A toxicologic and dermatologic assessment of cinnamyl phenylpropyl materials when used as fragrance ingredients

Food and Chemical Toxicology

Volumn 49, Issue SUPPL. 2, 2011, Pages

  Belsito, D ^a   Bickers, D ^a   Bruze, M ^b   Calow, P ^c   Dagli, M ^d   Fryer, A D ^e   Greim, H ^f   Miyachi, Y ^g   Saurat, J H ^h   Sipes, I G ⁱ  

^a NewYork Presbyterian Hospital   (United States)

^b LUND UNIVERSITY HOSPITAL   (Sweden)

^c Science and Public Policy   (United States)

^d UNIVERSITY OF SÃO PAULO   (Brazil)

^e OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^f TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^g KYOTO UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^h UNIVERSITY OF GENEVA   (Switzerland)

ⁱ UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

Author keywords

Cinnamyl phenylpropyl; Fragrance ingredients; Review; Safety

Indexed keywords

3 PHENYL 1 PROPANOL; 3 PHENYLPROPYL CINNAMATE; 3 PHENYLPROPYL FORMATE; 3 PHENYLPROPYL ISOBUTYRATE; 3 PHENYLPROPYL PROPIONATE; CINNAMYL PHENYLPROPYL; FRAGRANCE; METHYL 3 PHENYLPROPIONATE; UNCLASSIFIED DRUG;

ABSORPTION; ACUTE TOXICITY; CARCINOGENICITY; CHEMICAL STRUCTURE; CONCENTRATION RESPONSE; DETOXIFICATION; DRUG EXPOSURE; GENOTOXICITY; HUMAN; METABOLISM; MUTAGENICITY; NONHUMAN; PHOTOALLERGY; PHOTOTOXICITY; REPRODUCTIVE TOXICITY; REVIEW; SKIN TOXICITY; TOXICOKINETICS;

ANIMALS; CINNAMATES; CONSUMER PRODUCT SAFETY; HUMANS; IRRITANTS; MUCOUS MEMBRANE; PERFUME; PROPANOLS; RISK ASSESSMENT; SKIN; TOXICITY TESTS;

MAMMALIA;

EID: 84155160709     PISSN: 02786915     EISSN: 18736351     Source Type: Journal    
DOI: 10.1016/j.fct.2011.07.053     Document Type: Review

References (93)

1. Anders M.W. Biotransformation and bioactivation of xenobiotics by the kidney. Intermediary Xenobiotic Metabolism in Animals 1989, Taylor and Francis, New York, pp. 81-97. D.H. Hutson, J. Caldwell, G.D. Paulson (Eds.).
2. Bhatia S.P., Letizia C.S., Api AM. Fragrance material review on 3-phenyl-1-propanol. Food and Chemical Toxicology 2011, 49(Suppl. 2):S246-S251.
3. Bhatia S.P., Letizia C.S., Api A.M. Fragrance material review on 3-phenylpropyl cinnamate. Food and Chemical Toxicology 2011, 49(Suppl. 2):S252-S255.
4. Bhatia S.P., Letizia C.S., Api A.M. Fragrance material review on 3-phenylpropyl isobutyrate. Food and Chemical Toxicology 2011, 49(Suppl. 2):S242-S245.
5. Bickers D., Calow P., Greim H., Hanifin J.M., Rogers A.E., Saurat J.H., Sipes I.G., Smith R.L., Tagami H. A toxicologic and dermatologic assessment of cinnamyl alcohol, cinnamaldehyde and cinnamic acid when used as fragrance ingredients. Food and Chemical Toxicology 2005, 43(6):799-836.
6. Cadby P., Troy W.R., Vey M. Consumer exposure to fragrance ingredients: providing estimates for safety evaluation. Regulatory Toxicology and Pharmacology 2002, 36:246-252.
7. Caldwell J., Nutley B. Comparative metabolism of cinnamic acid in rats and mice and its variation with dose. British Journal of Pharmacology 1986, 88(Suppl.):423.
8. Carter H.E. The oxidation of branched-chain fatty acids. Symposia of the Society for Experimental Biology 1941, 5:47-63.
9. Council of Europe, 2000. Partial Agreement in the Social and Public Health Field. Chemically-defined Flavouring Substances. Groups: 2.2 aromatic alcohols, 5.2 aromatic aldehydes, 8.2 aromatic acids. Numbers, 22, 65, 102. Council of Europe Publishing, Strasbourg, pp. 74, 119, 205.
10. Copovi A., Lopez A., Faus V., Llinares F., Diez-Sales O., Herraez M. The " in vitro" human skin permeation-enhancing effect of the alpha-hydroxy acids and sodium lauryl sulphate. Perspectives in Percutaneous Penetration 1997, 5B:188-191.
11. Dakin H.D. The mode of oxidation in the animal organism of phenyl derivatives of fatty acids. Part IV. Further studies in the fate of phenylpropionic acid and some of its derivatives. Journal of Biological Chemistry 1909, 6:203-219.
12. Diez-Salez O., Lopez-Castellano A., Maiques-Lacer F.J., Herraez-Dominguez M. An in vitro percutaneous absorption study of non-ionic compounds across human skin. Die Pharmazie 1993, 48(9):684-686.
13. Deuel H.J. The oxidation and metabolism of triglycerides, fatty acids, and glycerol in the animal body. The Lipids, Their Chemistry and Biochemistry 1957, Vol. III:71-99. Wiley Interscience, New York, 291-301.
14. EPA (Environmental Protection Agency), 2010. Estimation Programs Interface Suite™ for Microsoft® Windows, v 4.00. United States Environmental Protection Agency, Washington, DC, USA.
15. Fahelbum I.M.S., James S.P. The absorption and metabolism of methyl cinnamate. Toxicology 1977, 7(1):123-132.
16. FEMA (Flavor and Extract Manufacturers Association), 1965. Recent progress in the consideration of flavoring ingredients under the Food Additives Amendment. 3. Gras Substances. Food Technology 19, 151-197.
17. FEMA (Flavor and Extract Manufacturers Association), 1979. Recent progress in the consideration of flavoring ingredients under the Food Additives Amendment 12. GRAS substances. Food Technology 33 (7), 65-73.
18. Fernandez X., Lizzani-Cuvelier L., Loiseau A.-M., Perichet C., Delbecque C., Arnaudo J.F. Chemical composition of the essential oils from Turkish and Honduras. Styrax. Flavour and Fragrance Journal 2005, 20(1):70-73.
19. FDA (Food and Drug Administration). Code of Federal Regulations, 21 CFR 172.515. Title 21 - Food and Drugs, vol. 3, Chapter I - Food and Drug Administration, Department of Health and Human Services. Part 172 - Food Additives Permitted for Direct Addition to Food for Human Consumption. Subpart F - Flavoring Agents and Related Substances, 515 - Synthetic Flavoring Substances and Adjuvants.
20. Feldman R.I., Weiner H. Horse liver aldehyde dehydrogenase. I. Purification and characterization. Journal of Biological Chemistry 1972, 247(1):260-266.
21. Fiorio R., Bronzetti G. Effects of cinnamaldehyde on survival and formation of HGPRT (-) mutants in V79 cells treated with methyl methanesulfonate, n-nitroso-n-methylurea, ethyl methanesulfonate and UV light. Mutation Research 1994, 324:51-57.
22. Fischer F.G., Bielig H.J. Biochemical hydrogenations. VII. Hydrogenation of unsaturated compounds in the animal body. Hoppe-Seyler's Z. Physiological Chemistry 1940, 266:73-98.
23. Ford R.A., Domeyer B., Easterday O., Maier K., Middleton J. Criteria for development of a database for safety evaluation of fragrance ingredients. Regulatory Toxicology and Pharmacology 2000, 31:166-181.
24. Galloway S.M., Armstrong M.J., Reuben C., Colman S., Brown B., Cannon C., Bloom A.D., Nakamura F., Ahmed M., Duk S., Rimpo J., Margolin B.H., Resnick M.A., Anderson B., Zeiger E. Chromosome aberration and sister chromatid exchanges in Chinese hamster ovary cells: evaluations of 108 chemicals. Environmental and Molecular Mutagenesis 1987, 10:1-175.
25. Grundschober F. Toxicological assessment of flavouring esters. Toxicology 1977, 8:387-390.
26. Goodwin T.W., Mercer E.I. Introduction to Plant Biochemistry 1972, Pergamon Books Oxford, England.
27. Hagan E.C., Hansen W.H., Fitzhugh O.G., Jenner P.M., Jones W.I., Taylor J.M., Long E.L., Nelson A.A., Brouwer J.B. Food flavorings and compounds of related structure. II. Subacute and chronic toxicity. Food and Cosmetic Toxicology 1967, 5:141-157.
28. Hardin B.D., Schuler R.L., Burg J.R., Booth G.M., Hazelden K.P., MacKenzie K.M., Piccirillo V.J., Smith K.N. Evaluation of 60 chemicals in a preliminary developmental toxicity test. Teratogenesis, Carcinogenesis and Mutagenesis 1987, 7:29-48.
29. Hayashi M., Sofuni T., Ishidate M. A pilot experiment for the micronucleus test. The multi-sampling at multi-dose levels method. Mutation Research 1984, 141:165-169.
30. Hayashi M., Kishi M., Sofuni T., Ishidate M. Micronucleus tests in mice on 39 food additives and eight miscellaneous chemicals. Food and Chemical Toxicology 1988, 26:487-500.
31. Heymann, E., 1980. Carboxylesterases and amidases. In: Enzymatic Basis Detoxication, vol. 2, chapter 16. Academic Press, pp. 291-323.
32. Hooth M.J., Sills R.C., Burka L.T., Haseman J.K., Witt K.L., Orzech D.P., Fuciarelli A.F., Graves S.W., Johnson J.D., Bucher J.R. Toxicology and carcinogenesis studies of microencapsulated trans-cinnamaldehyde in rats and mice. Food and Chemical Toxicology 2004, 42(11):1757-1768.
33. HPV (High Production Volume), 2001. The Flavor and Fragrance High Production Volume Consortia. Robust summary and test plan for cinnamyl derivatives. Submitted to the EPA, January 2001.
34. Hutt A.J., Caldwell J. Amino acid conjugations. Conjugation Reactions in Drug Metabolism 1990, 273-305. Taylor and Francis Ltd. G.J. Mulder (Ed.).
35. IFRA (International Fragrance Association), 2008. Volume of Use Survey, September 2008.
36. IFRA (International Fragrance Association), 2007. Use Level Survey, September 2007.
37. IFRA (International Fragrance Association), 2004. Use Level Survey, August 2004.
38. IFRA (International Fragrance Association), 2002. Use Level Survey, August 2002.
39. Ishidate M., Sofuni T., Yoshikaw K., Hayashi M., Nohmi T., Sawada M., Matsuoka A. Primary mutagenicity screening of food additives currently used in Japan. Food and Chemical Toxicology 1984, 22:623-636.
40. Johnson J.D., Reichelderfer D.L., Ryan M.J., Toft J.D., Yarrington J.T., Graves S.W., Hejtmancik M.R., Bucher J. Microencapsulated trans-cinnamaldehyde subchronic dosed-feed study using F344 rats and B6C3F1 mice. The Toxicologist 1998, 42:56.
41. JECFA (Joint Expert Committee on Food Additives), 2000. Safety evaluation of certain food additives. Who Food Additives Series: 46. Prepared by the Fifty-fifth meeting of the Joint FAO/WHO Expert Committee on Food Additives. World Health Organization, Geneva 2000.
42. Kassahun K., Farrell K., Abbott F. Identification and characterization of the glutathione and n-acetylcysteine conjugates of (e)-2-propyl-2,4-pentadienoic acid, a toxic metabolite of valproic acid, in rats and humans. Drug Metabolism and Disposition 1991, 19(2):525-535.
43. Kasamaki A., Takahashi H., Tsumura N., Niwa J., Fujita T., Urasawa S. Genotoxicity of flavoring agents. Mutation Research 1982, 105:387-392.
44. Kasamaki A., Urasawa S. Characteristic changes of Chinese hamster cells surviving treatment with flavoring agents. Mutation Research 1983, 189:313-318.
45. Kasamaki A., Yasuhara T., Urasawa S. Neoplastic transformation of Chinese hamster cells in vitro after treatment with flavoring agents. Journal of Toxicological Sciences 1987, 12:383-396.
46. Kasamaki A., Urasawa S. Transforming potency of flavoring agents in Chinese hamster cells. Journal of Toxicological Sciences 1985, 10:177-185.
47. Kay H.D., Raper H.S. The mode of oxidation of fatty acids with branched chains. III. The fate in the body of alpha-methylcinnamic acid, beta-phenyl-isobutyric acid, and gamma-phenyl-isovaleric acid. Biochemical Journal 1924, 18:153-160.
48. Larsen W., Nakayama H., Fischer T., Elsner P., Frosch P., Burrows D., Jordan W., Shaw S., Wilkinson J., Marks J., Sugawara M., Nethercott M., Nethercott J. Fragrance contact dermatitis - a worldwide multicenter investigation (Part III). Contact Dermatitis 2002, 46(3):141-144.
49. Lopez A., Faus V., Diez-Sales O., Herraez M. Skin permeation model of phenyl alcohols: comparison of experimental conditions. International Journal of Pharmaceutics 1998, 173(1-2):183-191.
50. Mantovani A., Stazi A.V., Macri C., Ricciardi C., Piccioni A., Badellino E. Prenatal (segment II) toxicity study of cinnamic aldehyde in the Sprague-Dawley rat. Food and Chemical Toxicology 1989, 27:781-786.
51. Martelli A., Brambilla-Campart G., Ghia M., Mereto E. Evaluation of the carcinogenic potential of cinnamaldehyde in a battery of in vivo short-term tests. Proceedings of the Eighty-Fourth Annual Meeting of the American Association for Cancer Research 34, 132, May 19-22 1993, Orlando, Florida.
52. Mereto E., Brambilla-Campart G., Ghia M., Martelli A., Brambilla G. Cinnamaldehyde-induced micronuclei in rodent liver. Mutation Research 1994, 322:1-8.
53. Mirsalis J.C., Tyson C.K., Steinmetz K.L., Loh E.K., Hamilton C.M., Bakke J.P., Spalding J.W. Measurement of unscheduled DNA synthesis and S-phase synthesis in rodent hepatocytes following in vivo treatment: testing of 24 compounds. Environmental and Molecular Mutagenesis 1989, 14:155-164.
54. National Toxicology Program, 2003. Toxicology and carcinogenesis studies of trans-cinnamaldehyde (microencapsulated) in F344/N Rats and B6C3F1 mice. NTP TR 514, NIH Publication No. 02-4448.
55. Nutley, B.P., 1990. Investigations into the metabolism of cinnamic acid, cinnamyl alcohol, and cinnamaldehyde in relation to their safety evaluation. A Thesis submitted for the Degree of Doctor of Philosophy in the University of London, Department of Pharmacology.
56. Nutley B., Farmer P., Caldwell J. Metabolism of trans-cinnamic acid in the rat and mouse and its variation with dose. Food and Chemical Toxicology 1994, 32:877-886.
57. Pathak M.A., Fitzpatrick T.B. Bioassay of natural and synthetic furocoumarins (psoralens). Journal of Investigative Dermatology 1959, 32:509-518.
58. Pathak M.A., Fitzpatrick T.B. Relationship of molecular configuration to the activity of furocoumarins which increase the cutaneous responses following long wave ultraviolet radiation. Journal of Investigative Dermatology 1959, 32(Part 2):255-262.
59. Peters, M., 1993. Metabolic and mechanistic studies in the safety evaluation of trans-cinnamaldehyde. A Thesis submitted for the Degree of Doctor of Philosophy in the University of London, Department of Pharmacology and Toxicology.
60. Peters M., Caldwell J. Studies on trans-cinnamaldehyde. The influence of dose size and sex on its disposition in the mouse and rat. Food and Chemical Toxicology 1994, 32:869-876.
61. Pietruszko R., Crawford K., Lester D. Comparison of substrate specificity of alcohol dehydrogenases from human liver, horse liver, and yeast towards saturated and 2-enoic alcohols and aldehydes. Archives of Biochemistry and Biophysics 1973, 159:50-60.
62. Pollitt R.J. Phenylpropionic acid in the urine of patients with phenylketonuria and normals. Clinica Chimica Acta 1974, 55:317-322.
63. Quarto di Palo F.M., Bertolini A.M. Cinnamic acid administration to renal patients. Atti Accad. Med. Lombarada 1961, 16:180-183.
64. RIFM (Research Institute for Fragrance Materials, Inc.), 1958. Toxicological screening of cinnamic aldehyde in rats. Class IV, Part 2. Unpublished report from Trubek Laboratories, Inc. RIFM report number 29142 (RIFM, Woodcliff Lake, NJ, USA).
65. RIFM (Research Institute for Fragrance Materials, Inc.), 1971a. Acute oral and dermal toxicity studies in rabbits. RIFM report number 2110, August 25 (RIFM, Woodcliff Lake, NJ, USA).
66. RIFM (Research Institute for Fragrance Materials, Inc.), 1971b. Repeated insult patch test on human subjects. RIFM report number 2730, August 30 (RIFM, Woodcliff Lake, NJ, USA).
67. RIFM (Research Institute for Fragrance Materials, Inc.), 1972a. Acute oral and dermal toxicity studies. RIFM report number 2712, May 1 (RIFM, Woodcliff Lake, NJ, USA).
68. RIFM (Research Institute for Fragrance Materials, Inc.), 1972b. The contact-sensitization potential of fragrance materials by maximization testing in humans. RIFM report number 1804, July 19 (RIFM, Woodcliff Lake, NJ, USA).
69. RIFM (Research Institute for Fragrance Materials, Inc.), 1975a. Acute toxicity studies in rats, mice, and rabbits. RIFM report number 2024, May 16 (RIFM, Woodcliff Lake, NJ, USA).
70. RIFM (Research Institute for Fragrance Materials, Inc.), 1975b. Report on human maximization studies. RIFM report number 1799, May 16 (RIFM, Woodcliff Lake, NJ, USA).
71. RIFM (Research Institute for Fragrance Materials, Inc.), 1975c. Report on human maximization studies. RIFM report number 1798, August 15 (RIFM, Woodcliff Lake, NJ, USA).
72. RIFM (Research Institute for Fragrance Materials, Inc.), 1976a. Acute toxicity studies in rats, mice, rabbits and guinea pigs. RIFM report number 2019, May 12 (RIFM, Woodcliff Lake, NJ, USA).
73. RIFM (Research Institute for Fragrance Materials, Inc.), 1976b. Report on human maximization studies. RIFM report number 1796, December 20 (RIFM, Woodcliff Lake, NJ, USA).
74. RIFM (Research Institute for Fragrance Materials, Inc.), 1977a. Acute toxicity study in rats, rabbits and guinea pigs. RIFM report number 1695, April 08 (RIFM, Woodcliff Lake, NJ, USA).
75. RIFM (Research Institute for Fragrance Materials, Inc.), 1977b. Report on human maximization studies. RIFM report number 1691, October 07 (RIFM, Woodcliff Lake, NJ, USA).
76. RIFM (Research Institute for Fragrance Materials, Inc.), 1977c. Report on human maximization studies. RIFM report number 1702, May 04 (RIFM, Woodcliff Lake, NJ, USA).
77. RIFM (Research Institute for Fragrance Materials, Inc.), 1981a. Acute toxicity studies. RIFM report number 1806, August 31 (RIFM, Woodcliff Lake, NJ, USA).
78. RIFM (Research Institute for Fragrance Materials, Inc.), 1981b. Report on human maximization studies. RIFM report number 1792, June 08 (RIFM, Woodcliff Lake, NJ, USA).
79. RIFM (Research Institute for Fragrance Materials, Inc.), 2002. Mutagenicity study of 3-phenyl-1-propanol (phenyl propylalcohol) in the Salmonella typhimurium/mammalian microsome reverse mutation assay (Ames-Test). RIFM report number 57447 (RIFM, Woodcliff Lake, NJ, USA).
80. RIFM (Research Institute for Fragrance Materials, Inc.), 2003. Topical photoallergy screening test of cinnamaldehyde and cinnamic acid in male albino hairless guinea pigs (Crl: IAF(HA)-hrBR) (Outbred)], including primary irritation, phototoxicity and contact hypersensitivity evaluations. RIFM report number 41273, January 15 (RIFM, Woodcliff Lake, NJ, USA).
81. Sasaki Y.F., Imanishi H., Ohta T., Shirasu Y. Effects of antimutagenic flavourings on SCEs induced by chemical mutagens in cultured Chinese hamster cells. Mutation Research 1987, 189:313-318.
82. Samuelsen O., Brenna J., Solheim E., Scheline R. Metabolism of the cinnamon constituent o-methoxycinnamaldehyde in the rat. Xenobiotica 1986, 16:845-852.
83. Sanyal R., Darroudi F., Parzefall W., Nagao M., Knasmüller S. Inhibition of the genotoxic effects of heterocyclic amines in human derived hepatoma cells by dietary bioantimutagens. Mutagenesis 1997, 12:297-303.
84. Snapper I., Yu T.F., Chiang Y.T. Cinnamic acid metabolism in man. Proceedings of the Society for Experimental Biology and Medicine 1940, 44:30-34.
85. Solheim E., Scheline R.S. Metabolism of alkenebenzene derivatives in the rat I. p-Methoxyallylbenzene (estragole) and p-Methoxypropenylbenzene (anethole). Xenobiotica 1973, 3(8):493-510.
86. Solheim E., Scheline R.S. Metabolism of alkenebenzene derivatives in the rat. II. Eugenol and isoeugenol methyl ethers. Xenobiotica 1976, 6(3):137-150.
87. Stoner G.D., Shimkin M.B., Kniazeff A.J., Weisburger J.H., Weisburger E.K., Go G.B. Test for carcinogenicity of food additives and chemotherapeutic agents by the pulmonary tumor response in strain A mice. Cancer Research 1973, 33:3069-3085.
88. Sund H., Theorell H. Alcohol dehydrogenases. The Enzymes, second ed. 1963, vol. 7, Chapter 2:25-83. Academic Press, New York. P.D. Boyer, H. Lardy, K. Myrback (Eds.).
89. Takenaka, T., Hasegawa, E., Takenaka, U., Saito, F., Odaka, T., 1986. Fundamental studies of safe compound perfumes for cosmetics. Part 1. The primary irritation of compound materials to the skin. Unknown Source, pp. 313-329.
90. VCF (Volatile Compounds in Food): database/Nijssen, L.M., Ingen-Visscher, C.A. van, Donders, J.J.H. (Eds.) - Version 11.1.1 - Zeist (The Netherlands), TNO Quality of Life, 1963-2010.
91. Williams R.T. Detoxication Mechanisms. The Metabolism and Detoxication of Drugs. Toxic Substances and Other Organic Compounds 1959, Chapman and Hall Ltd. second ed.
92. 1 mice. Cancer Research 1987, 47:2275-2283.
93. Zaitsev A.N., Maganova N.B. Embryotoxic effects of some aromatizers for food products. Voprosy Pitaniia 1975, 3:64-68.