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WHO FOOD ADDITIVES SERIES: 48

SAFETY EVALUATION OF CERTAIN
FOOD ADDITIVES AND CONTAMINANTS

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

Emulsifiers

   

Diacetyltartaric and fatty acid esters of glycerol

R

0-50 (temporary)b

Tartaric, acetic and fatty acid esters of glycerol, mixed

Wc

ADI withdrawnc

Quillaia extracts

R, Tb

0-5 (temporary)b

Enzyme preparation

   

Invertase from Saccharomyces cerevisiae

N

Acceptabled

Food colours

   

beta-Carotene from Blakeslea trispora

N,Tb

0-5 (group ADI )e

Curcumin

R

0-1 (temporary)b

Food salts

   

Calcium dihydrogen diphosphate

N

Included in the maximum tolerable daily intake of 70 mg/kg bw for phosphates, diphosphates, and polyphosphates

Monomagnesium phosphate

N,Tb

Sodium calcium polyphosphate

N

Trisodium diphosphate

N,Tb

Glazing agent

   

Hydrogenated poly-1-decene

R

0-6

Preservative

   

Natamycin (pimaricin)

N,Tb

0-0.3

Sweetening agent

   

D-Tagatose

S

0-80

Thickening agents

   

Carrageenan

R

ADI 'not specified'f (group ADI)g

Processed Eucheuma seaweed

R

Curdlan

R

ADI ‘not specified’f

Miscellaneous substances

   

Acetylated oxidized starch

N, Rh

ADI ‘not specified’f

alpha-Cyclodextrin

N

ADI "not specified"f

Sodium sulfate

S

ADI "not specified"f

a

N, new specifications prepared; R, existing specifications revised; S, specifications exist, revision not considered or required; T, the existing, new, or revised specifications are tentative and new information is needed; W, existing specifications withdrawn.

b

See Annex 3.

c

The ADI was withdrawn because the specifications for tartaric, acetic and fatty acid esters of glycerol, mixed, were combined with those of diacetyltartaric and fatty acid esters of glycerol under the latter name at the fifty-first meeting (WHO Technical Report Series, No. 891, 2000).

d

Invertase from Saccharomyces cerevisiae that meets the specifications developed at the present meeting was considered to be acceptable because S. cerevisiae is commonly used in the preparation of food. Its use should be limited by Good Manufacturing Practice.

e

Group ADI for beta-carotene from Blakeslea trispora and synthetic beta-carotene

f

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.

g

Group ADI for carrageenan and processed Euchema seaweed

h

The new specifications for acetylated oxidized starch were integrated into the revised specifications for modified starches.

Food additives considered for specifications only

Food additive

Specificationa

Acesulfame K (potassium salt)

R

Blackcurrant extract

R

Oxystearin

W

(+/–)-Malic acid

R

Pectins

R

Smoked flavourings

R

Tagetes extract

R

a

R, existing specifications revised; W, existing specifications withdrawn

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

Flavouring agent

No.

Specificationsa

Conclusions based on current intake

Pyrazine derivatives

2-Methylpyrazine

761

N

No safety concern

2-Ethylpyrazine

762

N

No safety concern

Propylpyrazine

763

N

No safety concern

Isopropylpyrazine

764

N

No safety concern

2,3-Dimethylpyrazine

765

N

No safety concern

2,5-Dimethylpyrazine

766

N

No safety concern

2,6-Dimethylpyrazine

767

N

No safety concern

2-Ethyl-3-methylpyrazine

768

N

No safety concern

2-Ethyl-6-methylpyrazine

769

N

No safety concern

2-Ethyl-5-methylpyrazine

770

N

No safety concern

2,3-Diethylpyrazine

771

N

No safety concern

2-Methyl-5-isopropylpyrazine

772

N

No safety concern

2-Isobutyl-3-methylpyrazine

773

N

No safety concern

2,3,5-Trimethylpyrazine

774

N

No safety concern

2-Ethyl-3,(5 or 6)-dimethylpyrazine

775

N

No safety concern

3-Ethyl-2,6-dimethylpyrazine

776

N

No safety concern

2,3-Diethyl-5-methylpyrazine

777

N

No safety concern

2,5-Diethyl-3-methylpyrazine

778

N

No safety concern

3,5-Diethyl-2-methylpyrazine

779

N

No safety concern

2,3,5,6-Tetramethylpyrazine

780

N

No safety concern

5-Methyl-6,7-dihydro-5H-cyclopentapyrazine

781

N

No safety concern

6,7-Dihydro-2,3-dimethyl-5H-cyclopentapyrazine

782

N

No safety concern

2-Isobutyl-3-methoxypyrazine

792

N

No safety concern

Acetylpyrazine

784

N

No safety concern

2-Acetyl-3-methylpyrazine

950

N

No safety concern

2-Acetyl-3-ethylpyrazine

785

N

No safety concern

2-Acetyl-3,(5 or 6)-dimethylpyrazine

786

N

No safety concern

Methoxypyrazine

787

N

No safety concern

(2,5 or 6)-Methoxy-3-methylpyrazine

788

N

No safety concern

2-Ethyl(or methyl)-(3,5 or 6)-methoxypyrazine

789

N

No safety concern

2-Methoxy-(3,5 or 6)-isopropylpyrazine

790

N

No safety concern

2-Methoxy-3-(1-methylpropyl)-pyrazine

791

N

No safety concern

(Cyclohexylmethyl)pyrazine

783

N

No safety concern

2-Methyl-3,5 or 6-ethoxypyrazine

793

N

No safety concern

2-(Mercaptomethyl)pyrazine

794

N

No safety concern

2-Pyrazinylethanethiol

795

N

No safety concern

Pyrazinylmethyl methyl sulfide

796

N

No safety concern

(3,5 or 6)-(Methylthio)-2-methylpyrazine

797

N

No safety concern

5-Methylquinoxaline

798

N

No safety concern

Pyrazine

951

N

No safety concern

5,6,7,8-Tetrahydroquinoxaline

952

N

No safety concern

Aromatic substituted secondary alcohols, ketones and related esters

alpha-Methylbenzyl alcohol

799

N

No safety concern

alpha-Methylbenzyl formate

800

N

No safety concern

alpha-Methylbenzyl acetate

801

N

No safety concern

alpha-Methylbenzyl propionate

802

N

No safety concern

alpha-Methylbenzyl butyrate

803

N

No safety concern

alpha-Methylbenzyl isobutyrate

804

N

No safety concern

para, alpha-Dimethylbenzyl alcohol

805

N

No safety concern

Acetophenone

806

N

No safety concern

4-Methylacetophenone

807

N

No safety concern

para-Isopropylacetophenone

808

N

No safety concern

2,4-Dimethylacetophenone

809

N

No safety concern

Acetanisole

810

N

No safety concern

alpha-Methylphenethyl butyrate

814

N, T

No safety concern

1-(para-Methoxyphenyl)-2-propanone

813

N

No safety concern

4-Phenyl-2-butanol

815

N

No safety concern

4-Phenyl-2-butyl acetate

816

N

No safety concern

4-(para-Tolyl)-2-butanone

817

N, T

No safety concern

4-(para-Methoxyphenyl)-2-butanone

818

N

No safety concern

4-Phenyl-3-buten-2-ol

819

N

No safety concern

4-Phenyl-3-buten-2-one

820

N

No safety concern

3-Methyl-4-phenyl-3-buten-2-one

821

N

No safety concern

1-Phenyl-1-propanol

822

N

No safety concern

alpha-Ethylbenzyl butyrate

823

N

No safety concern

Propiophenone

824

N

No safety concern

alpha-Propylphenethyl alcohol

825

N

No safety concern

1-(para-Methoxyphenyl)-1-penten-3-one

826

N

No safety concern

Ethyl benzoylacetate

834

N

No safety concern

Ethyl 2-acetyl-3-phenylpropionate

835

N

No safety concern

4-Acetal-6-t-butyl-1,1-dimethylindan

812

N

Additional data required

alpha-Isobutylphenethyl alcohol

827

N

No safety concern

4-Methyl-1-phenyl-2-pentanone

828

N

No safety concern

1-(4-Methoxyphenyl)-4-methyl-1-penten-3-one

829

N

No safety concern

3-Benzyl-4-heptanone

830

N

No safety concern

1-Phenyl-1,2-propanedione

833

N

No safety concern

Methyl beta-naphthyl ketone

811

N

No safety concern

Benzophenone

831

N

No safety concern

1,3-Diphenyl-2-propanone

832

N

No safety concern

Benzoin

836

N

No safety concern

Benzyl derivatives

Benzyl alcohol

025

R

No safety concern

Benzyl formate

841

N

No safety concern

Benzyl acetate

023

R

No safety concern

Benzyl propionate

842

N

No safety concern

Benzyl butyrate

843

N

No safety concern

Benzyl isobutyrate

844

N

No safety concern

Benzyl isovalerate

845

N

No safety concern

Benzyl trans-2-methyl-2-butenoate

846

N

No safety concern

Benzyl 2,3-dimethylcrotonate

847

N, T

No safety concern

Benzyl acetoacetate

848

N

No safety concern

Benzyl benzoate

024

R

No safety concern

Benzyl phenylacetate

849

N

No safety concern

Benzaldehyde

022

R

No safety concern

Benzaldehyde dimethyl acetal

837

N

No safety concern

Benzaldehyde glyceryl acetal

838

N

No safety concern

Benzaldehyde propylene glycol acetal

839

N

No safety concern

Benzoic acid

850

N

Evaluation not finalizedb

Methyl benzoate

851

N

No safety concern

Ethyl benzoate

852

N

No safety concern

Propyl benzoate

853

N

No safety concern

Hexyl benzoate

854

N

No safety concern

Isopropyl benzoate

855

N

No safety concern

sobutyl benzoate

856

N

No safety concern

IIsoamyl benzoate

857

N

No safety concern

cis-3-Hexenyl benzoate

858

N

No safety concern

Linalyl benzoate

859

N

No safety concern

Geranyl benzoate

860

N

No safety concern

Glyceryl tribenzoate

861

N, T

Evaluation not finalizedb

Propylene glycol dibenzoate

862

N, T

Evaluation not finalizedb

Methylbenzyl acetate (mixed ortho, meta, para)

863

N

No safety concern

para-Isopropylbenzyl alcohol

864

N

No safety concern

4-Ethylbenzaldehyde

865

N

No safety concern

Tolualdehydes (mixed ortho, meta, para)

866

N, T

No safety concern

Tolualdehyde glyceryl acetal

867

N

No safety concern

Cuminaldehyde

868

N

No safety concern

2,4-Dimethylbenzaldehyde

869

N

No safety concern

Benzyl 2-methoxyethyl acetal

840

N

No safety concern

Hydroxy- and alkoxy-substituted benzyl derivatives

4-Hydroxybenzyl alcohol

955

c

No safety concern

4-Hydroxybenzaldehyde

956

c

No safety concern

4-Hydroxybenzoic acid

957

c

No safety concern

2-Hydroxybenzoic acid

958

c

No safety concern

Butyl-para-hydroxybenzoate

870

N, T

Evaluation not finalizedb

Anisyl alcohol

871

N

No safety concern

Anisyl formate

872

N, T

No safety concern

Anisyl acetate

873

N

No safety concern

Anisyl propionate

874

N

No safety concern

Anisyl butyrate

875

N

No safety concern

Anisyl phenylacetate

876

N

No safety concern

Veratraldehyde

877

N

No safety concern

para-Methoxybenzaldehyde

878

N

No safety concern

para-Ethoxybenzaldehyde

879

N

No safety concern

Methyl ortho-methoxybenzoate

880

N

No safety concern

2-Methoxybenzoic acid

881

N

No safety concern

3-Methoxybenzoic acid

882

N

No safety concern

4-Methoxybenzoic acid

883

N

No safety concern

Methyl anisate

884

N

No safety concern

Ethyl para-anisate

885

N

No safety concern

Vanillyl alcohol

886

N

No safety concern

Vanillin

889

N

No safety concern

4-Hydroxy-3-methoxybenzoic acid

959

c

No safety concern

Vanillin acetate

890

N

No safety concern

Vanillin isobutyrate

891

N

No safety concern

Salicylaldehyde

897

N

No safety concern

2-Hydroxy-4-methylbenzaldehyde

898

N

No safety concern

Methyl salicylate

899

N

No safety concern

Ethyl salicylate

900

N

No safety concern

Butyl salicylate

901

N

No safety concern

Isobutyl salicylate

902

N

No safety concern

Isoamyl salicylate

903

N

No safety concern

Benzyl salicylate

904

N

No safety concern

Phenethyl salicylate

905

N

No safety concern

ortho-Tolyl salicylate

907

N

No safety concern

2,4-Dihydroxybenzoic acid

908

N

No safety concern

Vanillyl ethyl ether

887

N

No safety concern

Vanillyl butyl ether

888

N

No safety concern

Ethyl vanillin

893

N

No safety concern

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

960

c

No safety concern

Ethyl vanillin isobutyrate

953

N

No safety concern

Ethyl vanillin propylene glycol acetal

954

N, T

No safety concern

Piperonyl acetate

894

N

No safety concern

Piperonyl isobutyrate

895

N

No safety concern

Piperonal

896

N

No safety concern

Ethyl vanillin-d-glucopyranoside

892

N

No safety concern

Aliphatic acyclic diols, triols, and related agents

Glycerol

909

N, T

Evaluation not finalizedb

1,2,3-tris[(1-Ethoxy)ethoxy]propane

913

N

No safety concern

3-Oxohexadecanoic acid glyceride

917

N, T

Evaluation not finalizedb

Glycerol monostearate

918

N, T

Evaluation not finalizedb

Glyceryl monooleate

919

N, T

Evaluation not finalizedb

Triacetin

920

N, T

Evaluation not finalizedb

Glyceryl tripropionate

921

N, T

Evaluation not finalizedb

Tributyrin

922

N, T

Evaluation not finalizedb

Glycerol 5-hydroxydecanoate

923

N, T

Evaluation not finalizedb

Glycerol 5-hydroxydodecanoate

924

N, T

Evaluation not finalizedb

Propylene glycol

925

N, T

Evaluation not finalizedb

Propylene glycol stearate

926

N, T

Evaluation not finalizedb

1,2-Di[(1-ethoxy)ethoxy]propane

927

N

No safety concern

Lactic acid

930

N

No safety concern

Ethyl lactate

931

N

No safety concern

Butyl lactate

932

N

No safety concern

Potassium 2-(1’-ethoxy)ethoxypropanoate

933

N

No safety concern

cis-3-Hexenyl lactate

934

N

No safety concern

Butyl butyryllactate

935

N

No safety concern

Pyruvic acid

936

N

No safety concern

Pyruvaldehyde

937

N, T

No safety concern

Ethyl pyruvate

938

N

No safety concern

Isoamyl pyruvate

939

N

No safety concern

3-Oxohexanoic acid glyceride

910

N, T

No safety concern

3-Oxooctanoic acid glyceride

911

N, T

No safety concern

Heptanal glyceryl acetal (mixed 1,2 and 1,3 acetals)

912

N

No safety concern

3-Oxodecanoic acid glyceride

914

N, T

Evaluation not finalizedb

3-Oxododecanoic acid glyceride

915

N, T

Evaluation not finalizedb

3-Oxotetradecanoic acid glyceride

916

N, T

Evaluation not finalizedb

4-Methyl-2-pentyl-1,3-dioxolane

928

N

No safety concern

2,2,4-Trimethyl-1,3-oxacyclopentane

929

N

No safety concern

Aliphatic acyclic acetals

1,1-Dimethoxyethane

940

N

No safety concern

Acetal

941

N

No safety concern

Heptanal dimethyl acetal

947

N

No safety concern

4-Heptenal diethyl acetal

949

N

No safety concern

Octanal dimethyl acetal

942

N

No safety concern

2,6-Nonadienal diethyl acetal

946

N

No safety concern

Decanal dimethyl acetal

945

N

No safety concern

Citral dimethyl acetal

944

N

No safety concern

Citral diethyl acetal

948

N

No safety concern

Acetaldehyde ethyl cis-3-hexenyl acetal

943

N, T

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 needed

b

Further information is required to determine whether this substance is currently used as a flavouring agent.

c

Specifications will be considered at the fifty-ninth meeting of the Committee.

Flavouring agents considered for specifications only

No.

Flavouring agent

Specificationsa

10

Allyl tiglate

R

12

Allyl cyclohexane acetate

R

14

Allyl cyclohexane butyrate

R

15

Allyl cyclohexane valerate

R

16

Allyl cyclohexane hexanoate

R

22

Benzaldehyde

R

23

Benzyl acetate

R

24

Benzyl benzoate

R

25

Benzyl alcohol

R

42

Isoamyl formate

R

51

Isoamyl 2-methyl butyrate

R

58

Geranyl acetate

R

64

Rhodinyl propionate

R

70

Geranyl hexanoate

R

72

Geranyl isobutyrate

R

74

Rhodinly isobutyrate

R

77

Rhodinyl isovalerate

R

78

3,7-Dimethyl-2,6-octadien-1-yl-2-ethyl butanoate

R

95

Heptanal

R

101

Nonanal

R

107

Undecanal

R

111

Lauric acid

R,T

113

Myristic acid

R,T

115

Palmitic acid

R,T

116

Stearic acid

R,T

117

Propyl formate

R

119

n-Amyl formate

R

124

Isobutyl formate

R

170

n-Amyl heptanoate

R

172

Isobutyl heptanoate

R

178

Nonyl octantoate

R

180

Methyl laurate

R

182

Isoamyl laurate

R,T

184

Butyl stearate

R

191

trans-3-Heptenyl-2-methyl propanoate

R

205

Methyl 2-methylbutyrate

R

212

2-Methylbutyl 2-methylbutyrate

R

240

omega-6-Hexadecene lactone

R

249

cis-4-Hydroxy-6-dodecenoic acid lactone

R

260

2-Methylpentanal

R

265

2-Methylhexanoic acid

R

266

5-Methylhexanoic acid

R

270

2-Methyloctanal

R

273

2,6-Dimethyloctanal

R

275

2-Methylundecanal

R

304

Isopropyl formate

R

306

Isopropyl propionate

R

308

Isopropyl hexanoate

R

322

cis-5-Octen-1-ol

R

323

cis-5-Octenal

R

325

cis-6-Nonenal

R

326

4-Decenal

R

328

9-Decenoic acid

R

330

10-Undecenal

R

334

Methyl 3-hexenoate

R

344

Butyl 10-undecenoate

R

347

2-Methyl-3-pentenoic acid

R

348

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

R

350

Ethyl 2-methyl-3-pentenoate

R

352

Hexyl 2-methyl-3&4-pentenoate (mixture)

R

367

Terpinyl formate

R

370

Terpinyl butyrate

R

372

Terpinyl isovalerate

R

374

para-Menth-8-en-1-ol

R

388

alpha-Ionone

R

390

gamma-Ionone

R,T

401

Allyl-alpha-ionone

R

404

alpha-iso-Methylionone

R

416

5-Hydroxy-4-octanone

R

424

2-Hydroxy-2-cyclohexen-1-one

R

428

d-neo-Menthol

R

434

para-Menth-1-en-3-ol

R

440

2-Ethyl-1,3,3-trimethyl-2-norbornanol

R

442

Methyl 1-acetoxycyclohexyl ketone

R

448

1-Ethylhexyl tiglate

R

457

(1-Buten-1-yl) methyl sulfide

R

461

3-(Methylthio)propanol

R

478

3-(Methylthio)propyl acetate

R

490

Allyl thiopropionate

R,T

510

2-Propanethiol

R

531

2-Naphthalenethiol

R

543

Trithioacetone

R

562

2,5-Dimethyl-2,5-dihydroxy-1,4-dithiane

R

580

2-Methyl-2-(methyldithio)propanal

R

581

Ethyl 2-(methyldithio)propionate

R

591

Methyl 2-oxo-3-methyl-pentanoate

R

599

Geranyl acetoacetate

R

604

3-(Hydroxymethyl)-2-heptanone

R, T

609

1,4-Nonanediol diacetate

R,T

627

Aconitic acid

R,T

642

3-Phenylpropyl hexanoate

R,T

645

3-Phenylpropionaldehyde

R

648

Cinnamaldehyde ethylene glycol acetal

R

652

Cinnamyl butyrate

R

656

Cinnamaldehyde

R

660

Propyl cinnamate

R

663

Butyl cinnamate

R

666

Heptyl cinnamate

R

671

Phenethyl cinnamate

R

672

3-Phenylpropyl cinnamate

R

673

Cinnamyl cinnamate

R

676

alpha-Amylcinnamyl formate

R

677

alpha-Amylcinnamyl acetate

R

678

alpha-Amylcinnamyl isovalerate

R,T

681

alpha-Amylcinnamaldehyde dimethyl acetal

R

698

ortho-Tolyl acetate

R

711

para-Vinylphenol

R

719

Guaiacyl phenylacetate

R

720

Hydroquinone monoethyl ether

R

723

4-Ethyl-2,6-dimethoxyphenol

R

724

4-Propyl-2,6-dimethoxyphenol

R

726

4-Allyl-2,6-dimethoxyphenol

R

729

Dihydroxyacetophenone

R,T

732

Vanillylidene acetone

R

740

Furfuryl propionate

R

741

Furfuryl pentanoate

R

742

Furfuryl octanoate

R

743

Furfuryl 3-methylbutanoate

R

748

Amyl 2-furoate

R

749

Hexyl 2-furoate

R

750

Octyl 2-furoate

R

752

2-Phenyl-3-carboethoxyfuran

R,T

759

Furfuryl butyrate

R

760

Cinnamyl benzoate

R

a

R, existing specifications revised; S, specifications exist, revision not required; T, the existing, new or revised specifications are tentative and new information is required.

Contaminants

Contaminant

Tolerable intake and other toxicological recommendations

3-Chloro-1,2-propanediol

Provisional maximum tolerable daily intake (PMTDI): 2 µg/kg bw

1,3-Dichloro-2-propanol

Establishment of a tolerable intake was considered inappropriate because of the nature of toxicity (tumorigenic in various organs in rats and can interact with chromosomes and/or DNA). The Committee noted that the dose that caused tumours in rats (19 mg/kg bw per day) was about 20 000 times the highest estimated intake of 1,3-dichloro-2-propanol by consumers of soya sauce (1 µg/kg bw per day).

Polychlorinated dibenzodioxins, polychlorinated dibenzofurans, and dioxin-like polychlorinated biphenyls

Provisional tolerable monthly intake (PTMI): 70 pg/kg bw

 

















    See Also:
       Toxicological Abbreviations