Methyleugenol in the diet: Toxic and pathological aspects

Reviews in Food and Nutrition Toxicity

Volumn 3, Issue , 2005, Pages 1-60

  Johnson, Jerry D ^a   Abdo, Kamal M ^b  

^a BATTELLE MEMORIAL INSTITUTE   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84856516549     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (119)

1. 1 mice, Food and Chemical Toxicology, 39: 303–316.
2. Ames, B.N., McCann, J., and Yamasaki, E. (1975), Methods for detecting carcinogens and mutagens with Salmonella/mammalian microsome mutagenicity test, Mutation Research, 31: 347–364.
3. 2F-globulin: Association with Chemically Induced Renal Toxicity and Neoplasia in the Male Rat, Risk Assessment Forum document, U.S. Environmental Protection Agency: Washington, D.C., September, 1991.
4. Barr, D.B., Barr, J.R., Bailey, S.L., Lapeza, C.R., Jr., Beeson, M.D., Caudill, S.P., Maggio, V.L., Schecter, A., Masten, S.A., Lucier, G.W., Needham, L.L., and Sampson, E.J. (2000), Levels of methyleugenol in a subset of adults in the general U.S. population as determined by high resolution mass spectrometry, Environmental Health Perspectives, 108: 1–6.
5. Beroza, M., Inscoe, M.N., Schwartz, P.H., Jr., Keplinger, M.L., and Mastri, C.W. (1975), Acute toxicity studies with insect attractants, Toxicology and Applied Pharmacology, March 31: 421–429.
6. Berwald, Y. and Sachs, L. (1965), In vitro transformation of normal cells to tumor cells by carcinogenic hydrocarbons, Journal of National Cancer Institute, 35: 641–661.
7. Bobin, M.F., Gau, F., Pelltier, J., and Cotte, J. (1991), Etude de L’Arome Basilie, Rivista Italiana, EPPOS: 3–13.
8. Borchert, P., Wislocki, P.G., Miller, J.A., and Miller, E.C. (1973a), The metabolism of the naturally occurring hepatocarcinogen safrole to 1'-hydroxysafrole and the electrophilic reactivity of 1'-acetoxysafrole, Cancer Research, March, 33: 575–589.
9. Borchert, P., Miller, J.A., Miller, E.C., and Shires, T.K. (1973b), 1'-Hydroxysafrole, a proximate carcinogenic metabolite of safrole in the rat and mouse, Cancer Research, 33: 590–600.
10. Burkey, J.L., Sauer, J.M., McQueen, C.A., and Sipes, G.I. (2000), Cytotoxicity and genotoxicity of methyleugenol and related congeners — a mechanism of activation for methyleugenol, Mutation Research, 453: 25–33.
11. Brennan, R.J., Kandikonda, S., Khrimian, A.P., DeMilo, A.B., Liquido, N.J., and Schiestl, R.H. (1996), Saturated and monofluoro analogs of the oriental fruit fly attractant methyl eugenol show reduced genotoxic activities in yeast, Mutation Research, 369: 175–181.
12. Carlini, E.A., Kallmeier, K., and Zelger, J.L. (1981), Methyleugenol as a surgical anesthetic in rodents, Experientia, 37: 588–589.
13. Carlini, E.A., de Oliveira, A.B., and de Oliveira, G.G. (1983), Psychopharmacological effects of the essential oil fraction and the hydrolate obtained from the seeds of Licoria puchury-major, Journal of Ethnopharmacology, 8: 225–236.
14. CDCP/NIEHS, unpublished results. Information referenced in Barr et al., 2000.
15. CFR (1971), 40 CFR 180 — Part 180 — Tolerances and Exemptions from Tolerances for Pesticide Chemicals in or on Raw Agricultural Commodieties, Promulgated: 36 FR 22540, 11/25/71, U.S. Codes: 21 U.S.C. 346a, 371a.
16. CFR (1977), 21 CFR 172 — Part 172 — Food Additives Permitted for Direct Addition to Food for Human Consumption, Promulgated: 42 FR 14491 03/15/77. U.S. Codes: 21 U.S.C. 321, 341, 371, 379e.
17. CFR (1982), 40 CFR 180 — Part 180 Subpart D — Exemptions from Tolerances, Promulgated: 47 CFR 9002, 03/03/82. U.S. Codes: 21 U.S.C. 321(q), 346 (a) and 371.
18. CFR (1996), 21 CFR 172 — Subpart F — Flavoring Agents and Related Substances, Promulgated: 61 FR 1425, 04/01/96.
19. Chan, V.S.W. and Caldwell, J. (1992), Comparative induction of unscheduled DNA synthesis in cultured rat hepatocytes by allylbenzenes and their 1-hydroxy metabolites, Food and Chemical Toxicology, 30: 831–836.
20. ChemFinder (2003), Methyleugenol, available at http://www.chemfinder.camsoft.com/, CambridgeSoft (accessed December 2002).
21. Cheville, N.F. (Ed.) (1994), Ultrastructural Pathology: An Introduction to Interpretation, Ames, Iowa: Iowa State University Press, p. 319.
22. Devereux, T.R., Anna, C.H., Foley, J.F., White, C.M., Sills, R.C., and Barrett, J.C. (1999), Mutation of β-catenin is an early event in chemically induced mouse hepatocellular carcinogenesis, Oncogene, 18: 4726–4733.
23. de Vincenzi, M., Silano, M., Stacchini, P., and Scazzocchio, B. (2000), Constituents of aromatic plants: I. Methyleugenol, Fitoterapia, 71: 216–221.
24. Dockray, G. J. (1999), Topical review: Gastrin and gastric epithelial physiology, Journal of Physiology, 518: 315–324.
25. Dorange, J.L., Delaforge, M., Janiaud, P., and Padau, P. (1977), Mutagenic activity of metabolites of epoxy-diol pathway of safrole and analogues, C.R. Soc. Biol. (Paris), 171: 1041–1048.
26. Drinkwater, N.R., Miller, E.C., Miller, J.A., and Pitot, H.C. (1976), The hepatocarcinogenicity of estragole (1-allyl-4-methoxybenzene) and 1-hydroxyestragole in the mouse and the mutagenicity of 1-acetoxyestragole in bacteria, Journal of National Cancer Institute., 57: 1323–1331.
27. Eaton, E.L. and Klaassen, C.D. (1996), Principles of toxicology, in C.K. Klaassen, M.O. Amdur, and J. Doull (Eds.), Toxicology: The Basic Science of Poisons, New York: McGraw-Hill, p. 14.
28. Engelbrecht, J.A., Long, J.P., Nichols, D.E., and Barfknecht, C.F. (1972), Pharmacologic evaluation of 3,4-dimethoxyphenylpropenes and 3,4-dimethoxyphenylpropanediols, Archives Internationale de Pharmacodynamie, 199: 226–244.
29. Farm Chemical Handbook (1992), Meister Publishing, Willoughby, OH, p. C221.
30. Furia, T.E. and Bellanca, N. (Eds.) (1975), Fenaroli’s Handbook of Flavor Ingredients (1975), Cleveland, OH: The Chemical Rubber Co., 2nd ed., Vol. 2, p. 200.
31. Flavor and Extract Manufacturer Association of the Unites States (FEMA) (1978), Scientific Literature Review of Eugenol and Related Substances in Flavor Usage, Vol. 1, Accession No. PB 283–501. National Technical Information Service, U. S. Department of Commerce, Washington, D.C.
32. Fukui, H., Kinoshita, T., Maekawa, T., Okada, A., Waki, S., Hassan, M.D.S., Okamao, H., and Chiba, T. (1998), Regenerating gene protein may mediate gastric mucosal proliferation induced by hypergastrinemia in rats, Gastroenterology, 115: 1483–1493.
33. Gallo, M.A. (1996), History and scope of toxicology, in C.D. Klaassen, M.O. Amdur, and J. Doull (Eds.), Toxicology: The Basic Science of Poisons, New York: McGraw-Hill, 5th ed., p. 4.
34. 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., and Zeiger, E. (1987), Chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells: Evaluations of 108 chemicals, Environmental and Molecular Mutagenesis, 10 (Suppl. 10): 1–175.
35. Gardner, I., Bergin, P., Stening, P., Kenna, J.G., and Caldwell, J. (1996), Immunochemical detection of covalently modified protein adducts in livers of rats treated with methyleugenol, CRC, Critical Reviews in Toxicology, 9: 713–721.
36. Gardner, I., Wakazono, H., Bergin, P., de Waziers, I., Beauen, P., Kenna, J.G., and Caldwell, J. (1997), Cytochrome P450 mediated bioactivation of methyleugenol to 1-hydroxy-methyleugenol in Fischer 344 rat and human liver microsomes, Carcinogenesis, 18: 1775–1783.
37. Graves, S.W. and Runyon, S. (1995), Determination of methyleugenol in rodent plasma by high-performance liquid chromatography, Journal of Chromatography B., 663: 255–262.
38. Green, M.H.L. and Muriel, W.J. (1976), Mutagen testing using trp+ reversion in Escherichia coli, Mutation Research, 38: 3–32.
39. Greenberger, N.J. and Isselbacher, K.J. (1994), Disorders of absorption, in K.J. Isselbacher, E. Braunwald, J.D. Wilson, J.B. Martin, A.S. Fauci, and D.L. Kasper (Eds.), Harrison’s Principles of Internal Medicine, New York: McGraw-Hill, 13th ed., Vol. 2, p. 1389.
40. Guenthner, T.M. and Luo, G. (2001), Investigation of the role of the 2, 3-epoxidation pathway in the bioactivation and genotoxicity of dietary allylbenzene analogs, Toxicology, 160: 47–58.
41. Gumbiner, B.M. (1997), Carcinogenesis: A balance between β-catenin and APC, Current Biology, 7: R443–R446.
42. Hall, R.L. and Oser, B.I. (1965), Recent progress in the consideration of flavoring ingredients under the food additives amendment. III. GRAS substances, Food Toxicology, 253: 151–197.
43. Hays, W.J., Jr. and Laws, E.R., Jr. (Eds.) (1991), Handbook of Pesticide Toxicology, San Diego: Academic Press, pp. 613–614.
44. Higham, A., Bishop, A.E., Dimaline, R., Blackmore, C., Dobbins, A.C., Varro, A., Thompson, D.G., and Dockray, G.J. (1999), Mutations of Reg1-α in enterochromaffin-like cell tumors in patients with hypergastrinemia, Gastroenterology, 116: 1310–1318.
45. Hinkle, K.L. and Samuelson, L.C. (1999), Lessons from genetically engineered animal models. III. Lessons learned from gastrin gene deletion in mice, American Journal of Physiology — Gastrointestinal Liver Physiology, 277: 500–505.
46. Howes, A.J., Chan, V.S.W., and Caldwell, J. (1990), Structure-specificity of the genotoxicity of some naturally occurring alkenylbenzenes determined by the unscheduled DNA synthesis assay in rat hepatocytes, Food and Chemical Toxicology, 28: 537–542.
47. Howlett, F.M. (1912), The effect of oil of citronella on two species of Dacus, Entomol. Soc. Lond. Trans., Part II: 412–418.
48. Howlett, F.M. (1915), Chemical reactions of fruit flies, Bulletin of Entomological Research, 6: 297–305.
49. HSDB (1996), Methyleugenol, http://toxnet.nlm. Nih.gov/cgi-bin/sis/htmlgen?HSDB (and type 93-15-2) (accessed December 2002).
50. IARC (1976), IARC Monographs on the Evaluation of Carcinogenic Risks of Chemicals to Man, Vol. 10. IARC, Lyon, France.
51. Jain, N.C. (1986a), Clinical and laboratory evaluation of anemias and polycythemias, in N.C. Jain (Ed.), Schalm’s Veterinary Hematology, Philadelphia: Lea and Febiger, 4th ed., pp. 563–576.
52. Jain, N.C. (1986b), Qualitative and quantitative disorders of platelets, in N.C. Jain (Ed.), Schalm’s Veterinary Hematology, Phildelphia: Lea and Febiger, 4th ed., pp. 466–486.
53. Jenner, P.M., Hagan, E.C., Taylor, J.M., Cook, E.L., and Fitzhugh, O.G. (1964), Food flavourings and compounds of related structure. I. Acute oral toxicity, Food and Cosmetic Toxicology, 2: 327.
54. 1 mice, Journal of Agricultural and Food Chemistry, 48: 3620–3632.
55. Kada, T., Hirano, K., and Shirasu, Y. (1980), Screening of environmental chemical mutagens by the Rec-assay system with Bacillus subtilis, in F.J. DeSerres and A. Hollaender (Eds.), Chemical Mutagens, pp. 149–173.
56. Kanel, G.C. and Korula, J. (Eds.) (2000), Liver Biopsy Evaluation: Histological Diagnosis and Clinical Correlations, Philadelphia: W.B. Saunders, p. 4.
57. Kang, S. and Green, J.P. (1970), Correlation between activity and electronic state of hallucinogenic amphetamines, Nature, 226: 645.
58. Keith, L.H. (1976), Identification of organic compounds in unbleached treated Kraft Paper Mill wastewater, Current Research, 10: 555–564.
59. Keating, J.W. (1972), Report to RIFM, 5 July.
60. Kerckaert, G.A., Brauninger, R., LeBoeuf, R.A., and Isfort, R.J. (1996), Use of the Syrian Hamster embryo cell transformation assay for carcinogenicity prediction of chemicals currently being tested by the National Toxicology Program in rodent bioassays, Environmental Health Perspectives, 104: 1075–1084.
61. Lawrence, M. and Shu, C.K. (1993), Essential oils as components of mixtures: Their method of analysis and differentiation, in C.T. Ho and C.M. Manley (Eds.), Flavor Measurement, New York: Marcel Dekker.
62. 32P-postlabeled DNA-aromatic carcinogen adducts, Analytical Biochemistry, 174: 381–392.
63. Lewis, R.J., Jr. (Ed.) (2001), Hawley’s Condensed Chemical Dictionary, New York: John Wiley & Sons, p. 735.
64. Lide, D.R. (Ed.) (1998), CRC Handbook of Chemistry and Physics, Boca Raton: CRC Press, 78th ed., pp. 3–42.
65. Lima, C.C., Criddle, D.N., Coelho-de-Souze, A.N., Monte, F.J.Q., Jaffar, M., and Cardoso, J.H. (2000), Relaxant and antispasmodic actions of methyleugenol on guinea-pig ileum, Planta Medica, 66: 408–411.
66. Luo, G. and Guenthner, T.M. (1995), Metabolism of allylbenzene 2,3-oxide and estragole 2,3-oxide in the isolated perfused rat liver, J. Pharmacol. Exp. Ther., 272: 588–596.
67. MacGregor, J.T., Laurence, L.L., and Buttery, R.G. (1974), California bay oil. II. Biological effects of constituents, Journal of Agricultural and Food Chemistry, 22: 777–780.
68. McQueen, C.A., Kreiser, D.M., and Williams, G.M. (1983), The hepatocyte primary culture/DNA repair assay using mouse or hamster hepatocytes, Environmental Mutagenesis, 5: 1–8.
69. Miele, M., Dondero, R., Ciarallo, G., Mazzei., M. (2001a), Methyleugenol in Ocimum basilicum L. cv. Genovese Gigante, Journal of Agricultural and Food Chemistry, 49: 517–521.
70. Miele, M., Ledda, B., Falugi, C., and Mazzei, M. (2001b), Methyleugenol and eugenol variation in Ocimum basilicum cv. Genovese Gigante grown in greenhouse and in vitro, Boll. Soc. Ital. Biol. Sper., 77: 43–50.
71. Miller, E.C., Swanson, A.B., Phillips, D.H., Fletcher, T.L., Liem, A., and Miller, J.A. (1983), Structure-activity studies of the carcinogenesis in the mouse and rat of some naturally occurring and synthetic alkenylbenzene derivatives related to safrole and estragole, Cancer Research, 43: 1124–1134.
72. Mookherjee, B.D. and Wilson, R.A. (Eds.) (1996), Kirk-Othmer Encyclopedia of Chemical Technology, New York: John Wiley & Sons, pp. 1, 82, 94.
73. Morrison, R.T. and Boyd, R.N. (Eds.) (1974), Organic Chemistry, Boston: Allyn and Bacon, 3rd ed., pp. 372–400.
74. 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, Environmental Mutagenesis, 8, Suppl. 7: 1–199.
75. Moslen, M.T. (1996), Toxic responses of the liver, in C.D. Klaassen, M.O. Amdur, and J. Doull, Toxicology: The Basic Science of Poisons, New York: McGraw-Hill, pp. 403–416.
76. National Academy of Sciences (NAS) (1989), Poundage and Technical Effects Update of Substances Added to Food. Committee on Food Additives Survey Data, Food and Nutrition Board, Institute of Medicine, National Academy of Sciences, Washington, D.C.
77. NIOSH (1990), National Occupational Exposure Survey (1981–1983), unpublished provisional data as of July 1, 1990. NIOSH, Cincinnati, OH.
78. 1 Mice (Drinking Water and Feed Studies), National Toxicology Program. Toxicity Report Series No. 29. NIH Publication No. 93-3352. U.S. Department of Health and Human Services, Public Health Services, National Institutes of Health, Research Triangle Park, NC.
79. 1 Mice (Gavage Studies), Technical Report Series No. 491. NIH Publication No. 98-3950. U.S. DHHS, PHS, NIH, NTP, Research Triangle Park, NC.
80. NTP (2002), The 90-Day Gavage Toxicity Study of Estragole (CAS No. 140-67-0) in Fischer 344 Rats (Gavage Studies), Battelle Final Report (Study Number G004164-R), Columbus, OH.
81. Needham, L.L., Patterson, D.G., Jr., Burse, V.W., Paschal, D.C., Turner, W.E., and Hill, R.H., Jr. (1996), Reference range data for assessing exposure to selected environmental toxicants, Toxicology and Industrial Health, 12: 507–513.
82. Opdyke, D.L.J. (Ed.) (1979), Monographs on Fragrance Raw Materials, New York: Pergamon Press, p. 555.
83. Osborne, B.E., Plawiuk, M., Graham, C., Bier, C., Losos, G., Broxup, B., and Procter, B.G. (1981), A 91-Day Single Dose Level Dietary Study of Eugenyl Methyl Ether and Isoeugenyl Methyl Ether in the Albino Rat, Bio-Research Laboratories Ltd. Confidential Research Report No. 9203, submitted to FEMA (as described in reference by Smith et al., 2002).
84. Phillips, D.H., Miller, J.A., Miller, E.C., and Adams, B. (1981), Structures of the DNA adducts formed in mouse liver after administration of the proximate hepatocarcinogen 1-hydroxyestragole, Cancer Research, 41: 176.
85. Pitot, H.C. and Dragon, Y.P. (1996), Chemical Carcinogenesis, in C.D. Klaassen, M.O. Amdur, and J.D. Doull (Eds.), Toxicology: The Basic Science of Poisons, New York: McGraw-Hill, p. 201.
86. Radian (1991), NTP Chemical Repository: Methyleugenol, http://ntp-db.niehs.nih.gov/NTP_Reports/NTP_Chem_H&S/NTP_Chem9/Radian93-15-2.txt, US DHHS, PHS, NIH, National Toxicology Program (accessed December 2002).
87. 32P-Post-labeling analysis of DNA adducts formed in the livers of animals treated with safrole, estragole and other naturally-occurring alkenylbenzenes. I. Adult female CD-1 mice, Carcinogenesis, 5: 1613–1622.
88. Riaz, M., Ashraf, C.M., and Chaudhary, M.F. (1989), Studies of the essential oil of the Pakistani Laurus nobilis Linn in different seasons, Pakistan Journal of Scientific and Industrial Research, 32: 33–35.
89. Robinson, M. (1999), Review article: current perspectives on hypergastrinemia and entero-chromaffin-like-cell hyperplasia, Aliment Pharmacology and Therapy, 13: 5–10.
90. Rompelberg, C.J., Ploemen, J.H., Jespersen, S., van der Greef, J., Verhagen, H., and van Bladeren, P.J. (1996), Inhibition of rat, mouse, and human glutathione S-transferase by eugenol and its oxidation products, Chemical and Biological Interactions, January 5: 99: 85–97.
91. Rozengurt, E. and Walsh, J.H. (2001), Gastrin, CCK, signaling, and cancer, Annual Review of Physiology, 63: 49–76.
92. Sayyah, M., Valizadeh, J., and Kamalinejad, M. (2002), Anticonvulsant activity of the leaf essential oil of Laurus nobilis against pentylenetetrazole-and maximal electroshock-induced seizures, Phytomedicine, 9: 212–216.
93. Schiestl, R.H., Igarashi, S., and Hastings, P.J. (1988), Analysis of the mechanism for reversion of a disrupted gene, Genetics, 119: 237–247.
94. Schiestl, R.H., Chan, W.S., Gietz, R.D., Mehta, R.D., and Hastings, P.J. (1989), Safrole, eugenol and methyleugenol induce intrachromosomal recombination in yeast, Mutation Research, 224: 427–436
95. Sekizawa, J. and Shibamoto, T. (1982), Genotoxicity of safrole-related chemicals in microbial test systems, Mutation Research, 101: 127–140.
96. Sell, A.B. and Carlini, E.A. (1976), Anesthetic action of methyleugenol and other eugenol derivatives, Pharmacology, 14: 367–377.
97. Shaver, T.N. and Bull, D.L. (1980), Environmental fate of methyl eugenol, Bulletin of Environmental Contamination and Toxicology, 24: 619–626.
98. Shin, B.K., Lee, E.H., and Kim, H.M. (1997), Suppression of L-histidine decarboxylase mRNA expression by methyleugenol, Biochemical and Biophysical Research Communications, 232: 188–191.
99. Smith, R.L., Adams, T.B., Doull, J., Feron, V.J., Goodman, J.I., Marnett, L.J., Portoghese, P.S., Waddell, W.J., Wagner, B.M., Rogers, A.E., Caldwell, J., and Sipes, I.G. (2002), Safety assessment of allylalkoxybenzene derivatives used as flavouring substances — methyl eugenol and estragole, Food Chemical Toxicology, 40: 851–870.
100. Solheim, E. and Scheline, R. R. (1973), Metabolism of alkenebenzene derivatives in the rat. I. p-Methoxyallylbenzene (estragole) and p-methoxypropenylbenzene (anethole), Xenobiotics, 3: 493–510.
101. Solheim, E. and Scheline, R.R. (1976), Metabolism of alkenebenzene derivatives in the rat. II. Eugenol and isoeugenol methyl ethers, Xenobiotics, 6: 137–150.
102. SRI International (1990), Directory of Chemical Producers, United States of America, SRI, Menlo Park, CA., pp. 654, 8, 291, 292, 391.
103. Steiner, L.F. (1952), Methyl eugenol as an attractant for oriental fruit fly, Journal of Economic Entomology, 45: 241–248.
104. Steiner, L.F., Mitchell, W.C., Harris, E.J., Kozuma, T.T., and Fujimoto, M.S. (1965), Oriental fruit fly by male annihilation, Journal of Economic Entomology, 58: 961–964.
105. Steiner, L.F., Hart, W.G., Harris, E.J., Cunningham, R.T., Ohinata, K., and Kamakahi, D.C. (1970), Eradication of the oriental fruit fly from the Mariana Islands by the methods of male annihilation and sterile insect release, Journal of Economic Entomology, 63: 131–135.
106. Stillwell, W.G., Carman, J., Bell, L., and Horning, M.G. (1974), The metabolism of safrole and 2′,3′-epoxysafrole in the rat and guinea pig, Drug Metabolism and Disposal, 2: 489–98.
107. Stofberg, J. and Grundschober, F. (1987), Consumption ratio and food predominance of flavoring materials, Perfumer and Flavorist, 12: 27.
108. Szabadics, J. and Erdelyi, L. (2000), Pre-and post-synaptic effects of eugenol and related compounds on Helix pomatia L. neurons, Acta Bioligica Hungarica, 51: 265–273.
109. Thacke, D.C., Iatrapoulos, M.J., Hard, G.C., Hotz, K.J., Wang, C.X., Williams, G.M., and Wilson, A.G.E. (1995), A study of the mechanism of butachlor-associated gastric neoplasms in Sprague-Dawley rats, Experimental and Toxicological Pathology., 47: 107–116.
110. Thompson, D.C., Teodosiu, D., Egestad, B., Mickos, H., and Moldeus, P. (1990), Formation of glutathione conjugates during oxidation of eugenol by microsomal fractions of rat liver and lung, Biochemical Pharmacology, 39: 1587–1595.
111. Thompson, D.C., Constantin-Teodosiu, D., and Moldeus, P. (1991), Metabolism and cytotoxicity of eugenol in isolated rat hepatocytes, Chemico-Biological Interactions, 77: 137–147.
112. Thompson, D.C., Perera, K., Krol, E.S., and Bolton, J.L. (1998), O-Methoxy-4-alkylphenols that form quinone methides of intermediate reactivity are the most toxic in rat liver slices, Chemical Research in Toxicology, 8: 323–327.
113. Tsai, S.J. and Sheen L.Y. (1987), Essential oil of Ocimum basilicum L. cultivated in Taiwan, in L.W. Sze and F.C. Woo (Eds.), Trends in Food Science, Proceedings of the 7th World Congress of Food Science and Technology, Singapore: Institute of Food Science and Technology, pp. 66–70.
114. Tsai, R.S., Carrupt, P.A., Testa, B., and Caldwell, J. (1994), Structure-genotoxicity relationships of allylbenzenes and propenylbenzenes: a quantum chemical study, Chemical Research in Toxicology, 7: 73–76.
115. Wang, T.C., Koh, T.J., Varro, A., Cahill, R.J., Dangler, C.A., Fox, J.G., and Dockray, G.J. (1996), Processing and proliferative effects of human progastrin in transgenic mice, Journal of Clinical Investigation, 98: 1918–1929.
116. WHO (1981), Evaluation of Certain Food Additives and Contaminants, Twenty-sixth Report of the Joint FAO/WHO Expert Committee on Food Additives, Technical Report Series 669, WHO, Geneva, pp. 92–94.
117. Wie, M.B., Won, M.H., Lee, K.H., Shin, J.H., Lee, J.C., Suh, H.W., Song, D.K., and Kim, Y.H. (1997), Eugenol protects neuronal cells from excitotoxic and oxidative injury in primary cortical cultures, Neuroscience Letters, 225:93–96.
118. Williams, G.M., Dunke, V.C., and Ray, V.A. (1983), Cellular systems for toxicity testing, Annals of the NewYork Academy of Sciences, 407: 1–484.
119. Woo, Y., Lai, D., Arcos, J., Argus, M., Cimino, M., DeVito, S., and Keifer, L. (1997), Mechanism-based structure-activity relationship (SAR) analysis of carcinogenic potential of 30 NTP test chemicals, Environment Carcinogenesis and Ecotoxicology Reviews, C15: 139–160.