones may be administered to farm animals for
therapeutic or zootechnical purposes only. In particular, these conditions require the
administration of these substances by a veterinarian or under his direct responsibility.
In addition, the type of treatment, the types of products authorised,
the date of
treatment and the identity of the animals treated must be officially recorded by the
veterinarian.

the conditions

laid down in Directive 96/22/EC prohibit

Furthermore,
the
administration of hormones for therapeutic or zootechnical purposes to breeding
animals during the fattening period at the end of their reproductive life. Moreover,
they provide that meat or products from animals to which hormones have been
administered for therapeutic or zootechnical treatment should not be placed on the
market for human consumption unless they have been treated in accordance with the
provisions of Directive 96/22/EC and in so far as the withdrawal period laid down was
observed before the animals were slaughtered.

The overall evaluation of the available risk assessments of these substances and of the
entire body of available scientific information and data indicate that, as concerns the
excess intake of hormone residues and their metabolites, and in view of the intrinsic
properties of hormones and epidemiological findings, a risk to the consumer has been
identified.

Furthermore, given the intrinsic properties of sexual hormones and as it is not possible
to exclude that good veterinary practice is not systematically applied, and that
therefore the authorities should be provided with means of control of illegal use of
these hormones, Council Directive 96/23/EC of 29 April 1996 on measures to monitor
certain substances and residues thereof in live animals and animal products and
repealing Directives 85/358/EEC and 86/469/EEC and Decisions 89/187/EEC and
91/664/EEC 9, requires the authorities to carry out
investigations in the case of
suspected animals or positive laboratory results.

8

9

OJ L 125, 23.5.1996, p. 3.
OJ L 125, 23.5.1996, p. 10.

11

(10)

(11)

(12)

Taking into account the identified potential adverse effects to human health from the
administration of these hormones to farm animals for any purpose and after
consideration of the current need to continue to make available on the Community
market some of these substances that are currently used for therapeutic or zootechnical
treatment of farm animals and, taking also into account the strict conditions under
which Directive 96/22/EC authorises the use of these substances for therapeutic or
zootechnical purposes, it is appropriate to proceed with the consideration of these
substances under Regulation (EEC) No 2377/90 for the purpose of setting up
maximum residue limits.

Provided that there are no grounds for supposing that residues of the substance
concerned at the level proposed present a hazard for the health of the consumer,
maximum residue limits should be established in Annex I or Annex III of Council
Regulation (EEC) No 2377/90. However, given the overall evaluation on the risk
assessments of sexual hormones, as concerns possible excess intake of hormone
residues and their metabolites, a possible risk to the consumer needs to be regularly
reviewed on the basis of any new scientific evidence.

It is thus considered appropriate, without prejudice to other provisions of Community
law, in particular Directive 96/22/EC that Chlormadinone and Flugestone acetate (for
ovine milk) are inserted into Annex I to Regulation (EEC) No 2377/90 and that in
order to allow for the completion of scientific studies, Altrenogest and Flugestone
acetate (for caprine milk) are inserted into Annex III to Regulation (EEC) No 2377/90.

(13) However, it has to be stressed that, as a result of new information or a re-assessment of
existing information, Regulation (EEC) No 2377/90 can be amended in order to
protect human or animal health, in accordance with the procedures provided for in this
Regulation.

(14)

The Standing Committee on Veterinary Medicinal Products referred to in Article 8 of
Regulation (EEC) No 2377/90 has not delivered a favourable opinion on the
Commission proposed measures,

HAS ADOPTED THIS REGULATION:

Annexes I and III of Regulation (EEC) No 2377/90 are hereby amended as set out in the
Annex to this Regulation.

Article 1

12

Article 2

This Regulation shall enter into force on the third day following that of its publication in the
Official Journal of the European Communities.

It shall apply from the 60th day following its publication.

This Regulation shall be binding in its entirety and directly applicable in all Member States.

Done at Brussels, […]

For the Council
The President

13

A.The following substances are inserted in Annex I (List of pharmacologically active substances for which maximum residue limits have been fixed).

ANNEX

6. Agents acting on the reproductive system
6.1 Progestogens

Pharmacologicallyactive
substance(s)
Chlormadinone

Markerresidue
Chlormadinone

Animalspecies
Bovine

Flugestone acetate

Flugestone acetate

Ovine

MRLs Targettissues

4 µg/kg Fat
2 µg/kg

Liver
2,5 µg/kg Milk
1 µg/kg Milk

Otherprovisions
For zootechnical use only

For intravaginal use for
zootechnical purposes only

B. The following substances are inserted in Annex III (List of pharmacologically active substances used in veterinary medicinal products for which provisional
maximum residue limits have been fixed).

6. Agents acting on the reproductive system
6.1. Progestogens

Pharmacologicallyactive
substance(s)
Altrenogest

Markerresidue
Altrenogest

Animalspecies
Porcine

MRLs Targettissues

3 µg/kg Fat

Liver

3 µg/kg
3 µg/kg Kidney
3 µg/kg Fat
3 µg/kg
3 µg/kg Kidney
1 µg/kg Milk

Liver

Flugestone acetate

Flugestone acetate

Caprine

Equidae

14

Otherprovisions
Provisional MRLs expire on
01/01/2003; For zootechnical use
only

Provisional MRLs expire on
01/01/2003; For intravaginal use
for zootechnical purposes only