Scientific Opinion on the safety of allyl isothiocyanate for the proposed uses as a food additive

EFSA JournalVolume 8, Issue 12 1943 OpinionOpen Access Scientific Opinion on the safety of allyl isothiocyanate for the proposed uses as a food additive EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS)Search for more papers by this author EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS)Search for more papers by this author First published: 22 December 2010 https://doi.org/10.2903/j.efsa.2010.1943Citations: 8 Panel members: F. Aguilar, B. Dusemund, P. Galtier, J. Gilbert, D.M. Gott, S. Grilli, R. Gürtler, J. König, C. Lambré, J-C. Larsen, J-C. Leblanc, A. Mortensen, D. Parent-Massin, I. Pratt, I.M.C.M. Rietjens, I. Stankovic, P. Tobback, T. Verguieva, R.A. Woutersen Correspondence: ans@efsa.europa.eu Acknowledgement: The Panel wishes to thank the members of the Working Group A on Food Additives and Nutrient Sources: F. Aguilar, N. Bemrah, P. Galtier, J. Gilbert, S. Grilli, R. Gürtler, C. Lambré, J.C. Larsen, J-C. Leblanc, A. Mortensen, I. Pratt, Ch. Tlustos, I. Stankovic for the support provided to this scientific opinion. Adoption date: 8 December 2010 Published date: 22 December 2010 Question number: EFSA-Q-2009-00377 On request from: European Commission AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract The Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion on the safety of allyl isothiocyanate (AITC) when used as a food preservative. Rats appear to resemble humans in AITC metabolism, but have a much slower clearance than humans. AITC has been investigated in acute, short-term, subchronic toxicity studies and in carcinogenicity studies in rodents. AITC did not cause any developmental toxicity in rats, hamsters and rabbits. AITC may be fetotoxic to mice at doses higher than 6.0 mg/kg bw/day. AITC is not carcinogenic in mice but transitional cell papillomas of the urinary bladder of males were observed in a long-term rat study, however, AITC is not genotoxic in vivo in mice and rats. Hence it could be assumed that there is a threshold mechanism underlying these effects on urinary bladder. The Panel considered this long-term rat study as the pivotal study. The Panel derived an ADI of 0.018 mg/kg bw/day which was rounded up to 0.02 mg/kg bw/day based on a LOAEL of 9 mg/kg bw/day and applying an uncertainty factor of 500 in order to cover uncertainties resulting from extrapolation from the LOAEL to the NOAEL and from the absence of reproductive toxicity studies. The Panel noted that AITC intakes resulting only from application as an antispoilage agent could be estimated for children and adults at 0.3 up to 2.8 and 0.2 up to 1.6 times the ADI depending on the exposure scenario. Furthermore, the Panel noted that the mean daily total exposure to AITC from all sources including natural occurrence in food, use as a flavouring and application as an antispoilage agent, based on the more refined model, results in a two to four-fold exceedance of the ADI in children and up to eight-fold exceedance in 95th percentile adult consumers. References Ahmad P, Rahman FMM, Rahman A, and Begum R, 1966. XIII. Pharmacological and toxicological effects of food components. Proc. Int. Congr. Nutr. 7, 815– 819. Anderson HH and Hurwitz GK, 1953. Dodecylamine and other agents active against Ascaris lumbricoides and their toxicity in mammals. Arch Exp. Path. Pharmakol. 219, 119– 129. Auerbach C and Robson JM, 1947. Test of chemical substances for mutagenic action (allyl isothiocyanate). Sec. Biol. 62B, 284– 291. Azizan A and Blevins RD, 1995. Mutagenicity and antimutagenicity testing of six chemicals associated with the pungent properties of specific spices as revealed by the ames salmonella/microsomal assay. Arch. Environ. Con. Tox. 28, 248– 258. Bechtel D, Henderson L and Proudlock R, 1998. Lack of UDS activity in the livers of rats exposed to allylisothiocyanate. Teratogen. Carcin. Mut. 18, 209– 217. Bollard M, Stribbling S, Mitchell S and Caldwell J, 1997. The disposition of allyl isothiocyanate in the rat and mouse. Food Chem. Toxicol. 35(10–11), 933– 43. Bordi C, Bussolati G, Capella C, Cheng L, Horvath E and Furlan D, 2010. Endocrine Pathology: Differential Diagnosis and Molecular Advances. Ed: RV Lloyd; Second edition; Springer, Berlin. Borghoff SJ and Birnbaum LS, 1986. Age-related changes in the metabolism and excretion of allyl isothiocyanate. A model compound for glutathione conjugation. Drug Metab. Dispos. 14(4), 417– 22. Brand G and Jacquot L, 2002. Sensitization and desensitization to allylisothiocyanate (Mustard Oil) in the nasal cavity. Chem. Senses 27, 593– 598. Brooks BA, Miller KW and Babish JG, 1984. Mutagenicity of 3-glucosinolate plant metabolites using the Salmonella-typhimurium bioluminescence assay. Abstract 1717, Federation Proceedings. 43, 579. Bruggeman IM, Temmick JHM and Van Bladeren PJ, 1986. Gutathione and cysteine-mediated cytotoxicity of allyl and benzyl isothiocyanate. Toxicol. Appl. Pharm. 83, 349, 359. Brunton LL, Lazo JS, and Parker KL, 2006. Goodman & Gilman's The Pharmacological Basis of Therapeutics. Eleventh edition, McGraw-Hill Medical Publishing Division, New York. Cejpek K, Valusek J and Velisek J, 2000. Reactions of allyl isothiocyanate with alanine, glycine, and several peptides in model systems. J. Agr. Food Chem. 48 (8), 3560– 3565. Eder E, Neudecker T, Lutz D and Henschler D, 1980. Mutagenic potential of allyl and allylic compounds. Structure-activity relationship as determined by alkylating and direct in vitro mutagenic properties. Biochem. Pharmacol. 29, 993– 998. Eder E, Neudecker T, Lutz D and Henschler D, 1982. Correlation of alkylating and mutagenic activities of allyl and allylic compounds: Standard alkylation test vs. kinetic investigation. Chem.-Biol. Interact. 38, 303– 315. EFSA (European Food Safety Authority), 2004. Scientific Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies on a request from the Commission relating to the evaluation of allergenic foods for labeling purposes (Request N° EFSA-Q-2003-016). The EFSA Journal (2004) 32, 1– 197. Available at: www.efsa.europa.eu/en/scdocs/doc/32.pdf. EFSA (European Food Safety Authority), 2007. Scientific Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies on a request from the Commission related to a notification from IFF on mustard seed oil pursuant to Article 6, paragraph 11 of Directive 2000/13/EC. The EFSA Journal (2007) 481, 1– 7. Availbale at: www.efsa.europa.eu/en/scdocs/doc/481.pdf. EFSA (European Food Safety Authority), 2008. Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from Commission on FGE.85 Consideration of miscellaneous nitrogen-containing substances evaluated by JECFA (65th meeting). The EFSA Journal (2008) 804, 1– 30. Availbale at: www.efsa.europa.eu/en/scdocs/doc/804.pdf. Epstein SS, Arnold E, Andrea J, Bass W and Bishop Y, 1972. Detection of chemical mutagens by the dominant lethal assay in the mouse. Toxicol. Appl. Pharm. 23, 288– 325. FDA (Food and Drug Administration), 1993. Priority-based assessment of food additives (PAFA) database. Center for food safety and applied nutrition. pp 58. FDRL (Food and Drug Research Laboratories), 1973. Teratogenic evaluation of FDA 71–26 (Oil of Mustard) (PB-223 812), Washington DC, National Technical Information Service. Galloway SM, Armstrong MJ, Reuben C, Colman S, Brown B, Cannon C, Bloom AD, Nakamura F, Ahmed M, Duk S, Rimpo J, Margolin BH, Resnick MA, Anderson B and Zeiger E, 1987. Chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells: evaluations of 108 chemicals. Environ. Mol. Mutagen. 10(Suppl. 10), 1– 175. García A, Haza AI, Arranz N, Rafter J and Morales P, 2008. Protective effects of isothiocyanates alone or in combination with vitamin C towards N-nitrosodibutylamine or N-nitrosopiperidine-induced oxidative DNA damage in the single-cell gel electrophoresis (SCGE)/HepG2 assay. J Appl. Toxicol. 28(2), 196– 204. Hagan EC, Hansen WH, Fitzhuch OG, Jenner PM, Jones WI, Taylor JM, Long EL, Nelson AA and Brouwer JB, 1967. Food flavourings and compounds of related structure. II. Subacute and chronic toxicity. Food Cosmet. Toxicol. 5, 141– 157. Hitoshi GOI, Inouye S and Iwanami Y, 1985. Antifungal activity of powdery black mustard powdery wasabi (Japanese horseradish), and allyl isothiocyanate by gaseous contrac – antifungal activity of plant volatiles. Journal of Antibacterial and Antifungal Agents 13(5), 199– 204. IARC (International Agency for Research on Cancer), 1985. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, Vol. 36, Allyl Compounds, Aldehydes, Epoxides and Peroxides, Lyon, pp. 55– 68. Ioannou YM, Burka LT and Matthews HB, 1984. Allyl isothiocyanate: comparative disposition in rats and mice. Toxicol. Appl. Pharm. 75(2), 173– 81. IUNA (Irish Universities Nutrition Alliance), 2001 North/South Ireland Food Consumption Survey, 1997-1999. Available at: www.iuna.net/index.php/research/northsouth-food-survey. IUNA (Irish Universities Nutrition Alliance), 2005. National Children's Food Survey, 2004. Available at: www.iuna.net/childrens_survey/. JECFA (Joint FAO/WHO Expert Committee on Food Additives), 2006. Safety evaluation of certain food additives and contaminants. Sixty-fifth meeting of the Joint FAO/WHO Expert Committee on Food Additives, WHO Technical Report Series: 943. WHO, Geneva. available at: whqlibdoc.who.int/publications/2006/9241660562_eng.pdf. JECFA (Joint FAO/WHO Expert Committee on Food Additives), 2005. Compendium of food additive specifications. Section C, specifications of certain flavouring agents. Addendum 13. Geneva. Jenner PM, Hagan EC, Taylor JM, Cook EL and Fitzhugh OG, 1964. Food flavorings and compounds of related structure I. Acute oral toxicity. Food Cosmet. Toxicol. 2(3), 327– 343. Jiao D, Ho CT, Foiles P and Chung FL, 1994. Identification and quantification of the N-acetylcysteine conjugate of allyl isothiocyanate in human urine after ingestion of mustard. Cancer Epidem. Biomar. 3(6), 487– 92. Kasamaki A, Takahashi H, Tsumura N, Niwa J, Fujita T and Urasawa S, 1982. Genotoxicity of flavoring agents. Mutat. Res. 105, 387– 392. Kasamaki A and Urasawa S, 1985. Transforming potency of flavoring agents in Chinese hamster cells. J. Toxicol. Sci. 10, 177– 85. Kassie F and Knasmüller S, 2000. Genotoxic effects of allyl isothiocyanate (AITC) and phenethyl isothiocyanate (PEITC). Chem.-Biol. Interact. 127, 163– 180. Kawakishi S and Namiki M, 1982. Oxidative cleavage of the disulfide bond of cystine by allyl isothiocyanate. J. Agr. Food Chem. 30 (3), 618– 620. Kawakishi S and Kaneko T, 1987. Interaction of proteins with allyl isothiocyanate. J. Agr. Food Chem. 35, 85– 88. Kojima M and Ogawa K, 1971. Studies on the effects of isothiocyanates and their analogues on microorganisms. J. Ferment. Technol. 49, 740– 746. Langer, P. 1964. Study of chemical preservatives of the goitrogenic activity of raw cabage. Physiologia bohemoslov. 13, 542– 549. Langer P and Stolc V, 1965. Goitrogenic activity of allylisothiocyanate – a widespread natural mustard oil. Endocrinology 76(1), 151– 155. Lerbæk A, Rastogi SC, and Menneè T, 2004. Allergic contact dermatitis from allyl isothiocyanate in a Danish cohort of 259 selected patients. Contact Dermatitis 51, 79– 83. Lewerenz HJ, Plass R, Bleyl DWR and Macholz R, 1988. Short-term toxicity study of allyl isothiocyanate in rats. Die Nahrung 32(8), 723– 728. Maruyama T, Izuka H, Tobisawa Y, Matsuda T, Kurohane K and Imai Y, 2007. Influence of local treatments with capsaicin or allylisothiocyanate in the sensitization phase of a fluorescein-isothiocyanate-induced contact sensitivity model. International Archives of Allergy and Immunology 143(2), 144– 154. McGregor DB, Brown A, Cattanach P, Edwards I, McBride D, Riach C and Caspary WJ, 1988. Responses of the L5178Y tk+/tk- mouse lymphoma cell forward mutation assay III: 72 coded chemicals. Environ. Mol. Mutag. 12, 85– 154. McClain RM, 1994. Mechanistic considerations in the regulation and classification of chemical carcinogens. In Nutritional Toxicology ( F.N. Kotsonis, M. Mackey, and J. Hjelle, Eds.), pp. 273– 304. Raven Press, New York. Mitchell JC and Jordan WP, 1974. Allergic contact dermatitis from the radish, Raphanus sativus. Brit. J. Dermatol. 91 (issue 2), 1983– 189. Mortelmans K, Haworth S, Lawlor T, Speck W, Tainer B and Zeiger E, 1986. Salmonella mutagenicity tests II. Results from the testing of 270 chemicals. Environ. Mol. Mutag. 8(Suppl. 7), 1– 119. Murata M, Yamashita N, Inoue S, Kawanishi S, 2000. Mechanism of oxidative DNA damage induced by carcinogenic allyl isothiocyanate. Free Radical Bio. Med. 28(5), 797– 805. Musk SRR and Johnson IT, 1993. The clastogenic effects of isothiocyanates. Mutat. Res. 300, 111– 117. Musk SRR, Smith TK and Johnson IT, 1995. On the cytotoxicity and genotoxicity of allyl and phenethyl isothiocyanates and their parent glucosinolates sinigrin and gluconasturtiin. Mutat. Res. 348, 19– 23. Muztar AJ, Huque T, Ahmad P Slinger SJ, 1979. Effect of allyl isothiocyanate on plasma and urinary concentrations of some biochemical entities in the rat. Can J. Physiol. Pharm. 57(5), 504– 509. Neudecker T and Henschler D, 1985. Allyl isothiocyanate is mutagenic in salmonella typhimurium. Mutat. Res. 156, 33– 37. Nishie K and Daxenbichler ME, 1980. Toxicology of glucosinolates, related compounds (nitriles, R-goitrin, isothiocyanates) and vitamin U found in Cruciferae. Food Cosmet. Toxicol. 18, 159– 172. NTP (National Toxicology Program), 1982. Carcinogenesis Bioassay of Allyl Isothiocyanate (CAS no. 57-06-7) in F344/N Rats and B6C3F1 Mice (Gavage Study). Technical Report Series, 234. NTP-81-36, NIH Publication No 83-1790. Perchacek R, Vel$isek J and Hrabcova H, 1997. Decomposition products of allyl isothiocyanate in aqueous solutions. J. Agr. Food Chem. 45, 4584– 4588. Plackett DV, Holm VK, Johansen P, Ndoni S, Nielsen PV, Sipilainen-Malm T, Södergård and Verstichel S, 2005. Characterization of L-polylactide and L-polyactide-polyaprolactone copolymer films for use in chesse packaging applications. Packaging Technology and Science, 19, 1– 24. Rihová E, 1982. Mutagenic effects of allyl isothiocyanate in Escherichia coli WP 67. Folia Microbiol. 27, 25– 31. Rouzaud G, Young SA and Duncan AJ, 2004. Hydrolysis of Glucosinolates to Isothiocyanates after Ingestion of Raw or Microwaved Cabbage by Human Volunteers. Cancer Epidem. Biomar. 13, 125– 131. Ruddick JA, Newsome WH and Nash L, 1976. Correlation of teratogenicity and molecular structure: ethylenethiourea and related compounds. Teratology, 13, 263– 266. Rungapamestry V, Duncan AJ, Fuller Z and Ratcliffe B, 2007. Effect of meal composition and cooking duration on the fate of sulforaphane following consumption of broccoli by healthy human subjects. Brit. J. Nutr. 97, 644– 652. Schiffmann D, Eder E, Neudecker T and Henschler D, 1983. Induction of unscheduled DNA synthesis in HeLa cells by allylic compounds. Cancer Lett. 20, 263– 269. Shapiro TA, Fahey JW, Wade KL, Stephenson KK, Talalay P, 1998. Human metabolism and excretion of cancer chemoprotective glucosinolates and isothiocyanates of cruciferous vegetables. Cancer Epidem. Biomar. 7(12), 1091– 1100. Shelby MD, Erexson GL, Hook GJ and Tice RR, 1993. Evaluation of a three-exposure mouse bone marrow micronucleus protocol: Results with 49 chemicals. Environ. Mol. Mutag. 21(2), 160– 179. Stofberg J and Grundschober F, 1987. The consumption ratio and food predominance of flavoring materials. Perfumer Flavorist, 12, 27– 56. Suhr KI and Nielsen PV, 2005. Inhibition of Fungal Growth on Wheat and Rye Bread by Modified Atmosphere Packaging and Active Packaging Using Volatile Mustard Essential Oil. J. Food Sci. 70, M37– 44. TNO (Netherlands Organisation for Applied Scientific Research), 2009. VCF Volatile Compounds in Food : database / L.M. Nijssen; C.A. Ingen-Visscher; J.J.H. Donders [eds]. – Version 12.1 – Zeist (The Netherlands) : TNO Quality of Life, 1963-2009. www.vcf-online.nl/VcfHome.cfm. Uematsu Y, Hirata K, Suzuki K, Ueta T and Kamata K, 2002. Determination of Isothiocyanates and related compounds in mustard extracts and horseradish extract used as natural food additives. J. Food Hyg. Soc. Japan. 43(1), 10– 17. Uhl M, Laky B, Lhoste E, Kassie F, Kundi M, Knasmüller S, 2003. Effects of mustard sprouts and allylisothiocyanate on benzo(a)pyrene-induced DNA damage in human-derived cells: a model study with the single cell gel electrophoresis/Hep G2 assay. Teratogen. Carcin. Mut. 23(Suppl 1), 273– 282. Velísek J, Mikulcová R, Míková K, Woldie KB, Link J and Davídek J, 1995. Lebensmittel-Wissenschaft und-Technologie 28, 620– 624. Vernot EH, MacEwen JD, Haun CC, and Kinkead ER, 1977. Acute toxicity and skin corrosion data for some organic and inorganic compounds and aqueous solutions. Toxicol. Appl. Pharm. 42, 417– 423. Watson D, 1998. Natural Toxicants in Food. Sheffield Academic Press Ltd, Sheffield. Winther, M and Nielsen PV, 2006. The use of Allyl isothiocyanat to inhibition of cheese related moulds. Journal Food Protect. 69, 2430– 2435. Yamaguchi T, 1980. Mutagenecity of isothiocyanates, isocyanates and thioureas on Salmonella typhimurium. Agr. Biol. Chem. 44(12), 3017– 3018. Yu S and Ouyang A, 2009. TRPA1 in bradykinin-induced mechanical hypersensitivity of vagal C fibers in guinea pig oesophagus. Am J Physiol Gastrointest Liver Physiol, 296 (2), G255– 265. Zimmering S, Mason JM and Valencia R, 1989. Chemical mutagenesis testing in Drosophila. VII. Results of 22 coded compounds tested in larval feeding experiments. Environ. Mol. Mutagen. 14, 245– 251. Citing Literature Volume8, Issue12December 20101943 ReferencesRelatedInformation