CELEX: 31983L0228
Language: en
Date: 1983-04-18 00:00:00
Title: Council Directive 83/228/EEC of 18 April 1983 on the fixing of guidelines for the assessment of certain products used in animal nutrition

13 . 5 . 83                                Official Journal of the European Communities                              No L 126 / 23
                                                       COUNCIL DIRECTIVE
                                                           of 18 April 1983
                  on the fixing of guidelines for the assessment of certain products used in animal nutrition
                                                            ( 83 / 228 / EEC )
 THE COUNCIL OF THE EUROPEAN COMMUNITIES ,                                Whereas the guidelines have been drawn up on the basis
                                                                          of present scientific and technical knowledge and they
 Having regard to the Treaty establishing the European                    may be adapted if necessary to any developments in this
 Economic Community ,                                                     sphere ,
 Having regard to Council Directive 82 / 471 / EEC of
 30 June 1982 concerning certain products used in animal                  HAS ADOPTED THIS DIRECTIVE :
 nutrition ( J ), and in particular Article 7 thereof,
 Having regard to the proposal from the Commission ,                                               Article 1
 Whereas Directive 82 / 471 / EEC provides that the                       Member States shall prescribe that the dossiers on the
 products belonging to certain groups must be examined                    products listed in points 1.1 and 1.2 of the Annex to
 on the basis of a dossier forwarded officially to the                    Directive 82 / 471 / EEC are to be compiled in accordance
 Member States and the Commission ;                                       with the guidelines set out in the Annex hereto .
 Whereas such dossiers must make it possible to verify that
                                                                                                   Article 2
 the products in question comply with the general
 principles laid down in the Directive in respect of the
 inclusion of new products in the Annex ;                                 Member States shall bring into force the laws , regulations
                                                                          or administrative provisions necessary in order to comply
                                                                          with this Directive by 13 July 1984 at the latest . They
 Whereas it has been found necessary to provide for the                   shall forthwith inform the Commission thereof.
 dossiers to be compiled in accordance with common
 guidelines defining , for each principle , the scientific data
 which make it possible to identify and characterize the                                           Article 3
 products concerned and the studies necessary in order to
 evaluate their nutritional properties and biological                     This Directive is addressed to the Member States .
 effects ; whereas these guidelines must be applicable on
 the date on which Directive 82 / 471 / EEC itself enters
 into force ;
                                                                          Done at Luxembourg , 18 April 1983 .
 Whereas the guidelines are intended primarily as a general                                             For the Council
 guide; whereas , depending on the nature of the product or                                               The President
 its conditions of use , the extent of the studies necessary in
 order to evaluate its properties or its effects may vary ;                                                I. KIECHLE
  (') OJ No L 213 , 21 . 7 . 1982 , p. 8 .
 ---pagebreak--- No L 126 / 24                             Official Journal of the European Communities                                          13 . 5 . 83
                                                                ANNEX
             GUIDELINES         FOR      THE   ASSESSMENT OF CERTAIN                PRODUCTS        USED     IN     ANIMAL
                                                             NUTRITION
                                                            General aspects
             These 'guidelines' constitute a guide intended to establish dossiers on products listed in items 1 . 1 and 1 .2 of
             the Annex to Directive 82 / 471 / EEC , which have been obtained from culturing micro-organisms and
             which are likely to be admitted as a new source of proteins in animal nutrition . These dossiers should enable
             an assessment of such products based on the present state of knowledge and should ensure their compliance
             with the fundamental principles laid down for permitting their use , which are the subject of Article 6 ( 2 ) of
             the abovementioned Directive .
             All the studies outlined in this document may be required and , if necessary , additional information may be
             requested . As a general rule, all the information necessary to establish the identity of the micro-organism
             and the composition of the culture medium , and also the manufacturing process , characteristics ,
             presentation , conditions of use , methods of determination and nutritional properties of the product must
             be provided . The same applies to the information necessary to assess the tolerance of the product by the
             target species and the risks for man and the environment, which could result directly or indirectly from the
             use of the product . The toxicological studies required for this purpose will depend on the nature of the
             product, the animal species concerned and the metabolism of the product in laboratory animals .
             The documentation to be provided should include detailed reports , presented in the order and with the
             numbering proposed in these guidelines and should be accompanied by a summary . The omission of any
             proposed studies should be justified . The publications quoted as references should be attached .
                                                             Observations
             The term 'product', as used in these guidelines , refers to any proteinaceous product in the state in which it
             will be presented as feedingstuff or component of a feedingstuff.
             Any modification in the manufacturing process or in the conditions of use of a product will require
             notification and , if necessary , additional documentation for a new assessment .
                                                         Presentation of studies
               I. Micro-organism , culture medium and manufacturing process , characteristics of product , presentation
                    and conditions of use , methods of determination
              II . Studies on the nutritional properties of the product
             III . Studies on the biological consequences of the use of the product in animal nutrition
             IV . Other relevant studies
                                                              SECTION I
                        MICRO-ORGANISM CULTURE MEDIUM AND MANUFACTURING PROCESS ,
              CHARACTERISTICS OF PRODUCT, PRESENTATION AND CONDITIONS OF USE , METHODS
                                                        OF DETERMINATION
              1.       MICRO-ORGANISM
              1.1 .    Classification , provenance , morphology , biological properties , any genetic manipulation .
              1.2.     Innocuity, possible survival outside the fermenter and any environmental consequences .
              1.3 .    Constancy and purity of strains cultivated . Methods used to check these criteria .
              2.       CULTURE MEDIUM AND MANUFACTURING PROCESS
              2.1 .    Composition of substrate , added substances , ,etc .
              2.2 .    Manufacturing, dessication and purification processes . Devitalizing process for micro-organisms .
                       Methods used to check the constancy of composition of the culture product and the detection of any
                       chemical , physical and biological contamination during production .
              2.3 .    Technical processes of preparation for use .
 ---pagebreak--- 13 . 5 . 83                              Official Journal of the European Communities                                       No L 126 / 25
            3.      CHARACTERISTICS OF PRODUCT
            3.1 .   Physical and physico-chemical properties : macro- and micro-morphology , particle size , density ,
                    specific weight , hygroscopicity , solubility , electrostatic properties , etc .
            3.2 . Chemical composition and characteristics .
            3.2.1 . Content of moisture , crude protein , crude fat , crude cellulose , crude ash , carbohydrates . Limits of
                    variation of these contents .
            3.2.2 . Content of total ammonium , amide , nitrate and nitrite nitrogen , nucleic acids , protein . Qualitative
                    and quantitative composition of total and free amino acids , and purine and pyrimidine bases .
            3.2.3 . Qualitative and quantitative composition of total lipids : fatty acids , non-saponifiable matter, lipid
                    soluble pigments , phospholipids .
            3.2.4 . Composition of the carbohydrate fraction .
            3.2.5 . Qualitative and quantitative composition of inorganic components .
            3.2.6 . Qualitative and quantitative composition of vitamins .
            3.2.7 . Qualitative and quantitative composition of the other constituents : additives , residues of substrate
                    and solvents , other potentially harmful residues of the metabolism of the substrate , of the culture
                    medium , of the manufacturing process .
            3.3 .   Microbiological contamination of the product.
            3.4 .   Behaviour and stability of the product, as such and when mixed with feedingstuffs in current use,
                    during storage .
            4.      PRESENTATION AND CONDITIONS OF USE
            4.1 .   Proposed names of marketing the product .
            4.2 .   Proposed formulations for marketing the product .
            4.3 .   Intended use of the product in animal nutrition . Intended concentrations in the complete
                    feedingstuffs and in the intended quantities in the daily rations for the animal species
                    concerned .
            5.      METHODS OF DETERMINATION
                    Qualitative and quantitative methods for determination of the product in complete and
                    complementary feedingstuffs .
                    NB: Description of these methods should be accompanied by information as to specificity ,
                          sensitivity , limits of detection , margin of error , possible interferences by other substances .
                          Samples of the product in its various proposed presentations should be available.
                                                               SECTION II
                           STUDIES ON THE NUTRITIONAL PROPERTIES OF THE PRODUCT
            1.      ASSESSMENT OF PROTEIN VALUE
            1.1 .   Chemical , biochemical and microbiological studies .
            1.2 .   Studies on laboratory animals , compared with reference proteins .
            2.      STUDIES ON TARGET SPECIES
                    The following studies should be performed on each target species in comparison with a control
                    group receiving , under the same conditions of nutritional balance , a diet in current use containing
                    equivalent amounts of protein nitrogen , for ruminants of total nitrogen .
            2.1 .   Protein and energy supplementation value of the product in the rations under the proposed
                    conditions of use at various physiological stages of the animals ( e.g. growing period , pregnancy ,
                    laying).
            2.2 .   Influence of the product under the proposed conditions of use on growth rate , feed conversion rate ,
                    morbidity , mortality .
            2.3 .   Optimum nutritional levels of incorporation of the product in the rations .
            2.4 .   Effect of the product under the proposed conditions of use on the technological , organoleptic or
                    other qualities of edible products of animal origin .
             3.      EXPERIMENTAL CONDITIONS IN THE STUDIES ON TARGET SPECIES
                     Give a detailed description of the tests performed and provide the following data:
             3.1 .   Species , breed , age and sex of the animals , identification procedure.
 ---pagebreak--- No L 126 / 26                             Official Journal of the European Communities                                      13 . 5 . 83
            3.2 .    Number of test and control groups ; number of animals in each group ( the number should be large
                     enough for statistical analysis using suitable statistical parameters ).
            3.3 .    Levels of incorporation of the product , qualitative and quantitative composition of the ration and
                     its analysis .
             3.4 .   Location of each experiment , physiological state and animal health conditions , rearing conditions
                     ( these should reflect those used in practice in the Community ).
             3.5 .   Exact duration of testing and date of the analyses performed .
             3.6 .   Adverse effects which occurred during the experiment and time of their appearance .
                                                               SECTION III
             STUDIES CONCERNING THE BIOLOGICAL CONSEQUENCES OF THE USE OF THE PRODUCT
                                                       IN ANIMAL NUTRITION
             The studies outlined in this section are intended to permit assessment of the safety in use of the product in
             the target species , and of the risks for man and the environment which could result directly or indirectly
             from this use . The toxicological studies required for this purpose will depend on the nature of the product,
             the animal species concerned and the metabolism of the product in laboratory animals .
             1.      STUDIES ON TARGET SPECIES
                     The following studies should be performed on each target species in comparison with a control
                     group receiving , under the same conditions of nutritional balance , a diet in current use containing
                     equivalent amounts of protein nitrogen, for ruminants of total nitrogen .
             1.1 .   Maximum incorporation rates of the product in the daily ration without producing any adverse
                     effect .
              1.2 .  Possible effect of the product on fertility and reproduction , if appropriate .
              1.3 .   Effects of ingestion of the product under the proposed conditions of use on micro-organisms of the
                      flora of the alimentary tract and on colonization of pathogens in the alimentary tract.
             1.4 .   Investigation under the proposed conditions of use of possible residues of the product ( substrate ,
                     culture medium , solvents , contaminants ) in edible products of animal origin .
              1 .5 .  Investigation under the proposed conditions of use of possible residues of the product ( substrate ,
                      culture medium , solvents , contaminants ) in excreta .
             2.       STUDIES ON LABORATORY ANIMALS
              2.1 .   Metabolism
                      Fate of the product in the animal : absorption , accumulation , biotransformation , elimination .
             2.2 .    Mutagenicity
                      Investigations of potential mutagenicity due to contaminants ( in particular mycotoxins and
                      bacteria ) or residues of the product ( substrate , culture medium , solvents ) including in vitro
                      screening tests using metabolic activation systems .
             2.3 .    Toxicological studies
                      The following studies should be performed in comparison with control groups receiving, under the
                      same conditions of nutritional balance , a diet in current use containing equivalent amounts of
                      protein nitrogen . Toxic effects should be investigated to elucidate their cause and mechanisms and
                      to ascertain that they do not result from nutritional imbalance or from an overdosage of the product
                      in the diet .
             2.3.1 . Subchronic toxicity (at least 90 days)
                     In general , these studies should be carried out on two animal species , one of which being a rodent .
                     The product should be administered in the daily ration in at least two levels of incorporation . These
                     should be chosen so as to determine , if possible , a no-effect level and a level showing some adverse
                     effect . The animal groups should contain an adequate number of subjects of each sex . A control
                     group should always be included .
                     All relevant biological data should be recorded at appropriate intervals , particularly data on growth
                      rate , feed consumption , haematology , urine analysis , biochemical parameters , mortality , organ
 ---pagebreak--- 13 . 5 . 83                              Official Journal of the European Communities                                      No L 126 / 27
                    weights , gross pathology and histopathology of major organs and tissues . The results should be
                    presented in detail and , as far as possible , should include statistical assessment .
            2.3.2 . Chronic toxicity
                    In general , chronic toxicity studies should be carried out on two animal species , one of which being
                    a rodent . The product should be admininstered in the daily ration in at least two levels of
                    incorporation . Experiments should extend for a minimum of two years in the rat or 80 weeks in
                    mice . The animal groups should contain an adequate number of subjects of each sex . A control
                    group should always be included .
                    The biological examinations mentioned under point 2.3.1 should be carried out preferably on a
                    small satellite group of animals (a group separated from and dependent upon the main group ) at
                    appropriate intervals throughout the experiment and on the surviving animals at the end of the
                    experiment .
            2.3.3 . Carcinogenicity
                    For assessing carcinogenicity , particular attention should be paid to the time of appearance , the
                    histological types of any observed tumours and their incidence . Any effect on the incidence of
                    tumours and / or the incidence or progress of diseases should be assessed by reference to control
                    groups , as indicated in paragraph 2.3 . The results should be presented in detail and , as far as
                    possible , should include statistical assessment .
            2.4 .   Other studies
                    Reproduction studies should extend over at least two filial generations and may be combined with
                    embryotoxicity including teratogenicity studies . Particular attention should be paid to fertility ,
                    fecundity and observation on post-natal development of litters . Any other method that is
                    scientifically justifiable and likely to produce measurable results ( e.g. relay toxicity ) may be
                    provided .
            2.5 .   Experimental conditions in the studies on laboratory animals
                    Give detailed description of the tests performed and provide the following data :
            2.5.1 . Species , breed , strain and sex of animals .
            2.5.2 . Number of test and control groups , number of animals in each group ( the number should be large
                    enough for statistical analysis using suitable statistical parameters ).
            2.5.3 . Levels of incorporation of the product , qualitative and quantitative composition of the ration and
                    its analysis .
            2.5.4 . General rearing conditions throughout the period of testing .
            2.5.5 . Exact duration of testing and date of examinations performed .
            2.5.6 . Rate and timing of deaths for the various test groups .
            2.5.7 . Clinical symptoms and pathological alterations which occurred during the experiment and time of
                    their appearance .
            3.      STUDIES CONCERNING THE ENVIRONMENT
                    Depending on the nature of possible residues of the product ( substrate , culture medium , solvents ,
                    contaminants ) in excreta of target species , data on the fate of these residues in manure , soil and
                    water and also their effects on soil biology , plant growth and aquatic life may be required .
                                                             SECTION IV
                                                   OTHER RELEVANT STUDIES
            Depending on the nature and the conditions of use of the product , data on allergic effects , on irritation of
            the skin and mucus membranes of the eye , respiratory or digestive tract may be required to assess possible
            risks in handling the product and to prevent them .