FAO Nutrition Meetings
Report Series No. 40A,B,C
WHO/Food Add./67.29
TOXICOLOGICAL EVALUATION OF SOME
ANTIMICROBIALS, ANTIOXIDANTS, EMULSIFIERS,
STABILIZERS, FLOUR-TREATMENT AGENTS, ACIDS AND BASES
The content of this document is the result of the deliberations of the
Joint FAO/WHO Expert Committee on Food Additives which met at Rome,
13-20 December, 19651 Geneva, 11-18 October, 19662
1 Ninth Report of the Joint FAO/WHO Expert Committee on Food
Additives, FAO Nutrition Meetings Report Series, 1966 No. 40;
Wld Hlth Org. techn. Rep. Ser., 1966, 339
2 Tenth Report of the Joint FAO/WHO Expert Committee on Food
Additives, FAO Nutrition Meetings Report Series, 1967, in press;
Food and Agriculture Organization of the United Nations
World Health Organization
1967
CONTENTS
INTRODUCTION
NOTES ON THE BIOLOGICAL DATA
NOTES TO THE READER
ACCEPTABLE DAILY INTAKES FOR MAN OF SOME ANTI MICROBIALS, ANTIOXIDANTS
AND ANTIOXIDANT SYNERGISTS
ACCEPTABLE DAILY INTAKES FOR MAN OF SOME EMULSIFIERS AND STABILIZERS
ACCEPTABLE TREATMENT LEVELS FOR SOME FLOUR-TREATMENT AGENTS
ACCEPTABLE DAILY INTAKES FOR MAN OF SOME ACIDS AND BASES
ACCEPTABLE DAILY INTAKES FOR SOME OTHER FOOD ADDITIVES
THE MONOGRAPHS
ANTIMICROBIALS, ANTIOXIDANTS AND ANTIOXIDANT SYNERGISTS
Benzoic acid
Benzoate, Potassium
Benzoate, Sodium
Benzoate, Butyl p-Hydroxy
Benzoate, Ethyl p-Hydroxy
Benzoate, Methyl p-Hydroxy
Benzoate, Propyl p-Hydroxy
Butylated Hydroxytoluene
Diethyl Pyrocarbonate
EDTA, Calcium disodium
EDTA, Disodium
Hydrogen Peroxide
Isopropyl Citrate Mixture
Monoisopropyl Citrate see Isopropyl Citrate Mixture
Propionic acid
Propionate, Calcium
Propionate, Sodium
Sorbic acid
Sorbate, Calcium
Sorbate, Potassium
Sulfur Dioxide
Potassium Metabisulfite
Sodium Hydrogen Sulfite
Sodium Metabisulfite
Sodium Sulfite
EMULSIFIERS AND STABILIZERS
Acetic acid and fatty acid esters of glycerol
Cellulose, Hydroxypropyl Methyl
Cellulose, Methyl Ethyl
Cellulose, Sodium Carboxymethyl
Cholic acid (and Na salt)
Cholic acid, Desoxy- (and Na salt)
Citric acid and fatty acid esters of glycerol
Diacetyltartaric acid and fatty acid esters of glycerol
Diglyceride, acetylated, citrated, lactated or tartrated see Acetic
acid, Citric acid, etc.
Lactic acid and fatty acid esters of glycerol
Mixed tartaric acid and acetic acid and fatty acid esters of glycerol
Polyglycerol esters of fatty acids
Propylene glycol esters of fatty acids
FLOUR TREATMENT AGENTS
Azodicarbonamide
Chlorine
Iodate, Calcium
Iodate, Potassium
Nitrogen Oxides
Peroxides, Acetone
Peroxide, Calsium
Persulfate, Ammonium
Persulfate, Potassium
Stearyl Tartrate
ACIDS
Acetic acid
Adipic acid
Monocalcium phosphates
Citric acid
Fumaric acid
Gluconic acid see Glucono-delta-lactone
Glucono-delta-lactone (Glucosic acid)
Hydrochloric acid
DL-Lactic acid
DL-Malic acid
BASES
Carbonate, Ammonium
Carbonate, Calcium
Carbonate, Magnesium
Carbonate, Potassium
Carbonate, Sodium
Carbonate, Ammonium Hydrogen
Carbonate, Potassium Hydrogen
Carbonate, Sodium Hydrogen
Hydroxide, Ammonium
Hydroxide, Calcium
Hydroxide, Magnesium
Hydroxide, Potassium
Hydroxide, Sodium
Oxide, Calcium
Oxide, Magnesium
OTHERS
Mannitol
Polyvinylpyrrolidone
Sorbitol
INTRODUCTION
The monographs contained in this report are the result of the
deliberations of the ninth1 and tenth2 sessions of the Joint FAO/WHO
Expert Committee on Food Additives. Therefore the monographs should be
consulted together with these reports.
The opinions recorded are based upon scientific evidence made
available to the members at the time of the meeting. Every effort was
made to obtain all the information on each substance but it is almost
inevitable that some work has been missed. The committee offered its
apologies to these whose work may not have been taken into
consideration.
Specifications on these food additives will be forwarded as
working papers to the participants at the Fourth Session of the Codex
Committee on Food Additives September 1967, and to interested
organizations, and will also be available on request from the Joint
FAO/WHO Food Standards Branch (Codex Alimentarius), FAO, Rome.
1 FAO Nutrition Meetings Report Series, 1966, No. 40; Wld Hlth
Org. techn. Rep. Ser., 1966, 339
2 FAO Nutrition Meetings Report Series, in press; Wld Hlth Org.
techn. Rep. Ser., in press
NOTES ON THE BIOLOGICAL DATA
The Committee agreed that the monographs dealing with the
evaluation of the biological data should be drafted along the lines
adopted in the previous reports. The Committee at its tenth session
also agreed to support in principle the recommendations made by the
Scientific Group on Procedures for Investigating Intentional and
Unintentional Food Additives.1
Acceptable Daily Intake
The Committee decided to retain the method of expressing the
acceptable daily intake that had been adopted in earlier reports and,
in appropriate cases, to continue to divide the over-all zone of
acceptability into two parts. For detailed discussion see the Seventh
Report.2 The first part of the over-all acceptable daily intake zone
has been termed the unconditional zone of acceptability, and this
represents levels of use that are effective technologically, at least
for some purposes, and can be safely employed without further expert
advice. The second part consists of a conditional zone of
acceptability and represents levels of use that can be employed safely
but at which it is thought desirable that some degree of expert
supervision and advice should be readily available.
Acceptable Treatment Level
In regard to the flour-treatment agents, the main toxicological
and nutritional considerations are concerned with treated flour rather
than with the food additive itself. The Committee followed the
procedure adopted in the Seventh Report2 for benzoyl peroxide,
chlorine dioxide and potassium bromate and recommended levels of flour
treatment for this group of additives instead of setting an acceptable
level of daily intake.
Grouping of related food additives
As a number of food additives are closely related chemically and
toxicologically, the Committee adopted a system of grouping of food
additives. The acceptable daily intake is expected to cover all the
specified members of the group that may be included in the diet. In
some cases, a given food additive may be related to two groups, in
which case the level in the diet must not exceed the maximum
acceptable level for either group. The problem is not as complicated
as it may appear at first sight, since many of the substances in a
group of additives are likely to be used as alternatives to each
other.
1 Wld Hlth Org. techn. Rep. Ser., 1967, 348
2 FAO Nutrition Meetings, Report Series, 1964, 35; Wld Hlth
Org. tech. Rep. Ser., 1964, 281
Request for further work
Previous monographs have often listed further work that seemed to
be desirable. However, it is only in relatively few cases that the
studies requested have been done, although in some cases the work may
be urgently needed in the interests of the consumer. The Committee at
its ninth session, therefore agreed to request, in the monographs,
only work that is urgently needed in the interests of safety. All
other suggestions for further work that may seem desirable, but not so
urgently needed, are included under the heading "Comments".
The Committee draws the attention of manufacturers and users of
food additives to the fact in future, if a statement about farther
work being required is included in a monograph, this matter should
be given urgent attention. If the additive in question is one that is
already in use, its continued use will be supported by the Committee
only if the further work required has been carried out and the results
justify continuance of the use of the additive. If no action is taken
to provide the further evidence that is required, it will be assumed
that neither the manufacturers nor the users are interested in
continuing the use of the additive. In this case, the Committee may
well decide to recommend the prohibition of its use. If the food
additive is a new substance not yet in use and if further work has
been required, a conditional intake level may be established for a
limited period to allow the results of this additional work to be
submitted and studied.
References
Authors who have submitted papers relevant to a given monograph
but who are not mentioned in it may rest assured that their work has
been consulted. In the interest of brevity, however, the
bibliographies of some monographs may be restricted to more recent or
more extensive investigations in the field in question. The pioneering
achievements of the earlier workers in these fields are fully
appreciated.
NOTES TO THE READER
Further general remarks on the biological data and toxicological
evaluation in these monographs as well as reference to the other food
additives considered by the Joint Expert Committee may be found in a
publication entitled "Explanatory Notes on the Activities of the Joint
FAO/WHO Expert Committee on Food Additives".1
Any new information and comments relating: to biological data and
their evaluation should be addressed to: Food Additives Unit, World
Health Organization, Avenue Appia, Geneva, Switzerland.
1 Off-print from Tenth Report of the Joint FAO/WHO Expert Committee
on Food Additives
ACCEPTABLE DAILY INTAKES FOR MAN OF SOME ANTIMICROBIALS, ANTIOXIDANTS
AND ANTIOXIDANT SYNERGISTS
Over-all daily intake zone1
(mg/kg body-weight)
Compounds considered
Unconditional Conditional
Benzoic Acid
Benzoate, Potassium
Benzoate, Sodium 0-52 5-102
Benzoate, Butyl p-Hydroxy Decision postponed
Benzoate, Ethyl p-Hydroxy
Benzoate, Methyl p-Hydroxy 0-23 2-73
Benzoate, Propyl p-Hydroxy
Butylated Hydroxyanisole 0-0.54 0.5-24
Butylated Hydroxytoluene
EDTA, Disodium 0-1.255 1.25-2.55
EDTA, Calcium disodium
Hexamethylenetetramine Decision postponed
Hydrogen Peroxide Restricted uses
Isopropyl Citrate Mixture 0-7 7-20
1 The first part of the over-all acceptable intake zone is termed
unconditional and this represents levels which can be safely used
without further expert supervision and advice. The second part is
termed conditional and represents levels of use that can be
safely employed but at which it is thought desirable that some
degree of expert supervision and advice should be readily
available.
2 As sum of benzoic acid and sodium and potassium benzoate
(calculated as benzoic acid).
3 As sum of methyl, ethyl, and propyl esters of p-hydroxybenzoic
acid.
4 As sum of butylated hydroxytoluene and butylated hydroxyanisole.
5 As calcium disodium EDTA. The use of disodium EDTA is recommended
only for accurately chelating calcium.
ACCEPTABLE DAILY INTAKES FOR MAN OF SOME ANTIMICROBIALS, ANTIOXIDANTS
AND ANTIOXIDANT SYNERGISTS (continued)
Over-all daily intake zone
(mg/kg body-weight)
Compounds considered
Unconditional conditional
Propionic Acid
Propionate, Calcium
Propionate, Sodium 0-101 10-201
Sorbic Acid
Sorbate, Calcium 0-12.52 12.5-252
Sorbate, Potassium
Sulfur dioxide
Potassium metabisulfite
Sodium sulfite 0-0.353 0.35-1.53
Sodium metabisulfite
Sodium hydrogen sulfite
Antimicrobial for certain Acceptable level of
beverages treatment (ppm)
Diethyl Pyrocarbonate 0-300
1 As sum of propionic acid and calcium and sodium propionate
(calculated as propionic acid).
2 As sum of sorbic acid and calcium and potassium sorbate
(calculated as sorbic acid).
3 As sum of sulfur dioxide, sodium sulfite, sodium and potassium
metabisulfite and sodium hydrogen sulfite (calculated as SO2).
ACCEPTABLE DAILY INTAKES FOR MAN OF SOME EMULSIFIERS AND STABILIZERS
Over-all daily intake zone1
(mg/kg body-weight)
Compounds considered
Unconditional Conditional
Cellulose, Sodium Carbozymethyl- Higher levels
Cellulose, Hydroxypropyl Methyl- 0-302 for dietetic
Cellulose, methyl- or calorie
Cellulose, Methylethyl- control
purposes
Acetic acid and fatly acid
esters of glycerol
Citric acid and fatty acid
esters of glycerol
Lactic acid and fatty acid 0-1003
esters of glycerol4
Mixed tartaric and acetic
and fatty acid esters of
glycerol5
Diacetyltartaric acid and fatty
acids esters of glycerol5 0-25 25-50
Polyglycerol esters of fatty 0-12.5 12.5-25
acids
Propylene glycol esters of fatty 0-206 20-606
acid.
Cholic and Desoxycholic acids 0-1.25
and their salts
1 The first part of the over-all acceptable daily intake zone is
termed unconditional and this represents levels which can be
safely used without further expert supervision and advice. The
second part is termed conditional and represents levels of use
that can be safely employed but at which it is thought desirable
that some degree of expert supervision and advice should be
readily available.
2 As sum of these cellulose derivatives
3 As sum of these fatty emulsifiers.
4 The conditional zone of acceptability for the total intake of
D(-)-lactic acid is 0-100 mg/kg.
5 The zone of acceptability for the total food additives intake of
tartaric acid is 0-6 mg/kg (unconditional) and 6-20 mg/kg
(conditional).
6 As propylene glycol.
ACCEPTABLE TREATMENT LEVELS FOR SOME FLOUR-TREATMENT AGENTS
Name Acceptable levels of treatment(ppm)
Azodicarbonamide 0-45
Chlorine No level set
Iodate, Calcium Use not recommended
Iodate, Potassium Use not recommended
Nitrogen Oxides No level set
Peroxides, Acetone No level set
Peroxide, Calcium No level set
Persulfate, Ammonium No level set
Persulfate, Potassium No level set
Stearyl Tartrate 0-5001
1 See monograph on Stearyl tartrate
ACCEPTABLE DAILY INTAKES FOR MAN OF SOME ACIDS AND BASES
Over-all daily intake zone1
(mg/kg body-weight)
Compounds considered
Unconditional Conditional
Acids
Acetic acid Not limited
Adipic Acid 0-5
Citric Acid Not limited
Fumaric Acid 0-6 6-10
Glucono-delta-lactone 0-15 15-50
(gluconic acid)
Hydrochloric Acid Not limited
DL-Lactic Acid 0-1002
DL-Malic Acid 0-1003
Monocalcium Phosphates Not limited4
Bases
Carbonate, Ammonium )
Carbonate, Calcium )
Carbonate, Magnesium ) Not limited5
Carbonate Potassium )
Carbonate, Sodium )
Carbonate, Ammonium Hydrogen )
Carbonate, Potassium Hydrogen ) Not limited5
Carbonate Sodium Hydrogen )
Hydroxide, Ammonium )
Hydroxide Calcium )
Hydroxide, Magnesium ) Not limited5
Hydroxide Potassium )
Hydroxide, Sodium )
Oxide Calcium ) Not limited5
Oxide, Magnesium )
1 The first part of the over-all acceptable daily intake zone is
termed unconditional and this represents levels which can be
safely used without further expert supervision and advice. The
second part is termed conditional and represents levels of use
that can be safely employed but at which it is thought desirable
that some degree of expert supervision and advice should be
readily available.
2 Refers to content of D(-)-lactic acid.
3 Refers to content of D(-)-malic acid.
4 Subject to limits of phosphorus load given in the Seventh Report
(Wld Hlth Org. techn. Rep, Ser., 1964, 281, 31).
5 Provided that use is in accordance with good manufacturing
practice.
ACCEPTABLE DAILY INTAKES FOR MAN OF SOME OTHER FOOD ADDITIVES
Over-all daily intake zone1
(mg/kg body-weight)
Compounds considered
Unconditional Conditional
D-Mannitol 0-50 50-150
Sorbitol Not limited
Polyvinylpyrrolidone 0-1
1 The first part of the over-all acceptable daily intake zone is
termed unconditional and this represents levels which can be
safely used without further expert supervision and advice. The
second part is termed conditional and represents levels of use
that can be safely employed but at which it is thought desirable
that some degree of expert supervision and advice should be
readily available.
See Also:
Toxicological Abbreviations