INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
WORLD HEALTH ORGANIZATION
TOXICOLOGICAL EVALUATION OF CERTAIN
VETERINARY DRUG RESIDUES IN FOOD
WHO FOOD ADDITIVES SERIES 17
Prepared by:
The 26th meeting of the Joint FAO/WHO Expert
Committee on Food Additives (JECFA)
World Health Organization, Geneva 1982
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, 1982, No. 17
TOXICOLOGICAL EVALUATION OF CERTAIN FOOD ADDITIVES
The evaluations contained in this document
were prepared by the Joint FAO/WHO
Expert Committee on Food Additives*
Rome, 19-28 April 1982
INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
IPCS
* Twenty-sixth report of the Joint FAO/WHO Expert Committee on Food
Additives, Geneva, Wld Hlth Org. techn. Rep. Ser., 683, 1982.
INTRODUCTION
The monographs contained in this document have been prepared by
the Joint FAO/WHO Expert Committee on Food Additives which was held in
Rome, 19-28 April 1982.
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. Lintas, Istituto
Nazionale della Nutrizione, Rome, Italy; Dr J. E. Long, Food
Directorate, Health Protection Branch, Department of Health and
Welfare, Ottawa, Ontario, Canada; and Dr S. I. Shibko, Division of
Toxicology, Bureau of Food, Food and Drug Administration, Washington,
D.C., United States of America.
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. 683 (1982).
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 1982
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
Rome, 19-28 April 1982
Members invited by FAO
Dr W. H. B. Denner, Head, Food Additives Branch, Food Science
Division, Ministry of Agriculture, Fisheries and Food, London,
England
Mr D. F. Dodgen, Staff Scientist, Keller and Hackman, Washington
Washington, D.C., United States of America
Dr S. W. Gunner, Chief, Division of Chemical Evaluation, Bureau of
Chemical Safety, Food Directorate, Health Protection Branch,
Department of National Health and Welfare, Ottawa, Canada
Professor K. Kojima, College of Environmental Health, Asabu
University, Sagamihara-Shi, Kanagawa, Japan (Chairman)
Dr W. Kroenert, Head, Food Chemistry Division, Federal Health
Institute, Berlin (West)
Professor F. J. Pellerin, Faculty of Pharmacy, University of Paris XI,
Centre hospitalier Courentin Celton, Issy-les-Moulineaux, France
Members invited by WHO
Professor E. A. Bababunmi, Department of Biochemistry, University
of Ibadan, Ibadan, Nigeria
Dr H. Blumenthal, Director, Division of Toxicology, Bureau of Food,
Food and Drug Administration, Washington, D.C., United States of
America (Vice-Chairman)
Dr G. Nazario, Department of Food Standards, National Health Council,
Rio de Janeiro, Brazil
Dr E. Poulsen, Director, Institute of Toxicology, National Food
Institute, Soborg, Denmark
Professor M. J. Rand, Chairman, Department of Pharmacology, University
of Melbourne, Victoria, Australia (Rapporteur)
Dr A. Zaitsev, Head, Laboratory for the Hygienic Examination of Food
Additives, Institute of Nutrition, Academy of Medical Sciences,
Moscow, USSR
Observer invited by FAO
Mr A. Feberwee, Chairman, Codex Committee on Food Additives, c/o
Ministry of Agriculture and Fisheries, The Hague, Netherlands
Secretariat
Dr J. R. P. Cabral, Division of Chemical and Biological
Carcinogenesis, International Agency for Research on Cancer,
Lyons, France (WHO Temporary Adviser)
Mr R. Haigh, Principal Administrator, Commission of the European
Communities, Brussels, Belgium (WHO Temporary Adviser)
Dr Y. Hayashi, Division of Pathology, Biological Safety Research
Centre, National Institute of Hygienic Sciences, Tokyo, Japan
(WHO Temporary Adviser)
Dr V. L. Kossila, Animal Production Officer, Feed Resources, Animal
Production and Health Division, FAO, Rome, Italy
Dr G. D. Kouthon, Nutrition Officer, Food Policy and Nutrition
Division, FAO, Rome, Italy (Joint Secretary)
Dr L. G. Ladomery, Food Standard Officer, Food Quality and Standard
Service, FAO/WHO Food Standards Programme, Food Policy and
Nutrition Division, FAO, Rome, Italy
Dr C. Lintas, Istituto Nazionale della Nutrizione, Via Ardeatina 545,
Rome, Italy (WHO Temporary Adviser)
Dr R. K. Malik, Senior Officer, Food Quality and Standards Service,
Food Policy and Nutrition Division, FAO, Rome, Italy
Dr J. E. Long, Chief, Toxicological Evaluation Division, Food
Directorate, Health Protection Branch, Department of National
Health and Welfare, Ottawa, Ontario, Canada (WHO Temporary
Adviser)
Dr F. J. C. Roe, Institute of Cancer Research, University of London,
London, England (WHO Temporary Adviser)
Professor A. G. Rico, Laboratory of Radioelements and Metabolic
Studies (I.N.R.A.), National Veterinary School, Toulouse, France
(WHO Temporary Adviser)
Dr S. I. Shibko, Chief, Contaminants and Natural Toxicants Evaluation
Branch, Division of Toxicology, Bureau of Food, Food and Drug
Administration, Washington, D.C., United States of America (WHO
Temporary Adviser)
Dr P. Shubik, Resident Fellow, Green College College, University of
Oxford, England (WHO Temporary Adviser)
Professor R. C. Truhaut, Director, Toxicological Research Centre,
René Descartes University, Paris, France (WHO Temporary
Adviser)
Dr G. Vettorazzi, Toxicologist, International Programme on Chemical
Safety, Division of Environmental Health, WHO, Geneva,
Switzerland (Joint Secretary)
Dr E. Weisenberg, Director, Institute for the Standardisation and
Control of Pharmaceuticals, Ministry of Health, Jerusalem, Israel
(WHO Temporary Adviser)
Mr A. Yamamoto, Office of Health Studies, Department of Environmental
Health, Environment Agency, Tokyo, Japan (WHO Temporary
Adviser)
ACCEPTABLE DAILY INTAKES AND INFORMATION ON SPECIFICATIONS
Specifications1 ADI for man (mg/kg of
body weight) [and other
toxicological decisions]
A. Specific food additives
Antioxidants
anoxomer NT 0-82
butylated hydroxyanisole
(BHA) R 0-0.52,3
Emulsifying agents
sorbitan monolaureate R 0-254
sorbitan monoleate R 0-254
stearyl monoglyceridyl
citrate R No ADI allocated
succinylated monoglycerides R No ADI allocated
Enzymes
glucose isomerase (isolated
from Streptomyces
violaceoniger) S ADI not specified2,5
protease (isolated from
Streptomyces fradiae) N ADI not specified2,5
Flavouring agents
ethyl lactate R ADI not specified5
eugenol R 0-2.5
alpha-ionone R 0-0.052
ß-ionone R 0-0.052
ACCEPTABLE DAILY INTAKES AND INFORMATION ON SPECIFICATIONS (Con't)
Specifications1 ADI for man (mg/kg of
body weight) [and other
toxicological decisions]
Food colours
Natural food colours
annatto extracts R 0-0.0656
anthocyanins S ADI not allocated9
anthocyanins (grape-skin
extract) N 0-2.5
beet red RT ADI withdrawn7
carmines R 0-5.08
curcumin R 0-0.12
turmeric R 0-2.52
Synthetic food colours
Amaranth R 0-0.752
Brown HT (formerly
Chocolate Brown HT) S 0-0.252
Lithol rubine BK R ADI not allocated9
Patent Blue V R ADI not allocated9
Quinoline Yellow RT 0-0.52
Sunset Yellow FCF R 0-2.510
Inorganic salts and buffering agents
phosphates and
polyphosphates11 R, S, N, NT [70]12
sodium aluminium
phosphate, acidic NT 0-62
sodium aluminium
phosphate, basic N 0-62
ACCEPTABLE DAILY INTAKES AND INFORMATION ON SPECIFICATIONS (Con't)
Specifications1 ADI for man (mg/kg of
body weight) [and other
toxicological decisions]
Inorganic salts and buffering agents
ammonium carbonate R ADI not specified5
ammonium hydrogen
carbonate (formerly
ammonium bicarbonate) R ADI not specified5
magnesium silicate R ADI not specified5
Sweetening agents
sorbitol R ADI not specified5
calcium and sodium
cyclamates S 0-1113
saccharin, potassium and
and sodium salts R 0-2.52
Thickening agents
gum arabic R ADI not specified5
gum ghatti ST ADI not allocated9
modified starches O, R, RT, S ADI not specified5,14
starch sodium
octenyl succinate R ADI not specified
Miscellaneous food additives
quillaia extracts O ADI not allocated15
sodium hydrogen DL-malate N ADI not specified5,16
ammonium acetate O ADI not specified5,17
sucrose acetate isobutyrate
(SAIB) RT ADI not allocated9
ethyl cellulose R 0-2518
ACCEPTABLE DAILY INTAKES AND INFORMATION ON SPECIFICATIONS (Con't)
Specifications1 ADI for man (mg/kg of
body weight) [and other
toxicological decisions]
B. Contaminants
Metals
copper - [0.05-0.5]19,20
tin (inorganic; including
stannous chloride) - [2.0]20,21
zinc - [0.3-1.0]19,20
Xenobiotic anabolic agents
trenbolone acetate O ADI not allocated22
zeranol O ADI not allocated22
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. Temporary acceptance.
3. Group ADI. As BHA, BHT, TBHQ singly or in combination.
4. Group ADI. As the sum of the sorbitan esters of lauric, oleic,
palmitic and stearic acid.
5. 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 an acceptable daily intake (ADI) is not deemed
necessary.
6. The ADI is in terms of the carotenoid content expressed as bixin.
7. The previous temporary ADI "not specified" allocated in the
eighteenth report of the Committee and extended in the twenty-
second report has been withdrawn since the additional information
requested in the earlier evaluations was not available.
8. The ADI includes ammonium carmine or the equivalent of calcium,
potassium or sodium salts.
9. No sufficient toxicological data were available.
10. The previous ADI of 0-5.0 mg/kg of body weight was revised in the
light of reconsideration of earlier studies together with newer
studies.
11. Aluminium-containing phosphates are not included.
12. 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 and the additives listed in Annex 4. 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 proportionately higher, and the reverse
relationship would also apply.
13. Expressed as cyclamic acid.
14. Does not include starches modified by the use of the crosslinking
agent epichlorohydrin.
15. No specifications are available on these substances.
16. Group ADI. The group ADI "not specified" for DL-malic acid and
bases now includes sodium and potassium hydrogen DL-malates.
17. Group ADI. Included in the group ADI for other ammonium salts and
acetates.
18. Group ADI including ethyl cellulose, hydroxypropyl cellulose,
hydroxylpropyl methyl cellulose, methyl cellulose, methyl ethyl
cellulose, and sodium carboxymethyl cellulose.
19. Daily dietary requirement/maximum tolerable daily intake.
Expressed in mg/kg of body weight.
20. Provisional.
21. Maximum tolerable daily intake.
22. Necessary documentation on residue levels was not available for
full evaluation of this compound.
CONTENTS
THE MONOGRAPHS
Food additives
Ammonium carbonate and ammonium hydrogen carbonate (formerly
ammonium bicarbonate)
Annatto extracts
anoxomer
Anthocyanins
Arabic gum
Carmines
Cyclamates, calcium, sodium and cyclohexyalmine
Ethyl-L-lactate
Eugenol
Glucose isomerase (Streptomyces violaceoniger)
Modified starches:
acetylated distarch adipate
acetylated distarch glycerol
acetylated distarch phosphate
acid-treated starches
dextrins
hydroxypropyl distarch glycerol
hydroxypropyl starch
phosphated distarch phosphate
starch acetate
starch sodium octenyl succinate
Phosphoric acid and phosphate salts
Protease (Streptomyces fradiae)
Quillaia extracts
Saccharin
Sodium aluminium phosphate (acidic and basic)
Sorbitan monoesters of palmitic, stearic, oleic
and lauric acids and triesters of stearic acid
Sucrose acetate isobutyrate (SAIB)
Sunset Yellow FCF
Turmeric and curcumin
Food contaminants
Copper
Tin and stannous chloride
Zinc
ANNEX I
ANNEX II
See Also:
Toxicological Abbreviations