Cytotoxicity and Genotoxicity of Ethoxyquin Used As an Antioxidant

References

• Taimr, L. Study of the mechanism of the antioxidant action of ethoxyquin. Angew. Makromol. Chem. 1994, 217, 119–128.
   Google Scholar
• Brannegan, D.R. Analysis of ethoxyquin and its oxidation products using supercritical fluid extraction and high performance liquid chromatography with chemiluminescent nitrogen detection. M.S. thesis, Virginia Polytechnic Institute and State University, Blacksburg, VA, 2000. http://scholar.lib.vt.edu/theses/available/etd-03302000-20440044/ ( accessed April 18, 2014)
   Google Scholar
• deKoning, A.J. The antioxidant ethoxyquin and its analogues: A review. Int. J. Food Prop. 2002, 5, 451–461.
   Google Scholar
• Lauridsen, C.; Jacobsen, K.; Hansen, T.K. The influence of dietary ethoxyquin on the vitamin-E status in broilers. Arch. Anim. Nutr. 1995, 47, 245–254.
   Web of Science ®Google Scholar
• Renner, H.W. Antimutagenic effect of an antioxidant in mammals. Mutat. Res. 1984, 135, 125–129.
   PubMed Web of Science ®Google Scholar
• Renner, H.W.; Knoll, M. Antimutagenic effects on male germ cells of mice. Mutat. Res. 1984, 140, 127–129.
   PubMed Web of Science ®Google Scholar
• Błaszczyk, A.; Skolimowski, J. Comparative analysis of cytotoxic, genotoxic and antioxidant effects of 2,2,4,7-tetramethyl-1,2,3,4-tetrahydroquinoline and ethoxyquin on human lymphocytes. Chem. Biol. Interact. 2006, 162, 70–80.
   PubMed Web of Science ®Google Scholar
• Stankiewicz, A.; Skrzydlewska, E.; Makieła, M. Effects of amifostine on liver oxidative stress caused by cyclophosphamide administration to rats. Drug Metab. Drug Interact. 2002, 19, 67–82.
   PubMedGoogle Scholar
• Ray, S.; Pandit, B.; Ray, S.D.; Das, S.; Chakraborty, S. Cyclophosphamide induced lipid peroxidation and changes in cholesterol content: Protective role of reduced glutathione, Int. J. PharmTech Res. 2010, 2, 704–718.
   Google Scholar
• Cabral, J.R.P.; Neal, G.E. The inhibitory effects of ethoxyquin on the carcinogenic action of aflatoxin B1 in rats. Cancer Lett. 1983, 19, 125–132.
   PubMed Web of Science ®Google Scholar
• Manson, M.M.; Green, J.A.; Driver, H.E. Ethoxyquin alone induces preneoplastic changes in rat kidney whilst preventing induction of such lesions in liver by aflatoxin B1. Carcinogenesis 1987, 8, 723–728.
   PubMed Web of Science ®Google Scholar
• Bamler, T.K.; Slone, D.H.; Eaton, D.L. Effects of dietary oltipraz and ethoxyquin on aflatoxin B1 biotransformation in non-human primates. Toxicol. Sci. 2000, 54, 30–41.
   PubMed Web of Science ®Google Scholar
• Bailey, C.A.; Srinivasan, L.J.; McGeachin, R.B. The effect of ethoxyquin on tissue peroxidation and immune status of single comb White Leghorn cockerels. Poultry Sci. 1996, 75, 1109–1112.
   PubMed Web of Science ®Google Scholar
• Dunkley, W.L.; Ronning, M.; Franke, A.A.; Robb, J. Supplementing rations with tocopherol and ethoxyquin to increase oxidative stability of milk. J. Dairy Sci. 1967, 50, 492–499.
   Web of Science ®Google Scholar
• The Code of Federal Regulations, 46 CFR 148.04-9 - Fishmeal or scrap, ground or pelletized; fishmeal or scrap, ground and pelletized (mixture). 2010. http://www.gpo.gov/fdsys/granule/CFR-2010-title46-vol5/CFR-2010-title46-vol5-sec148-04-9/content-detail.html ( accessed July 27, 2014).
   Google Scholar
• United States Environmental Protection Agency. Reregistration Eligibility Decision (RED). Ethoxyquin. 2004. http://www.epa.gov/oppsrrd1/REDs/0003red.pdf ( accessed September 24, 2014).
   Google Scholar
• The Japan Food Chemical Research Foundation. MRLs list: Compositional specification for foods. 2013. http://www.ffcr.or.jp/zaidan/ffcrhome.nsf/pages/mrls-p ( accessed April 1, 2015).
   Google Scholar
• EUR-Lex. Regulation (EC) No. 396/2005 of the European Parliament and of the Council of 23 February 2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin and amending Council Directive 91/414/EEC. Official Journal of the European Union 2005, L 70/1.
   Google Scholar
• Aoki, Y.; Kotani, A.; Miyazawa, N.; Uchida, K.; Igarashi, Y.; Hirayama, N.; Hakamata, H.; Kusu, F. Determination of ethoxyquin by high-performance liquid chromatography with fluorescence detection and its application to the survey of residues in food products of animal origin. J. AOAC Int. 2010, 93, 277–283.
   PubMed Web of Science ®Google Scholar
• Lundebye, A.K.; Hove, H.; Mage, A.; Bohne, V.J.B.; Hamre, K. Levels of synthetic antioxidants (ethoxyquin, butylated hydroxytoluene and butylated hydroxyanisole) in fish feed and commercially farmed fish. Food Addit. Contam. 2010, 27, 1652–1657.
   Web of Science ®Google Scholar
• Dzanis, D.A. Safety of ethoxyquin in dog foods. J. Nutr. 1991, 121, S163–S164.
   PubMed Web of Science ®Google Scholar
• Leong, V.Y.M.; Brown, T.P. Toxicosis in broiler chicks due to excess dietary ethoxyquin. Avian Dis. 1992, 36, 1102–1106.
   PubMed Web of Science ®Google Scholar
• McIntosh, G.H.; Charnock, J.S.; Phillips, P.H.; Baxter, G.J. Acute intoxication of marmosets and rats fed high-concentrations of the dietary antioxidant Ethoxyquin-66. Aust. Vet. J. 1986, 63, 385–386.
   PubMed Web of Science ®Google Scholar
• Drewhurst, I. Ethoxyquin. JMPR Evaluations. 1998. http://www.inchem.org/documents/jmpr/jmpmono/v098pr09.htm ( accessed April 18, 2014).
   Google Scholar
• Brandao, F.M. Contact-dermatitis to ethoxyquin. Contact Dermatitis 1983, 9, 240.
   PubMed Web of Science ®Google Scholar
• Savini, C.; Morelli, R.; Piancastelli, E.; Restani, S. Contact-dermatitis due to ethoxyquin. Contact Dermatitis 1989, 21, 342–343.
   PubMed Web of Science ®Google Scholar
• Alanko, K.; Jolanki, R.; Estlander, T.; Kanerva, L. Occupational ‘multivitamin allergy’ caused by the antioxidant ethoxyquin. Contact Dermatitis 1998, 39, 263–264.
   PubMed Web of Science ®Google Scholar
• Rodríguez-Trabado, A.; Miró i Balagué, J.; Guspi, R. Hypersensitivity to the antioxidant ethoxyquin. Actas Dermosifiliogr. 2007, 98, 580.
   PubMedGoogle Scholar
• US Food and Drug Administration, Animal and Veterinary. FDA requests that ethoxyquin levels be reduced in dog foods. 1997. http://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm127828.htm ( accessed July 27, 2014).
   Google Scholar
• Puglia, C.; Powell, S. Inhibition of cellular antioxidants: A possible mechanism of toxic cell injury. Environ. Health Perspect. 1984, 57, 307–311.
   PubMed Web of Science ®Google Scholar
• Decker, E.A. Phenolics: Prooxidants or antioxidants? Nutr. Rev. 1997, 55, 396–398.
   Google Scholar
• Sakihama, Y.; Cohen, M.F.; Grace, S.C.; Yamasaki, H. Plant phenolic antioxidant and prooxidant activities: Phenolics-induced oxidative damage mediated by metals in plants. Toxicology 2002, 177, 67–80.
   PubMed Web of Science ®Google Scholar
• Galati, G.; O’Brien, P.J. Potential toxicity of flavonoids and other dietary phenolics: Significance for their chemopreventive and anticancer properties. Free Radic. Biol. Med. 2004, 37, 287–303.
   PubMed Web of Science ®Google Scholar
• Taimr, L.; Smelhausova, M.; Prusikova, M. The reaction of 1-cyano-1-methylethyl radical with antidegradant ethoxyquin and its aminyl and nitroxide derivatives. Angew. Makromol. Chem. 1993, 206, 199–207.
   Google Scholar
• Halliwell, B.; Whiteman, M. Measuring reactive species and oxidative damage in vivo and in cell culture: How should you do it and what do the results mean? Br. J. Pharmacol. 2004, 142, 231–255.
   Google Scholar
• Willcox, J.K.; Ash, S.L.; Catignani, G.L. Antioxidants and prevention of chronic disease. Crit. Rev. Food Sci. Nutr. 2004, 44, 275–295.
   PubMed Web of Science ®Google Scholar
• Błaszczyk, A. DNA damage induced by ethoxyquin in human peripheral lymphocytes. Toxicol. Lett. 2006, 163, 77–83.
   PubMed Web of Science ®Google Scholar
• Błaszczyk, A.; Skolimowski, J. Synthesis and studies on antioxidants: Ethoxyquin (EQ) and its derivatives. Acta Pol. Pharm. 2005, 62, 111–115.
   PubMedGoogle Scholar
• Błaszczyk, A.; Skolimowski, J. Apoptosis and cytotoxicity caused by ethoxyquin and two of its salts. Cell. Mol. Biol. Lett. 2005, 10, 15–21.
   PubMed Web of Science ®Google Scholar
• Błaszczyk, A.; Osiecka, R.; Skolimowski, J. Induction of chromosome aberrations in cultured human lymphocytes treated with ethoxyquin. Mutat. Res. 2003, 542, 117–128.
   PubMed Web of Science ®Google Scholar
• Reddy, B.S.; Hanson, D.; Mathews, L.; Sharma, C. Effect of micronutrients, anti-oxidant and related-compounds on the mutagenicity of 3,2’-dimethyl-4-aminobiphenyl, a colon and breast carcinogen. Food Chem. Toxicol. 1983, 21, 129–132.
   PubMed Web of Science ®Google Scholar
• Ohta, T.; Moriya, M,; Kaneda, Y.; Watanabe, K.; Miyazawa, T.; Sugiyama, F.; Shirasu, Y. Mutagenicity screening of feed additives in the microbial system. Mutat. Res. 1980, 77, 21–30.
   PubMed Web of Science ®Google Scholar
• Hedenstedt, A. Mutagenicity of disulfiram and ethoxyquin. Mutat. Res. 1982, 97, 191.
   Web of Science ®Google Scholar
• National Toxicology Program. Study ID: 620987. Studies on ethoxyquin: CAS 91-53-2. Salmonella typhimurium. 1989. http://tools.niehs.nih.gov/cebs3/ntpViews/?activeTab=detail&studyNumber=620987 ( accessed April 1, 2015).
   Google Scholar
• Gupta, P.K.; Boobis, A. Ethoxyquin (Addendum). In Joint FAO/WHO Meeting on Pesticide Residues. Pesticide Residues in Food—2005, Geneva, Switzerland, September 20–29, 2005; FAO/WHO: Rome, 2005; pp 241–253.
   Google Scholar
• Joner, P.E. Butylhydroxyanisol (BHA), butylhydroxytoluene (BHT) and ethoxyquin (EMQ) tested for mutagenicity. Acta Vet. Scand. 1977, 18, 187–193.
   PubMed Web of Science ®Google Scholar
• Little, A.D. Ethoxyquin. National Toxicology Program, Executive summary of safety and toxicity information. Chemical Committee Draft Report. Ethoxyquin. CAS number 91-53-2. 1990. http://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/ethoxyquin_508.pdf ( accessed July 27, 2014).
   Google Scholar
• National Toxicology Program. Study ID: 247323; Studies on ethoxyquin: CAS 91-53-2. Chromosome aberration test. Sister chromatid exchange test. 1991. http://tools.niehs.nih.gov/cebs3/ntpViews/?studyNumber=247323_SCE;http://tools.niehs.nih.gov/cebs3/ntpViews/?studyNumber=247323_CA ( accessed April 1, 2015).
   Google Scholar
• Gille, J.J.P.; Pasman, P.; Vanberkel, C.G.M.; Joenje, H. Effect of antioxidants on hyperoxia-induced chromosomal breakage in chinese-hamster ovary cells—Protection by carnosine. Mutagenesis 1991, 6, 313–318.
   PubMed Web of Science ®Google Scholar
• Rabbitts, T.H. Chromosomal translocations in human cancer. Nature 1994, 372, 143–149.
   PubMed Web of Science ®Google Scholar
• Bryant, P.E. Mechanisms of radiation-induced chromatid breaks. Mutat. Res. 1998, 404, 107–111.
   PubMed Web of Science ®Google Scholar
• Augustyniak, A.; Niezgoda, A.; Skolimowski, J.; Kontek, R.; Błaszczyk, A. Cytotoxicity and genotoxicity of ethoxyquin dimers. Bromatol. Chem. Toksykol. 2012, XLV, 228–234.
   Google Scholar
• Skolimowski, J.; Cieślinska, B.; Żak, M.; Osiecka, R.; Błaszczyk, A. Modulation of ethoxyquin genotoxicity by free radical scavengers and DNA damage repair in human lymphocytes. Toxicol. Lett. 2010, 193, 194–199.
   PubMed Web of Science ®Google Scholar
• Barret, J.C. Mechanisms of multistep carcinogenesis and carcinogen risk assessment. Environ. Health Perspect. 1993, 100, 9–20.
   PubMed Web of Science ®Google Scholar
• Autrup, H. Genetic polymorphisms in human xenobiotica matabolizing enzymes as susceptibility factors in toxic response. Mutat. Res. 2000, 464, 65–76.
   PubMed Web of Science ®Google Scholar
• Bohne, V.J.; Hamre, K.; Arukwe, A. Hepatic biotransformation and metabolite profile during a 2-week depuration period in Atlantic salmon fed graded levels of the synthetic antioxidant, ethoxyquin. Toxicol. Sci. 2006, 93, 11–21.
   PubMed Web of Science ®Google Scholar
• Reszka, E.; Wąsowicz, W. Significance of genetic polymorphisms in glutathione S-transferase multigene family and lung cancer risk. Int. J. Occup. Med. Environ. Health 2001, 14, 99–113.
   PubMedGoogle Scholar
• Dong, L.M.; Potter, J.D.; White, E.; Ulrich, C.M.; Cardon, L.R.; Peters, U. Genetic susceptibility to cancer. JAMA 2008, 299, 2423–2436.
   PubMed Web of Science ®Google Scholar
• Persson, I.; Johansson, I.; Ingelman-Sundberg, M. In vitro kinetics of two human CYP1A1 variant enzymes suggested to be associated with interindividual differences in cancer susceptibility. Biochem. Biophys. Res. Commun. 1997, 231, 227–230.
   PubMed Web of Science ®Google Scholar
• Hagmar, L.; Stromberg, U.; Bonassi, S.; Hansteen, I.-L.; Knudsen, L.E.; Lindholm, C.; Norppa, H. Impact of types of lymphocyte chromosomal aberrations on human cancer risk: Results from Nordic and Italian cohorts. Cancer Res. 2004, 64, 2258–2263.
   PubMed Web of Science ®Google Scholar
• Ørnsrud, R. Ethoxyquin in Fish Feed; The National Institute of Nutrition and Seafood Research: xx, 2011. http://nifes.no/en/ethoxyquin-in-fish-feed/ ( accessed April 1, 2015).
   Google Scholar
• US Food and Drug Administration. Guidance for industry studies to evaluate the safety of residues of veterinary drugs in human food: Genotoxicity testing, VICH GL23(R). 2012. http://www.fda.gov/AnimalVeterinary/default.htm ( accessed April 18, 2014).
   Google Scholar
• Ørnsrud, R.; Arukwe, A.; Bohne, V.; Pavlikova, N.; Lundebye, A.K. Investigations on the metabolism and potentially adverse effects of ethoxyquin dimer, a major metabolite of the synthetic antioxidant ethoxyquin in salmon muscle. J. Food Prot. 2011, 74, 1574–1580.
   PubMed Web of Science ®Google Scholar
• Bohne, V.J.B.; Lundebye, A.K.; Harare, K. Accumulation and depuration of the synthetic antioxidant ethoxyquin in the muscle of Atlantic salmon (Salmo salar L.). Food Chem. Toxicol. 2008, 46, 1834–1843.
   PubMed Web of Science ®Google Scholar