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