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WHO FOOD ADDITIVES SERIES: 52

ANNEX 4

ACCEPTABLE DAILY INTAKES, OTHER TOXICOLOGICAL INFORMATION,
AND INFORMATION ON SPECIFICATIONS

Food additives evaluated toxicologically

Food additive

Specificationsa

Acceptable daily intake (ADI in mg/kg bw) and other toxicological recommendations

alpha-Amylase from Bacillus licheniformis containing a genetically engineered alpha-amylase gene from B. licheniformis

N

ADI "not specified"d

Annatto extract (solvent-extracted bixin)"Annatto B"b

R, T

0-7 (temporary); for preparations containing not less than 85% pigment (as bixin, of which not more than 2.5% is norbixin)c

Annatto extract (solvent-extracted norbixin)"Annatto C"

R, T

0-0.4 (temporary); for preparations containing not less than 85% pigment (as norbixin)c

Annatto extract (oil-processed bixin suspension)"Annatto D"

R, T

No ADI established, since no data on toxicity were available

Annatto extract (aqueous-processed bixin)"Annatto E"

R, T

0-4 (temporary); for a preparations containing not less than 25% pigment (as bixin, of which not more than 7% is nor bixin)c

Annatto extract (alkali-processed norbixin)"Annatto F"

R, T

0-0.4 (temporary); for a preparation containing not less than 35% pigment (as norbixin)c

Annatto extract (alkali-processed norbixin, not acid-precipitated) "Annatto G"

R, T

No ADI established, since no data on toxicity were available

Curcumin

R

0-3

Diacetyltartaric and fatty acid esters of glycerol

0-50

D-Tagatose

R

0-125 (temporary)

Laccase from Myceliophthora thermophila expressed in Aspergillus oryzae

N

ADI "not specifiedd"

Mixed xylanase, beta-glucanase enzyme preparation, produced by a strain of Humicola insolens

N

ADI "not specifiedd"

Neotame

N

0-2

Polyvinyl alcohol

N

0-50

Quillaia extract (type 1)e

R

0-5

Quillaia extract (type 2)e

N

No ADI established owing to limited information on the qualitative and quantitative composition

Xylanase from Thermomyces lanuginosus expressed in Fusarium venenatum

N

ADI "not specified"d

a

N: new specifications prepared; R: existing specifications revised; T: tentative specifications

b

To ensure clarity of the text, the Committee adopted for this report the designations B, C, D, E, F, G, as employed in the submitted information, to refer to the different extracts under evaluation

c

The ADI is established for the extract as tested biologically and specified. It is not expressed in relation to content of bixin and/or norbixin

d

ADI "not specified" is used to refer to a food substance of very low toxicity which, on the basis of the available data (chemical, biochemical, toxicological and other) and the total dietary intake of the substance arising from its use at the levels necessary to achieve the desired effects and from its acceptable background levels in food, does not, in the opinion of the Committee, represent a hazard to health. For that reason, and for the reasons stated in the individual evaluations, the establishment of an ADI expressed in numerical form is not deemed necessary. An additive meeting this criterion must be used within the bounds of good manufacturing practice, i.e. it should be technologically efficacious and should be used at the lowest level necessary to achieve this effect, it should not conceal food of inferior quality or adulterated food, and it should not create a nutritional imbalance

e

Quillaia extract (type 1): saponin content of 20-26%; quillaia extract (type 2): saponin content of 75-90%

Food Additives considered for specifications only

Food additive

Specificationsa

beta-Carotene from Blakeslea trispora

R

Magnesium silicate

R

Monomagnesium phosphate

S, T

Natamycin

R

Sucrose esters of fatty acids

R

Talc

R

Trisodium diphosphate

R, T

a

R: existing specifications revised; S: specifications maintained (revision considered but not required); T: the existing specifications are tentative, information required

Flavouring agents evaluated by the Procedure for the Safety Evaluation of Flavouring Agents

A. Alicyclic, alicyclic-fused and aromatic-fused ring lactones

Flavouring agent

No.

Specificationsa

Conclusion based on current intake

4-Hydroxy-4-methyl-5-hexenoic acid gamma-lactone

1157

N

No safety concern

(+/-) 3-Methyl-gamma-decalactone

1158

N

No safety concern

4-Hydroxy-4-methyl-7-cis-decenoic acid gamma-lactone

1159

N

No safety concern

Tuberose lactone

1160

N

No safety concern

Dihydromintlactone

1161

N

No safety concern

Mintlactone

1162

N

No safety concern

Dehydromenthofurolactone

1163

N

No safety concern

(+/-)-(2,6,6-Trimethyl-2-hydroxycyclohexylidene)acetic acid gamma-lactone

1164

N

No safety concern

Sclareolide

1165

N

No safety concern

Octahydrocoumarin

1166

N

No safety concern

2-(4-Methyl-2-hydroxyphenyl) propionic acid gamma-lactone

1167

N

No safety concern

3-Propylidenephthalide

1168

N

No safety concern

3-n-Butylphthalide

1169

N

No safety concern

3-Butylidenephthalide

1170

N

No safety concern

Dihydrocoumarin

1171

R

No safety concern

6-Methylcoumarin

1172

N

No safety concern

a

N: new specifications prepared; R: revised specifications

B. Aliphatic di- and trienals and related alcohols, acids, and esters

Flavouring agent

No.

Specificationsa

Conclusion based on current intake

2,4-Pentadienal

1173

N

No safety concern

(E,E)-2,4-Hexadien-1-ol

1174

N

No safety concern

trans,trans-2,4-Hexadienal

1175

N

No safety concern

(E,E)-2,4-Hexadienoic acid

1176

N

See footnoteb

Methyl sorbate

1177

N

No safety concern

Ethyl sorbate

1178

N

No safety concern

2,4-Heptadienal

1179

N

No safety concern

(E,E)-2,4-Octadien-1-ol

1180

N

No safety concern

trans,trans-2,4-Octadienal

1181

N

No safety concern

2-trans,6-trans-Octadienal

1182

N

No safety concern

2,4-Nonadien-1-ol

1183

N

No safety concern

2,6-Nonadien-1-ol

1184

N

No safety concern

2,4-Nonadienal

1185

N

No safety concern

Nona-2-trans-6-cis-dienal

1186

N

No safety concern

2-trans-6-trans-Nonadienal

1187

N

No safety concern

(E,Z)-2,6-Nonadien-1-ol acetate

1188

N

No safety concern

(E,E)-2,4-Decadien-1-ol

1189

N

No safety concern

2-trans,4-trans-Decadienal

1190

N

No safety concern

Methyl (E)-2-(Z)-4-decadienoate

1191

N

No safety concern

Ethyl trans-2-cis-4-decadienoate

1192

N

No safety concern

Ethyl 2,4,7-decatrienoate

1193

N

No safety concern

Propyl 2,4-decadienoate

1194

N

No safety concern

2,4-Undecadienal

1195

N

No safety concern

trans,trans-2,4-Dodecadienal

1196

N

No safety concern

2-trans-6-cis-Dodecadienal

1197

N

No safety concern

2-trans-4-cis-7-cis-Tridecatrienal

1198

N

No safety concern

a

N, new specifications prepared

b

An ADI of 0-25mg/kg bw was established at the seventeenth meeting. The ADI was maintained and the use of the chemical as a flavouring agent subsumed in the ADI. R: existing specifications revised

C. Aliphatic branched-chain unsaturated alcohols, aldehydes, acids and related esters

Flavouring agent

No.

Specificationsa

Conclusion based on current intake

(+/-) 2-Methyl-1-butanol

1199

N

No safety concern

3-Methyl-2-buten-1-ol

1200

N

No safety concern

2-Methyl-2-butenal

1201

N

No safety concern

3-Methyl-2-butenal

1202

N

No safety concern

Ammonium isovalerate

1203

N

No safety concern

3-Methylcrotonic acid

1204

N

No safety concern

trans-2-Methyl-2-butenoic acid

1205

N,T

No safety concern

Isobutyl 2-butenoate

1206

N

No safety concern

2-Methylallyl butyrate

1207

N

No safety concern

4-Methyl-2-pentenal

1208

N

No safety concern

2-Methyl-2-pentenal

1209

N

No safety concern

2-Methyl-2-pentenoic acid

1210

N

No safety concern

2,4-Dimethyl-2-pentenoic acid

1211

N

No safety concern

2-Methylheptanoic acid

1212

N

No safety concern

Isobutyl angelate

1213

N

No safety concern

2-Butyl-2-butenal

1214

N

No safety concern

2-Isopropyl-5-methyl-2-hexenal

1215

N

No safety concern

2-Ethyl-2-heptenal

1216

N

No safety concern

2-Methyl-2-octenal

1217

N

No safety concern

4-Ethyloctanoic acid

1218

N,T

No safety concern

dl-Citronellol

1219

R

See footnoteb

Citronellal

1220

N

No safety concern

3,7-Dimethyl-6-octenoic acid

1221

N

No safety concern

Rhodinol

1222

N

No safety concern

Geraniol

1223

N

No safety concern

Nerol

1224

N

No safety concern

Citral

1225

R

See footnoteb

8-Ocimenyl acetate

1226

N

No safety concern

2,6-Dimethyl-10-methylene-2,6,11-dodecatrienal

1227

N

No safety concern

3,7,11 -Trimethyl-2,6,10-dodecatrienal

1228

N

No safety concern

12-Methyltridecanal

1229

N

No safety concern

Farnesol

1230

N

No safety concern

a

N: new specifications prepared; R: existing specifications revised; T: the existing, new or revised specifications are tentative and new information is required

b

A group ADI of 0-0.5 mg/kg bw expressed as citral, was established for citral, citronellol, geranyl acetate, linalool and linalyl acetate at the twenty-third meeting. The ADI was maintained and the use of the chemical as a flavouring agent subsumed in the ADI

D. Aliphatic and aromatic ethers

Flavouring agent

No.

Specificationsa

Conclusion based on current intake

sec-Butyl ethyl ether

1231

N

No safety concern

1 -Ethoxy-3-methyl-2-butene

1232

N

No safety concern

1,4-Cineole

1233

N

No safety concern

Eucalyptol

1234

N

No safety concern

Nerol oxide

1235

N

No safety concern

2,2,6-Trimethyl-6-vinyltetrahydropyran

1236

N

No safety concern

Tetrahydro-4-methyl-2-(2-methylpropen-1-yl) pyran

1237

N

No safety concern

Theaspirane

1238

N

No safety concern

Cycloionone

1239

N

No safety concern

1,5,5,9-Tetramethyl-13-oxatricyclo (8.3.0.0(4,9)) tridecane

1240

N

No safety concern

Anisole

1241

N

No safety concern

o-Methylanisole

1242

N

No safety concern

p-Methyl anisole

1243

N

No safety concern

p-Propylanisole

1244

N

No safety concern

2,4-Dimethylanisole

1245

N

No safety concern

1-Methyl-3-methoxy-4-isopropyl benzene

1246

N

No safety concern

Carvacryl ethyl ether

1247

N

No safety concern

1,2-Dimethoxybenzene

1248

N

No safety concern

m-Dimethoxybenzene

1249

N

No safety concern

p-Dimethoxybenzene

1250

N

No safety concern

3,4-Dimethoxy-1 -vinylbenzene

1251

N

No safety concern

Benzyl ethyl ether

1252

N

No safety concern

Benzyl butyl ether

1253

R

No safety concern

Methyl phenethyl ether

1254

N

No safety concern

Diphenyl ether

1255

N

No safety concern

Dibenzyl ether

1256

R

No safety concern

beta-Naphthyl methyl ether

1257

N

No safety concern

beta-Naphthyl ethyl ether

1258

N

No safety concern

beta-Naphthyl isobutyl ether

1259

N

No safety concern

a

N: new specifications prepared; R: revised specifications

E. Hydropropenylbenzenes

Flavouring agent

No.

Specificationsa

Conclusions based on current intake

Isoeugenol

1260

N

No safety concern

Isoeugenyl formate

1261

N

No safety concern

Isoeugenyl acetate

1262

N

No safety concern

Isoeugenyl phenylacetate

1263

N,T

No safety concern

Propenylguaethol

1264

N

No safety concern

4-Propenyl-2,6-dimethoxyphenol

1265

N

No safety concern

Isoeugenyl methyl ether

1266

N

No safety concern

Isoeugenyl ethyl ether

1267

N

No safety concern

Isoeugenyl benzyl ether

1268

N

No safety concern

a

N, new specifications prepared; T, T, the existing, new or revised specifications are tentative and new information is required

F. Linear and branched-chain aliphatic unsaturated, unconjugated alcohols, aldehydes, acids and related esters

Flavouring agent

No.

Specificationsa

Conclusion based on current intake

Isoprenyl acetate

1269

N

No safety concern

4-Pentenyl acetate

1270

N

No safety concern

3-Hexenal

1271

N

No safety concern

3-Hexenyl formate

1272

N

No safety concern

Ethyl 5-hexenoate

1273

N,T

No safety concern

cis-3-Hexenyl propionate

1274

N

No safety concern

cis-3-Hexenyl isobutyrate

1275

N

No safety concern

(Z)-3-Hexenyl (E)-2-butenoate

1276

N

No safety concern

cis-3-Hexenyl tiglate

1277

N

No safety concern

cis-3-Hexenyl valerate

1278

N

No safety concern

3-Hexenyl 2-hexenoate

1279

N

No safety concern

(Z)-4-Hepten-1-ol

1280

N

No safety concern

Ethyl cis-4-heptenoate

1281

N

No safety concern

(Z)-5-Octenyl propionate

1282

N

No safety concern

(Z,Z) -3,6-Nonadien-1-ol

1283

N

No safety concern

(E)-3,(Z)-6-Nonadien-1-ol

1284

N

No safety concern

(E,Z)-3,6-Nonadien-1-ol acetate

1285

N

No safety concern

9-Decenal

1286

N

No safety concern

4-Decenoic acid

1287

N

No safety concern

cis-4-Decenyl acetate

1288

N

No safety concern

a

N, new specifications prepared; T, the existing, new or revised specifications are tentative and new information is required

G. Simple aliphatic and aromatic sulfides and thiols

Flavouring agent

No.

Specificationsa

Conclusion based on current intake

erythro and threo-3-Mercapto-2-methylbutan-1-ol

1289

N

No safety concern

(+/-)2-Mercapto-2-methylpentan-1-ol

1290

N

No safety concern

3-Mercapto-2-methylpentan-1-ol (racemic)

1291

N,T

No safety concern

3-Mercapto-2-methylpentanal

1292

N

No safety concern

4-Mercapto-4-methyl-2-pentanone

1293

N

No safety concern

(+/-) Ethyl 3-mercaptobutyrate

1294

N

No safety concern

Ethyl 4-(acetylthio)butyrate

1295

N

No safety concern

spiro(2,4-Dithia-1-methyl-8-oxabicyclo(3.3.0) octane-3,3'-(1'-oxa-2'-methyl)-cyclopentane)

1296

N,T

No safety concern

2-(Methylthio)ethanol

1297

N

No safety concern

Ethyl 5-(methylthio)valerate

1298

N

No safety concern

2,3,5-Trithiahexane

1299

N

No safety concern

Diisopropyl trisulfide

1300

N

No safety concern

a

N, new specifications prepared; T, the existing, new or revised specifications are tentative and new information is required

Flavouring agents considered for specifications only

No.

Flavouring agent

Specificationsa

No.

Flavouring agent

Specificationsa

42

Isoamyl formate

R

170

n-Amyl heptanoate

R

53

Citronellyl formate

R,T

180

Methyl laurate

R

54

Geranyl formate

R

205

Methyl 2-methylbutyrate

R

55

Neryl formate

R,T

212

2-Methylbutyl 2-methylbutyrate

R

56

Rhodinyl formate

R

57

Citronellyl acetate

R

237

6-Hydroxy-3,7-dimethyloctanoic acid lactone

R

60

Rhodinyl acetate

R

61

Citronellyl propionate

R

62

Geranyl propionate

R

244

3-Heptyldihydro-5-methyl-2(3H)-furanone

R

65

Citronellyl butyrate

R

66

Geranyl butyrate

R

272

3,7-Dimethyl-1-octanol

R

68

Rhodinyl butyrate

R,T

302

2,6-Dimethyl-4-heptanone

R

71

Citronellyl isobutyrate

R

303

2,6-Dimethyl-4-heptanol

R

73

Neryl isobutyrate

R

322

cis-5-Octen-1-ol

R

95

Heptanal

R

323

cis-5-Octenal

R

98

Octanal

R

325

cis-6-NonenalR

R

101

Nonanal

R

329

9-Undecenal

R

104

Decanal

R

332

Linoleic and linolenic acid (mixture)

R

107

Undecanal

R

110

Lauric aldehyde

R

337

Methyl cis-4-octenoateR

R

112

Myristaldehyde

R

338

Ethyl cis-4-octenoateR

R

117

Propyl formate

R

346

Methyl linoleate & Methyl linolenate (mixture)

R

119

n-Amyl formate

R

124

Isobutyl formate

R

348

2,6-Dimethyl-6-hepten-1-ol

R

349

2,6-Dimethyl-5-heptenal

R

556

3-Mercaptohexyl hexanoate

R

358

Linalyl formate

R

360

Linalyl propionate

R

557

1-Mercapto-2-propanone

R,T

384

beta-Damascone

R

559

2-Keto-4-butanethiol

R

385

alpha-Damascone

R

568

Allyl methyl disulfide

R

396

Dehydrodihydroionone

R

569

Methyl 1-propenyl disulfide

R

397

Dehydrodihydroionol

R

570

Propenyl propyl disulfide

R,T

399

Methyl-beta-ionone

R,T

571

Methyl 3-methyl-1-butenyl disulfide

R

409

3-Hydroxy-2-pentanone

R

410

2,3-Pentadione

R

583

Methyl ethyl trisulfide

R

417

2,3-Undecadione

R

586

Allyl methyl trisulfide

R

419

Ethylcyclo-pentenolone

R

590

Methyl 2-hydroxy-4-methylpentanoate

R

592

Citronelloxyacetaldehyde

R

422

3-Ethyl-2-hydroxy-4-methylcyclopent-2-en-1-one

R

603

Ethyl 2,4-dioxohexanoate

R

423

5-Ethyl-2-hydroxy-3-methylcyclopent-2-en-1-one

R

604

3-(Hydroxymethyl)-2-heptanone

R

435

Piperitone

R

605

1,3-Nonanediol acetate (mixed esters)

R,T

443

l-Menthol ethylene glycol carbonate

R

615

Butyl ethyl malonate

R,T

625

Dibutyl sebacate

R

465

2-Methylthioacetaldehyde

R

628

Ethyl aconitate (mixed esters)

R,T

468

4-(Methylthio)butanal

R

470

2-(Methylthio)methyl-2-butenal

R

631.2

3-Methyl-2-oxobutanoic acid, sodium salt

R,T

471

2,8-Dithianon-4-ene-4-carboxaldehyde

R,T

632.2

3-Methyl-2-oxopentanoic acid, sodium salt

R,T

473

Methylthiomethyl butyrate

R

633.2

4-Methyl-2-oxopentanoic acid, sodium salt

R,T

479

Methyl thiomethyl hexanoate

R

668

Linalyl cinnamate

R

480

Ethyl 3-(methylthio) butyrate

R

669

Terpinyl cinnamate

R

704

p-Tolyl laurate

R

488

S-Methyl 4-methylpentanethioate

R

735

2-Phenylphenol

R

737

2,3,6-Trimethylphenol

R

489

S-Methyl hexanethioate

R

918

Glyceryl monostearate

R

495

1 -Methylthio-2-propanone

R

923

Glycerol 5-hydroxydecanoate

R

502

Di(butan-3-one-1-yl)sulfide

R

504

S-Methyl benzothioate

R,T

924

Glycerol 5-hydroxydodecanoate

R

519

2-Ethylhexanethiol

R

937

Pyruvaldehyde

R

548

4-Methoxy-2-methyl-2-butanethiol

R

a

R, existing specifications revised; S, existing specifications were maintained; T, the existing, new, or revised specifications are tentative and new information is required

Evaluation of a water-treatment agent

Agent

Specificationsa

Tolerable daily intake (TDI) and other toxicological recommendations

Sodium dichloroisocyanurate (NaDCC)

N

0-2.0 mg/kgbw for anhydrous NaDCC; applicable for intake from drinking-water treated with NaDCC for the purpose of disinfection

a N, new specifications prepared

Evaluation of a nutritional source of iron

Source

Specificationsa

Toxicological recommendation

Ferrous glycinate (processed with citric acid)

N

Suitable for use as a source of iron for supplementation and fortification, providing that the total intake of iron does not exceed the provisional maximum tolerable daily intake of 0.8mg/kg bwper day

a N, new specifications prepared

Contaminants

Contaminant

Tolerable intake and other toxicological recommendations

Cadmium

Provisional tolerable weekly intake (PTWI) of 7g/kg bw (maintained)

Methylmercury

Provisional tolerable weekly intake (PTWI) of 1.6g/kgbw












    See Also:
       Toxicological Abbreviations