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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    WORLD HEALTH ORGANIZATION



    TOXICOLOGICAL EVALUATION OF SOME
    FOOD COLOURS, ENZYMES, FLAVOUR
    ENHANCERS, THICKENING AGENTS, AND
    CERTAIN FOOD ADDITIVES



    WHO FOOD ADDITIVES SERIES 6







    The evaluations contained in this publication were prepared by the
    Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
    4-13 June 19741


    World Health Organization     Geneva     1975






              

    1  Eighteenth Report of the Joint FAO/WHO Expert Committee on
    Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 557.
    FAO Nutrition Meetings Report Series, 1974, No. 54.

    The monographs contained in the present volume are also issued by the
    Food and Agriculture Organization of the United Nations, Rome, as

    FAO Nutrition Meetings Report Series, No. 55

    ISBN 95 4 166006 6

    (c) FAO and WHO 1975

    CONTENTS

    INTRODUCTION

    ALLOCATION OF ACCEPTABLE DAILY INTAKES (ADIs)

    TOXICOLOGICAL EVALUATION: FLAVOURING SUBSTANCES AND FLAVOUR ENHANCERS

    TOXICOLOGICAL EVALUATION: FOOD COLOURS

    TOXICOLOGICAL EVALUATION: FOOD ENZYMES

    TOXICOLOGICAL EVALUATION: THICKENING AGENTS

    TOXICOLOGICAL EVALUATION: MISCELLANEOUS FOOD ADDITIVES

    THE MONOGRAPHS

         FLAVOURING SUBSTANCES AND FLAVOUR ENHANCERS

         Calcium and Sodium-5'-ribonucleotides
         Ethylmaltol
         Fumaric acid
         Guanylic acid, calcium and disodium salts
         Inosinic acid, calcium and disodium salts

         FOOD COLOURS

         Allura red AC
         Annatto extracts
         Azorubine
         Beet red
         Brilliant black PN
         Canthaxanthine
         Caramel colour (ammonia process)
         -apo-8'-Carotenal
         -Carotene
         -apo-8'-Carotenoic acid, Ethyl and Methyl esters
         Chlorophyllin copper complex, potassium and sodium salts
         Cochineal and carminic acid
         Erythrosine
         Green S
         Indanthrene blue RS
         Indigotine
         Iron oxides and hydrated iron oxides
         Orange RN
         Patent blue V
         Ponceau 4R
         Ponceau 6R

         Quinoline yellow
         Turmeric and curcumin
         Yellow 2G

         FOOD ENZYMES

         Microbial carbohydrase (Aspergillus niger)
         Microbial glucose oxidase (Aspergillus niger)
         Microbial rennet (Endothia parasitica)
         Microbial rennet (Mucor miehei)
         Microbial rennet (Mucor pusillus)

         THICKENING AGENTS

         Hydroxypropyl distarch phosphate
         Oxidized starches
         Pectin (amidated)
         Xantham gum

         MISCELLANEOUS FOOD ADDITIVES

         Ammonium salts of phosphatidic acid
         Calcium, potassium and sodium ferrocyanide
         Dimethylpolysiloxane
         Dioctyl sodium sulfosuccinate
         Glucono-delta-lactone
         Glycerol esters of wood rosins

    ANNEX 1.    Reports and other documents resulting from
         previous meetings of the Joint FAO/WHO Expert Committee
         on Food Additives

    ANNEX 2.    Membership of the Eighteenth Joint FAO/WHO
         Expert Committee on Food Additives

    INDEX
    

    INTRODUCTION

         The monographs contained in this document are the result of the 
    deliberations of the Joint FAO/WHO Expert Committee on Food Additives
    which met in Rome from 4 to 13 June 1974. Since the report1 of this
    meeting contains comments on the same substances, these monographs
    should be read or consulted in conjunction with the report.

         The present monographs follow the standard format adopted by the
    FAO/WHO Expert Committee on Food Additives when dealing with the
    toxicological evaluation of food additives. Each monograph attempts to
    provide, in a condensed form, as full an account as possible of all
    the biochemical and toxicological data made available to the Expert
    Committee on Food Additives at the time of the meeting. Some of the
    substances examined at this meeting have been evaluated in previous
    meetings. Monographs formerly published on the same compounds have
    been incorporated, in a revised form, into the monographs contained in
    this document. References to previous monographs are found in the
    introductory explanation at the beginning of each monograph and a
    comprehensive list of earlier publications is provided in Annex I of
    this document.

         As a number of food additives are closely related chemically and
    toxicologically, the Committee at its Seventeenth meeting adopted the
    same position that has been adopted in its seventh and later reports,
    that of a system of grouping additives for purposes of evaluation.
    When a given food additive is related to two or more groups, its level
    in the diet must not exceed the maximum acceptable level for either
    group. In order to facilitate the location of each substance under
    each grouping, an extensive index has been included at the end of this
    document. The index contains the names of the compounds included under
    the general title in each monograph plus a number of synonyms. An
    asterisk (*) indicated the title of the monograph containing the
    biochemical and toxicological data for each compound included in this
    document.

         Any new information and comments on the biological data and their
    evaluation should be addressed to:

    Division of Environmental Health
    Food Additives Unit
    World Health Organization
    Avenue Appia
    1211 Geneva, Switzerland

              

    1  Toxicological Evaluation of Certain Food Additives Report of the
    Joint FAO/WHO Expert Committee on Food Additives, FAO Nutrition
    Meetings Report Series No. 54. Wld Hlth Org. techn. Rep. Ser., 1974,
    No. 557.

    ALLOCATION OF ACCEPTABLE DAILY INTAKE

         The acceptable daily intake (ADI) for man, expressed on a body
    weight basis, is the amount of a food additive that can be taken daily
    in the diet, even over a lifetime, without risk.

         An ADI is allocated only to substances for which the available
    data include either the results of adequate short-term and long-term
    toxicological investigations or satisfactory information on the
    biochemistry and metabolic fate of the compound, or both.

         An ADI may be allocated temporarily, pending the provision of
    additional data within a stated period of time. This measure implies
    that the toxicological data are adequate to ensure the safety in use
    of the additive during the time for which the temporary ADI applies.
    If the additional data requested do not become available within the
    stated period, the temporary ADI may be withdrawn at a future meeting
    of the Committee.

         An ADI without an explicit indication of the upper limit of
    intake ("ADI not specified") may be assigned to substances of very low
    toxicity, especially those that are food constituents or that may be
    considered as foods or normal metabolites in man. The expression "ADI
    not specified" has been adopted by the Joint FAO/WHO Expert Committee
    on Food Additives at its Eighteenth session as a more suitable
    expression than "ADI not limited" previously used. However, an
    additive having an "ADI not specified" must meet the criteria of good
    manufacturing practice - for example it should have proven
    technological efficacy and be used at the minimum level of efficacy,
    it should not conceal inferior food quality or adulteration, and it
    should not create a nutritional imbalance.

         The expression "No ADI allocated" is applicable to substances for
    which the available information is not sufficient to establish their
    safety or when the specifications are not adequate to establish their
    identity.

         The expression "Not to be used" is applicable to substances for
    which there is sufficient information on which to base such decision.

         There may be circumstances in which the ADI is not applicable.
    Thus it may be exceeded for special dietary purposes - for example, in
    the case of modified celluloses, to reduce the energy content of the
    diet. On the other hand, the ADI for glutamic acid and glutamates does
    not extend to foods for infants under three months old.

         In previous reports a conditional ADI was allocated to a number
    of substances, often in addition to an unconditional ADI. Variations
    in the rules for applying conditional ADIs have given rise to some
    confusion. For this reason, the Committee considers that the
    allocation of conditional ADIs should be abandoned.

         ADIs are intended as guides only and may be exceeded, after
    consultation with experts, in circumstances in which there may be
    important advantages in doing so. In the opinion of the Committee, an
    ADI provides a sufficiently large safety margin to ensure that there
    need be no undue concern about occasionally exceeding it provided the
    average intake over longer periods of time does not exceed it.

    TOXICOLOGICAL EVALUATION: FLAVOURING SUBSTANCES AND FLAVOUR ENHANCERS
                                                                        

                                                   Acceptable daily
    Substances                                     intake for man
                                                   (mg/kg bw)
                                                                        

    Calcium-5'-ribonucleotides                     ADI not specified1

    Ethylmaltol                                    0-2

    Ethylmethylphenyl glycidate                    No ADI allocated2

    Fumaric acid                                   0-6

    Guanylic acid, calcium and disodium salts      ADI not specified1

    Inosinic acid, calcium and disodium salts      ADI not specified1

    Maltol3                                        No ADI allocated2

    d,1-Menthol and 1-Menthol3                     0-0.2

    Sodium-5'-ribonucleotides                      ADI not specified1
                                                                        

    1  The statement "ADI not specified" means that, on the basis of the
    available data (toxicological, biochemical, and other), the total
    daily intake of the substance, arising from its use or uses at the
    levels necessary to achieve the desired effect and from its acceptable
    background in food, does not, in the opinion of the Committee,
    represent a hazard to health. For this reason, and for the reasons
    stated in individual evaluations, the establishment of an acceptable
    daily intake (ADI) in mg/kg bw is not deemed necessary.

    2  The additional information requested in the earlier evaluation
    was not made available. The previous temporary ADI was withdrawn.

    3  No toxicological monograph was issued at this meeting. See
    Eighteenth Report (Wld Hlth Org. techn Rep. Ser., No. 557).

    TOXICOLOGICAL EVALUATION: FOOD COLOURS
                                                                        

                                                   Acceptable daily
    Substances                                     intake for man
                                                   (mg/kg bw)
                                                                        

    Allura Red AC                                  No ADI allocated1

    Annatto extracts3                              0-1.252

    Azorubine                                      0-0.52

    Beet Red                                       ADI not specified2,5

    Brilliant Black PN                             0-2.52

    Canthaxanthine                                 0-25

    Caramel colour (ammonia process)4              0-1002

    Carotenes (natural)6                           No ADI allocated1

    -apo-8'-carotenal7                            0-5

    -Carotene7                                    0-5

    -apo-8'-Carotenoic acid, and ethyl methyl
    esters7                                        0-5

    Chlorophyllin Copper Complex, potassium and
    sodium salts                                   0-152

    Cochineal and Carminic acid                    No ADI allocated1
                                                                        

    1  Evaluation not possible on data provided.

    2  Temporary acceptance.

    3  Expressed as bixin.

    4  Based on a product having a colour intensity of 20 000 EBC units.

    5  The statement "ADI not specified" means that, on the basis of the
    available data (toxicological, biochemical, and other), the total
    daily intake of the substance, arising from its use or uses at the
    levels necessary to achieve the desired effect and from its acceptable
    background in food, does not, in the opinion of the Committee,
    represent a hazard to health. For this reason, and for the reasons
    stated in individual evaluations, the establishment of an acceptable
    daily intake (ADI) in mg/kg bw is not deemed necessary.

    6  No toxicological monograph was issued at this meeting. See
    Eighteenth Report (Wld Hlth Org. techn. Rep. Ser., No. 557).

    7  As the sum of -carotene, -apo-8'-carotenal, and -apo-8'-
    carotenoic acid, methyl and ethyl esters.

    TOXICOLOGICAL EVALUATION: FOOD COLOURS (con't)
                                                                        

                                                   Acceptable daily
    Substances                                     intake for man
                                                   (mg/kg bw)
                                                                        

    Curcumin                                       0-0.12

    Erythrosine                                    0-2.5

    Green S                                        No ADI allocated1

    Indanthrene Blue RS                            No ADI allocated1

    Indigotine                                     0-5

    Iron oxides and hydrated iron oxides           ADI not specified4

    Lycopene5                                      No ADI allocated3

    Orange GGN5                                    No ADI allocated3

    Orange RN                                      No ADI allocated3

    Orchil and orcein5                             No ADI allocated3

    Patent Blue V                                  No ADI allocated1

    Persian Berries5                               No ADI allocated3

    Ponceau 4R                                     0-0.1252

    Ponceau 6R                                     No ADI allocated3

    Quinoline yellow                               0-0.52

    Turmeric                                       0-2.52

    Yellow 2G                                      No ADI allocated3
                                                                        

    1  The additional information requested in the earlier evaluation
    was not made available. The previous temporary ADI was withdrawn.

    2  Temporary acceptance.

    3  Evaluation not possible on data provided.

    4  The statement "ADI not specified" means that, on the basis of 
    the available data (toxicological, biochemical, and other), the total 
    daily intake of the substance, arising from its use or uses at the 
    levels necessary to achieve the desired effect and from its acceptable
    background in food, does not, in the opinion of the Committee, 
    represent a hazard to health. For this reason, and for the reasons 
    stated in individual evaluations, the establishment of an acceptable 
    daily intake (ADI) in mg/kg bw is not deemed necessary.

    5  No toxicological monograph was issued at this meeting. See
    Eighteenth Report (Wld Hlth Org. techn. Rep. Ser., No. 557).

    TOXICOLOGICAL EVALUATION: FOOD ENZYMES
                                                                        

                                                   Acceptable daily
    Substances                                     intake for man
                                                   (mg/kg bw)
                                                                        

    Microbial carbohydrase (Aspergillus niger)   ADI not specified1

    Microbial glucose oxidase
    (Aspergillus niger)                          ADI not specified1

    Microbial lipase (Aspergillus oryzae)        ADI not specified1

    Microbial rennet (Endothia parasitica)       ADI not specified1

    Microbial rennet (Mucor miehei)              ADI not specified1

    Microbial rennet (Mucor pusillus)            ADI not specified1
                                                                        

    1  The statement "ADI not specified" means that, on the basis of the
    available data (toxicological, biochemical, and other), the total
    daily intake of the substance, arising from its use or uses at the
    levels necessary to achieve the desired effect and from its acceptable
    background in food, does not, in the opinion of the Committee,
    represent a hazard to health. For this reason, and for the reasons
    stated in individual evaluations, the establishment of an acceptable
    daily intake (ADI) in mg/kg bw is not deemed necessary.

    TOXICOLOGICAL EVALUATION: THICKENING AGENTS
                                                                        

                                                   Acceptable daily
    Substances                                     intake for man
                                                   (mg/kg bw)
                                                                        

    Hydroxypropyl distarch phosphate               ADI not specified1

    Oxidized starches                              ADI not specified1

    Pectin (amidated)                              0-252

    Tara gum4                                      No ADI allocated3

    Xantham gum                                    0-10
                                                                        

    1  The statement "ADI not specified" means that, on the basis of the
    available data (toxicological, biochemical, and other), the total
    daily intake of the substance, arising from its use or uses at the
    levels necessary to achieve the desired effect and from its acceptable
    background in food, does not, in the opinion of the Committee,
    represent a hazard to health. For this reason, and for the reasons
    stated in individual evaluations, the establishment of an acceptable
    daily intake (ADI) in mg/kg bw is not deemed necessary.

    2  Temporary acceptance.

    3  Evaluation not possible on data provided.

    4  No toxicological monograph was issued at this meeting. See
    Eighteenth Report, (Wld Hlth Org. techn. Rep. Set., No. 557).

    TOXICOLOGICAL EVALUATION: MISCELLANEOUS FOOD ADDITIVES
                                                                        

                                                   Acceptable daily
    Substances                                     intake for man
                                                   (mg/kg bw)
                                                                        

    Aluminium potassium or sodium sulfate1         Decision postponed

    Aluminium sulfate1                             Decision postponed

    Ammonium salts of phosphatic acid2             0-30

    Calcium, potassium and sodium ferrocyanide3    0-0.025

    Cyclamates, calcium and sodium salts1          No ADI allocated4

    Dimethylpolysiloxane                           0-1.5

    Dioctyl sodium sulfosuccinate                  0-2.55

    Glucono-delta-lactone6                         0-50

    Glycerol esters of wood rosins                 Decision postponed

    Mannitol1                                      0-505

    Saccharin, potassium and sodium salts1         0-57

    Sorboyl palmitate1                             No ADI allocated4
                                                                        

    1  No toxicological monograph was issued at this meeting. See
    Eighteenth Report, (Wld Hlth Org. techn. Rep. Ser., No. 557).

    2  The phosphorous content is to be included in the ADI for
    phosphates.

    3  Calculated as sodium ferrocyanide.

    4  Evaluation not possible on data provided.

    5  Temporary acceptance.

    6  Calculated as total gluconic acid from all sources.

    7  For dietetic uses, the ADI is 0-15 mg/kg bw.





















    See Also:
       Toxicological Abbreviations