IPCS INCHEM Home


    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    WORLD HEALTH ORGANIZATION



    TOXICOLOGICAL EVALUATION OF CERTAIN
    FOOD ADDITIVES AND FOOD CONTAMINANTS



    WHO FOOD ADDITIVES SERIES 18




    Geneva, 11-20 April 1983




         The International Programme on Chemical Safety (IPCS),
    established in 1980, is a joint venture of the United Nations
    Environment Programme (UNEP), the International Labour Organisation
    (ILO), and the World Health Organization (WHO). The overall objectives
    of the IPCS are to establish the scientific basis for assessment of
    the risk to human health and the environment from exposure to
    chemicals, through international peer-review processes, as a
    prerequisite for the assistance in strengthening national capacities
    for the sound management of chemicals.

         The Inter-Organization Programme for the Sound Management of
    Chemicals (IOMC) was established in 1995 by UNEP, ILO, the Food and
    Agriculture Organization of the United Nations, WHO, the United
    Nations Industrial Development Organization and the Organisation for
    Economic Co-operation and Development (Participating Organizations),
    following recommendations made by the 1992 UN Conference on
    Environment and Development to strengthen cooperation and increase
    coordination of the policies and activities pursued by the
    Participating Organizations, jointly or separately, to achieve the
    sound management of chemicals in relation to human health and the
    environment.

    WHO Food Additives Series, 1983, No. 18

    TOXICOLOGICAL EVALUATION OF CERTAIN FOOD ADDITIVES AND CONTAMINANTS

    The evaluations contained in this document
    were prepared by the Joint FAO/WHO
    Expert Committee on Food Additives*

    Geneva, 11-20 April 1983

    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    IPCS

              

    *    Twenty-seventh report of the Joint FAO/WHO Expert Committee on
         Food Additives, Geneva, Wld Hlth Org. techn. Rep. Ser.,
         696, 1983.

    INTRODUCTION

         The monographs contained in this document have been prepared by
    the Joint FAO/WHO Expert Committee on Food Additives which was held in
    Geneva, 11-20 April 1983.

         The editing and printing of this document have been possible
    through the technical and financial contributions of the Lead
    Institutions of the International Programme on Chemical Safety (IPCS)
    which support the activities of the Joint FAO/WHO Expert Committee on
    Food Additives as far as the participation of WHO to this Committee is
    concerned.

         A special acknowledgement is given to the following experts for
    preparing the drafts of the monographs: Dr C. L. Galli, Professor of
    Experimental Toxicology, University of Milan, Milan, Italy; Dr C.
    Lintas, Research Chemist, Istituto Nazionale della Nutrizione, Rome,
    Italy; Dr B. MacGibbon, Principal Medical Officer, Division of
    Toxicology, Environmental Pollution and Prevention, Department of
    Health and Social Security, London, England; Dr I. C. Munro, Director-
    General, Food Directorate, Health Protection Branch, Department of
    National Health and Welfare, Ottawa, Canada; Dr S. I. Shibko, Chief,
    Contaminants and Natural Toxicants Evaluation Branch, Division of
    Toxicology, Bureau of Foods, FDA, Washington, D.C., United States of
    America; and Dr R. Walker, Department of Biochemistry, University of
    Surrey, Guildford, England

         Dr G. Vettorazzi, Toxicologist, International Programme on
    Chemical Safety, edited and reviewed the final manuscript for
    consistency with the toxicological evaluations contained in the WHO
    Technical Report Series, No. 696 (1983).

         Any comments or new information on the biological and
    toxicological data on the compounds reported in this document should
    be addressed to: Joint WHO Secretary of the Joint FAO/WHO Expert
    Committee on Food Additives, International Programme on Chemical
    Safety, World Health Organization, Avenue Appia, 1211 Geneva 27,
    Switzerland.

    IPCS 1983

         For rights of reproduction of this document, in part or
    in toto, application should be made to the International Programme
    on Chemical Safety (IPCS), World Health Organization, Geneva,
    Switzerland.

         The designations employed and the presentation of the material in
    this publication do not imply the expression of any opinion whatsoever
    on the part of the Central Unit of the International Programme on
    Chemical Safety concerning the legal status of any country, territory,
    city or area or of its authorities, or concerning the delimitation of
    its frontiers or boundaries.

         The mention of specific companies or of certain manufacturers'
    products does not imply that they are endorsed or recommended by the
    International Programme on Chemical Safety in preference to others of
    a similar nature that are not mentioned.
    

    JOINT FAO/WHO EXPERT COMMITTEE ON FOOD ADDITIVES

    Geneva, 11-20 April 1983

    Members invited by FAO

    Dr W. H. B. Denner, Principal Scientific Officer, Food Science
         Division, Ministry of Agriculture, Fisheries and Food, London,

    Dr S. W. Gunner, Director, Bureau of Chemical Safety, Food
         Directorate, Health Protection Branch, Department of National
         Health and Welfare, Ottawa, Canada (Vice-Chairman)

    Professor K. Kojima, College of Environmental Health, Azabu
         University, Sagamihara-Shi, Kanagawa, Japan

    Dr W. Kroenert, Head, Food Chemistry Division, Federal Health
         Institute, Berlin (West)

    Dr J. P. Modderman, Division of Chemistry and Physics, Bureau of Food,
         Food and Drug Administration, Department of Health and Human
         Services, Washington, D.C., United States of America

    Professor F. J. Pellerin, Faculty of Pharmacy, University of Paris XI,
         Centre hospitalier Corentin-Celton, Issy-les-Moulineaux, France

    Members invited by WHO

    Professor E. A. Bababunmi, Department of Biochemistry, College of
         Medicine, University of Ibadan, Ibadan, Nigeria

    Dr H. Blumenthal, Director, Division of Toxicology, Bureau of Foods,
         Food and Drug Administration, Washington, D.C., United States of
         America (Chairman)

    Dr I. C. Munro, Director-General, Food Directorate, Health Protection
         Branch, Department of National Health and Welfare, Ottawa, Canada

    Dr G. Nazario, Food Standards Committee, National Health Council, Rio
         de Janeiro, Brazil

    Dr E. Poulsen, Director, Institute of Toxicology, National Food
         Institute, Soborg, Denmark

    Professor M. J. Rand, Professor of Pharmacology, Department of
         Pharmacology, University of Melbourne, Victoria, Australia
         (Rapporteur)

    Professor P. Shubik, Senior Research Fellow, Green College, Oxford,
         England

    Dr A. N. Zaicev, Head, Laboratory for the Hygienic Examination of
         Food Additives, Institute of Nutrition, Academy of Medical
         Sciences, Moscow, USSR

    Observers invited by FAO

    Dr P. B. Czedick-Eysenberg, Commission on Food Chemistry,
         International Union for Pure and Applied Chemistry, Oxford,
         England

    Mr A. Feberwee, Chairman, Codex Committee on Food Additives, Ministry
         of Agriculture and Fisheries, The Hague, Netherlands

    Dr R. Mathews, Director, Food Chemicals Codex, National Academy of
         Sciences, Washington, D.C., United States of America

    Secretariat

    Dr J. R. Cabral, Unit of Mechanisms and Carcinogenesis, Division of
         Environmental Carcinogenesis, International Agency for Research
         on Cancer, Lyon, Prance (WHO Temporary Adviser)

    Dr B. H. Dieterich, Director,Division of Environmental Health, WHO,
         Geneva, Switzerland (Joint Secretary)

    Dr C. L. Galli, Professor of Experimental Toxicology, University of
         Milan, Milan, Italy (WHO Temporary Adviser)

    Mr R. Haigh, Principal Administrator, Commission of the European
         Communities, Brussels, Belgium (WHO Temporary Adviser)

    Dr Y. Hayashi, Director, Division of Pathology, Biological Safety
         Research Centre, National Institute of Hygienic Sciences, Tokyo,
         Japan (WHO Temporary Adviser)

    Professor N. Ito, Professor and Chairman, Department of Pathology,
         Nagoya City University Medical School, Nagoya City, Japan (WHO
         Temporary Adviser)

    Dr V. Kossila, Animal Production Officer, Feed Resources, Animal
         Production and Health Division, FAO, Rome, Italy

    Dr G. P. Kouthon, Nutrition Officer Food Policy and Nutrition
         Division, FAO, Rome, Italy (Joint Secretary)

    Dr C. Lintas, Research Chemist, Department of Food Chemistry,
         National Institute of Nutrition, Rome, Italy (WHO Temporary
         Adviser)

    Dr B. MacGibbon, Principal Medical Officer, Division of Toxicology,
         Environmental Pollution and Prevention, Department of Health and
         Social Security, London, England (WHO Temporary Adviser)

    Dr M. Mercier, Manager, International Programme on Chemical Safety,
         Division of Environmental Health, WHO, Geneva, Switzerland

    Dr N. Rao Maturu, Food Standards Officer, Food Policy and Nutrition
         Division, FAO, Rome, Italy

    Mr R. Read, International Programme on Chemical Safety, Division of
         Environmental Health, WHO, Geneva, Switzerland (Consultant)

    Professor A. G. Rico, Professor of Biochemistry and Toxicology,
         Laboratory of Radioelements and Metabolic Studies, National
         Veterinary School, Toulouse, France (FAO Consultant)

    Dr S. I. Shibko, Chief, Contaminants and Natural Toxicants Evaluation
         Branch, Division of Toxicology, Bureau of Foods, Food and Drug
         Administration, Washington, D.C., United States of America
         (WHO Temporary Adviser)

    Professor R. Truhaut, Professor of Toxicology, Toxicological Research
         Centre, René Descartes University, Paris, France (WHO Temporary
         Adviser)

    Dr G. J. van Esch, Director of Sector Toxicology and Food Analysis,
         National Institute of Public Health, Bilthoven, Netherlands
         (WHO Temporary Adviser)

    Dr R. Walker, Department of Biochemistry, University of Surrey,
         Guildford, England (WHO Temporary Adviser)

        ACCEPTABLE DAILY INTAKE (ADI) AND INFORMATION ON SPECIFICATIONS

                                                            ADI for man (mg/kg of
                                        Specifications1     body weight) and other
                                                            toxicological decisions

    A.  SPECIFIC FOOD ADDITIVES

    Antioxidants

    Butylated hydroxyanisole
    (BHA)                               S                   0-0.53,8

    Butylated hydroxytoluene
    (BHT)                               R                   0-0.53,8

    Extraction solvents

    Dichloromethane (methylene
    chloride)                           RT                  ADI withdrawn9

    1,1,2-Trichloroethylene             RT                  No ADI allocated2

    Flavouring agents

    trans-Anethole                      R                   0-2.53

    Benzyl acetate                      R                   0-53

    (+)-Carvone and (-)-carvone         R                   0-1.03,5

    Ethyl methylphenylglycidate         ST                  No ADI allocated2

    Food colours

    Azorubine                           S                   0-4

    Ponceau 4R                          S                   0-4

    Preservatives

    Calcium benzoate                    N                   0-56

    Sweetening agents

    Acesulfame potassium                R                   0-9

    Hydrogenated glucose syrup          N                   0-253

    Lactitol                            N                   ADI not specified4

    Thaumatin                           N                   No ADI allocated2

                                                            ADI for man (mg/kg of
                                        Specifications1     body weight) and other
                                                            toxicological decisions

    Xylitol                             R                   ADI not specified4

    Thickening agents

    Ethylhydroxyethyl cellulose         NT                  0-253,7

    Karaya gum                          R                   0-203

    Tragacanth gum                      R                   No ADI allocated2

    Miscellaneous food additives

    Ammonium phosphate, monobasic       S                   [70]10

    Insoluble polyvinylpyrrolidone
    (PVPP)                              RT                  ADI not specified4

    Polyvinylpyrrolidone (PVP)          S                   0-253

    Potassium bromate                   R                   Temporary acceptance14

    L-(+)-Tartaric acid,
    ammonium, calcium, and
    magnesium salts                     0                   No ADI allocated11

    DL-(±)-Tartaric acid,
    ammonium, calcium, and
    magnesium salts                     R                   No ADI allocated12

    B.  CONTAMINANTS

    Metals

    Arsenic                             -                   [0.002]13

    Iron                                -                   [0.8]13,15

    Xenobiotic anabolic agents

    Trenbolone acetate                  -                   Provisional acceptance

    Zeranol                             -                   Provisional acceptance

                               Specifications only

                                                                Specifications1

    Bacillus licheniformis alpha-amylase                        R

    DL-Calcium malate                                           R

    Carbon dioxide                                              RT

    Carob bean gum                                              RT

                                                                Specifications1

    Castor oil                                                  R

    Collagen                                                    O

    Diethyl ether                                               RT

    Dioctyl sodium sulfosuccinate                               R

    Disodium pyrophosphate                                      RT

    Ethyl nonanoate                                             R

    Glutaraldehyde                                              O

    Isomalt                                                     RT

    Magnesium chloride                                          R

    Magnesium di-L-glutamate                                    R

    Magnesium gluconate                                         R

    Magnesium hydroxide carbonate                               R

    Magnesium lactate (DL and L isomers)                        R

    Modified starches                                           RT

    Nitrous oxide                                               S

    Pentapotassium triphosphate                                 S

    Polyethylene glycols                                        R

    Polyglycerol esters of fatty acids                          R

                               Specifications only

                                                                Specifications1

    Potassium dihydrogen citrate                                R

    Potassium nitrate                                           R

    Potassium polyphosphate                                     S

    Propyl gallate                                              R

    Sodium dihydrogen citrate                                   RT

    Sodium fumarate                                             RT

    Sorbitol syrups                                             R

    Sucrose esters of fatty acids                               R

    Sucroglycerides                                             R

    Talc                                                        R

    Tetrasodium pyrophosphate                                   RT

    Triammonium citrate                                         R
        Notes

    1.   N, new specifications prepared; O, specifications not prepared;
         R, existing specifications revised; S, specifications exist,
         revision not considered; T, the existing, new or revised
         specifications are tentative and comments are invited.

    2.   Insufficient toxicological data were available, or specifications
         were unsatisfactory.

    3.   Temporary acceptance.

    4.   The statement "ADI not specified" means that, on the basis of the
         available data (chemical, biochemical, toxicological, and other),
         the total daily intake of the substance, arising from its use 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 the individual evaluations, the
         establishment of a numerical figure for an acceptable daily
         intake (ADI) is not deemed necessary.

    5.   As the sum of the isomers.

    6.   Group ADI for benzoic acid and its calcium, potassium and sodium
         salts expressed as benzoic acid.

    7.   Group ADI for modified celluloses.

    8.   Group ADI. As BHA, BHT, and TBHQ, singly or in combination. Note
         that the ADI for BHA and BHT is temporary.

    9.   The existing ADI was withdrawn since the available data were
         inadequate.

    10.  This figure represents the maximum tolerable daily intake (MTDI)
         of phosphates. It is not an ADI. The MTDI is expressed as
         phosphorus and it applies to the sum of phosphates naturally
         present in food. It also applies to diets that are nutritionally
         adequate in respect of calcium. However, if the calcium intake
         were high, the intake of phosphate could be proportionally
         higher, and the reverse relationship would also apply.

    11.  No ADI could be allocated in this case since no specifications
         were prepared.

    12.  No information was available on the use of this substance as a
         food additive.

    13.  Provisional maximum tolerable daily intake.

    14.  The previous acceptance of potassium bromate for the treatment of
         flour used for baking products was changed to a temporary
         acceptance with a maximum treatment level of 75 mg potassium
         bromate per kg of flour.

    15.  This figure applies to iron from all sources except for iron
         oxides used as colouring agents/supplemental iron taken during
         pregnancy and lactation, and supplemental iron for specific
         clinical requirements.

    CONTENTS

    THE MONOGRAPHS

    Food Additives

    Acesulfame potassium*

    Azorubine

    Benzoic acid and its calcium, potassium and sodium salts

    Butylated hydroxyanisole (BHA)

    Butylated hydroxytoluene (BHT)

    Dichloromethane (Methylene chloride)

    Ethylmethylphenylglycidate

    Karaya gum

    Lactitol

    Polyvinylpyrrolidone (PVPP), insoluble

    Ponceau 4R

    Potassium bromate

    Sulfur dioxide and sulfites

    1,1,2-Trichloroethylene (TCE)

    Xylitol

    Food Contaminants

    Arsenic

    Iron

    ANNEX I

    ANNEX II

              

    *    Monograph addendum.
    





















    See Also:
       Toxicological Abbreviations