TOXICOLOGY AND CARCINOGENESIS STUDIES OF β-MYRCENE (CAS NO. 123-35-3) IN F344/N RATS AND B6C3F1 MICE (GAVAGE STUDIES)

NTP Technical Report on the Toxicology and Carcinogenesis Studies Series

Volumn TR-557, Issue , 2010, Pages 1-169

  Chan, P C ^a   Cesta, M F ^a   Sills, R C ^a,f   Bishop, J B ^a   Bristol, D W ^a   Bucher, J R ^a   Chhabra, R S ^a   Foster, P M ^a   Herbert, R A ^a,f   Hooth, M J ^a   King Herbert, A P ^a   Kissling, G E ^a   Malarkey, D E ^a,f   Roycroft, J H ^a   Sanders, J M ^a   Smith, C S ^a   Travlos, G S ^a   Walker, N J ^a   Witt, K L ^a   Hejtmancik, M R ^b   Ryan, M J ^b   Vasconcelos, D Y ^b   Hamlin, M H ^c   Cimon, K J ^c,f   Peckham, J C ^c,f   Wolfe, G W ^d   Seung, H S ^d   Brecher, S ^e   Iyer, S ^e   Tharakan, V S ^e   Boyce, J T ^f   Lieuallen, W G ^f   Elmore, S A ^f   Suttie, A W ^f   Turnier, J C ^f   Crockett, P W ^g   Betz, L J ^g   McGowan, K P ^g   Gunnels, S R ^h   Coker, K K ^h   Gideon, P A ^h   Hall, B F ^h   Harper, L M ^h   Powers, J I ^h   Serbus, D C ^h   more..

^a National Toxicology Program

^b BATTELLE MEMORIAL INSTITUTE   (United States)

^c EXPERIMENTAL PATHOLOGY LABORATORIES INC   (United States)

^d TherImmune Research Corporation

^e DYNAMAC CORPORATION   (United States)

^f NTP Pathology Working Group

^g SRA International Inc ^*

^h Biotechnical Services Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85149238474     PISSN: 23788917     EISSN: 23788925     Source Type: Book Series    
DOI: None     Document Type: Review

References (103)

1. 1H FT-NMR Spectra (1992). 2nd ed. (C.J. Pouchert and J. Behnke, Eds.), Spectrum 41B. Aldrich Chemical Company, Inc., Milwaukee, WI.
2. The Aldrich Library of FT-IR Spectra (1997). 2nd ed., Vol II, Spectrum I: 46B. Aldrich Chemical Company, Inc., Milwaukee, WI.
3. Anderson, B.E., Zeiger, E., Shelby, M.D., Resnick, M.A., Gulati, D.K., Ivett, J.L., and Loveday, K.S. (1990). Chromosome aberration and sister chromatid exchange test results with 42 chemicals. Environ. Mol. Mutagen. 16 (Suppl. 18), 55-137.
4. 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.
5. Austin, C.A., Shephard, E.A., Pike, S.F., Rabin, B.R., and Phillips, I.R. (1988). The effect of terpenoid compounds on cytochrome P-450 levels in rat liver. Biochem. Pharmacol. 37, 2223-2229.
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. Bieler, G.S., and Williams, R.L. (1993). Ratio estimates, the delta method, and quantal response tests for increased carcinogenicity. Biometrics 49, 793-801.
8. 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.
9. Borghoff, S.J., Short, B.G., and Swenberg, J.A. (1990). Biochemical mechanisms and pathobiology of alpha 2u-globulin nephropathy. Annu. Rev. Pharmacol. Toxicol. 30, 349-367.
10. Chatterjee, B., Demyan, W.F., Song, C.S., Garg, B.D., and Roy, A.K. (1989). Loss of androgenic induction of alpha 2u-globulin gene family in the liver of NIH black rats. Endocrinology 125, 1385-1388.
11. Code of Federal Regulations (CFR) 21, Part 58.
12. Code of Federal Regulations (CFR) 21, § 172.510.
13. Code of Federal Regulations (CFR) 21, § 172.515.
14. Code of Federal Regulations (CFR) 40, § 414.101
15. Cox, D.R. (1972). Regression models and life-tables. J. R. Stat. Soc. B34, 187-220.
16. 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.
17. CRC Handbook of Chemistry and Physics (1981). 62nd ed. (R.C. Weast and M.J. Astle, Eds.), p. C-378. CRC Press, Inc. Boca Raton, FL.
18. Cronn, P.L., Truitt, S.G., and Campbell, M.J. (1983). Chemical characterization of plywood veneer dryer emissions. Atmos. Environ. 17, 201-212.
19. Crowell, P.L., Ren, Z., Lin, S., Vedejs, E., and Gould, M.N. (1994). Structure-activity relationships among monoterpene inhibitors of protein isoprenylation and cell proliferation. Biochem. Pharmacol. 47, 1405-1415.
20. da-Silva, V.A., de-Freitas, J.C., Mattos, A.P., Paiva-Gouvea, W., Presgrave, O.A., Fingola, F.F., Menezes, M.A., and Paumgartten, F.J. (1991). Neurobehavioral study of the effect of beta-myrcene on rodents. Braz. J. Med. Biol. Res. 24, 827-831.
21. Delgado, I.F., Nogueira, A.C., Souza, C.A., Costa, A.M., Figueiredo, L.H., Mattos, A.P., Chahoud, I., and Paumgartten, F.J. (1993a). Peri- and postnatal developmental toxicity of beta-myrcene in the rat. Food Chem. Toxicol. 31, 623-628.
22. Delgado, I.F., Carvalho, R.R., Nogueira, A.C., Mattos, A.P., Figueiredo, L.H., Oliveira, S.H., Chahoud, I., and Paumgartten, F.J. (1993b). Study on embryo-foetotoxicity of beta-myrcene in the rat. Food Chem. Toxicol. 31, 31-35.
23. De-Oliveira, A.C.A.X., Ribeiro-Pinta, L.F., Otto, S.S., Goncalves, A., and Paumgartten, F.J.R. (1997). Induction of liver monooxygenases by β-myrcene. Toxicology 124, 135-140.
24. 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.
25. Dunn, O.J. (1964). Multiple comparisons using rank sums. Technometrics 6, 241-252.
26. Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Am. Stat. Assoc. 50, 1096-1121.
27. Freitas, J.C.B., Presgrave, O.A.F., Fingola, F.F., Menezes, M.A., and Paumgartten, F.J. (1993). Effect of beta-myrcene on pentobarbital sleeping time. Braz. J. Med. Biol. Res. 26, 519-523.
28. Gart, J.J., Chu, K.C., and Tarone, R.E. (1979). Statistical issues in interpretation of chronic bioassay tests for carcinogenicity. JNCI 62, 957-974.
29. Gervasi, P.G., Citti, L., Del Monte, M., Longo, V., and Benetti, D. (1985). Mutagenicity and chemical reactivity of epoxidic intermediates of the isoprene metabolism and other structurally related compounds. Mutat. Res. 156, 77-82.
30. Girard, D.M., and Sager, D.B. (1987). The use of Markov chains to detect subtle variation in reproductive cycling. Biometrics 43, 225-234.
31. Gomes-Carneiro, M.R., Viana, M.E.S., Felzenszwalb, I., and Paumgartten, F.J.R. (2005). Evaluation of β-myrcene, α-terpinene and (+)- and (-)-"-pinene in the Salmonella/microsome assay. Food Chem. Toxicol. 43, 247-252.
32. Guenther, A., Zimmerman, P., and Wildermuth, M. (1994). Natural volatile organic compound emission rate estimates for U.S. woodland landscapes. Atmos. Environ. 28, 1197-1210.
33. Hard, G.C. (2008). Some aids to histological recognition of hyaline droplet nephropathy in 90-day toxicity studies. Toxicol. Pathol. 36, 1014-1017.
34. Hard, G.C., and Seely, J.C. (2005). Recommendations for the interpretation of renal tubule proliferative lesions occurring in rat kidneys with advanced chronic progressive nephropathy (CPN). Toxicol. Pathol. 33, 641-649.
35. Hard, G.C., Rodgers, I.S., Baetcke, K.P., Richards, W.L., McGaughy, R.E., and Valcovic, L.R. (1993). Hazard evaluation of chemicals that cause accumulation of alpha 2u-globulin, hyaline droplet nephropathy, and tubule neoplasia in the kidneys of male rats. Environ. Health Perspect. 99, 313-349.
36. Hawley’s Condensed Chemical Dictionary (1993). 12th ed. (R.J. Lewis, Sr., Ed.). Van Nostrand Reinhold, New York.
37. Haworth, S., Lawlor, T. Mortelmans, K., Speck, W., and Zeiger, E. (1983). Salmonella mutagenicity test results for 250 chemicals. Environ. Mutagen. 5 (Suppl. 1), 3-142.
38. Heddle, J.A., Hite, M., Kirkhart, B., Mavournin, K., MacGregor, J.T., Newell, G.W., and Salamone, M.F. (1983). The induction of micronuclei as a measure of genotoxicity. A report of the U.S. Environmental Protection Agency Gene-Tox Program. Mutat. Res. 123, 61-118.
39. Integrated Laboratory Systems (ILS) (1990). Micronucleus Data Management and Statistical Analysis Software, Version 1.4. ILS, Inc., P.O. Box 13501, Research Triangle Park, NC 27707.
40. Ishida, T., Asakawa, Y., Takemoto, T., and Aratani, T. (1981). Terpenoids biotransformation in mammals. III: Biotransformation of α-pinene, β-pinene, pinane, 3-carene, carane, myrcene, and p-cymene in rabbits. J. Pharm. Sci. 70, 406-415.
41. Jonckheere, A.R. (1954). A distribution-free k-sample test against ordered alternatives. Biometrika 41, 133-145.
42. Kaplan, E.L., and Meier, P. (1958). Nonparametric estimation from incomplete observations. J. Am. Stat. Assoc. 53, 457-481.
43. Kauderer, B., Zamith, H., Paumgartten, F.J.R., and Speit, G. (1991). Evaluation of the mutagenicity of β-myrcene in mammalian cells in vitro. Environ. Mol. Mutagen. 18, 29-34.
44. Kodama, R., Yano, T., Furukawa, K., Noda, K., and Ide, H. (1976). Studies on the metabolism of d-limonene (p-mentha-1,8-diene). IV. Isolation and characterization of new metabolites and species differences in metabolism. Xenobiotica 6, 377-389.
45. Kolicheski, M.B., Cocco, L.C., Mitchell, D.A., and Kaminski, M. (2007.) Synthesis of myrcene by pyrolysis of β-pinene: Analysis of decomposition reactions. J. Analyt. Appl. Pyrolysis 80, 92-100.
46. Kostiainen, R. (1995). Volatile organic compounds in the indoor air of normal and sick houses. Atmos. Environ. 29, 693-702.
47. Kuney, J.H. (1994). Chemcyclopedia 1995. American Chemical Society, Washington, D.C.
48. Lehman-McKeeman, L.D., and Caudill, D. (1992).
49. Lehman-McKeeman, L.D., Rodriguez, P.A., Takigiku, R., Caudill, D., and Fey, M.L. (1989). d-Limoneneinduced male rat-specific nephrotoxicity: Evaluation of the association between d-limonene and α2u-globulin. Toxicol. Appl. Pharmacol. 99, 250-259.
50. Lock, E.A., and Hard, G.C. (2004). Chemically induced renal tubule tumors in the laboratory rat and mouse: Review of the NCI/NTP database and categorization of renal carcinogens based on mechanistic information. Crit. Rev. Toxicol. 34, 211-299.
51. Lorente, I., Ocete, M.A., Zarzuelo, A., Cabo, M.M., and Jimenez, J. (1989). Bioactivity of the essential oil of Bupleurum fruticosum. J. Nat. Prod. 52, 267-272.
52. Lorenzetti, B.B., Souza, G.E., Sarti, S.J., Santos Filho, D., and Ferreira, S.H. (1991). Myrcene mimics the peripheral analgesic activity of lemongrass tea. J. Ethnopharmacol. 34, 43-48.
53. 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.
54. 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.
55. MacInnes, J.I., Nozik, E.S., and Kurtz, D.T. (1986). Tissue-specific expression of the rat alpha 2u globulin gene family. Mol. Cell Biol. 6, 3563-3567.
56. Madyastha, K.M., and Srivatsan, V. (1987). Metabolism of β-myrcene in vivo and in vitro: Its effects on rat liver microsomal enzymes. Xenobiotica 17, 539-549.
57. 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.
58. Melnick, R.L. (2002). Carcinogenicity and mechanistic insights on the behavior of epoxides and epoxide-forming chemicals. Ann. N.Y. Acad. Sci. 982, 177-189.
59. Melnick, R.L., and Sills, R.C. (2001). Comparative carcinogenicity of 1,3-butadiene, isoprene, and chloroprene in rats and mice. Chem. Biol. Interact. 135-136, 27-42.
60. The Merck Index (1996). 12th ed. (S. Budavari, Ed.), p. 1085. Merck and Company, Whitehouse Station, NJ.
61. 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.
62. Miyazawa, M., and Murata, T. (2000). Biotransformation of β-myrcene by the larvae of common cutworm (Spodoptera litura). J. Agric. Food Chem. 48, 123-125.
63. Morrison, D.F. (1976). Multivariate Statistical Methods, 2nd ed., pp. 170-179. McGraw-Hill Book Company, New York.
64. Myhr, B., McGregor, D., Bowers, L., Riach, C., Brown, A.G., Edwards, I., McBride, D., Martin R., and Caspary, W.J. (1990). L5178Y mouse lymphoma cell mutation assay results with 41 compounds. Environ. Mol. Mutagen. 16 (Suppl. 18), 138-167.
65. 1 Mice (Gavage Studies). Technical Report Series No. 347. NIH Publication No. 90-2802. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
66. 1 Mice (Inhalation Studies). Technical Report Series No. 434. NIH Publication No. 93-3165. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
67. Newmark, F.M. (1978). Hops allergy and terpene sensitivity: An occupational disease. Ann. Allergy 41, 311-312.
68. Opdyke, D.L.J. (1976). Fragrance raw materials monographs: β-myrcene. Food Cosmet. Toxicol. 14, 615.
69. Paumgartten, F.J., Delgado, I.F., Alves, E.N., Nogueira, A.C., de-Farias, R.C., and Neubert D. (1990). Single dose toxicity study of beta-myrcene, a natural analgesic substance. Braz. J. Med. Biol. Res. 23, 873-877.
70. Piegorsch, W.W., and Bailer, A.J. (1997). Statistics for Environmental Biology and Toxicology, Section 6.3.2. Chapman and Hall, London.
71. 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.
72. 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.
73. 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.
74. 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.
75. Rao, V.S.N., Menezes, A.M.S., and Viana, G.S.B. (1990). Effect of myrcene on nociception in mice. J. Pharm. Pharmacol. 42, 877-878.
76. Russin, W.A., Hoesly, J.D., Elson, C.E., Tanner, M.A., and Gould, M.N. (1989). Inhibition of rat mammary carcinogenesis by monoterpenoids. Carcinogenesis 10, 2161-2164.
77. Schmid, W. (1975). The micronucleus test. Mutat. Res. 31, 9-15.
78. Seely, J.C., Haseman, J.K., Nyska, A., Wolf, D.C., Everitt, J.I., and Hailey, J.R. (2002). The effect of chronic progressive nephropathy on the incidence of renal tubule cell neoplasms in control Male F344 rats. Toxicol. Pathol. 30, 681-686.
79. Shelby, M.D. (1988). The genetic toxicity of human carcinogens and its implications. Mutat. Res. 204, 3-15.
80. 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.
81. 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.
82. 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.
83. Shirley, E. (1977). A non-parametric equivalent of Williams’ test for contrasting increasing dose levels of a treatment. Biometrics 33, 386-389.
84. SRI International (1996). Directory of Chemical Producers, United States, 1996. SRI International, Menlo Park, CA.
85. Stolle, A., Bonrath, W., and Ondruschka, B. (2008). Kinetic and mechanistic aspects of myrcene production via thermal-induced β-pinene rearrangement. J. Analyt. Appl. Pyrolysis 83, 26-36.
86. Straus, D.S. (1981). Somatic mutation, cellular differentiation, and cancer causation. JNCI 67, 233-241.
87. Swenberg, J.A., and Lehman-McKeeman, L.D. (1999). Alpha 2-urinary globulin-associated nephropathy as a mechanism of renal tubule cell carcinogenesis in male rats. IARC Sci. Publ. 147, 95-118.
88. 2u-globulin nephropathy. Toxicol. Appl. Pharmacol. 97, 35-46.
89. Tarone, R.E. (1975). Tests for trend in life table analysis. Biometrika 62, 679-682.
90. 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.
91. Turner, S.D., Tinwell, H., Piegorsch, W., Schmezer, P., and Ashby, J. (2001). The male rat carcinogens limonene and sodium saccharin are not mutagenic to male Big Blue rats. Mutagenesis. 17, 329-332.
92. Watabe, T., Hiratsuka, A., Isobe, M., and Ozawa, N. (1980). Metabolism of d-limonene by hepatic microsomes to nonmutagenic epoxides toward Salmonella typhimurium. Biochem. Pharmacol. 29, 1068-1071.
93. Watson, W.P., Cottrell, L., Zhang, D., and Golding, B.T. (2001). Metabolism and molecular toxicology of isoprene. Chem. Biol. Interact. 135-136, 223-238.
94. Wilkins, C.K., and Larsen, K. (1995). Identification of volatile (micro) biological compounds from household waste and building materials by thermal desorption-capillary gas chromatography-mass spectroscopy. J. High Resolut. Chromatogr. 18, 373-377.
95. Wilkins, K. (1994). Volatile organic compounds from household waste. Chemosphere 29, 47-53.
96. 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.
97. Williams, D.A. (1972). The comparison of several dose levels with a zero dose control. Biometrics 28, 519-531.
98. 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.
99. Wilt, F.M., Miller, G.C., and Everett, R.L. (1988). Monoterpene concentrations in litter and soil of single-leaf pinyon woodlands of the western Great Basin U.S.A. Great Basin Nat. 48, 228-231.
100. 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.
101. Zamith, H.P., Vidal, M.N., Speit, G., and Paumgartten, F.J. (1993). Absence of genotoxic activity of beta-myrcene in the in vivo cytogenetic bone marrow assay. Braz. J. Med. Biol. Res. 26, 93-98.
102. 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.
103. Zeiger, E., Anderson, B., Haworth, S., Lawlor, T., and Mortelmans, K. (1992). Salmonella mutagenicity tests: V. Results from the testing of 311 chemicals. Environ. Mol. Mutagen. 19 (Suppl. 21), 2-141.