Toxicological evaluation of some food
additives including anticaking agents,
antimicrobials, antioxidants, emulsifiers
and thickening agents
WHO FOOD ADDITIVES SERIES NO. 5
The evaluations contained in this publication
were prepared by the Joint FAO/WHO Expert
Committee on Food Additives which met in Geneva,
25 June - 4 July 19731
World Health Organization
Geneva
1974
1 Seventeenth Report of the Joint FAO/WHO Expert Committee on
Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 539;
FAO Nutrition Meetings Report Series, 1974, No. 53.
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. 53A
ISBN 92 4 166005 8
(C) FAO and WHO 1974
CONTENTS
INTRODUCTION
ALLOCATION OF ACCEPTABLE DAILY INTAKES (ADI)
TOXICOLOGICAL EVALUATION: ANTICAKING AGENTS
TOXICOLOGICAL EVALUATION: ANTIMICROBIALS
TOXICOLOGICAL EVALUATION: ANTIOXIDANTS AND SYNERGISTS
TOXICOLOGICAL EVALUATION: EMULSIFIERS
TOXICOLOGICAL EVALUATION: THICKENING AGENTS
TOXICOLOGICAL EVALUATION: MISCELLANEOUS FOOD ADDITIVES
THE MONOGRAPHS
ANTICAKING AGENTS
Calcium, Potassium, Sodium Ferrocyanide
Salts of Myristic, Palmitic and Stearic Acids
Silicon Dioxide and Certain Silicates
ANTIMICROBIALS
Acetic Acid and its Potassium and Sodium Salts
Benzoic Acid and its Potassium and Sodium Salts
Cupric Sulfate
Diethyl Pyrocarbonate
Formic Acid
Hexamethylenetetramine
Hydrogen Peroxide
p-Hydroxybenzoate, Butyl
p-Hydroxybenzoate, Ethyl, Methyl, Propyl Esters
Nitrate, Potassium and Sodium Salts
Nitrite, Potassium and Sodium Salts
Propionic Acid and its Calcium, Potassium and Sodium Salts
Sodium Diacetate
Sorbic Acid and its Calcium, Potassium and Sodium Salts
Sulfur Dioxide and Sulfites
ANTIOXIDANTS
Ascorbic Acid and its Potassium and Sodium Salts
Ascorbyl Palmitate and Stearate
Butylated Hydroxyanisole
Butylated Hydroxytoluene
Citric Acid and its Calcium, Potassium and Sodium salts
Ethylenediaminetetraacetate, Disodium and Calcium Disodium Salts
Gallates, Dodecyl, Octyl and Propyl
Guaiac Resin
Isoascorbic Acid and its Sodium Salt
Isopropyl Citrate Mixture and Monoisopropyl Citrate
Nordihydroguaiaretic Acid
Stearyl Citrate
Thiodipropionic Acid and Dilauryl Ester
Alpha-Tocopherol and Mixed Toxopherols Concentrate
EMULSIFIERS
Acetic and Fatty Acid Esters of Glycerol
Ammonium Salts of Phosphatidic Acids
Cholic and Desoxycholic Acid and their Salts
Citric and Fatty Acid Esters of Glycerol
Diacetyl Tartaric and Fatty Acid Esters of Glycerol
Esters of Glycerol and Thermally Oxidized Soybean
Fatty Acids
Hydroxylated Lecithin
Lactic and Fatty Acid Esters of Glycerol
Lecithin
Mixed Tartaric, Acetic and Fatty Acid Esters of Glycerol
Mono- and Diglycerides
Polyglycerol Esters of Fatty Acids
Polyglycerol Esters of Interesterified Ricinoleic Acid
Polyoxyethylene (20) Sorbitan Monoesters of Lauric
Oleic, Palmitic and Stearic Acid and Triester of Stearic Acid
Polyoxyethylene (8) and Polyoxyethylene (40) Stearates
Propylene Glycol Alginate
Propylene Glycol Esters of Fatty Acids
Sorbitan Monoesters of Palmitic and Stearic Acids and
Triesters of Stearic Acid
Sucrose Esters of Fatty Acids, and Sucroglycerides
THICKENING AGENTS
A. CELLULOSES
Microcrystalline Cellulose
Modified Celluloses
B. VEGETABLE GUMS
Arabic Gum
Carob Bean Gum
Guar Gum
Karaya Gum
Tragacanth Gum
C. MODIFIED STARCHES AND DEXTRINS
Acetylated Distarch Adipate
Acetylated Distarch Glycerol
Acetylated Distarch Phosphate
Acid-treated Starches
Alkali-treated Starches
Amylose and Amylopectin
Bleached Starches
Distarch Glycerol
Distarch Phosphate
Enzyme-treated Starches
Hydroxypropyl Distarch Glycerol
Hydroxypropyl Distarch Phosphate
Hydroxypropyl Starch
Monostarch Phosphate
Oxidized Starches
Phosphated Distarch Phosphate
Starch Acetate
Starch Sodium Succinate
White and Yellow Dextrins
D. OTHERS
Agar
Alginic Acid and its Ammonium, Calcium, Potassium
and Sodium Salts
Carrageenan and Furcellaran
Pectin
MISCELLANEOUS
Calcium Acetate, Chloride, Gluconate and Sulfate
Food-Grade Mineral Oil
L-Glutamic Acid and its Ammonium, Calcium, Monosodium
and Potassium Salts
Lactic Acid and its Ammonium, Calcium, Potassium and
Sodium Salts
Oxystearin
Phosphoric Acid, Polyphosphates and their Calcium,
Magnesium, Potassium and Sodium Salts
Polyvinyl Pyrrolidone
1,2 - Propylene Glycol
Sorbitol
Stearoyl Lactylic Acid, Calcium and Sodium Salts
Tartaric Acid and its Potassium, Potassium-Sodium and
Sodium Salts
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 Seventeenth 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 Geneva from 25 June to 4 July 1973. 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
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.
All 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 1 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 (*) indicates the title of the monograph containing the
biochemical and toxicological data for each compound included in this
document.
1 Toxicological Evaluation of Certain Food Additives with a
Review of General Principles and of Specifications - Seventeenth
Report of the Joint FAO/WHO Expert Committee on Food Additives,
FAO Nutrition Meetings Report Series, No. 53; Wld Hlth Org. techn.
Rep. Ser., 1974, No. 539.
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 27
Switzerland
ALLOCATION OF ACCEPTABLE DAILY INTAKES (ADI)
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 ("not limited") 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. An additive having a
"not limited" ADI 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.
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.
"No ADI allocated" is applicable in the absence of sufficient
information to establish safety, or of adequate specifications.
"Not to be used" is applicable where there is sufficient
information on which to base such a decision.
TOXICOLOGICAL EVALUATION: ANTICAKING AGENTS
Acceptable daily
Substances intake for man
(mg/kg bw)
Calcium, potassium, sodium ferrocyanide 0-0.0251
Salt of myristic, palmitic, and
stearic acids (aluminum, ammonium,
calcium, magnesium, potassium,
sodium) Not limited
Silicon dioxide and certain silicates
(aluminum, calcium, sodium alumino
silicate) Not limited
Magnesium silicate (talc and magnesium
trisilicate) Not limited1
1 Temporary acceptance.
TOXICOLOGICAL EVALUATION: ANTIMICROBIALS
Acceptable daily
Substances intake for man
(mg/kg bw)
Acetic acid and its potassium and Not limited
sodium salts
Benzoic acid and its potassium and 0-5
sodium salts1
Diethyl pyrocarbonate2 Not to be used
Formic acid 0-3
Cupric sulfate No ADI3
Hexamethylenetetramine 0-0.15
Hydrogen peroxide No ADI4
p-Hydroxybenzoate, butyl No ADI
allocated5
p-Hydroxybenzoate, ethyl6 0-10
p-Hyroxybenzoate, methyl6 0-10
p-Hydroxybenzoate, propyl6 0-10
Nitrate, potassium and sodium salts7 0-5
Nitrite, potassium and sodium salts8 0-0.29
Propionic acid and its calcium, potassium,
and sodium salts Not limited
Sodium diacetate 0-15
Sorbic acid and its calcium, potassium
and sodium salts10 0-25
Sulfur dioxide and sulfites (sodium and
potassium metabisulfites, sodium sulfite,
sodium hydrogen sulfite)11 0-0.7
1 As sum of benzoic acid and sodium and potassium benzoate
(expressed as benzoic acid).
2 The treatment level allocated in previous reports is withdrawn.
3 Maximum acceptable daily load = 0.5 mg/kg bw expressed as Cu.
4 This substance is to be used only as an emergency measure when
better methods of milk preservation are not available.
5 Evaluation not possible with data provided.
6 As sum of ethyl, methyl, and propyl esters of p-hydroxybenzoic
acid.
7 As sodium nitrate.
8 As sodium nitrite.
9 Temporary acceptance.
10 As sum of sorbic acid and calcium, potassium, and sodium
sorbates (expressed as sorbic acid).
11 As SO2.
TOXICOLOGICAL EVALUATION: ANTIOXIDANTS AND SYNERGISTS
Acceptable daily
Substances intake for man
(mg/kg bw)
Ascorbic acid and its potassium and
sodium salts 0-151
Ascorbyl palmitate and stearate2 0-1.25
Butylated hydroxyanisole 0-0.53
Butylated hydroxytoluene 0-0.53
Citric acid and its calcium, potassium, and
sodium salts Not limited
Ethylenediaminetetraacetate, disodium and
calcium disodium salts4 0-2.5
Gallates, dodecyl, octyl, propyl5 0-0.2
Guaiac resin 0-2.5
Isoascorbic acid and its sodium salt 0-5
Isopropyl citrate mixture and monoisopropyl
citrate6 0-14
Nordihydroguaiaretic acid No ADI
allocated7
Stearyl citrate 0-50
Thiodipropionic acid and dilauryl ester8 0-3
alpha-Tocopherol and mixed tocopherols
concentrate9 0-2
1 This figure is in addition to the ascorbic and acid present
naturally in foods.
2 As ascorbyl stearate or ascorbyl palmitate, or the sum of both.
3 As BHA, BHT, or the sum of both. Temporary acceptance.
4 As CaNa2EDTA (no excess of Na2EDTA should remain in foods).
5 As sum of dodecyl, octyl, and propyl gallate. Temporary
acceptance. (n-Octyl gallate should not be used in beverages.)
6 As monoisopropyl citrate.
7 Evaluation not possible with data provided.
8 As thiodipropionic acid.
9 As alpha-tocopherol.
TOXICOLOGICAL EVALUATION: EMULSIFIERS
Acceptable daily
Substances intake for man
(mg/kg bw)
Acetic and fatty acid esters of glycerol Not limited
Ammonium salts of phosphatidic acid 0-151
Cholic and desoxycholic acid and their salts 0-1.25
Citric and fatty acid esters of glycerol Not limited
Diacetyl tartaric and fatty acid esters of
glycerol 0-50
Esters of glycerol and thermally oxidized Decision
soybean fatty acid postponed2
Hydroxylated lecithin No ADI
allocated3
Lactic and fatty acid esters of glycerol Not limited
Lecithin Not limited
Mixed tartaric, acetic and fatty acid
esters of glycerol4 Not limited
Mono- and diglycerides Not limited
Polyglycerol esters of fatty acids 0-255
Polyglycerol esters of interesterified
ricinoleic acid 0-7.5
Polyoxyethylene (20) sorbitan esters of lauric,
stearic, palmitic and oleic acids and
triesters of stearic acid6 0-25
Polyoxyethylene (8) and polyoxyethylene (40)
stearate7 0-25
Propylene glycol alginate8 0-25
Propylene glycol esters of fatty acids9 0-25
Sorbitan esters of palmitic and stearic acids
and triesters of stearic acid10 0-25
Sucrose esters of fatty acids and sucroglycerides 0-2.52
1 Temporary acceptance.
2 Previously allocated temporary ADI is withdrawn.
3 Evaluation not possible with data provided.
4 Provided that the total food additive intake of tartaric acid
does not exceed 30 mg/kg.
5 As polyglycerol esters of palmitic acid.
6 As total polyoxyethylene (20) sorbitan esters.
7 As total of polyoxyethylene (8) and (40) stearates.
8 The contribution from propylene glycol alginate to total
dietary propylene glycol intake from all sources should be included in
the ADI for propylene glycol.
9 As propylene glycol.
10 As total sorbitan esters.
TOXICOLOGICAL EVALUATION: THICKENING AGENTS
Acceptable daily
Substances intake for man
(mg/kg bw)
A. Celluloses
Hydroxypropyl cellulose1 0-25
Hydroxypropyl methyl cellulose1 0-25
Methyl cellulose1 0-25
Methylethyl cellulose1 0-25
Microcrystalline cellulose Not limited
Sodium carboxymethyl cellulose1 0-25
B. Vegetable gums
Arabic gum Not limited
Carob bean gum No ADI
allocated2
Guar gum Not limited
Karaya gum No ADI
allocated2
Tragacanth gum No ADI
allocated2
C. Modified starches and dextrins
Acetylated distarch adipate Not limited
Acetylated distarch glycerol Not limited
Acetylated distarch phosphate Not limited
Acid-treated starches Not limited
Alkali-treated starches Not limited
Amylose and amylopectin Not limited
Bleached starches Not limited
Distarch gylcerol Not limited
Distarch phosphate Not limited
Enzyme-treated starches Not limited
Hydroxypropyl distarch glycerol Not limited
Hydroxypropyl distarch phosphate No ADI
allocated2
Hydroxypropyl starch Not limited
Monostarch phosphate Not limited
1 As the sum of total modified celluloses. The ADI may be
exceeded for dietetic purposes, i.e., when use is primarily intended
to take advantage of the noncaloric properties of these additives.
2 Evaluation not possible with data provided.
TOXICOLOGICAL EVALUATION: THICKENING AGENTS
(continued)
Acceptable daily
Substances intake for man
(mg/kg bw)
Oxidized starches Not limited1
Phosphated distarch phosphate Not limited
Starch acetate Not limited
Starch sodium succinate No ADI
allocated2
White and yellow dextrins Not limited
D. Others
Agar Not limited
Alginic acid and its ammonium, calcium,
potassium, and sodium salts3 0-50
Carrageenan and furcellaran 0-75
Pectin (non-amidated) Not limited
Pectin (amidated) 0-251
1 Temporary acceptance.
2 Evaluation not possible with data provided.
3 As alginic acid.
TOXICOLOGICAL EVALUATION: MISCELLANEOUS FOOD ADDITIVES
Acceptable daily
Substances intake for man
(mg/kg bw)
Calcium acetate, choride gluconate and sulfate Not limited
Food-grade mineral oil Not limited
L-glutamic acid, its ammonium, calcium, mono-
sodium, and potassium salts1 0-120
Lactic acid and its ammonium, calcium,
potassium, and sodium salts Not limited2
Oxystearin 0-25
Phosphoric acid and its salts 0-703
Polyvinyl pyrrolidone No ADI
allocated4
1,2-propylene glycol 0-25
Sorbitol Not limited
Stearoyl lactylic acid, calcium and sodium salts 0-20
Tartaric acid (and its potassium, sodium, and
potassium-sodium salts)5 0-30
1 As glutamic acid, additional to glutamic acid intake from all
non-additive dietary sources. ADI not applicable to infants under 12
weeks of age.
2 Neither D(-)-lactic acid nor (DL)-lactic acid should be used
in infant foods.
3 Total dietary phosphorus load for man. Attention should be paid
to the reverse relationship with calcium intake.
4 Evaluation not possible with data provided. Previously
allocated conditional ADI is withdrawn.
5 As L(+)-tartaric acid.
See Also:
Toxicological Abbreviations