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Fragrance raw materials monographs
Fragrance raw matcrials monographs
925
INDOLE
Synonyms: Benzopyrrole; l-benzazole. Structure: C~,H4"NH. CH: CH. Description and physical properties: EOA Spec. no. 21. Occurrence: Reported to occur in over two dozcn essential oils including neroli oil and in the oils extracted from the flowers of Jasminum grandiftorum, bitter orange and Jasminum odoratissinium L. (Gildemeister & Hoffman, 1966). Preparation: By the reduction of indoxyl, indoxyl carboxylic acid or indigo (Bedoukian, 1967). Uses: In public use since the early 1900s. Use in fragrances in the USA amounts to about 4000 Ib/yr. Concentration in final product (o/): ,Usual Maximum
Soap 0-001 0"01
Detergent 0.0001 0"001
Creams,lotions 0.0005 0.003
Perfume 0'03 0. !
Analytical data: Gas chromatogram, RIFM no. 70-71 ; infra-red curve, RIFM no. 70-71.
Status Indole was granted GRAS status by FEMA (1965) and is approved by the FDA for food use (21 CFR 12 I. 1164). The Council of Europe (1970) included indole in the list of admissible artificial flavouring substances at a level of 1 ppm. The Food Chemicals Codex (1972) has a monograph on indole. Biological data Acute toxicity. The acute oral LDs0 value in rats was reported as 1 ml/kg (0'64-1.57 ml/ kg) (Smyth, Carpenter, Weft, Pozzani & Striegel, 1962). The single skin-penetration LD~o for rabbits was reported as 0"79 ml/kg (0"59- 1.07 ml/kg) and 8 hr was the maximum period of concentrated vapour inhalation that caused no deaths in rats (Smyth et al. 1962). Irritation. Indole was reported not to be irritating to the uncovered rabbit belly (Smyth et al. 1962). Sensitization. A maximization test (Kligman, 1966) was carried out on 25 volunteers. The material was tested at a concentration of 1% in petrolatum and produced no sensitization reactions (Kligman, 1970). Metabolism. Indole is oxidized to 3-hydroxyindole (indoxyl) which is conjugated with glucuronic and sulphuric acids before excretion. The sulphate conjugate seems to be the main product in rabbits and, even with relatively large doses of indole, the sulphate conjugation always exceeds that of glucuronic acid (Williams, 1959). References Bedoukian. P. Z. (1967). PerJi~meryand Flat~orinq Synthetics. 2nd ed., p. 192. Elsevier Publishing Co., New York. Council of Europe (1970). Natural and Artificial Flavouring Substances. Partial Agreement in the Social and Public Health Field. List A(l), Series 1, no. 562, p. 79. Strasbourg. Flavoring Extract Manufacturers' Association (1965). Survey of flavoring ingredient usage levels. No. 2593. Fd Technol., Champaign 19(2), part 2, 155. Food Chemicals Codex (1972). 2nd ed. Prepared by the Committee on Specifications, Food Chemicals Codex, of the Committee on Food Protection. p. 389. National Academy of Sciences- National Research Council Publ. 1406, Washington, D.C.
926
D . L . J . OPI)YKE
Gildcmeister, E. u. Hoffman, F. (1966). Die .'/ittTerischen Ole. Vol. Illd, p. 812. Akademie Verlag, Berlin. Kligman, A. M. (1966}. The identitication of contact allergens by human assay. III. The maximization test. A procedure for screening and rating contact scnsitizcrs. J. i,ve.st. Derm. 47, 393. Kligman, A. M. (1970). Report to RIFM, 4 January. Smyth. H. F. Jr., Carpenter, C. P,, Weil, C. S., Pozzani. U. C. & Striegcl, Jean A. (1962}. Range-finding toxicity data: List VI. Am. ind H)'g. Ass..I. 23, 95. Williams. R. T. (1959). Detoxication Mechanisms. The Metabolism and Detoxication of Dru.qs. 7bxic Substances and Other Or.qanic Compounds. 2nd cd., p. 668. Chapman & Hall Ltd., London.
925
INDOLE
Synonyms: Benzopyrrole; l-benzazole. Structure: C~,H4"NH. CH: CH. Description and physical properties: EOA Spec. no. 21. Occurrence: Reported to occur in over two dozcn essential oils including neroli oil and in the oils extracted from the flowers of Jasminum grandiftorum, bitter orange and Jasminum odoratissinium L. (Gildemeister & Hoffman, 1966). Preparation: By the reduction of indoxyl, indoxyl carboxylic acid or indigo (Bedoukian, 1967). Uses: In public use since the early 1900s. Use in fragrances in the USA amounts to about 4000 Ib/yr. Concentration in final product (o/): ,Usual Maximum
Soap 0-001 0"01
Detergent 0.0001 0"001
Creams,lotions 0.0005 0.003
Perfume 0'03 0. !
Analytical data: Gas chromatogram, RIFM no. 70-71 ; infra-red curve, RIFM no. 70-71.
Status Indole was granted GRAS status by FEMA (1965) and is approved by the FDA for food use (21 CFR 12 I. 1164). The Council of Europe (1970) included indole in the list of admissible artificial flavouring substances at a level of 1 ppm. The Food Chemicals Codex (1972) has a monograph on indole. Biological data Acute toxicity. The acute oral LDs0 value in rats was reported as 1 ml/kg (0'64-1.57 ml/ kg) (Smyth, Carpenter, Weft, Pozzani & Striegel, 1962). The single skin-penetration LD~o for rabbits was reported as 0"79 ml/kg (0"59- 1.07 ml/kg) and 8 hr was the maximum period of concentrated vapour inhalation that caused no deaths in rats (Smyth et al. 1962). Irritation. Indole was reported not to be irritating to the uncovered rabbit belly (Smyth et al. 1962). Sensitization. A maximization test (Kligman, 1966) was carried out on 25 volunteers. The material was tested at a concentration of 1% in petrolatum and produced no sensitization reactions (Kligman, 1970). Metabolism. Indole is oxidized to 3-hydroxyindole (indoxyl) which is conjugated with glucuronic and sulphuric acids before excretion. The sulphate conjugate seems to be the main product in rabbits and, even with relatively large doses of indole, the sulphate conjugation always exceeds that of glucuronic acid (Williams, 1959). References Bedoukian. P. Z. (1967). PerJi~meryand Flat~orinq Synthetics. 2nd ed., p. 192. Elsevier Publishing Co., New York. Council of Europe (1970). Natural and Artificial Flavouring Substances. Partial Agreement in the Social and Public Health Field. List A(l), Series 1, no. 562, p. 79. Strasbourg. Flavoring Extract Manufacturers' Association (1965). Survey of flavoring ingredient usage levels. No. 2593. Fd Technol., Champaign 19(2), part 2, 155. Food Chemicals Codex (1972). 2nd ed. Prepared by the Committee on Specifications, Food Chemicals Codex, of the Committee on Food Protection. p. 389. National Academy of Sciences- National Research Council Publ. 1406, Washington, D.C.
926
D . L . J . OPI)YKE
Gildcmeister, E. u. Hoffman, F. (1966). Die .'/ittTerischen Ole. Vol. Illd, p. 812. Akademie Verlag, Berlin. Kligman, A. M. (1966}. The identitication of contact allergens by human assay. III. The maximization test. A procedure for screening and rating contact scnsitizcrs. J. i,ve.st. Derm. 47, 393. Kligman, A. M. (1970). Report to RIFM, 4 January. Smyth. H. F. Jr., Carpenter, C. P,, Weil, C. S., Pozzani. U. C. & Striegcl, Jean A. (1962}. Range-finding toxicity data: List VI. Am. ind H)'g. Ass..I. 23, 95. Williams. R. T. (1959). Detoxication Mechanisms. The Metabolism and Detoxication of Dru.qs. 7bxic Substances and Other Or.qanic Compounds. 2nd cd., p. 668. Chapman & Hall Ltd., London.