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)
ß-apo-8'-Carotenal
ß-Carotene
ß-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
ß-apo-8'-carotenal7 0-5
ß-Carotene7 0-5
ß-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 ß-carotene, ß-apo-8'-carotenal, and ß-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.