WORLD HEALTH ORGANIZATION
WHO Food Additives Series 1972, No. 1
TOXICOLOGICAL EVALUATION OF SOME
ENZYMES, MODIFIED STARCHES AND
CERTAIN OTHER SUBSTANCES
The evaluations contained in this publication were prepared by the
Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
16-24 June 19711
World Health Organization
Geneva
1972
1 Fifteenth Report of the Joint FAO/WHO Expert Committee on Food
Additives, Wld Hlth Org. techn. Rep. Ser., 1972, No. 488; FAO
Nutrition Meetings Report Series, 1972, No. 50.
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. 50A
(c) FAO and WHO 1972
CONTENTS
INTRODUCTION
ALLOCATION OF ACCEPTABLE DAILY INTAKES
TOXICOLOGICAL EVALUATION: ENZYMES
TOXICOLOGICAL EVALUATION: MODIFIED STARCHES
TOXICOLOGICAL EVALUATION: MISCELLANEOUS FOOD ADDITIVES
THE MONOGRAPHS
ENZYMES
Mixed Microbial Carbohydrase and Protease
Microbial Carbohydrase
Microbial Glucose Oxidase
Microbial Rennet
Microbial Rennet
Microbial Rennet
MODIFIED STARCHES
Oxidized Starches
Starch Acetate
Hydroxypropyl Starch
Hydroxypropyl Distarch Glycerol
Distarch Phosphate
Hydroxypropyl Distarch Phosphate
Phosphated Distarch Phosphate
Acetylated Distarch Phosphate
Distarch Glycerol
Acetylated Distarch Glycerol
Acetylated Distarch Adipate
MISCELLANEOUS FOOD ADDITIVES
Caramel Colours (Ammonia process)
Esters of Glycerol and Thermally Oxidized Soy Bean Fatty Acids
Hexamethylenetetramine
Microcrystalline Cellulose
Propylene Glycol Alginate
Stearoyl Lactylic Acid, Calcium and Sodium Salts
Tin and Stannous Chloride
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 Fifteenth Joint FAO/WHO Expert Committee on
Food Additives
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 16 to 24 June 1971. Since the report1 of this
meeting also contains comments on groups of as well as individual
substances considered, these monographs should be read in conjunction
with the report.
Any new information and comments relating to the biological data and
their evaluation should be addressed to: Food Additives unit, World
Health Organization. Avenue Appia, Geneva, Switzerland.
Specifications on the food additives considered have been prepared,
and these will be issued in a separate document entitled
"Specifications for the Identity and Purity of Some Enzymes and
Certain Other Substances".2 Comments relating to specifications
should be addressed to: Food Policy and Food Science Service,
Nutrition Division, FAO, Rome, Italy.
1 Fifteenth Report of the Joint FAO/WHO Expert Committee on Food
Additives, FAO Nutrition Meetings Report Series; Wld Hlth Org. techn.
Rep. Ser., 1972, No. 488.
2 FAO Nutrition Meetings Report Series, WHO/Food Add./71 (In
preparation).
ALLOCATION OF ACCEPTABLE DAILY INTAKES
It is generally recognized that all chemicals are toxic to animals and
man if large enough amounts are administered. Even those so-called
innocuous substances, when given in excessive doses, may induce
untoward effects as a result of various non-specific actions, e.g.
physical obstructions of the G.I. tract, alteration of osmotic
pressure and nutritional imbalance. A limit on the daily intake of a
substance is therefore essential for the protection of the health of
the consumer. The Committee therefore followed previous practice,
where appropriate, in allocating acceptable daily intakes (ADI) to the
food additives considered.
An unconditional ADI was allocated only to those substances for
which the biological data available included either the results of
adequate short-term and long-term toxicological investigations or
information on the biochemistry and metabolic fate of the compound or
both.
A conditional ADI was allocated for specific purposes arising from
special dietary requirements. (None was allocated at this meeting.)
A temporary ADI was allocated when the available data were not fully
adequate to establish the safety of the substance and it was
considered necessary that the additional evidence be provided within a
stated period of time. If the further data requested do not become
available within the stated period, it is possible that the temporary
ADI will be withdrawn by a future committee.
Whereas all the ADIs are subject to periodic review, especially when
additional data are available, reconsideration of temporary ADIs is
obligatory after the date specified. The decision arrived at will
depend on the information available at the time of review. It is
certainly not intended that the temporary status of the ADI for a food
additive will continue to be maintained indefinitely.
"Not limited". The Committee took cognizance of the fact that the
level of use of certain food additives is limited by good
manufacturing practice and that they are food components or possess a
very low toxicity. For these additives the Committee established no
limit except as based on good manufacturing practice.
For those additives for which the available information was grossly
inadequate to establish safety, no ADI was allocated.
TOXICOLOGICAL EVALUATION: ENZYMES
Evaluation1 Monographs Specifications
I. Animal-derived enzyme preparations
1. Rennet Not limited No Yes
2, Rennet, animal Not limited No Yes
3. Pepsin Not limited No Yes
4. Trypsin Not limited No Yes
5. Lipase, animal Not limited No Yes
6. Catalase (bovine liver) Not limited No Yes
II. Plant-derived enzyme preparations
1. Bromelain Not limited No Yes
2. Ficin Decision No Yes2
postponed
3. Malt-carbohydrases Not limited No Yes
4. Papain Not limited No Yes
III. Microbially-derived enzyme preparations
1. Aspergillus niger var.
(a) Carbohydrase Not limited3 Yes Yes2
(b) Glucose oxidase Not limited3 Yes Yes2
2. Aspergillus oryzae var.
(a) Carbohydrases Decision No Yes2
postponed
(b) Protease Decision No Yes2
postponed
(c) Lipase Decision No Yes2
postponed
TOXICOLOGICAL EVALUATION: ENZYMES (continued)
Evaluation1 Monographs Specifications
3. Bacillus cereus
Microbial rennet Decision No Yes2
postponed
4. Bacillus subtilis var.
Carbohydrases and Not limited Yes Yes
proteases mixed
5. Endothia parasitica
Microbial rennet Not limited3 Yes Yes2
6. Mucor miehei
Microbial rennet Not limited3 Yes Yes2
7. Mucor pusillus
Microbial rennet Not limited3 Yes Yes2
8. Micrococcus lysodeikticus
Catalase Decision No Yes2
postponed
9. Rhizopus oryzae
Carbohydrase Not limited No Yes
TOXICOLOGICAL EVALUATION: ENZYMES (continued)
Evaluation1 Monographs Specifications
10. Saccharomyces sp.
Carbohydrase Not limited No Yes
11. Miscellaneous
Irpex lacteus Decision No No
(microbial rennet) postponed
Penicillium amagasakiense Decision No No
(microbial glucose oxidase) postponed
Arthrobacter Decision No No
(microbial carbohydrase) postponed
1 Not limited, except by good manufacturing practice.
2 Tentative specifications.
3 Temporary.
TOXICOLOGICAL EVALUATION: MODIFIED STARCHES1
Evaluation2 Monograph Specification
Oxidized starches Not limited Yes Yes
Starch acetate Not limited Yes Yes
Hydroxypropyl starch Not limited Yes Yes
Hydroxypropyl distarch
glycerol Not limited Yes Yes
Distarch phosphate Not limited Yes Yes
Phosphated distarch phosphate Not limited Yes Yes
Acetylated distarch phosphate Not limited Yes Yes
Distarch glycerol Not limited Yes Yes
Acetylated distarch glycerol Not limited Yes Yes
Acetylated distarch adipate Not limited Yes Yes
Hydroxypropyl distarch Not Yes Yes3
phosphate acceptable
1 For results of evaluation on other modified starches see Annex 4, Thirteenth
Report, Wld Hlth Org. techn. Rep. Ser., No. 445.
2 Use limited by good manufacturing practice; temporary acceptance.
3 Tentative specification.
TOXICOLOGICAL EVALUATION: CERTAIN OTHER SUBSTANCES
Acceptable
daily intake Monograph Specifications
Substances for man1
(mg/kg
body weight)
Caramel colours
(a) made by the ammonia or
ammonium sulfate process 0-1002,3 Yes Yes6
(b) made by other processes Not limited4 No Yes
Choline salts Not limited4 No No
Esters of glycerol and thermally
oxidized soy bean fatty acid 0-752 Yes Yes6
Thermally oxidized soy bean oil No ADI No Yes6
Hexamethylenetetramine 0-52 Yes Yes
Microcrystalline cellulose Not limited4 Yes Yes
Propylene glycol alginate 0-25 Yes Yes
Stearoyl lactylate, calcium and
sodium salts 0-20 Yes Yes
Tin and stannous chloride No ADI5 Yes Yes
1 Unconditional unless otherwise stated.
2 Temporary ADI.
3 The level of 4-methylimidazole should not exceed 200 mg/kg based on a product
having a colour intensity of 20 000 EBC (European Brewing Convention) Units.
4 Use limited by good manufacturing practice.
5 See the Monograph.
6 Tentative specifications.
See Also:
Toxicological Abbreviations