A safety assessment of coumarin taking into account species-specificity of toxicokinetics

Food and Chemical Toxicology

Volumn 44, Issue 4, 2006, Pages 462-475

  Felter, S P ^a   Vassallo, J D ^a   Carlton, B D ^b   Daston, G P ^a  

^a PROCTER AND GAMBLE COMPANY   (United States)

^b Rhodia Inc   (United States)

Author keywords

Coumarin; Human; Risk assessment

Indexed keywords

CIMETIDINE; COUMARIN;

ARTICLE; CLARA CELL; CLINICAL TRIAL; CYTOTOXICITY; DIARRHEA; DIZZINESS; DRUG DETOXIFICATION; DRUG FATALITY; DRUG METABOLISM; DRUG MIXTURE; DRUG SAFETY; DRUG TOLERANCE; GENOTOXICITY; HUMAN; HYPERPLASIA; KIDNEY CARCINOMA; KIDNEY DISEASE; LIVER TOXICITY; LUNG CARCINOMA; LUNG TOXICITY; LUNG TUMOR; MAXIMUM TOLERATED DOSE; NONHUMAN; PROSTATE CARCINOMA; RISK ASSESSMENT; TERATOGENICITY; TOXICOKINETICS; VOMITING;

ANIMALS; ANTICOAGULANTS; COUMARINS; DOGS; ENVIRONMENTAL EXPOSURE; HUMANS; MICE; PRIMATES; RATS; RISK ASSESSMENT; SPECIES SPECIFICITY; TOXICITY TESTS;

RODENTIA;

EID: 33644867949     PISSN: 02786915     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.fct.2005.08.019     Document Type: Article

References (112)

1. M. Andrejak, M. Gersberg, C. Sgro, G. Decocq, J.D. Hamel, M. Morin, and V. Gras French harmacovigilance survey evaluating the hepatic toxicity of coumarin Pharmacoepidemiology and Drug Safety 7 Suppl. 1 1998 S45 S50
2. A.M. Api Lack of effect of coumarin on the formation of micronuclei in an in vivo mouse micronucleus assay Food and Chemical Toxicology 39 2001 837 841
3. J. Baron, and J.M. Voigt Localization, distribution, and induction of xenobiotic metabolizing enzymes and aryl hydrocarbon hydroxylase activity within lung Pharmacology and Therapeutics 47 1990 419 445
4. H.M. Becker, G. Niedermaier, and K.H. Orend Benzopyrone in the therapy of postreconstructive edema. A clinical double-blind study Fortschritte Der Medizin (Munchen) 103 1985 593
5. A.P.A. Beinssen Possible coumarin hepatotoxicity (Letter) Medical Journal of Australia 161 1994 725
6. S.L. Born, P.A. Rodriguez, C.L. Eddy, and L.D. Lehman-McKeeman Synthesis and reactivity of coumarin 3,4-epoxide Drug Metabolism and Disposition 25 1997 1318 1324
7. S.L. Born, A.S. Fix, D. Caudill, and L.D. Lehman-Mckeeman Selective Clara cell injury in mouse lung following acute administration of coumarin Toxicology and Applied Pharmacology 151 1998 45 56
8. S.L. Born, D. Caudill, B.J. Smith, and L.D. Lehman-McKeeman In vitro kinetics of coumarin 3,4-epoxidation: application to species differences in toxicity and carcinogenicity Toxicological Sciences 58 2000 23 31
9. S.L. Born, J.K. Hu, and L.D. Lehman-McKeeman o-Hydroxyphenylacetaldehyde is a hepatotoxic metabolite of coumarin Drug Metabolism and Disposition 28 2000 218 223
10. S.L. Born, D. Caudill, K.L. Fliter, and M.P. Purdon Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation Drug Metabolism and Disposition 30 2002 483 487
11. S.L. Born, A.M. Api, R.A. Ford, F.R. Lefever, and D.R. Hawkins Comparative metabolism and kinetics of coumarin in mice and rats Food and Chemical Toxicology 41 2003 247 258
12. A. Buckpitt, A. Chang, A. Weir, L. Van Winkle, X. Duan, R. Philpot, and C. Plopper Relationship of cytochrome P450 activity to Clara cell cytotoxicity. IV. Metabolism of naphthalene and naphthalene oxide in microdissected airways from mice, rats, and hamsters Molecular Pharmacology 47 1995 74 81
13. M. Burian, J. Freudenstein, M. Tegtmeier, B. Naser-Hijazi, H.H. Henneicke-von Zepelin, and W. Legrum Single copy of variant CYP2A6 alleles does not confer susceptibility to liver dysfunction in patients treated with coumarin International Journal of Clinical Pharmacology and Therapeutics 41 4 2003 141 147
14. B.D. Carlton, J.-C. Aubrun, and G.S. Simon Effects of coumarin following perinatal and chronic exposure in Sprague-Dawley rats and CD-1 rats Fundamental and Applied Toxicology 30 1996 145 151
15. Casley-Smith, J.R., 1997. Personal communication with B. Carlton.
16. J.R. Casley-Smith Benzo-pyrones in the treatment of lymphoedema International Angiology 18 1999 31 41
17. J.R. Casley-Smith, and J.R. Casley-Smith Frequency of coumarin hepatotoxicity Medical Journal of Australia 162 1995 391
18. J.R. Casley-Smith, R.G. Morgan, and N.B. Piller Treatment of lymphedema of the arms and legs with 5,6-benzo-[a]-pyrone New England Journal of Medicine 329 1993 1158 1163
19. J.R. Casley-Smith, C.T. Wang, J.R. Casley-Smith, and C. Zi-hai Treatment of filarial lymphoedema and elephantiasis with 5,6-benzo-alpha-pyrone (coumarin) British Medical Journal 307 1993 1037 1041
20. T.S. Chang, J.L. Gan, K.D. Fu, and W.Y. Huang The use of 5,6 benzo-[alpha]-pyrone (coumarin) and heating by microwaves in the treatment of chronic lymphedema of the legs Lymphology 29 1996 106 111
21. G.F. Chen, Y.M. Tang, B. Green, D.X. Lin, F.P. Guengerich, A.K. Daly, N.E. Caporaso, and F.F. Kadlubar Low frequency of CYP2A6 gene polymorphism as revealed by a one-step polymerase chain reaction method Pharmacogenetics 9 1999 327 332
22. S. Cholerton, M.E. Idle, A. Vas, F.J. Gonzalesz, and J.R. Idle Comparison of a novel thin-layer chromatographic fluorescence detection method with a spectrophotofluorometric method for the determination of 7-hydroxycoumarin in human urine Journal of Chromatography 575 1992 325 330
23. L. Clodius, and N.B. Piller Conservative therapy for postmastectomy lymphedema Chirurgia Plastica 4 1978 193 202
24. D. Cox, R. O'Kennedy, and R.D. Thornes The rarity of liver toxicity in patients treated with coumarin (1,2-benzopyrone) Human and Experimental Toxicology 8 1989 501 506
25. G. Cruzan, J.R. Cushman, L.S. Andrews, G.C. Granville, R.R. Miller, C.J. Hardy, D.W. Coombes, and P.A. Mullins Sub-chronic inhalation studies of styrene in CD rats and CD1 mice Fundamamental and Applied Toxicology 35 1997 152 165
26. G. Cruzan, J.R. Cushman, L.S. Andrews, G.C. Granville, K.A. Johnson, C.J. Hardy, D.W. Coombes, P.A. Mullins, and W.R. Brown Chronic toxicity/oncogenicity study of styrene in CD rats by inhalation exposure for 104 weeks Toxicological Sciences 46 1998 266 281
27. G. Cruzan, J.R. Cushman, L.S. Andrews, G.C. Granville, K.A. Johnson, C. Bevan, C.J. Hardy, D.W. Coombes, P.A. Mullins, and W.R. Brown Chronic toxicity/oncogenicity study of styrene in CD-1 mice by inhalation exposure for 104 weeks Journal of Applied Toxicology 21 2001 185 198
28. F.H. Dexeus, C.J. Logothetis, A. Sella, K. Fitz, R. Amato, J.M. Reuben, and N. Dozier Phase II study of coumarin and cimetidine in patients with metastatic renal cell carcinoma Journal of Clinical Oncology 8 1990 325 329
29. A.J. Edwards, R.J. Price, A.B. Renwick, and B.G. Lake Lack of effect of coumarin on unscheduled DNA synthesis in the in vivo rat hepatocyte DNA repair assay Food and Chemical Toxicology 38 2000 403 409
30. EFSA (European Food Safety Authority), 2004. Opinion of the Scientific Panel on Food Additives, Flavouring, Processing Aids and Materials in Contact with Food (AFC) on a Request from the Commission Related to Coumarin. Question Number EFSA-Q-2003-118. Adopted on 6 October 2004. The EFSA Journal 104, 1-36. Available from: 〈http://www.efsa.eu.int/science/afc/afc_opinions/726_en. html〉.
31. D. Egan, R. O'Kennedy, E. Moran, D. Cox, E. Prosser, and R.D. Thornes The pharmacology, metabolism, analysis, and applications of coumarin and coumarin-related compounds Drug Metabolism and Review 22 1990 503 529
32. J.G. Evans, L.F. Gaunt, and B.G. Lake Two-year toxicity study on coumarin in the baboon Food and Cosmetic Toxicology 17 1979 187 193
33. P. Fernandez-Salguero, S.M. Hoffman, S. Cholerton, H. Mohrenweiser, H. Raunio, A. Rautio, O. Pelkonen, J.D. Huang, W.E. Evans, J.R. Idle, and F.J. Gonzalez A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles American Journal of Human Genetics 57 1995 651 660
34. G. Feuer, L. Goldberg, and K.I. Gibson Liver response tests. VII. Coumarin metabolism in relation to the inhibition of rat-liver glucose-6-phophatase Food and Cosmetics Toxicology 4 1966 157 167
35. F. Floc'h, F. Mauger, J.-R. Desmurs, A. Gard, F. Bagneris, and B. Carlton Coumarin in plants and fruits: implications in perfumery Perfumer and Flavorist 27 2002 32 37
36. R.A. Ford, D.R. Hawkins, B.C. Mayo, and A.M. Api The in vivo dermal absoption and metabolism of [4-14C]coumarin by rats and by human volunteers under simulated conditions of use in fragrances Food and Chemical Toxicology 39 2001 153 162
37. J.R. Foster, T. Green, L.L. Smith, R.W. Lewis, P.M. Hext, and I. Wyatt Methylene chloride-an inhalation study to investigate pathological and biochemical events occurring in the lungs of mice over an exposure period of 90 days Fundamental and Applied Toxicology 18 1992 376 388
38. K. Fukuda, K. Takemoto, and H. Tsurata Inhalation carcinogenicity of trichloroethylene in mice and rats Industrial Health 21 1983 243 254
39. T. Green, A. Toghill, and J.R. Foster The role of cytochromes P-450 in styrene induced pulmonary toxicity and carcinogenicity Toxicology 169 2001 107 117
40. H. Hadidi, K. Zahlsen, J.R. Idle, and S. Cholerton A single amino acid substitution (Leu160His) in cytochrome P450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin Food and Chemical Toxicology 35 1997 903 907
41. H. Hadidi, Y. Irshaid, C.B. Vagbo, A. Brunsvik, S. Cholerton, K. Zahlsen, and J.R. Idle Variability of coumarin 7- and 3-hydroxylation in a Jordanian population is suggestive of a functional polymorphism in cytochrome P450 CYP2A6 European Journal of Clinical Pharmacology 54 1998 437 441
42. E.C. Hagan, W.H. Hansen, O.G. Fitzhugh, P.M. Jenner, W.I. Jones, J.M. Taylor, E.L. Long, A.A. Nelson, and J.B. Brouwer Food flavourings and compounds of related structure. II. Subacute and chronic toxicity Food and Cosmetics Toxicology 12 1967 141 157
43. S. Harada, S. Misawa, D.P. Agarwal, and H.W. Goedde Liver alcohol dehydrogenase and aldehyde dehydrogenase in Japanese-isoenzyme variation and its possible role in alcohol intoxication American Journal of Human Genetics 32 1980 8 15
44. S. Harada, D.P. Agarwal, and H.W. Goedde Aldehyde dehyrogenase deficiency as cause of facial flushing reaction to alcohol in Japanese Lancet 2 1981 982
45. D.R. Hawkins, and R.A. Ford Comparative metabolism and pharmacokinetics of (14)C-coumarin in the mouse after gavage or dietary administration The Toxicologist 36 1 1997 141 Part 2
46. P. Honkakoski, J. Maenpaa, J. Leikola, M. Pasanen, R. Juvonen, M.A. Lang, O. Pelkonene, and H. Raunio Cytochrome P4502A-mediated coumarin 7-hydroxylation and testosterone hydroxylation in mouse and rat lung Pharmacological Toxicology 72 1993 107 112
47. 14C-coumarin comparative metabolism and pharmacokinetics in the mouse after gavage and dietary administration, February, 1995.
48. A.S. Hussain, K.A. Hoffmann, and W.A. Ritschel Transdermal Uptake of the Lymphoactive Coumarin/7-OH Coumarin. Excerpta Medica 1992 Elsevier Science Publishers Amsterdam, The Netherlands pp. 235-238
49. T. Huwer, H.J. Altmann, W. Grunow, S. Lehnardt, M. Przybylski, and G. Eisenbrand Coumarin mercapturic acid isolated from rat urine indicates metabolic formation of coumarin 3, 4-epoxide Chemical Research in Toxicology 4 1991 586 590
50. IPCS (International Programme on Chemical Safety), 1994. Assessing human health risks of chemicals: derivation of guidance values for health-based exposure limits. Geneva, World Health Organization, Environmental Health Criteria 170.
51. S. Jamal, J.R. Casley-Smith, and J.R. Casley-Smith The effects of 5,6 benzo-[a]-pyrone (coumarin and DEC) on filiaritic lymphoedema and elephantiasis in India. Preliminary results Annals of Tropical Medicine and Parasitology 83 1989 287 296
52. M. Kaighen, and R.T. Williams The metabolism of [3-14C] coumarin Journal of Medicinal Chemistry 3 1961 25 43
53. U. Klotz, and E. Ammon Clinical and toxicological consequences of the inductive potential of ethanol European Journal of Clinical Pharmacology 54 1998 7 12
54. S. Koch, I. Beurton, S. Bresson-Hadni, B. Monnot, S. Hrusovsky, M.C. Becker, C. Vanlemmens, J.P. Carbillet, and J.P. Miguet Coumarin-induced acute cytolotic hepatitis. Two cases Gastroenterologie Clinique et Biologique 21 1997 223 225
55. B. Lake Coumarin metabolism, toxicity, and carcinogenicity: relevance for human risk assessment Food and Chemical Toxicology 37 1999 423 453
56. B.G. Lake, and P. Grasso Comparison of the hepatotoxicity of coumarin in the rat, mouse, and Syrian hamster: a dose and time response study Fundamental and Applied Pharmacology 97 1996 311 323
57. B.G. Lake, T.J.B. Gray, J.G. Evans, D.F.V. Lewis, J.A. Beamand, and K.L. Hue Studies on the mechanism of coumarin-induced toxicity in rat hepatocytes: comparison with dihydrocoumarin and other coumarin metabolites Toxicology and Applied Pharmacology 97 1989 311 323
58. Loprinzi, C.L., 1997. Personal communication with B. Carlton.
59. C.L. Loprinzi, and J. Sloan Coumarin-induced hepatotoxicity Journal of Clinical Oncology 15 1997 3167 3168
60. C.L. Loprinzi, J.W. Kugler, J.A. Sloan, T.W. Rooke, S.K. Quella, P. Novotny, R.B. Mowat, J.C. Michalak, P.J. Stella, R. Levitt, L.K. Tschetter, and H. Windschitl Lack of effect of coumarin in women with lymphedema after treatment for breast cancer New England Journal of Medicine 340 1999 346 350
61. D. Lucas, R. Ferrara, E. Gonzales, A. Alfobres, M. Manno, and F. Berthou Cytochrome CYP2E1 phenotyping and genotyping in the evaluation of health risks from exposure to polluted environments Toxicology Letters 124 2001 71 81
62. A.B. Lumsden, A. McLean, and D. Lamb Goblet and Clara cells of human distal airways: evidence for smoking induced changes in their numbers Thorax 39 1984 844 849
63. D. Mahvi, H. Bank, and R. Harley Morphology of a naphthalene-induced bronchiolar lesion American Journal of Pathology 86 1977 559 572
64. C. Maltoni, G. Lefermine, and G. Cotti Experimental research on trichloroethylene carcinogenesis C. Maltoni M.A. Mehlman Archives of Research on Industrial Carcinogenesis vol. 5 1986 Princeton Scientific Princeton, NJ 1 393
65. M.E. Marshall, and J.L. Mohler Treatment of renal cell carcinoma with coumarin: a review Journal of Irish Colleges of Physicians and Surgeons 22 1993 6 9
66. M.E. Marshall, L. Mendelsohn, K. Butler, J. Cantrell, J. Harvey, and J. Macdonald Treatment of non-small cell carcinoma with coumarin (1,2-benzopyrone) and cimetidine Cancer Treatment Reports 71 1987 91 92
67. M.E. Marshall, L. Mendelsohn, K. Butler, L. Riley, J. Cantrell, C. Wiseman, R. Taylor, and J. Macdonald Treatment of metastatic renal cell carcinoma with coumarin (1,2-benzopyrone) and cimetidine: a pilot study Journal of Clinical Oncology 5 1987 862 866
68. M.E. Marshall, K. Butler, J. Cantrell, C. Wiseman, and L. Mendelsohn Treatment of advanced malignant melanoma with coumarin and cimetidine: a pilot study Cancer Chemotherapy and Pharmacology 24 1989 65 66
69. Mayo, B., 1996. 14C-coumarin dermal absorption in man. Huntingdon Life Sciences Report RIF 30/943257.
70. J. Mohler, B. Williams, I. Thompson, and M.E. Marshall Coumarin (1,2-benzopyrone) for the treatment of prostatic carcinoma Journal of Irish Colleges of Physicians and Surgeons 22 1993 12 15
71. M. Negishi, R. Lindberg, B. Burkhart, T. Ichikawa, P. Honkakoski, and M. Lang Mouse steroid 15α-hydroxylase gene family: identification of Type II P-450 15α as coumarin 7-hydroxylase Biochemistry 28 1989 4169 4172
72. P.T. Nhamburo, S. Kimura, O.W. McBride, A. Kozak, H.V. Geloin, and F.J. Gonzalez The human CYP2F gene subfamily: identification of a cDNA encoding a new cytochrome P450, cDNA-directed expression, and chromosome mapping Biochemistry 29 1990 5491 5499
73. NTP (National Toxicology Program), 1986. Toxicology and Carcinogenesis Studies of Dichloromethane in F344/N Rats and B6C3F1 Mice, NTP TR 306. US Department of Health and Human Services, Public Health Service, National Institutes of Health.
74. NTP (National Toxicology Program), 1990. Toxicology and Carcinogenesis Studies of trichloroethylene (without epichlorohydrin) in F344/N Rats and B6C3F1 Mice (Gavage Study), NTP TR 243. US Department of Health and Human Services, Public Health Service, National Institutes of Health.
75. NTP (National Toxicology Program), 1992. Toxicology and Carcinogenesis Studies of Naphthalene in B6C3F1 Mice, NTP TR 410. US Department of Health and Human Services, Public Health Service, National Institutes of Health.
76. NTP (National Toxicology Program), 1993a. Toxicology and Carcinogenesis Studies of Coumarin in F344/N Rats and B6C3F1 Mice (Gavage Study), NTP TR 422. US Department of Health and Human Services, Public Health Service, National Institutes of Health.
77. NTP (National Toxicology Program), 1993b. Toxicology and Carcinogenesis Studies of 3,4-Dihydrocoumarin in F344/N Rats and B6C3F1 Mice, NTP TR 423. US Department of Health and Human Services, Public Health Service, National Institutes of Health.
78. NTP (National Toxicology Program), 2000. Toxicology and Carcinogenesis Studies of Naphthalene in F344/N Rats (Inhalation Studies), NTP TR 500. US Department of Health and Human Services, Public Health Service, National Institutes of Health.
79. K.A.F. O'Brien, L.L. Smith, and G.M. Cohen Differences in naphthalene-induced toxicity in the mouse and rat Chemico-Biological Interactions 55 1985 109 122
80. J. Odum, J.R. Foster, and T. Green A mechanism for the development of Clara cell lesions in the mouse lung after exposure to trichloroethylene Chemico-Biological Interactions 83 1992 135 153
81. M. Oscarson Genetic polymorphisms in the cytochrome P450 2A6 (CYP2A6) gene: implications for the interindividual differences in nicotine metabolism Drug Metabolism and Disposition 29 2001 91 95
82. M. Oscarson, R.A. McLellan, H. Gullsten, Q.Y. Yue, M.A. Lang, M.L. Bernal, B. Sinues, A. Hirvonen, H. Raunio, O. Pelkonen, and M. Ingleman-Sundberg Characterization and PCR-based detection of a CYP2A6 gene deletion found at a high frequency in a Chinese population FEBS Letters 448 1999 105 110
83. M. Pasanen, Z. Rannala, A. Tooming, E.A. Sotaniemi, O. Pelkonen, and A. Rautio Hepatitis A impairs the function of human hepatic CYP2A6 in vivo Toxicology 123 1997 177 184
84. T. Paschke, M. Riefler, A. Schuler-Metz, L. Wolz, G. Scherer, C.M. McBride, and G. Bepler Comparison of cytochrome P450 2A6 polymorphism frequencies in Caucasians and African-Americans using a new one-step PCR-RFLP genotyping method Toxicology 168 2001 259 268
85. R. Pearce, D. Greenway, and A. Parkinson Species differences and interindividual variation in liver microsomal cytochrome P450 2A enzymes: effects on coumarin, dicoumarol and testosterone oxidation Archives of Biochemistry and Biophysics 298 1992 211 225
86. O. Pelkonen, A. Raution, H. Raunio, and M. Pasanen CYP2A6: a human coumarin 7-hydroxylase Toxicology 144 2000 139 147
87. C.G. Plopper, A.T. Mariassy, and L.H. Hill Ultrastructure of the nonciliated bronchiolar epithelial (Clara) cell of mammalian lung: I. A comparison of rabbit, guinea pig, rat, hamster, and mouse Experimental Lung Research 1 1980 139 154
88. H. Raunio, T. Syngelma, M. Pasanen, R. Juvonen, P. Honkakoski, M.A. Kairaluoma, E. Sotaniemi, M.A. Lang, and O. Pelkonen Immunochemical and catalytical studies on hepatic coumarin 7-hydroxylase in man, rat and mouse Biochemical Pharmacology 37 1988 3889 3895
89. H. Raunio, A. Rautio, H. Gullsten, and O. Pelkonen Polymorphisms of CYP2A6 and its practical consequences British Journal of Clinical Pharmacology 52 2001 357 363
90. A. Rautio, H. Kraul, A. Koho, E. Salmela, and O. Pelkonen Interindividual variability of coumarin 7-hydroxylation in healthy volunteers Pharmacogenetics 2 1992 227 233
91. W.A. Ritschel, and S.A. Hussain Transdermal absorption and topical bioavailability of coumarin Methods and Findings in Experimental and Clinical Pharmacology 10 1988 165 169
92. W.A. Ritschel, M.E. Brady, H.I.S. Tan, K.A. Hoffmann, I.M. Yiu, and K.W. Grummich Pharmacokinetics of coumarin and its 7-hydroxy-metabolites upon intravenous and peroral administration of coumarin in man European Journal of Clinical Pharmacology 12 1977 457 461
93. W.A. Ritschel, M.E. Brady, and H.I.S. Tan First-pass effect of coumarin in man International Journal of Clinical Pharmacology and Biopharmacy 17 1979 99 103
94. SCF, 1997. Opinion on coumarin (a constituent of natural flavouring source materials limited by Annex II of flavourings directive 88/388/EEC), expressed on 16 December 1994. Reports of the Scientific Committee for Food (Thirty-sixth series). European Commission, Directorate General Industry. Luxembourg. Available from: 〈http://europa.eu.int/comm/food/fs/sc/scf/ reports/scf_reports_36.pdf〉.
95. C.J. Serabjit-Singh, S.J. Nishio, R.M. Philpot, and C.G. Plopper The distribution of cytochrome P-450 monooxygenase in cells of the rabbit lung: an ultrastructural immunocytochemical characterization Molecular Pharmacology 33 1988 279 289
96. W.H. Shilling, R.F. Crampton, and R.C. Longland Metabolism of coumarin in man Nature London 221 1969 664 665
97. T. Shimada, H. Yamazaki, and F.P. Guengerich Ethnic-related differences in coumarin 7-hydroxylation activities catalyzed by cytochrome P4502A6 in liver microsomes of Japanese and Caucasian populations Xenobiotica 26 1996 395 403
98. Swenberg, J.A., 2003. Covalent binding index study of coumarin. Report of Laboratory of Molecular Carcinogenesis and Mutagenesis, University of North Carolina, Chapel Hill, NC USA 27599, April 2003. Submitted by European Flavour and Fragrance Association (EFFA), Square Marie-Louise, 49, B-1000, Brussels. Cited in EFSA, 2004.
99. R.D. Thornes Prevention of recurrence of malignant melanoma by coumarin (1,2-benzopyrone) Journal of Irish Colleges of Physicians and Surgeons 22 1993 17 19
100. R.D. Thornes, and G. Lynch Combination of cimetidine with other drugs for treatment of cancer New England Journal of Medicine 308 1983 591
101. R.D. Thornes, G. Lynch, and M.V. Sheehan Cimetidine and coumarin therapy of melanoma Lancet 2 1982 328
102. D. Thornes, L. Daly, G. Lynch, H. Browne, A. Tanner, F. Keane, S. O'Loughlin, T. Corrigan, P. Daly, and G. Edwards Prevention of recurrence of high risk malignant melanoma by coumarin European Journal of Surgical Oncology 15 1989 431 435
103. I. Ueno, and I. Hirono Non-carcinogenic response to coumarin in Syrian golden hamsters Food and Chemical Toxicology 19 1981 353 355
104. J.D. Vassallo, S.W. Morall, K.L. Fliter, S.M. Curry, G.P. Daston, and L.D. Lehman-McKeeman Liquid chromatographic determination of the glutathione conjugate and ring opened metabolites formed from coumarin epoxidation Journal of Chromatography B: Biomedical Sciences and Applications 794 2003 257 271
105. J.D. Vassallo, S.M. Hicks, G.P. Daston, and L.D. Lehman-McKeeman Metabolic detoxification determines species differences in coumarin-induced hepatotoxicity Toxicological Sciences 80 2004 249 257
106. J.D. Vassallo, S.M. Hicks, S.L. Born, and G.P. Daston Roles for epoxidation and detoxification of coumarin in determining species differences in Clara cell toxicity Toxicological Sciences 82 2004 26 33
107. J.A.A. West, C.H. Chichester, A.R. Buckpitt, N.K. Tyler, P. Brennan, C. Helton, and C.G. Plopper Heterogeneity of Clara cell glutathione. A possible basis for differences in cellular responses to pulmonary cytotoxicants American Journal of Respiratory Cell and Molecular Biology 23 2000 27 36
108. J.G. Widdicombe, and R.J. Pack The Clara cell European Journal of Respiratory Disease 63 1982 202 220
109. S. Yamano, J. Tatsuno, and F.J. Conzalez The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes Biochemistry 29 1990 1322 1329
110. A. Yoshida, G. Wang, and V. Dave Determination of genotypes of human aldehyde dehydrogenase ALDH2 Locus American Journal of Human Genetics 35 1983 1107 1116
111. J.J. Yourick, and R.L. Brounaugh Percutaneous absorption and metabolism of coumarin in human and rat skin Journal of Applied Toxicology 17 1997 153 158
112. K.S. Zanker, G. Blumel, J. Lange, and J.R. Siewert Coumarin in melanoma patients: an experimental and clinical study Drugs Under Experimental and Clinical Research 10 1984 767 774