TOXICOLOGY AND CARCINOGENESIS STUDIES OF 2-METHYLIMIDAZOLE (CAS NO. 693-98-1) IN F344/N RATS AND B6C3F1MICE (FEED STUDIES)

NTP Technical Report on the Toxicology and Carcinogenesis Studies Series

Volumn TR-516, Issue , 2004, Pages 1-302

  Chan, P C ^a   Bristol, D W ^a   Bucher, J R ^a   Burka, L T ^a   Hailey, J R ^a   Haseman, J K ^a   Maronpot, R R ^a   Roycroft, J H ^a   Smith, C S ^a   Travlos, G S ^a   Witt, K L ^a   Richter, W ^a   Hebert C D ^a   Farnell, D R ^a   Health, J E ^a   Hardisty, J F ^a   Brecher, S ^a   Picut, C ^a   Cimon, K J ^b   Dixon, D ^c   Flake, G P ^c   Herbert, R A ^c   Hill, G D ^c   Maurer, J ^d   Pearse, G ^c   Peckham, J C ^b   Sills, R C ^c   Tani, Y ^c   Nyska, A ^c   Shackelford, C C ^b   Crockett, P W ^a   Betz, L J ^a   McGowan, K P ^a   Scott, J T ^a   Gunnels, S R ^a   Carver, P H ^a   Gideon, P A ^a   Harper, L M ^a   Serbus, D C ^a   more..

^a ILS Inc ^*

^b EXPERIMENTAL PATHOLOGY LABORATORIES INC   (United States)

^c National Toxicology Program

^d Pathology Associates International

Author keywords

[No Author keywords available]

Indexed keywords

EID: 70649100020     PISSN: 23788917     EISSN: 23788925     Source Type: Book Series    
DOI: None     Document Type: Review

References (100)

1. Adams, M.L., Meyer, E.R., and Cicero, T.J. (1998). Imidazoles suppress rat testosterone secretion and testicular interstitial fluid formation in vivo. Biol. Reprod. 59, 248-254.
2. The Aldrich Library of 13C and 1H Spectra (1992). C. J. Pouchert and J. Behnke, Eds. Aldrich Chemical Company, Inc., Milwaukee, WI.
3. The Aldrich Library of FT-IR Spectra (1981). 1st ed. (Charles J. Pouchert, Ed.). Aldrich Chemical Company, Inc., Milwaukee, WI.
4. The Aldrich Library of NMR Spectra (1974). Vol. 10 (Charles J. Pouchert and J. Behnke, Eds.). Aldrich Chemical Company, Inc., Milwaukee, WI.
5. Ashby, J., and Tennant, R.W. (1991). Definitive relationships among chemical structure, carcinogenicity and mutagenicity for 301 chemicals tested by the U.S. NTP. Mutat. Res. 257, 229-306.
6. Bailer, A.J., and Portier, C.J. (1988). Effects of treatment-induced mortality and tumor-induced mortality on tests for carcinogenicity in small samples. Biometrics 44, 417-431.
7. Beard, J.L., Brigham, D.E., Kelley, S.K., and Green, M.H. (1998). Plasma thyroid hormone kinetics are altered in iron-deficient rats. J. Nutr. 128, 1401-1408.
8. Biegel, L.B., Cook, J.C., O'Connor, J.C., Aschiero, M., Arduengo, A.J., III, and Slone, T.W. (1995). Subchronic toxicity study in rats with 1-methyl-3-propylimidazole2-thione (PTI): Effects on the thyroid. Fundam. Appl. Toxicol. 27, 185-194.
9. Bieler, G.S., and Williams, R.L. (1993). Ratio estimates, the delta method, and quantal response tests for increased carcinogenicity. Biometrics 49, 793-801.
10. Boorman, G.A., Montgomery, C.A., Jr., Eustis, S.L., Wolfe, M.J., McConnell, E.E., and Hardisty, J.F. (1985). Quality assurance in pathology for rodent carcinogenicity studies. In Handbook of Carcinogen Testing (H.A. Milman and E.K. Weisburger, Eds.), pp. 345-357. Noyes Publications, Park Ridge, NJ.
11. Capen, C.C. (1997). Mechanistic data and risk assessment of selected toxic end points of the thyroid gland. Toxicol. Pathol. 25, 39-48.
12. Chappel, C.I., and Howell, J.C. (1992). Caramel colours-A historical introduction. Food Chem. Toxicol. 30, 351-357.
13. Chemical Economics Handbook [database online] (1995). Dialog 359. Available from SRI Consulting, Menlo Park, CA.
14. Code of Federal Regulations (CFR) 21, Part 58.
15. Comer, C.P., Chengelis, C.P., Levin, S., and Kotsonis, F.N. (1985). Changes in thyroidal function and liver UDP-glucuronosyltransferase activitity in rats following administration of a novel imidazole (SC 37211). Toxicol. Appl. Pharmacol. 80, 427-436.
16. Cox, D.R. (1972). Regression models and life-tables. J. R. Stat. Soc. B34, 187-220.
17. Crawford, B.D. (1985). Perspectives on the somatic mutation model of carcinogenesis. In Advances in Modern Environmental Toxicology. Mechanisms and Toxicity of Chemical Carcinogens and Mutagens (M.A. Mehlman, W.G. Flamm, and R.J. Lorentzen, Eds.), pp. 13-59. Princeton Scientific Publishing Co., Inc., Princeton, NJ.
18. Dixon, W.J., and Massey, F.J., Jr. (1957). Introduction to Statistical Analysis, 2nd ed., pp. 276-278, 412. McGraw-Hill Book Company, Inc., New York.
19. Dunn, O.J. (1964). Multiple comparisons using rank sums. Technometrics 6, 241-252.
20. Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Am. Stat. Assoc. 50, 1096-1121.
21. Eliasson, E., Johnsson, I., and Ingelman-Sundberg, M. (1990). Substrate-, hormone-, and cAMP-regulated cytochrome P450 degradation, Proc. Natl. Acad. Sci. USA 87, 3225.
22. Gaworski, C.L., Aranyi, C., Vana, S., Rajendran, N., Abdo, K, Levine, B.S., and Hall A., III (1991). Prechronic inhalation toxicity studies of 2-mercaptobenzimidazole (2-MBI) in F344/N rats. Fundam. Appl. Toxicol. 16, 161-171.
23. Ferrari, F., Baggio, G., and Mangiafico, V. (1987). Effects of imidazole and some imidazole-derivatives on lisuride-induced mounting and aggressiveness. Psychopharmacology 93, 19-24.
24. Hargreaves, M.B., Jones, B.C., Smith, D.A., and Gescher, A. (1994). Inhibition of p-nitrophenol hydroxylase in rat liver microsomes by small aromatic and heterocyclic molecules. Drug Metab. Dispos. 22, 806-810.
25. Haseman, J.K. (1998). National Toxicology Program experience with dietary restriction: Does the manner in which reduced body weight is achieved affect tumor incidence? Int. J. Toxicol. 17, 119-134.
26. Haseman, J.K., and Lockhart, A.M. (1993). Correlations between chemically related site-specific carcinogenic effects in long-term studies in rats and mice. Environ. Health Perspect. 101, 50-54.
27. Haseman, J.K., Young, E., Eustis, S.L., and Hailey, J.R. (1997). Body weight-tumor incidence correlations in long-term rodent carcinogenicity studies. Toxicol. Pathol. 25, 256-263.
28. Hirai, O., Miyamae, Y., Fujino, Y., Izumi, H., Miyamoto, A., and Noguchi, H. (1991). Prior bleeding enhances the sensitivity of the in vivo micronucleus test. Mutat. Res. 264, 109-114.
29. Hollander, M., and Wolfe, D.A. (1973). Nonparametric Statistical Methods, pp. 120-123. John Wiley and Sons, New York.
30. Huang, Y., Zhang, S., and Yang, R. (1983). Survey of communal industrial production of caramel by the ammonium process. Tiaowei Fushipin Keji 3, 11-12 (Abstr.).
31. Huff, J., Cirvello, J., Haseman, J., and Bucher, J. (1991). Chemicals associated with site-specific neoplasia in 1394 long-term carcinogenesis experiments in laboratory rodents. Environ. Health Perspect. 93, 247-271.
32. Integrated Laboratory Systems (ILS) (1990). Micronucleus Data Management and Statistical Analysis Software, Version 1.4. ILS, P.O. Box 13501, Research Triangle Park, NC 27707.
33. Johnson, J.D., Reichelderfer, D., Zutshi, A., Graves, S., Walters, D., and Smith, C. (2002). Toxicokinetics of 2-methylimidazole in male and female F344 rats. J. Toxicol. Environ. Health 65, 869-879.
34. Jonckheere, A.R. (1954). A distribution-free k-sample test against ordered alternatives. Biometrika 41, 133-145.
35. Kaplan, E.L., and Meier, P. (1958). Nonparametric estimation from incomplete observations. J. Am. Stat. Assoc. 53, 457-481.
36. Lewis, R.J., Sr. (1996). Sax's Dangerous Properties of Industrial Materials, 9th ed., p. 2, 250. Van Nostrand Reinhold, New York.
37. McClain, R.M. (1989). The significance of hepatic microsomal enzyme induction and altered thyroid function in rats: Implications for thyroid gland neoplasia. Toxicol. Pathol. 17, 294-306.
38. McClain, R.M. (1992). Thyroid gland neoplasia: Nongenotoxic mechanisms. Toxicol. Lett. 64-65, 397-408.
39. McClain, R.M., and Rice, J.M. (1999). A mechanistic relationship between thyroid follicular cell tumours and hepatocellular neoplasms in rodents. IARC Sci. Publ. 147, 61-67.
40. McConnell, E.E. (1992). Thyroid follicular cell carcinogenesis: results from 343 2-year carcinogenicity studies conducted by the NCI/NTP. Regul. Toxicol. Pharmacol. 16, 177-88.
41. McConnell, E.E., Solleveld, H.A., Swenberg, J.A., and Boorman, G.A. (1986). Guidelines for combining neoplasms for evaluation of rodent carcinogenesis studies. JNCI 76, 283-289.
42. MacGregor, J.T., Wehr, C.M., Henika, P.R., and Shelby, M.D. (1990). The in vivo erythrocyte micronucleus test: Measurement at steady state increases assay efficiency and permits integration with toxicity studies. Fundam. Appl. Toxicol. 14, 513-522.
43. Malgor, L.A., Valsecia, M.E., Verges, E.G., and de Markowsky, E.E. (1995). Enhancement of erythroid colony growth by triiodothyronine in cell cultures from bone marrow of normal and anemic rats with chronic renal failure. Acta Physiol. Pharmacol. Ther. Lationoam. 45, 79-86.
44. Maronpot, R.R., and Boorman, G.A. (1982). Interpretation of rodent hepatocellular proliferative alterations and hepatocellular tumors in chemical safety assessment. Toxicol. Pathol. 10, 71-80.
45. Material Safety Data Sheet (MSDS) (1995). MDL Information Systems, Inc., San Leandro, CA.
46. Material Safety Data Sheet (MSDS) (2003). 2-Methylimidazole (http://msds.pdc.cornell.edu/ msds/msdsdod/a397/m198336.htm).
47. Matyasovszky, P., and Jeszenszky, Z. (1985). Determination of caramels in wines by gel chromatography and gas chromatography. Borgazdasag 33, 105-110 (Abstr.).
48. Miller, J.A., and Miller, E.C. (1977). Ultimate chemical carcinogens as reactive mutagenic electrophiles. In Origins of Human Cancer (H.H. Hiatt, J.D. Watson, and J.A. Winsten, Eds.), pp. 605-627. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.
49. Miyachi, H., and Nagatsu, Y. (2002). Biomimetic oxidation of 2-methylimidazole derivative with a chemical model system for cytochrome P-450. Chem. Pharm. Bull. (Tokyo) 50, 1137-1140.
50. Moree-Testa, P., Saint-Jalm, Y., and Testa, A. (1984). Identification and determination of imidazole derivatives in cigarette smoke. J. Chromatogr. 290, 263-274.
51. Morgan, S.E., and Edwards, W.C. (1986). Pilot studies in cattle and mice to determine the presence of 4-methylimidazole in milk after oral ingestion. Vet. Hum. Toxicol. 28, 240-242.
52. Motoi, Y., Yoshioka, M., Hirose, H., Ishino, S., Nakajima, Y., Miyazaki, S., Miyamoto, S., Sudou, M., Monda, T., and Murai, M. (1997). Central nervous disorder of calves consuming colostrums containing 4-methylimidazole or colostrums from cows fed excess ammoniated hay. Jpn. Agric. Res. Q. 31, 225-231.
53. Muller, L., Sivertsen, T., and Langseth, W. (1998). Ammoniated forage poisoning: Concentrations of alkylimidazoles in ammoniated forage and in milk, plasma and urine in sheep and cow. Acta Vet. Scand. 39, 511-514.
54. Murray, M. (1987). Mechanisms of the inhibition of cytochrome P-450-mediated drug oxidation by therapeutic agents. Drug Metab. Rev. 18, 55-81.
55. National Institute for Occupational Safety and Health (NIOSH) (1990). National Occupational Exposure Survey (1981 to 1983), unpublished provisional data as of July 1, 1990. Cincinnati, OH.
56. Nagasaka, A. and Hidaka, H. (1976). Effect of antithyroid agents 6-propyl-2-thiouracil and 1-methyl-2-mercaptoimidazole on human thyroid iodine peroxidase. J. Clin. Endocrinol. Metab. 43, 152-158.
57. National Toxicology Program (NTP) (2004). Toxicity Studies of 2- and 4-Methylimidazole (CAS Nos. 693-98-1 and 822-36-6) Administered in Feed to F344/N Rats and B6C3F1 Mice. Toxicity Report Series No. 67. NIH Publication No. 04-4409. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
58. Nishie, K., Waiss, A.C., Jr., and Keyl, A.C. (1969). Toxicity of methylimidazoles. Toxicol. Appl. Pharmacol. 14, 301-307.
59. Nishie K., Waiss, A.C., Jr., and Keyl, A.C. (1970). Pharmocology of alkyl and hydroxyalkylpyrazines. Toxicol. Appl. Pharmacol. 17, 244-249.
60. Ohta, K., Yamaguchi, J.I., Akimoto, M., Fukushima, K., Suwa, T., and Awazu, S. (1996). Retention mechanism of imidazoles in connective tissue. I. Binding to elastin. Drug Metab. Dispos. 24, 1291-1297.
61. Ohta, K., Fukasawa, Y., Yamaguchi, J., Kohno, Y., Fukushima, K., Suwa, T., and Awazu, S. (1998). Retention mechanism of imidazoles in connective tissue. IV. Identification of a nucleophilic imidazolone metabolite in rats. Biol. Pharm. Bull. 21, 1334-1337.
62. Paynter, O.E., Burin, R.B., Jaeger, R.B., and Gregorio, C.A. (1988). Groitogens and thyroid follicular cell neoplasia: Evidence for a threshold process. Regul. Toxicol. Pharmacol. 8, 102-119.
63. Perdok, H.B., and Leng, R.A. (1987). Hyperexcitability in cattle fed ammoniated roughages. Anim. Feed Sci. Technol. 17, 121-143.
64. Piegorsch, W.W., and Bailer, A.J. (1997). Statistics for Environmental Biology and Toxicology, Section 6.3.2. Chapman and Hall, London.
65. Portier, C.J., and Bailer, A.J. (1989). Testing for increased carcinogenicity using a survival-adjusted quantal response test. Fundam. Appl. Toxicol. 12, 731-737.
66. Portier, C.J., Hedges, J.C., and Hoel, D.G. (1986). Age-specific models of mortality and tumor onset for historical control animals in the National Toxicology Program's carcinogenicity experiments. Cancer Res. 46, 4372-4378.
67. Rao, G.N. (1996). New diet (NTP-2000) for rats in the National Toxicology Program toxicity and carcinogenicity studies. Fundam. Appl. Toxicol. 32, 102-108.
68. Rao, G.N. (1997). New nonpurified diet (NTP-2000) for rodents in the National Toxicology Program's toxicology and carcinogenesis studies. J. Nutr. 127, 842s-846s.
69. Ray, A.C., Raisor, M.J., Herd, D.B., Murphy, M.J., and Reagor, J.C. (1984). Methylimidazole content of ammoniated forages associated with toxicity in cattle. In American Association of Veterinary Laboratory Diagnosticians 27th Annual Proceedings, pp. 337-348.
70. Sakuma, H., Kusama, M., Yamaguchi, K., Matsuki, T., and Sugawara, S. (1984). The distribution of cigaret smoke components between mainstream and sidestream smoke. II. Bases. Beitr. Tabakforsch. Int. 22, 199-209 (Abstr.).
71. Sanders, J.M., Griffin, R.J., Burka, L.T., and Matthews, H.B. (1998). Disposition of 2-methylimidazole in rats. J. Toxicol. Environ. Health 54A, 121-132.
72. Sax's Dangerous Properties of Industrial Materials (1996). 9th ed. (R.J. Lewis, Ed.) Van Nostrand Reinhold, New York.
73. Shelby, M.D. (1988). The genetic toxicity of human carcinogens and its implications. Mutat. Res. 204, 3-15.
74. Shelby, M.D., and Witt, K.L. (1995). Comparison of results from mouse bone marrow chromosome aberration and micronucleus tests. Environ. Mol. Mutagen. 25, 302-313.
75. Shelby, M.D., and Zeiger, E. (1990). Activity of human carcinogens in the Salmonella and rodent bone-marrow cytogenetics tests. Mutat. Res. 234, 257-261.
76. Shelby, M.D., Erexson, G.L., Hook, G.J., and Tice, R.R. (1993). Evaluation of a three-exposure mouse bone marrow micronucleus protocol: Results with 49 chemicals. Environ. Mol. Mutagen. 21, 160-179.
77. Shirley, E. (1977). A non-parametric equivalent of Williams' test for contrasting increasing dose levels of a treatment. Biometrics 33, 386-389.
78. Sigma Library of FT-IR Spectra (1986). 1st ed. (Charles J. Pouchert and John R. Campbell, Eds.). Sigma Chemical Company, Inc., St. Louis, MO.
79. Sivertsen, T., Muller, L., Solheim, E., and Langseth, W. (1997). Ammoniated forage poisoning; new alkylimidazoles isolated from ammoniated forage and milk (concentrations, toxicity to mice and possible significance). J. Vet. Pharmacol. Therap. 20, 290-291.
80. Straus, D.S. (1981). Somatic mutation, cellular differentiation, and cancer causation. JNCI 67, 233-241.
81. Suzuki, Y., Nagae, Y., Ishikawa, T., Watanabe, Y., Nagashima, T., Matsukubo, K., and Shimizu, H. (1989). Effect of erythropoietin on the micronucleus test. Environ. Mol. Mutagen. 13, 314-318.
82. Tarone, R.E. (1975). Tests for trend in life table analysis. Biometrika 62, 679-682.
83. Taurog, A. (1976). The mechanism of action of the thioureylene antithyroid drugs. Endocrinology. 98, 1031-1046.
84. Temple, A.R., Done, A.K., and Clement, M.S. (1971). Studies of glucuronidation: III. The measurement of punitrophenyl glucuronide. J. Lab. Clin. Med. 77, 1015-1019.
85. Tennant, R.W., Margolin, B.H., Shelby, M.D., Zeiger, E., Haseman, J.K., Spalding, J., Caspary, W., Resnick, M., Stasiewicz, S., Anderson, B., and Minor, R. (1987). Prediction of chemical carcinogenicity in rodents from in vitro genetic toxicity assays. Science 236, 933-941.
86. Thomas, G.A., and Williams, E.D. (1991). Evidence for and possible mechanisms of non-genotoxic carcinogenesis in the rodent thyroid. Mutat. Res. 248, 357-370.
87. Thomas, G.A., and Williams, E.D. (1999). Thyroid stimulating hormone (TSH)-associated follicular hypertrophy and hyperplasia as a mechanism of thyroid carcinogenesis in mice and rats. IARC Sci. Publ. 147, 45-59.
88. U.S. Environmental Protection Agency (USEPA) (2000). Toxic Substances Control Act Chemical Substance Inventory. Office of Toxic Substances. Washington, D.C.
89. Voogd, C.E., van der Stel, J.J., and Jacobs, J.J. (1979). The mutagenic action of nitroimidazoles. IV. A comparison of the mutagenic action of several nitroimidazoles and some imidazoles. Mutat. Res. 66, 207-221.
90. Weiss, W.P., Conrad, H.R., Martin, C.M., Cross, R.F., and Shockey, W.L. (1986). Etiology of ammoniated hay toxicosis. J. Anim. Sci. 63, 525-532.
91. Wiggins, L.F. (1956). Some recent studies on ammoniated molasses. Sugar J. 18, 18-20.
92. Williams, D.A. (1971). A test for differences between treatment means when several dose levels are compared with a zero dose control. Biometrics 27, 103-117.
93. Williams, D.A. (1972). The comparison of several dose levels with a zero dose control. Biometrics 28, 519-531.
94. Williams, D.A. (1986). A note on Shirley's nonparametric test for comparing several dose levels with a zero-dose control. Biometrics 42, 183-186.
95. Witt, K.L., Knapton, A., Wehr, C.M., Hook, G.J., Mirsalis, J., Shelby, M.D., and MacGregor, J.T. (2000). Micronucleated erythrocyte frequency in peripheral blood of B6C3F1 mice from short-term, prechronic, and chronic studies of the NTP Carcinogenesis Bioassay Program. Environ. Mol. Mutagen. 36, 163-194.
96. Wong, J.M., and Bernhard, R.A. (1988). Effect of nitrogen source on pyrazine formation. J. Agric. Food Chem. 36, 123-129.
97. Yamaguchi, T., and Nakagawa, K. (1983). Reduction of induced mutability with xanthine- and imidazolederivatives through inhibition of metabolic activation. Agric. Biol. Chem. 47, 1673-1677.
98. Yoshikawa, S., and Fujiwara, M. (1981). Determination of 4(5)-methylimidazole in food by thin layer chromatography. J. Food Hyg. Soc. Jap. 22, 189-196 (Abstr.).
99. Zeiger, E., Anderson, B., Haworth, S., Lawlor, T., and Mortelmans, K. (1988). Salmonella mutagenicity tests: IV. Results from the testing of 300 chemicals. Environ. Mol. Mutagen. 11 (Suppl. 12), 1-158.
100. Zeiger, E., Haseman, J.K., Shelby, M.D., Margolin, B.H., and Tennant, R.W. (1990). Evaluation of four in vitro genetic toxicity tests for predicting rodent carcinogenicity: Confirmation of earlier results with 41 additional chemicals. Environ. Mol. Mutagen. 16 (Suppl. 18), 1-14.