INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
WORLD HEALTH ORGANIZATION
SAFETY EVALUATION OF CERTAIN
FOOD ADDITIVES
WHO FOOD ADDITIVES SERIES: 42
Prepared by the Fifty-first meeting of the Joint FAO/WHO
Expert Committee on Food Additives (JECFA)
World Health Organization, Geneva, 1999
IPCS - International Programme on Chemical Safety
ANNEX 4
ACCEPTABLE DAILY INTAKES, OTHER TOXICOLOGICAL INFORMATION, AND
INFORMATION ON SPECIFICATIONS
1. Food additives
Substance Specificationsa ADI and other
toxicological recommendations
Enzyme preparations
alpha-Acetolactase R ADI 'not specified'
decarboxylase
Maltogenic amylase R ADI 'not specified'
Flavouring agents
trans-Anethole S 0-2 mg/kg bw
Furfural N No ADIb
Menthol R 0-4 mg/kg bw
Food colours
Curcumin R,T 0-1 mg/kg bw
(temporary)c
Riboflavin from genetically N 0-0.5 mg/kg bw
modified Bacillus subtilis (group ADI with
synthetic riboflavin
and
riboflavin-5'-phosphate)
Glazing agent
Mineral oil (medium- R
and low-viscosity
Class Id 0-1 mg/kg bw
(temporary) c
Class IIe and class IIIf 0-0.01 mg/kg bw
(temporary group
ADI)c
Preservatives
Calcium hydrogen sulfitec S;T )
Calcium metabisulfite O )
Calcium sulfite O )
Potassium hydrogen sulfite O )
Potassium metabisulfitec R,T ) Group ADI, 0-0.7
Potassium sulfitec R,T ) mg/kg bwg
Sodium hydrogen sulfitec R,T )
Sodium metabisulfitec R,T )
Sodium sulfitec R,T )
Sodium thiosulfatec R,T )
Sulfur dioxide R )
Substance Specificationsa ADI and other
toxicological recommendations
Sweetening agent
Stevioside O No ADI allocatedb
Thickening agents
Carrageenan R ) Group ADI 'not
) specified'
) (temporary)c
Processed Eucheuma seaweed R
Sodium carboxymethyl
cellulaose, enzymatically R Group ADI 'not
hydrolysed specified'h
Miscellaneous substances
gamma-Cyclodextrin N ) ADI 'not specified'
) (temporary)c
Glucono-delta-lactone R )
Calcium gluconate R )
Magnesium gluconate R,T ) Group ADI 'not
Potassium gmuconate R ) specified'
Sodium gluconate R )
Polyglycitol syrup N Group ADI 'not
specified'i
a N, new specifications prepared; O, no specifications prepared;
R, existing specifications revised; S, specifications exist,
revision not considered or not required; T, the existing, new, or
revised specifications are tentative and comments are invited
b Data were insufficient for establishing an ADI
c See Annex 4.
d Including P70(H) oil
e Including N70(H) and N70(A) oils
f Including P15(H), N15(H), and N10(A) oils
g The Committee reiterated its recommendation made at the thirtieth
meeting that, when a suitable alternative method of preservation
exists, its use should be encourages, particularly in those
applications (e.g. control of enzymic browning in fresh salad
vegetables) in which the use of sulfites may lead to high levels
of acute exposure and which have most commonly been associated
with life-threatening adverse reactions. Appropriate labelling
would help to alert individuals who cannot tolerate sulfites.
h Included in the group ADI for modified celluloses: ethyl
cellulose, ethylhydroxyethyl cellulose, hydroxypropyl cellulose,
hydroxypropyl methyl cellulose, methyl cellulose, methyl ethyl
cellulose, and sodium carboxymethyl cellulose
i Group ADI for materials conforming to the specifications for
polyglycitol syrup and maltitol syrup
2. Substances evaluated using the procedure for the safety evaluation
of flavouring agents
A. Flavouring agents evaluated toxicologically and considered for specifications
Flavouring agent No. Specificationsa Conclusions based
on current levels
of intake
Saturated aliphatic acyclic secondary alcohols, ketones, and related saturated and unsaturated
esters
Acetone 0139 N )
Isopropyl alcohol 0277 N )
2-Butanone 0278 N ) No safety concern
2-Pentanone 0279 N )
2-Pentanol 0280 N )
3-Hexanone 0281 N )
3-Hexanol 0282 N )
2-Heptanone 0283 N ) No safety concern
2-Heptanol 0284 N )
3-Heptanone 0285 N )
3-Heptanol 0286 N )
4-Heptanone 0287 N ) No safety concern
2-Octanone 0288 N )
2-Octanol 0289 N )
3-Octanone 0290 N )
3-Octanol 0291 N )
2-Nonanone 0292 N )
2-Nonanol 0293 N ) No safety concern
3-Nonanone 0294 N )
3-Decanol 0295 N )
2-Undecanone 0296 N )
2-Undecanol 0297 N )
2-Tridecanone 0298 N ) No safety concern
2-Pentadecanone 0299 N,T )
3-Methyl-2-butanol 0300 N )
4-Methyl-2-pentanone 0301 N,T )
2,6-Dimethyl-4-heptanone 0302 N,T )
2,6-Dimethyl-4-heptanol 0303 N ) No safety concern
Isopropyl formate 0304 N,T )
Isopropyl acetate 0305 R )
Flavouring agent No. Specificationsa Conclusions based
on current levels
of intake
Isopropyl propionate 0306 N )
Isopropyl butyrate 0307 N )
Isopropyl hexanoate 0308 N ) No safety concern
Isopropyl isobutyrate 0309 N )
Isopropyl isovalerate 0310 N )
Isopropyl myristate 0311 N )
Isopropyl tiglate 0312 N ) No safety concern
3-Octyl acetate 0313 N )
1-Ethylhexyl tiglate (3-octyl tiglate) 0448 N )
Linear and branched-chain aliphatic unsaturated unconjugated alcohols, aldehydes, acids,
and related esters
4-Pentenoic acid 0314 N )
cis-3-Hexen-1-ol 0315 N )
cis-3-Hexenal 0316 N,T ) No safety concern
3-Hexenoic acid 0317 N )
4-Hexen-1-ol 0318 N )
cis-4-Hexenal 0319 N,T )
4-Heptenal 0320 N )
cis-3-Octen-1ol 0321 N ) No safety concern
cis-5-Octen-1-ol 0322 N )
cis-5-Octenal 0323 N )
cis-6-Nonen-1-ol 0324 N )
cis-6-Nonenal 0325 N )
4-Decenal 0326 N ) No safety concern
5&6-Decenoic acid 0327 N )
9-Decenoic acid 0328 N )
9-Undecenal 0329 N,T )
10-Undecenal 0330 N )
10-Undecenoic acid 0331 N,T ) No safety concern
Linoleic acid 0332 N )
Oleic acidb 0333 N )
Methyl 3-hexenoate 0334 N,T )
Ethyl 3-hexenoate 0335 N )
cis-3-Hexenyl cis-3-hexenoate 0336 N ) No safety concern
Methyl cis-4-octeboate 0337 N,T )
Ethyl cis-4-octeoate 0338 N,T )
Flavouring agent No. Specificationsa Conclusions based
on current levels
of intake
Ethyl cis-4,7-octadienoate 0339 N )
Methyl 3-nonenoate 0340 N )
Ethyl trans-4-decenoate 0341 N,T ) No safety concern
Methyl 9-undecenoate 0342 N,T )
Ethyl 10-undecenoate 0343 N )
Butyl 10-undecenoate 0344 N )
Ethyl oleate 0345 N )
Methyl linoleate & methyl 0346 N ) No safety concern
linolenate (mix)
2-Methyl-3-pentenoic acid 0347 N,T )
2,6-Dimethyl-6-hepten-1-ol 0348 N,T )
2,6-Dimethyl-5-heptenal 0349 N )
Ethyl-2-methyl-3-pentenoate 0350 N,T )
Ethyl-2-methyl-4-pentenoate 0351 N ) No safety concern
Hexyl-2-methyl-3&4-pentenoate 0352 N,T )
Ethyl-2-methyl-3,4-pentadienoate 0353 N,T ) Evaluation
deferredc
Linear and branched-chain aliphatic unsaturated unconjugated alcohols, aldehydes, acids,
and related esters
Methyl 3,7-dimethyl-6-octenoate 0354 N ) No safety concern
2-Methyl-4-pentenoic acid 0355 N )
Aliphatic acyclic and alicyclic terpenoid tertiary alcohols and structurally related substances
Linaloold 0356 R )
Tetrahydrolinalool 0357 N,T )
Linalyl formate 0358 N ) No safety concern
Linalyl acetate 0359 R )
Linalyl propionate 0360 N )
Linalyl butyrate 0361 N )
Linalyl isobutyrate 0362 N )
Linalyl isovalerate 0363 N ) No safety concern
Linalyl hexanoate 0364 N )
Linalyl octanoate 0365 N )
alpha-Terpineol 0366 N )
Terpinyl formate 0367 N )
Terpinyl acetate 0368 N ) No safety concern
Terpinyl propionate 0369 N )
Terpinyl butyrate 0370 N )
Flavouring agent No. Specificationsa Conclusions based
on current levels
of intake
Terpinyl isobutyrate 0371 N,T )
Terpinyl isovalerate 0372 N,T )
para-Menth-3-en-1-ol 0373 N,T ) No safety concern
4-Carvomenthenol 0439 N,T )
para-Menth-8-en-1-ol (ß-terpineol) 0374 N )
2-Ethyl-1,3,3-trimethyl-2-norbornanol 0440 N,T ) No safety concern
4-Thujanol 0441 N )
Methyl 1-acetoxycyclohexyl ketone 0442 N,T Additional data
required
Carvone and structurally related substances
para-Menthan-2-one 0375 N )
para-Menthan-2-ol 0376 N )
Dihydrocarvone 0377 N ) No safety concern
Dihydrocarveol 0378 N )
Dihydrocarvyl acetate 0379 N )
(+) Carvonee 0380a R )
(-) Carvone 0380b R,T )
Carveol 0381 N ) No safety concern
Carvyl acetate 0382 N )
Carvyl propionate 0383 N )
Ionones and structurally related substances
ß-Damascone 0384 N,T )
alpha-Damascone 0385 N,T )
delta-Damascone 0386 N ) No safety concern
Damascenone 0387 N )
alpha-Iononef 0388 R )
ß-Ionone 0389 R )
gamma-Ionone 0390 N )
alpha-Ionol 0391 N ) No safety concern
ß-Ionol 0392 N )
Dihydro-alpha-ionone 0393 N )
Dihydro-ß-ionone 0394 N,T )
Dihydro-ß-ionol 0395 N )
Dehydrodihydroionone 0396 N,T ) No safety concern
Dehydrodihydroionol 0397 N,T )
Methyl alpha-ionone 0398 N,T )
Flavouring agent No. Specificationsa Conclusions based
on current levels
of intake
Methyl-ß-ionone 0399 N ) No safety concern
Methyl-delta-ionone 0400 N,T No safety concern
Allyl-alpha-ionone 0401 N No safety concern
1,4-Dimethyl-4-acetyl-1-cyclohexene 0402 N,T Not evaluated
alpha-Irone 0403 N No safety concern
alpha-iso-Methylionone 0404 N No safety concern
Aliphatic acyclic and alicyclic alpha-diketones and related substances
Acetoin 0405 N )
2-Acetoxy-3-butanone 0406 N )
Butan-3-one-2-yl butanoate 0407 N ) No safety concern
Diacetyl 0408 N )
3-Hydroxy-2-pentanone 0409 N )
2,3-Pentanedione 0410 N )
4-Methyl-2,3-pentanedione 0411 N )
2,3-Hexanedione 0412 N ) No safety concern
3,4-Hexanedione 0413 N )
5-Methyl-2,3-hexanedione 0414 N )
2,3-Heptanedione 0415 N )
5-Hydroxy-4-octanone 0416 N )
2,3-Undecadione 0417 N ) No safety concern
Methylcyclopentenolone 0418 N )
Ethylcyclopentenolone 0419 N )
3,4-Dimethyl-1,2-cyclopentanedione 0420 N )
3,5-Dimethyl-1,2-cyclopentanedione 0421 N,T )
3-Ethyl-2-hydroxy-4-methyl- 0422 N ) No safety concern
cyclopent-2-en-1-one )
5-Ethyl-2-hydroxy-3-methyl- 0423 N )
cyclopent-2-en-1-one )
2-Hydroxy-2-cyclohexen-1-one 0424 N )
1-Methyl-2,3-cyclohexadione 0425 N )
2-Hydroxy-3,5,5-trimethyl-2- 0426 N ) No safety concern
cyclohexen-1-one )
Flavouring agent No. Specificationsa Conclusions based
on current levels
of intake
Menthol and structurally related substances
Mentholg 0427 R )
(+) neo-Menthol 0428 N,T )
Menthone 0429 N ) No safety concern
(±) Isomenthone 0430 N )
Menthyl acetate 0431 N )
Menthyl isovalerate 0432 N )
(-) Menthyl lactate 0433 N )
para-Menth-1-en-3-ol 0434 N,T ) No safety concern
Piperitone 0435 N )
(-) Menthol ethylene glycol carbonate 0443 N )
(-) Menthol 1- and 2-propylene 0444 N )
glycol carbonate )
(-) Menthone 1,2-glycerol ketal 0445 N ) No safety concern
(±) Menthone 1,2-glycerol ketal 0446 N )
Monomenthyl succinate 0447 N )
a N, new specifications prepared; O, no specifications prepared; R, existing
specifications revised; S, specifications exist, revision not considered or
not required; T, the existing, new, or revised specifications are tentative
and comments are invited
b The ADIs 'not specified' for calcium, potassium, and sodium salts of oleic acid
established at the thirty-third meeting of the Committee (Annex 1, reference 83)
were maintained.
c The evaluation of this substance was deferred, pending review of a 90-day study
of toxicity that was not available at the meeting.
d The group ADI of 0-0.5 mg/kg bw established at the twenty-third meeting (Annex 1,
reference 50) for citral, geranyl acetate, citronellol, linalool, and linalyl
acetate, expressed as citral, was maintained.
e The ADI of 0-1 mg/kg bw for (+)-carvone established at the thirty-seventh meeting
(Annex 1, reference 94) was maintained.
f The group ADI of 0-0.1 mg/kg bw for alpha-ionone and ß-ionone established at the
twenty-eighth meeting (Annex 1, reference 66) was maintained.
g An ADI of 0-4 mg/kg bw was established for menthol at the present meeting (see
section 1 of this Table).
B. Flavouring agents considered for specifications only
Flavouring agent No. Specificationsa
Saturated aliphatic acyclic branched-chain primary alcohols,
aldehydes, and acidsb
Isobutyl alcohol 0251 R
Isobutyraldehyde 0252 N
Isobutyric acid 0253 N
2-Methylbutyraldehyde 0254 N
2-Methylbutyric acid 0255 N
2-Ethylbutyraldehyde 0256 N
2-Ethylbutyric acid 0257 N
3-Methylbutyraldehyde 0258 N
Isovaleric acid 0259 N
2-Methylpentanal 0260 N,T
2-Methylvaleric acid 0261 N
3-Methylpentanoic acid 0262 N
3-Methyl-1-pentanol 0263 N
4-Methylpentanoic acid 0264 N
2-Methylhexanoic acid 0265 N
5-Methylhexanoic acid 0266 N
2-Ethyl-1-hexanol 0267 N
3,5,5-Trimethyl-1-hexanol 0268 N
3,5,5-Trimethylhexanal 0269 N
2-Methyloctanal 0270 N
4-Methyloctanoic acid 0271 N,T
3,7-Dimethyl-1-octanol 0272 N
2,6-Dimethyloctanal 0273 N
4-Methylnonanoic acid 0274 N
2-Methylundecanal 0275 N
Aliphatic lactonesb
4-Hydroxybutyric acid lactone 0219 N
(gamma-butyrolactone)
gamma-Valerolactone 0220 N
4-Hydroxy-3-pentenoic acid lactone 0221 N
5-Ethyl-3-hydroxy-4-methyl-2(5H)- 0222 N
furanone
gamma-Hexalactone 0223 N
delta-Hexalactone 0224 N
gamma-Heptalactone 0225 N
gamma-Octalactone 0226 N
4,4-Dibutyl-gamma-butyrolactone 0227 N
delta-Octalactone 0228 N
gamma-Nonalactone 0229 R
Hydroxynonanoic acid, delta-lactone 0230 N
Flavouring agent No. Specificationsa
gamma-Decalactone 0231 N
delta-Decalactone 0232 N
gamma-Undecalactone 0233 R
5-Hydroxyundecanoic acid lactone 0234 N
gamma-Dodecalactone 0235 N
delta-Dodecalactone 0236 N
6-Hydroxy-3,7-dimethyloctanoic acid 0237 N
lactone
delta-Tetradecalactone 0238 N
omega-Pentadecalactone 0239 N,T
omega-6-Hexadecenlactone 0240 N
epsilon-Decalactone 0241 N,T
epsilon-Dodecalactone 0242 N
4,5-Dimethyl-3-hydroxy-2,5- 0243 N
dihydrofuran-2-one
3-Heptyldihydro-5-methyl-2(3H)-furanone 0244 N
5-Hydroxy-2,4-decadienoic acid 0245 N
delta-lactone
5-Hydroxy-2-decenoic acid delta-lactone 0246 N
5-Hydroxy-7-decenoic acid delta-lactone 0247 N,T
5-Hydroxy-8-undecenoic acid 0248 N,T
delta-lactone
cis-4-Hydroxy(1,4-dodecenoic acid 0249 N,T
lactone (1,4-dodec-6-enolactone)
gamma-Methyldecalactone 0250 N
Mixture of 5-hydroxy-2-decenoic acid 0276 O
delta-lactone, 5-hydroxy-2-dodecenoic
acid delta-lactone, and
5-hydroxy-2-tetradecenoic acid
delta-lactone
4-Hydroxy-3-methyloctanoic acid 0437 N
gamma-lactone
5-Hydroxy-2-dodecenoic acid 0438 N
delta-lactone
a N, new specifications prepared; O, no specifications prepared;
R, existing specifications revised; T, the existing, new, or revised
specifications are tentative and comments are invited
b These substances were evaluated at the forty-ninth meeting of JECFA
in June 1997.
3. Food additives considered for specifications only
Food additive Specificationsa
Acetone (extraction solvent) R
Aluminium powder R
Calcium propionate S
Calcium sorbate R
Canthaxanthin R
Carnauba wax R
Carob bean gum R
Carotenes (algal) R
Caretenes (vegetal) R
Carthamus red R
Carthamus yellow R
Citric acid R,T
Cochineal extract R
Diacetyltartaric and fatty acid R
esters of glycerol
Dichloromethane R
Ethyl-para-hydroxybenzoate R
Ferrous gluconate R,T
Ferrous sulfate R,T
Furfuryl alcohol (flavouring agent) N
Guar gum R
Gum arabic R
Hexane R
4-Hexylresorcinol R
Isobutyl alcohol (extraction solvent) R
Methyl-para-hydroxybenzoate R
Microcrystalline cellulose R
Nitrogen R
Petroleum jelly R
Polydextroses R
Potassium sorbate R
Propan-2-ol R
Propionic acid R
Propyl-para-hydroxybenzoate R
Shellac R
Sodium sorbate O
Sorbitan monolaurate R
Sucrose esters of fatty acids R
Talc R
Tartaric, acetic, and fatty acid W
esters of glycerol, mixed
Thaumatin R,T
Xanthan gum R
a N, new specifications prepared; O, no specifications prepared;
R, existing specifications revised; S, specifications exist,
revision not considered or not required; T, the existing, new,
or revised specifications are tentative and comments are invited;
W, existing specifications withdrawn
4. Food additives considered for evaluation of national intake assessments
Substance Conclusions Recommendations to CCFAC
Benzoates Intake estimates based on GSFAa levels and range of foods Review draft GSFA additive levels for:
in which use is allowed, integrated with national data on food Category 1.6.2 Ripened cheese
consumption exceed the ADI of 0-5 mg/kg bw for mean Category 1.6.4 Processed cheese
consumers in the three countriesb that submitted such data. Category 1.6.5 Cheese analogues
In data submitted by nine countriesb, the estimated mean Category 4.2.2.3 Vegetables in
intake of consumers did not exceed the ADI. vinegar or brine
High consumers may exceed the ADI, but the available data Category 9.2.4.2 Crangon crangon
were insufficient to estimate the number of high consumers or and Crangon vulgaris
the magnitude or duration of intake at levels above the ADI. Category 9.3 Fish products,
semi-preserved
Category 10.2.1 Liquid eggs
Category 14.1.4.1 Carbonated
water-based soft drinks
Butylated hydroxyanisole Intake estimates based on GSFAa levels and range of foods Review draft GSFA additive levels for:
in which use is allowed, integrated with national data on food Category 2 Edible fats and oils
consumption, exceed the ADI of 0-0.5 mg/kg bw for mean Category 4.2.2.2 Dried vegetables
consumers in the three countriesb that submitted such data. Category 4.1.3 Cocoa products
In data submitted by 10 countriesb, the estimated mean Category 8.3.1 Processed
intake of consumers did not exceed the ADI. comminuted meat
High consumers may exceed the ADI, but the available data Category 9.2.1 Frozen fish, fillets, and
were insufficient to estimate the number of high consumers or products
the magnitude or duration of intake at levels above the ADI. Category 12.5.1 Ready-to-eat soup
and broths
Category 13.6 Food supplements
Butylated hydroxytoluene Intake estimates based on GSFAa levels and range of foods Review draft GSFA additive levels for:
in which use is allowed, integrated with national data on food Category 2 Edible fats and oils
consumption exceed the ADI of 0-0.3 mg/kg bw for mean Category 5.3 Chewing gum
consumers in the three countriesb that submitted such data. Category 9.2 Fish and fish products
In data submitted by 10 countriesb, the estimated mean and
high intake of consumers did not exceed the ADI.
Substance Conclusions Recommendations to CCFAC
Sulfites Intake estimates based on GSFAa levels and range of foods Review draft GSFA additive levels for:
in which use is allowed, integrated with national data on food Category 4.1.2.2 Dried fruits
consumption exceed the ADI of 0-0.7 mg/kg bw for mean Category 4.1.2.5 Jams, jellies, and
consumers in the three countriesb that submitted such data. marmelades
In data submitted by 10 countriesb, the estimated mean Category 4.1.2.8 Fruit preparations,
intake of consumers did not exceed the ADI. including pulp and fruit toppings
High consumers may exceed the ADI, but the available data Category 4.2.2.2 Dried vegetables
were insufficient to estimate the number of high consumers or Category 4.2.2.5 Vegetable, nut, and
the magnitude or duration of intake at levels above the ADI. seed purees and spreads
Category 11.1 White and semi-white
sugar
Category 14.1.2.3 Concentrates for
fruit juice
Categories 14.2.3 and 14.2.4 Wines,
fruit wines
tert-Butylhydroquinone Intake estimates based on GSFAa levels and range of foods Review draft GSFA additive levels for:
in which use is allowed, integrated with national data on food Category 2 Edible fats and oils
consumption exceed the ADI of 0-0.7 mg/kg bw for mean Category 9.2 Fish and fish products
consumers in the three countriesb that submitted such data. Category 14.1.4.1 Carbonated
In data submitted by six countriesb, the estimated mean water-based soft drinks
intake of consumers did not exceed the ADI.
High consumers may exceed the ADI, but the available data
were insufficient to estimate the number of high consumers or
the magnitude or duration of intake at levels above the ADI.
CCFAC, Codex Committee on Food Additives and Contaminants; GSFA, General Standard on Food Additives
a Intake estimates derived on the basis of GSFA additive levels integrated with national food consumption data result in gross overestimates
of actual intake in any one country because the GSFA levels are generally compiled by adopting the highest level of use for any one food
category submitted by member states or non-governmental organizations. The range of food uses specified in the GSFA is also usually much
wider than in national standards.
b Eleven countries made submissions: Australia, Brazil, China, Finland, France, India, Japan, New Zealand, Spain, the United Kingdom, and
the United States (two countries, Australia and New Zealand, made a joint submission).
See Also:
Toxicological Abbreviations