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WHO FOOD ADDITIVES SERIES: 50

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

Alitame

R

0–1 mg/kg bwb

Cross-linked sodium carboxy cellulose

N

Included in the group ADI ‘not specified’c with methyl other modified celluloses

Mineral oils (low- and medium-viscosity)

Class Id

R

0–10 mg/kg bw

Class IIe and Class IIIf

R

0–0.01 mg/kg bw (group ADI) (temporary)g

Nitrite

S

0–0.07 mg/kg bw (expressed as nitrite ion)

Nitrate

S

0–3.7 mg/kg bw (expressed as nitrate ion)

Salatrim (short- and long-chain acyltriglyceride molecules)

R

Adequate information was not available to evaluate safety and nutritional effects.

a

N, new specifications prepared; R, existing specifications revised; S, existing specifications were not considered.

b

ADI was established at the forty-sixth meeting (WHO Technical Report Series, No. 868, 1997). Evaluation of a 90-day study of teolerance in patients with diabetes was postponed.

c

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 that meets 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 its effect, it should not conceal food of inferior quality or adulterated food, and it should not create a nutritional imbalance.

d

Including P70(H) oil.

e

Including N70(H) and N70(A) oils.

f

Including P15(H), N15(H), and N10(A) oils

g

See Annex 3.

Food additive considered for specifications only

Food additive

Specificationsa

Amyloglucosidase from Aspergillus niger, var.

R

aR, existing specifications revised

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

A. Alicyclic primary alcohols, aldehydes, acids and related esters

Flavouring agent

No.

Specificationsa

Conclusions based on current intake

Cyclohexanecarboxylic acid

961

N

No safety concern

Methyl cyclohexanecarboxylate

962

N

No safety concern

Ethyl cyclohexanecarboxylate

963

N

No safety concern

Cyclohexaneethyl acetate

964

N

No safety concern

Cyclohexaneacetic acid

965

N

No safety concern

Ethyl cyclohexanepropionate

966

N

No safety concern

2,2,3-Trimethylcyclopent-3-en-1-yl acetaldehyde

967

N

No safety concern

cis-5-Isopropenyl-cis-2-methylcyclopentan-1-carboxaldehyde

968

N

No safety concern

Campholene acetate

969

N

No safety concern

alpha-Campholenic alcohol

970

N

No safety concern

para-Menth-1-en-9-al

971

N

No safety concern

1-para-Menthen-9-yl acetate

972

N

No safety concern

para-Mentha-1,8-dien-7-al

973

N

No safety concern

para-Mentha-1,8-dien-7-ol

974

N

No safety concern

para -Mentha-1,8-dien-7-yl acetate

975

N

No safety concern

1,2,5,6-Tetrahydrocuminic acid

976

N

No safety concern

2,6,6-Trimethylcyclohexa-1,3-dienyl methanal

977

N

No safety concern

2,6,6-Trimethyl-1-cyclohexen-1-acetaldehyde

978

N

No safety concern

2,6,6-Trimethyl-1&2-cyclohexen-1-carboxaldehyde

979

N

No safety concern

2-Formyl-6,6-dimethylbicyclo[3.1.1]hept-2-ene(Myrtenal)

980

N

No safety concern

Myrtenol

981

N

No safety concern

Myrtenyl acetate

982

N

No safety concern

6,6-Myrtenyl formate

983

N

No safety concern

Santalol (alpha and beta)

984

N

No safety concern

Santalyl acetate (alpha and beta)

985

N

No safety concern

10-Hydroxymethylene-2-pinene

986

N

No safety concern

a N, new specifications prepared

B. Phenethyl alcohol, aldehyde, acid and related acetals and esters

Flavouring agent

No.

Specificationsa

Conclusions based on current intake

Phenethyl alcohol

987

N

No safety concern

Phenethyl formate

988

N

No safety concern

Phenethyl acetate

989

N

No safety concern

Phenethyl propionate

990

N

No safety concern

Phenethyl butyrate

991

N

No safety concern

Phenethyl isobutyrate

992

N

No safety concern

Phenethyl 2-methylbutyrate

993

N

No safety concern

Phenethyl isovalerate

994

N

No safety concern

Phenethyl hexanoate

995

N

No safety concern

Phenethyl octanoate

996

N

No safety concern

Phenethyl tiglate

997

N

No safety concern

Phenethyl senecioate

998

N

No safety concern

Phenethyl phenylacetate

999

N

No safety concern

Acetaldehyde phenethyl propyl acetal

1000

N

No safety concern

Acetaldehyde butyl phenethyl acetal

1001

N

No safety concern

Phenylacetaldehyde

1002

N

No safety concern

Phenylacetaldehyde dimethyl acetal

1003

N

No safety concern

Phenylacetaldehyde glyceryl acetal

1004

N

No safety concern

Phenylacetic acid

1007

N

No safety concern

Methyl phenylacetate

1008

N

No safety concern

Ethyl phenylacetate

1009

N

No safety concern

Propyl phenylacetate

1010

N

No safety concern

Isopropyl phenylacetate

1011

N

No safety concern

Butyl phenylacetate

1012

N

No safety concern

Isobutyl phenylacetate

1013

N

No safety concern

Isoamyl phenylacetate

1014

N

No safety concern

Hexyl phenylacetate

1015

N

No safety concern

3-Hexenyl phenylacetate

1016

N

No safety concern

Octyl phenylacetate

1017

N

No safety concern

Rhodinyl phenylacetate

1018

N

No safety concern

Linalyl phenylacetate

1019

N

No safety concern

Geranyl phenylacetate

1020

N

No safety concern

Citronellyl phenylacetate

1021

N

No safety concern

Santalyl phenylacetate (alpha and beta)

1022

N

No safety concern

para-Tolylacetaldehyde

1023

N

No safety concern

para-Isopropylphenylacetaldehyde

1024

N

No safety concern

Methyl para-tert-butylphenylacetate

1025

N

No safety concern

Phenoxyacetic acid

1026

N

No safety concern

Ethyl (para-tolyloxy)acetate

1027

N

No safety concern

2-Phenoxyethyl isobutyrate

1028

N

No safety concern

Sodium 2-(4-methoxyphenoxy)propanoate

1029

N

No safety concern

a N, new specifications prepared

C. Sulfur-containing heterocyclic compounds

Flavouring agent

No.

Specificationsa

Conclusions based on current intake

Thiamine hydrochloride

1030

N

No safety concern

4-Methyl-5-thiazoleethanol

1031

N

No safety concern

Thiazole

1032

N

No safety concern

2-(1-Methylpropyl)thiazole

1033

N

No safety concern

2-Isobutylthiazole

1034

N

No safety concern

4,5-Dimethylthiazole

1035

N

No safety concern

2,4,5-Trimethylthiazole

1036

N

No safety concern

2-Isopropyl-4-methylthiazole

1037

N

No safety concern

4-Methyl-5-vinylthiazole

1038

N

No safety concern

2,4-Dimethyl-5-vinylthiazole

1039

N

No safety concern

Benzothiazole

1040

N

No safety concern

2-Acetylthiazole

1041

N

No safety concern

2-Propionylthiazole

1042

N

No safety concern

4-Methylthiazole

1043

N

No safety concern

2-Ethyl-4-methylthiazole

1044

N

No safety concern

4,5-Dimethyl-2-isobutyl-3-thiazoline

1045

N

No safety concern

2-Isobutyl-4,6-dimethyldihydro-1,3,5-dithiazine and 4-isobutyl-2,6-dimethyldihydro-1,3,5-dithiazine (mixture)

1046

N

No safety concern

2-Isopropyl-4,6-dimethyl and 4-isopropyl-2,6-dimethyldihydro-1,3,5-dithiazine (mixture)

1047

N

No safety concern

2,4,6-Triisobutyl-5,6-dihydro-4H-1,3,5-dithiazine

1048

N

No safety concern

2,4,6-Trimethyldihydro-4H-1,3,5-dithiazine

1049

N

No safety concern

5-Methyl-2-thiophenecarboxaldehyde

1050

N

No safety concern

3-Acetyl-2,5-dimethylthiophene

1051

N

No safety concern

2-Thienylmercaptan

1052

N

No safety concern

2-Thienyl disulfide

1053

N

No safety concern

2-Ethoxythiazole

1056

N

No safety concern

2-Methyl-5-methoxythiazole

1057

N

No safety concern

4,5-Dimethyl-2-ethyl-3-thiazoline

1058

N

No safety concern

2-(2-Butyl)-4,5-dimethyl-3-thiazoline

1059

N

No safety concern

a N, new specifications prepared

D. Sulfur-substituted furan derivatives

Flavouring agent

No.

Specificationsa

Conclusions based on current intake

2-Methyl-3-furanthiol

1060

N

No safety concern

2-Methyl-3-(methylthio)furan

1061

N

No safety concern

2-Methyl-5-(methylthio)furan

1062

N

No safety concern

2,5-Dimethyl-3-furanthiol

1063

N

No safety concern

Methyl 2-methyl-3-furyl disulfide

1064

N

No safety concern

Propyl 2-methyl-3-furyl disulfide

1065

N

No safety concern

Bis(2-methyl-3-furyl) disulfide

1066

N

No safety concern

Bis(2,5-dimethyl-3-furyl) disulfide

1067

N

No safety concern

Bis(2-methyl-3-furyl) tetrasulfide

1068

N

No safety concern

2-Ethanethoic acid, S-(2-methyl-3-furanyl) ester

1069

N

No safety concern

2,5-Dimethyl-3-furan thioisovalerate

1070

N

No safety concern

2,5-Dimethyl-3-thiofuroylfuran

1071

N

No safety concern

Furfuryl mercaptan

1072

N

No safety concern

S-Furfuryl thioformate

1073

N

No safety concern

S-Furfuryl thioacetate

1074

N

No safety concern

S-Furfuryl thiopropionate

1075

N

No safety concern

Furfuryl methyl sulfide

1076

N

No safety concern

Furfuryl isopropyl sulfide

1077

N

No safety concern

Methyl furfuryl disulfide

1078

N

No safety concern

Propyl furfuryl disulfide

1079

N

No safety concern

2,2'-(Thiodimethylene)difuran

1080

N

No safety concern

2,2'-(Dithiodimethylene)difuran

1081

N

No safety concern

2-Methyl-3-, 5- or 6-(furfurylthio)pyrazine

1082

N

No safety concern

S-Methyl thiofuroate

1083

N

No safety concern

4-[(2-Furanmethyl)thio]-2-pentanone

1084

N

No safety concern

3-[(2-Methyl-3-furyl)thio]-4-heptanone

1085

N

No safety concern

2,6-Dimethyl-3-[(2-methyl-3-furyl)thio]-4-heptanone

1086

N

No safety concern

4-[(2-Methyl-3-furyl)thio]-5-nonanone

1087

N

No safety concern

Ethyl 3-(furfurylthio)propionate

1088

N

No safety concern

2-Methyl-3-thioacetoxy-4,5-dihydrofuran

1089

N

No safety concern

2-Methyl-3-tetrahydrofuranthiol

1090

N

No safety concern

2,5-Dimethyl-3-tetrahydrofuranthiol, cis and trans isomers

1091

N

No safety concern

2,5-Dimethyl-3-thioacetoxy-tetrahydrofuran, cis and trans isomers

1092

N

No safety concern

a N, new specifications prepared

E. Alicyclic ketones, secondary alcohols and related esters

Flavouring agent

No.

Specificationsa

Conclusions based on current intake

3,3,5-Trimethyl cyclohexanol

1099

N

No safety concern

Cyclohexanone

1100

N

No safety concern

Cyclopentanone

1101

N

No safety concern

2-Methylcyclohexanone

1102

N

No safety concern

3-Methylcyclohexanone

1103

N

No safety concern

4-Methylcyclohexanone

1104

N

No safety concern

1-Methyl-1-cyclopenten-3-one

1105

N

No safety concern

2-Hexylidene cyclopentanone

1106

N

No safety concern

3-Methyl-2-cyclohexen-1-one

1107

N

No safety concern

2,2,6-Trimethylcyclohexanone

1108

N

No safety concern

2-sec-Butylcyclohexanone

1109

N

No safety concern

4-Isopropyl-2-cyclohexenone

1110

N

No safety concern

Tetramethylethylcyclohexenone (mixture of isomers)

1111

N

No safety concern

Isophorone

1112

N

No safety concern

3-Methyl-5-propyl-2-cyclohexen-1-one

1113

N

No safety concern

3-Methyl-2-(2-pentenyl)-2-cyclopenten-1-one

1114

N

No safety concern

Isojasmone

1115

N

No safety concern

(E)-2-(2-Octenyl)cyclopentanone

1116

N

No safety concern

2-(3,7-Dimethyl-2,6-octadienyl)cyclopentanone

1117

N

No safety concern

a N, new specifications prepared

F. Aliphatic secondary alcohols, ketones and related esters

Flavouring agent

No.

Specificationsa

Conclusions based on current intake

3-Decanone

1118

N

No safety concern

5-Methyl-5-hexen-2-one

1119

N

No safety concern

6-Methyl-5-hepten-2-one

1120

N

No safety concern

3,4,5,6-Tetrahydropseudoionone

1121

N

No safety concern

6,10-Dimethyl-5,9-undecadien-2-one

1122

N

No safety concern

2,6,10-Trimethyl-2,6,10-pentadecatrien-14-one

1123

N

No safety concern

3-Penten-2-one

1124

N

No safety concern

4-Hexen-3-one

1125

N

No safety concern

2-Hepten-4-one

1126

N

No safety concern

3-Hepten-2-one

1127

N

No safety concern

3-Octen-2-one

1128

N

No safety concern

2-Octen-4-one

1129

N

No safety concern

3-Decen-2-one

1130

N

No safety concern

4-Methyl-3-penten-2-one

1131

N

No safety concern

5-Methyl-3-hexen-2-one

1132

N

No safety concern

5-Methyl-2-hepten-4-one

1133

N

No safety concern

6-Methyl-3,5-heptadien-2-one

1134

N

No safety concern

(E)-7-Methyl-3-octen-2-one

1135

N

No safety concern

3-Nonen-2-one

1136

N

No safety concern

(E) and (Z)-4,8-Dimethyl-3,7-nonadien-2-one

1137

N

No safety concern

(E)-6-Methyl-3-hepten-2-one

1138

N

No safety concern

(E,E)-3,5-Octadien-2-one

1139

N

No safety concern

3-Octen-2-ol

1140

N

No safety concern

(E)-2-Octen-4-ol

1141

N

No safety concern

2-Pentyl butyrate

1142

N

No safety concern

(+/–)Heptan-3-yl acetate

1143

N

No safety concern

(+/–)Heptan-2-yl butyrate

1144

N

No safety concern

(+/–)Nonan-3-yl acetate

1145

N

No safety concern

2-Pentyl acetate

1146

N

No safety concern

1-Penten-3-one

1147

N

No safety concern

1-Octen-3-one

1148

N

No safety concern

2-Pentyl-1-buten-3-one

1149

N

No safety concern

1-Penten-3-ol

1150

N

No safety concern

1-Hexen-3-ol

1151

N

No safety concern

1-Octen-3-ol

1152

N

No safety concern

1-Decen-3-ol

1153

N

No safety concern

(E,R)-3,7-Dimethyl-1,5,7-octatrien-3-ol

1154

N

No safety concern

6-Undecanone

1155

N

No safety concern

2-Methylheptan-3-one

1156

N

No safety concern

a N, new specifications prepared

Flavouring agents considered for specifications only

No.

Flavouring agent

Specificationsa

111

Lauric acid

R

113

Myristic acid

R

115

Palmitic acid

R

116

Stearic acid

R

182

Isoamyl laurate

R

310

Isopropyl isovalerate

R

390

gamma-Ionone

R

455

Butyl sulfide

R

476

Ethyl 3-methylthiopropionate

R

483

Ethyl thioacetate

R

490

Allyl thiopropionate

R

492

Methylthio 2-(acetyloxy)propionate

R

493

Methylthio 2-(propionyloxy) propionate

R

540

1,6-Hexanedithiol

R

542

1,9-Nonanedithiol

R

551

2-Mercaptopropionic acid

R

553

Ethyl 3-mercaptopropionate

R

564

Dimethyl disulfide

R

566

Propyl disulfide

R

601

Ethyl 3-hydroxyhexanoate

R

602

Ethyl 3-oxohexanoate

R

606

Laevulinic acid

R

608

Butyl levulinate

R

609

1,4-Nonanediol diacetate

R

614

Diethyl malonate

R

616

Dimethyl succinate

R

617

Diethyl succinate

R

622

Diethyl tartrate

R

624

Diethyl sebacate

R

625

Dibutyl sebacate

R

626

Ethylene brassylate

R

627

Aconitic acid

R

642

3-Phenylpropyl hexanoate

R

678

alpha-Amylcinnamyl isovalerate

R

729

Dihydroxyacetophenone

R

745

5-Methylfurfural

R

752

2-Phenyl-3-carbethoxyfuran

R

814

alpha-Methylphenethyl butyrate

R

817

4-(para-Tolyl)-2-butanone

R

847

Benzyl 2,3-dimethylcrotonate

R

861

Glyceryl tribenzoate

R

862

Propylene glycol dibenzoate

S

866

Tolualdehydes (mixed ortho, meta and para)

R

870

Butyl para-hydroxybenzoate

S

872

Anisyl formate

R

910

3-Oxohexanoic acid diglyceride

R

911

3-Oxooctanoic acid glyceride

R

914

3-Oxodecanoic acid glyceride

R

915

3-Oxododecanoic acid glyceride

R

916

3-Oxotetradecanoic acid glyceride

R

917

3-Oxohexadecanoic acid glyceride

R

918

Glyceryl monostearate

R,T

919

Glyceryl monooleate

R,T

921

Glyceryl tripropanoate

S

922

Tributyrin

S

923

Glycerol 5-hydroxydecanoate

S,T

924

Glycerol 5-hydroxydodecanoate

S,T

926

Propylene glycol stearate

R

937

Pyruvaldehyde

S,T

943

Acetaldehyde ethyl cis-3-hexenyl acetal

R

954

Ethyl vanillin propylene glycol acetal

R

955

4-Hydroxybenzyl alcohol

N

956

4-Hydroxybenzaldehyde

N

957

4-Hydroxybenzoic acid

N

958

2-Hydroxybenzoic acid

N

959

4-Hydroxy-3-methoxy benzoic acid

N

960

Vanillin erythro- and threo-butan-2,3-diol acetal

N

a

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

Flavouring agents for which confirmation of flavour use was required

The Committee could not complete its evaluation of 18 substances at its fifty-seventh meeting, pending confirmation that they were in current use as flavouring agents. The Committee received information from the flavour industry on these substances, and concluded that flavour uses have been established for 16 of them. The conclusions of the Committee are summarized in the following table.

No.

Flavouring agent

Evaluation based on current intake as a flavouring agent

850

Benzoic acida

No safety concern

861

Glyceryl tribenzoate

No safety concern

862

Propylene glycol dibenzoate

No safety concern

870

Butyl-para-hydroxybenzoate

No safety concern

909

Glycerolb

Evaluation not finalized, pending definition of ‘flavouring agent’

914

3-Oxodecanoic acid glyceride

No safety concern

915

3-Oxododecanoic acid glyceride

No safety concern

916

3-Oxotetradecanoic acid glyceride

No safety concern

917

3-Oxohexadecanoic acid glyceride

No safety concern

918

Glyceryl monostearatec

No safety concern

919

Glyceryl monooleatec

No safety concern

920

Triacetind

No safety concern

921

Glyceryl tripropionate (Tripropionin)

No safety concern

922

Tributyrin

No safety concern

923

Glycerol 5-hydroxydecanoate

No safety concern

924

Glycerol 5-hydroxydodecanoate

No safety concern

925

Propylene glycole

Evaluation not finalized, pending definition of ‘flavouring agent’

926

Propylene glycol stearatef

No safety concern















    See Also:
       Toxicological Abbreviations