NTP TECHNICAL REPORT ON THE TOXICOLOGY AND CARCINOGENESIS STUDIES OF ETHYLBENZENE (CAS NO. 100-41-4) IN F344/N RATS AND B6C3F1 MICE (INHALATION STUDIES)

NTP Technical Report on the Toxicology and Carcinogenesis Studies Series

Volumn TR-466, Issue , 1999, Pages 1-231

  Chan, P C ^b   Bridge, D A ^b   Bucher, J R ^b   Chapin, R E ^b   Hailey, J R ^d   Haseman, J K ^b   Mahler, J ^b   Maronpot, R R ^b   Rao, G N ^b   Roycroft, J H ^b   Smith, C S ^b   Travlos, G S ^b   Walters, D B ^b   Witt, K L ^a   Aranyi, C ^b   Kirkpatrick, D T ^b   Snelson, A ^b   Hardisty, J F ^b   Shackelford, C C ^b,e   Brecher, S ^b   Seely, J C ^b   Barlow, N ^c   Dixon, D ^d   Herbert, R A ^d   Radovsky, A ^d   Torii, M ^d   Wolf, D ^f   Asanoi, S ^d   Boorman, G A ^d   Cattley, R ^f   Hellman, J ^d   Sills, R C ^d   Morris, R W ^b   Lloyd, S R ^b   Mintz, N G ^b   Gunnels, S R ^b   Harper, L M ^b   Macri Hanson, A M ^b   Rathman, E S ^b   more..

^a OAK RIDGE ASSOCIATED UNIVERSITIES   (United States)

^b PATHCO Inc ^*

^c NORTH CAROLINA STATE UNIVERSITY   (United States)

^d National Toxicology Program

^e EXPERIMENTAL PATHOLOGY LABORATORIES INC   (United States)

^f Chemical Industry Institute of Toxicology

Author keywords

[No Author keywords available]

Indexed keywords

EID: 34247890694     PISSN: 23788917     EISSN: 23788925     Source Type: Book Series    
DOI: None     Document Type: Review

References (103)

1. American Conference of Governmental Industrial Hygienists (ACGIH) (1986). Documentation of the Threshold Limit Values and Biological Exposure Indices, 5th ed. Cincinnati, OH.
2. American Conference of Governmental Industrial Hygienists (ACGIH) (1996). 1996 Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH.
3. Andersson, K., Fuxe, K., Nilsen, O.G., Toftgård, R., Eneroth, P., and Gustafsson, J.-Å. (1981). Production of discrete changes in dopamine and noradrenaline levels and turnover in various parts of the rat brain following exposure to xylene, ortho-, meta-, and para-xylene, and ethylbenzene. Toxicol. Appl. Pharmacol. 60, 535-548.
4. Angerer, J., and Lehnert, T. (1979). Occupational chronic exposure to organic solvents. VIII. Phenolic compounds - metabolites of alkylbenzenes in man. Simultaneous exposure to ethylbenzene and xylenes. Int. Arch. Occup. Environ. Health 43, 145-150.
5. Armitage, P. (1971). Statistical Methods in Medical Research, pp. 362-365. John Wiley and Sons, Inc., New York.
6. 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.
7. Bardodej, Z., and Bardodejova, E. (1970). Biotransformation of ethylbenzene, styrene, and alphamethylstyrene in man. Am. Ind. Hyg. Assoc. J. 31, 206-209.
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. Busby, W.F., Jr., Wang, J.-S., Stevens, E.K., Padykula, R.E., Aleksejczyk, R.A., and Berchtold, G.A. (1990). Lung tumorigenicity of benzene oxide, benzene dihydrodiols and benzene diolepoxides in the BLU:Ha newborn mouse assay. Carcinogenesis 11, 1473-1478.
10. Caspary, W.J., Lee, Y.J., Poulton, S., Myhr, B.C., Mitchell, A.D., and Rudd, C.J. (1988). Evaluation of the L5178Y mouse lymphoma cell mutagenesis assay: Quality-control guidelines and response categories. Environ. Mol. Mutagen. 12 (Suppl. 13), 19-36.
11. Chemical Engineering News. 11 April 1994; 72, 13.
12. Chin, B.H., McKelvey, J.A., Tyler, T.R., Calisti, L.R., Kozbelt, S.J., and Sullivan, L.J. (1980). Absorption, distribution, and excretion of ethylbenzene, ethylcyclohexane, and methylethylbenzene isomers in rats. Bull. Environ. Contam. Toxicol. 24, 477-483.
13. Climie, I.J.G., Hutson, D.H., and Stoydin, G. (1983). The metabolism of ethylbenzene hydroperoxide in the rat. Xenobiotica 13, 611-618.
14. Code of Federal Regulations (CFR) 21, Part 58.
15. Cox, D.R. (1972). Regression models and life-tables. J. R. Stat. Soc. B34, 187-220.
16. Cragg, S.T., Clarke, E.A., Daly, I.W., Miller, R.R., Terrill, J.B., and Quellette, R.E. (1989). Subchronic inhalation toxicity of ethylbenzene in mice, rats, and rabbits. Fundam. Appl. Toxicol. 13, 399-408.
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. Dean, B.J. (1978). Genetic toxicology of benzene, toluene, xylenes and phenols. Mutat. Res. 47, 75-97.
19. Dean, B.J., Brooks, T.M., Walker, G.H., and Hutson, D.H. (1985). Genetic toxicity testing of 41 industrial chemicals. Mutat. Res. 153, 57-77.
20. Deutsche Forschungsgemeinschaft (DFG) (1985). Gesundheitsschadliche Arbeitsstoffe. Toxikologisch Arbeitsmedizinische Begrundung von MAK-Werten. 11th ed. VCH Verlagsgesellschaft, Weinheim.
21. Dinse, G.E., and Haseman, J.K. (1986). Logistic regression analysis of incidental-tumor data from animal carcinogenicity experiments. Fundam. Appl. Toxicol. 6, 44-52.
22. Dinse, G.E., and Lagakos, S.W. (1983). Regression analysis of tumour prevalence data. Appl. Statist. 32, 236-248.
23. Dutkiewicz, T., and Tyras, H. (1967). A study of the skin absorption of ethylbenzene in man. Br. J. Ind. Med. 24, 330-332.
24. Elovaara, E., Engström, K., Nickels, J., Aitio, A., and Vainio, H. (1985). Biochemical and morphological effects of long term inhalation exposure of rats to ethylbenzene. Xenobiotica 15, 299-308.
25. Engström, J., and Bjurstrom, R. (1978). Exposure to xylene and ethylbenzene. II. Concentration in subcutaneous adipose tissue. Scand. J. Work Environ. Health 4, 195-203.
26. Engström, K., Elovaara, E., and Aitio, A. (1985). Metabolism of ethylbenzene in the rat during longterm intermittent inhalation exposure. Xenobiotica 15, 281-286.
27. Engström, K.M. (1984). Metabolism of inhaled ethylbenzene in rats. Scand. J. Work Environ. Health 10, 83-87.
28. Eustis, S.L., Hailey, J.R., Boorman, G.A., and Haseman, J.K. (1994). The utility of multiple-section sampling in the histopathological evaluation of the kidney for carcinogenicity studies. Toxicol. Pathol. 22, 457-472.
29. Farris, G.M., Everitt, J.I., Irons, R.D., and Popp, J.A. (1993). Carcinogenicity of inhaled benzene in CBA mice. Fundam. Appl. Toxicol. 20, 503-507.
30. Federal Register (1987). Twentieth Report of the Interagency Testing Committee to the Administrator; Receipt of Report and Request for Comments Regarding Priority List of Chemicals. Vol. 52, pp. 19,020-19,026.
31. Federal Register (1989). Ethyl Benzene. Vol. 54, pp. 2460-2461.
32. Fishbein, L. (1985). An overview of environmental and toxicological aspects of aromatic hydrocarbons. IV. Ethylbenzene. Sci. Total Environ. 44, 269-287.
33. Freundt, K.J., Römer, K.G., and Federsel, R.J. (1989). Decrease of inhaled toluene, ethyl benzene, m-xylene, or mesitylene in rat blood after combined exposure to ethyl acetate. Bull. Environ. Contam. Toxicol. 42, 495-498.
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. Environ. Mol. Mutagen. 10 (Suppl. 10), 1-175.
35. 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.
36. Gromiec, J.P., and Piotrowski, J.K. (1984). Urinary mandelic acid as an exposure test for ethylbenzene. Int. Arch. Occup. Environ. Health 55, 61-72.
37. Hardin, B.D., Bond, G.P., Sikov, M.R., Andrew, F.D., Beliles, R.P., and Niemeier, R.W. (1981). Testing of selected workplace chemicals for teratogenic potential. Scand. J. Work Environ. Health 7, 66-75.
38. Haseman, J.K. (1984). Statistical issues in the design, analysis and interpretation of animal carcinogenicity studies. Environ. Health Perspect. 58, 385-392.
39. 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.
40. Hawley's Condensed Chemical Dictionary (1987). 11th ed. (N.I. Sax and R.J. Lewis, Sr., Eds.), p. 479. Van Nostrand Reinhold, New York.
41. Heylin, M. (1987). Facts & figures for the chemical industry. Chem. Eng. News 65, 23-76.
42. Hollander, M., and Wolfe, D.A. (1973). Nonparametric Statistical Methods, pp. 120-123. John Wiley and Sons, New York.
43. International Labor Office (ILO) (1983). Encyclopedia of Occupational Health and Safety. Vol. I and II, p. 214. ILO, Geneva, Switzerland.
44. Kaplan, E.L., and Meier, P. (1958). Nonparametric estimation from incomplete observations. J. Am. Stat. Assoc. 53, 457-481.
45. Kurokawa, Y., Hayashi, Y., Maekawa, A., Takahashi, M., Kokubo, T., and Odashima, S. (1983). Carcinogenicity of potassium bromate administered orally to F344 rats. JNCI 71, 965-972.
46. Lewis, R.J., Sr., Ed. (1992). Sax's Dangerous Properties of Industrial Materials. 8th ed., p. 1579. Van Nostrand Reinhold, New York.
47. Lonneman, W.A., Bellar, T.A., and Altshuller, A.P. (1968). Aromatic hydrocarbons in the atmosphere of the Los Angeles basin. Environ. Sci. Tech. 2, 1017-1020.
48. 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.
49. - mouse lymphoma cell forward mutation assay: III. 72 coded chemicals. Environ. Mol. Mutagen. 12, 85-154.
50. MacGregor, J.T., Wehr, C.M., and Langlois, R.G. (1983). A simple fluorescent staining procedure for micronuclei and RNA in erythrocytes using Hoescht 33258 and pyronin Y. Mutat. Res. 120, 269-275.
51. 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.
52. McKnight, B., and Crowley, J. (1984). Tests for differences in tumor incidence based on animal carcinogenesis experiments. J. Am. Stat. Assoc. 79, 639-648.
53. Maltoni, C., Conti, B., Cotti, G., and Belpoggi, F. (1985). Experimental studies on benzene carcinogenicity at the Bologna Institute of Oncology: Current results and ongoing research. Am. J. Ind. Med. 7, 415-446.
54. 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.
55. The Merck Index (1983). 10th ed. (M. Windholz, Ed.), p. 546. Merck and Company, Rahway, NJ.
56. The Merck Index (1989). 11th ed. (S. Budavari, Ed.), p. 595. Merck and Company, Rahway, NJ.
57. 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.
58. Mutti, A., and Franchini, I. (1987). Toxicity of metabolites to dopaminergic systems and the behavioural effects of organic solvents. Br. J. Ind. Med. 44, 721-723.
59. Mutti, A., Falzoi, M., Romanelli, A., Bocchi, M.C., Ferroni, C., and Franchini, I. (1988). Brain dopamine as a target for solvent toxicity: Effects of some monocyclic aromatic hydrocarbons. Toxicology 49, 77-82.
60. Naskali, L., Oksanen, H., and Tähti, H. (1994). Astrocytes as targets for CNS effects of organic solvents in vitro. Neurotoxicology 15, 609-612.
61. National Cancer Institute (NCI) (1976). Guidelines for Carcinogen Bioassay in Small Rodents. Technical Report Series No. 1. NIH Publication No. 76-801. U.S. Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health, Bethesda, MD.
62. National Institute of Occupational Safety and Health (NIOSH) (1979). Ethylbenzene Data Sheet for Prioritized NIOSH/OSHA Substances for the National Toxicology Program. NIOSH, Rockville, MD.
63. National Institutes of Health (NIH) (1978). Open Formula Mouse and Rat Ration (NIH-07). Specification NIH-11-1335. U.S. Department of Health, Education, and Welfare, Public Health Service, NIH, Bethesda, MD.
64. National Research Council (1981). The Alkyl Benzenes. National Academy Press, Washington, DC.
65. 1 Mice (Gavage Studies). Technical Report Series No. 289. NIH Publication No. 86-2545. 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. 371. NIH Publication No. 90-2826. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
67. 1 Mice (Gavage Studies). Technical Report Series No. 369. NIH Publication No. 89-2824. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
68. 1 Mice (Inhalation Studies). Toxicity Study Report Series No. 10. NIH Publication No. 92-3129. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
69. Nestmann, E.R., Lee, E.G.-H., Matula, T.I., Douglas, G.R., and Mueller, J.C. (1980). Mutagenicity of constituents identified in pulp and paper mill effluents using the Salmonella/mammalianmicrosome assay. Mutat. Res. 79, 203-212.
70. Norppa, H., and Vainio, H. (1983). Induction of sister-chromatid exchanges by styrene analogues in cultured human lymphocytes. Mutat. Res. 116, 379-387.
71. Ono, A., Sekita, K., Ohno, K., Hirose, A., Ogawa, Y., Saito, M., Naito, K., Kaneko, T., Furuya, T., and Matsumoto, K. (1995). Reproductive and developmental toxicity studies of toluene. I. Teratogenicity study of inhalation exposure in pregnant rats. J. Toxicol. Sci. 20, 109-134.
72. Otson, R., Williams, D.T., and Bothwell, P.D. (1982). Volatile organic compounds in water at thirty Canadian potable water treatment facilities. J. Assoc. Off. Anal. Chem. 65, 1370-1374.
73. Plappert, U., Barthel, E., and Seidel, H.J. (1994). Reduction of benzene toxicity by toluene. Environ. Mol. Mutagen. 24, 283-292.
74. Pyykko, K., Paavilainen, S., Metsa-Ketela, T., and Laustiola, K. (1987). The increasing and decreasing effects of aromatic hydrocarbon solvents on pulmonary and hepatic cytochrome P-450 in the rat. Pharmacol. Toxicol. 60, 288-293.
75. 1 mice. Toxicol. Appl. Pharmacol. 99, 421-444.
76. 14C]benzene by cynomolgus monkeys and chimpanzees. Toxicol. Appl. Pharmacol. 114, 277-284.
77. Sadtler Standard Spectra. IR No. 246; UV No. 97; NMR No. 10210M. Sadtler Research Laboratories, Philadelphia.
78. Schmid, W. (1976). The micronucleus test for cytogenetic analysis. In Chemical Mutagens. Principles and Methods for their Detection (A. Hollaender, Ed.), Vol. 4, pp. 31-53. Plenum Press, New York.
79. 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.
80. 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.
81. Smyth, H.F., Jr., Carpenter, C.P., Weil, C.S., Pozzani, U.C., and Striegel, J.A. (1962). Rangefinding toxicity data: List VI. Am. Ind. Hyg. Assoc. J. 23, 95-107.
82. Snyder, R., and Hedli, C.C. (1996). An overview of benzene metabolism. Environ. Health Perspect. 104 (Suppl. 6), 1165-1171.
83. Storage and Retrieval of Water Quality Information (STORET) (1986). Water Quality Control Information System [database]. U.S. Environmental Protection Agency, Washington, DC.
84. Straus, D.S. (1981). Somatic mutation, cellular differentiation, and cancer causation. JNCI 67, 233-241.
85. Susten, A.S., Niemeier, R.W., and Simon, S.D. (1990). In vivo percutaneous absorption studies of volatile organic solvents in hairless mice. II. Toluene, ethylbenzene and aniline. J. Appl. Toxicol. 10, 217-225.
86. Tarone, R.E. (1975). Tests for trend in life table analysis. Biometrika 62, 679-682.
87. Tegeris, J.S., and Balster, R.L. (1994). A comparison of the acute behavioral effects of alkylbenzenes using a functional observational battery in mice. Fundam. Appl. Toxicol. 22, 240-250.
88. 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.
89. Toftgard, R., and Nilsen, O.G. (1982). Effects of xylene and xylene isomers on cytochrome P-450 and in vitro enzymatic activities in rat liver, kidney, and lung. Toxicology 23, 197-212.
90. Ungvary, G., and Tatrai, E. (1985). On the embryotoxic effects of benzene and its alkyl derivatives in mice, rats, and rabbits. Arch. Toxicol. 8 (Suppl.), 425-430.
91. United States Code (U.S.C.) 42 § 7412.
92. 2u-globulin: Association with Chemically Induced Renal Toxicity and Neoplasia in the Male Rat. EPA/625/3-91/019F. Risk Assessment Forum, USEPA, Washington, DC.
93. U.S. International Trade Commission (USITC) (1985). Synthetic Organic Chemicals. United States Production and Sales, 1984. USITC Publication No. 1745. USITC, Washington, DC.
94. Vaalavirta, L., and Tähti, H. (1995). Effects of selected organic solvents on the astrocyte membrane ATPase in vitro. Clin. Exp. Pharmacol. Physiol. 22, 293-294.
95. Verschueren, K. (1983). Handbook of Environmental Data on Organic Chemicals, 2nd ed., p. 628. Van Nostrand and Reinhold Company, New York, NY.
96. Wallace, L., Pellizzari, E., Hartwell, T., Rosenzweig, M., Erickson, M., Sparacino, C., and Zelon, H. (1984). Personal exposure to volatile organic compounds. I. Direct measurements in breathing-zone air, drinking water, food and exhaled breath. Environ. Res. 35, 293-319.
97. Wolf, M.A., Rowe, V.K., McCollister, R.L., and Oyen, F. (1956). Toxicological studies of certain alkylated benzenes and benzene. A.M.A. Arch. Ind. Health 14, 387-398.
98. Wolf, M.S., Daum, S.M., Lorimer, W.V., Selikoff, I.J., and Aubrey, B.B. (1977). Styrene and related hydrocarbons in subcutaneous fat from polymerization workers. J. Toxicol. Environ. Health 2, 997-1005.
99. Yant, W.P., Schrenk, H.H., Waite, C.P., and Patty, F.A. (1930). Acute response of guinea pigs to vapors of some new commercial organic compounds. II. Ethylbenzene. Public Health Rep. 45, 1241-1250.
100. 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.
101. 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.
102. 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.
103. Zhu, H., Li, Y., and Trush, M.A. (1995). Differences in xenobiotic detoxifying activities between bone marrow stromal cells from mice and rats: Implications for benzene-induced hematotoxicity. J. Toxicol. Environ. Health 46, 183-201.