NTP TECHNICAL REPORT ON THE TOXICOLOGY AND CARCINOGENESIS STUDIES OF o-NITROTOLUENE (CAS NO. 88-72-2) IN F344/N RATS AND B6C3F1 MICE (FEED STUDIES)

NTP Technical Report on the Toxicology and Carcinogenesis Studies Series

Volumn TR-504, Issue , 2002, Pages 1-368

  Dunnick, J K ^b   Bristol, D W ^b   Bucher, J R ^b   Burka, L T ^b   Hailey, J R ^b,d   Haseman, J K ^b   Herbert, R A ^b,d   Maronpot, R R ^b   Orzech, D P ^b   Peddada, S D ^b   Rao, G N ^b   Roycroft, J H ^b   Sills, R C ^b,d   Smith, C S ^b   Travlos, G S ^b   Witt, K L ^a   Hebert C D ^b   Prejean, J D ^b   Richter, W R ^b   Heath, J E ^b,e   Thompson, R B ^b   Hardisty, J F ^b   Okerberg, C ^b,f   Shackelford, C C ^b,f   Brecher, S ^b   Hildebrandt, P K ^b   Everitt, J ^c   Flake, G P ^d   Nyska, A ^d,d   Suwa, T ^d   Jokinen, M P ^g   Farnell, D R ^e   Ozaki, K ^d   Pletcher, J ^g   Qualls, C ^h   Morris, R W ^b   Betz, L J ^b   McGowan, K P ^b   Scott, J T ^b   Gunnels, S R ^b   Barker, M P ^b   Harper, L M ^b   Paal, E S ^b   Serbus, D C ^b   Sharp, W D ^b   Willis, R A ^b   more..

^a INTEGRATED LABORATORY SYSTEMS   (United States)

^b ILS Inc ^*

^c Chemical Industry Institute of Toxicology

^d National Toxicology Program

^e SOUTHERN RESEARCH INSTITUTE   (United States)

^f EXPERIMENTAL PATHOLOGY LABORATORIES INC   (United States)

^g Pathology Associates International

^h GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84874458822     PISSN: 23788917     EISSN: 23788925     Source Type: Book Series    
DOI: None     Document Type: Review

References (133)

1. Abshire, A.D., and Hughes, C.S. (1982). Toluene. In Chemical Economics Handbook, pp. 300.7202z300.7203a. SRI International, Palo Alto, CA.
2. The Aldrich Library of Infrared Spectra (1981). 3rd ed. (C.J. Pouchert, Ed.), Spectrum No. 803h. Aldrich Chemical Company, Inc., Milwaukee.
3. ®. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices, p. 52. Cincinnati, OH.
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. Attanoos, R.L., and Gibbs, A.R. (1997). Pathology of malignant mesothelioma. Histopathology 30, 403-418.
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. Barbin, A., Froment, O., Boivin, S., Marion, M., Belpoggi, F., Maltoni, F., and Montesano, R. (1997). p53 gene mutation pattern in rat liver tumors induced by vinyl chloride. Cancer Res. 57, 1695-1698.
8. Bieler, G.S., and Williams, R.L. (1993). Ratio of estimates, the delta method, and quantal response tests for increased carcinogenicity. Biometrics 49, 793-801.
9. 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.
10. Booth, C.J., and Sundberg, J.P. (1995). Hemangiomas and hemangiosarcomas in inbred laboratory mice. Lab. Anim. Sci. 45, 497-502.
11. Butterworth, B.E., Smith-Oliver, T., Earle, L., Loury, D.J., White, R.D., Doolittle, D.J., Working, P.K., Cattley, R.C., Jirtle, R., Michalopoulos, G., and Strom, S. (1989). Use of primary cultures of human hepatocytes in toxicology studies. Cancer Res. 49, 1075-1084.
12. Chism, J.P., and Rickert, D.E. (1985). Isomer- and sexspecific bioactivation of mononitrotoluenes: Role of enterohepatic circulation. Drug Metab. Dispos. 13, 651-657.
13. Chism, J.P., and Rickert, D.E. (1989). In vitro activation of 2-aminobenzyl alcohol and 2-amino-6-nitrobenzyl alcohol, metabolites of 2-nitrotoluene and 2,6-dinitrotoluene. Chem. Res. Toxicol. 2, 150-156.
14. Chism, J.P., Turner, M.J., Jr., and Rickert, D.E. (1984). The metabolism and excretion of mononitrotoluenes by Fisher 344 rats. Drug Metab. Dispos. 12, 596-602.
15. Chiu, C.W., Lee, L.H., Wang, C.Y., and Bryan, G.T. (1978). Mutagenicity of some commercially available nitro compounds for Salmonella typhimurium. Mutat. Res. 58, 11-22.
16. Ciss, M., Dutertre, H., Huyen, N., Phu-Lich, N., and Truhaut, R. (1980a). Etude toxicologique des nitrotoluènes: Toxicité aiguë et toxicité subaiguë. Dakar Méd. 25, 303-311.
17. Ciss, M., Huyen, N., Dutertre, H., Phu-Lich, N., and Truhaut, R. (1980b). Etude toxicologique des nitrotoluènes: Toxicité à long terme. Dakar Méd. 25, 293-302.
18. Code of Federal Regulations (CFR) 21, Part 58.
19. Cox, D.R. (1972). Regression models and life-tables. J. R. Stat. Soc. B34, 187-220.
20. 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.
21. Cristaudo, A., Vivaldi, A., Sensales, G., Guglielmi, G., Ciancia, E., Elisei, R., and Ottenga, F. (1995). Molecular biology studies on mesothelioma tumor samples: Preliminary data on H-Ras, p21, and SV40. J. Environ. Pathol. Toxicol. Oncol. 14, 29-34.
22. deBethizy, J.D., and Rickert, D.E. (1983). Sequential enzyme-catalyzed metabolism of 4-nitrotoluene to S-(4-nitrobenzyl)glutathione. Biochem. Biophys. Res. Commun. 114, 500-504.
23. deBethizy, J.D., and Rickert, D.E. (1984). Metabolism of nitrotoluenes by freshly isolated Fisher 344 rat hepatocytes. Drug Metab. Dispos. 12, 45-50.
24. Doolittle, D.J., Sherrill, J.M., and Butterworth, B.E. (1983). Influence of intestinal bacteria, sex of the animal, and position of the nitro group on the hepatic genotoxicity of nitrotoluene isomers in vivo. Cancer Res. 43, 2836-2842.
25. Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J. Am. Stat. Assoc. 50, 1096-1121.
26. 1 mice. Fundam. Appl. Toxicol. 22, 411-421.
27. Elwell, M.R., Stedham, M.A., and Kovatch, R.M. (1990). Skin and subcutis. In Pathology of the Fischer Rat. Reference and Atlas (G.A. Boorman, S.L. Eustis, M.R. Elwell, C.A. Montgomery, Jr., and W.F. MacKenzie, Eds.), pp. 261-277. Academic Press, Inc., San Diego.
28. Elwell, M.R., Dunnick, J.K., Hailey, J.R., and Haseman, J.K. (1996). Chemicals associated with decreases in the incidence of mononuclear cell leukemia in the Fischer rat. Toxicol. Pathol. 24, 238-245.
29. Forsten, I. (1973). Pollution abatement in a munitions plant. Environ. Sci. Technol. 7, 806-810.
30. Furukawa, A., Ohuchida, A., and Wierzba, K. (1989). In vivo mutagenicity tests on polyploid inducers. Environ. Mol. Mutagen. 14, 63-64.
31. 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.
32. 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.
33. Guengerich, F.P. (1992). Roles of the vinyl chloride oxidation products 2-chlorooxirane and 2-chloroacetaldehyde in the in vitro formation of etheno adducts of nucleic acid bases. Chem. Res. Toxicol. 5, 2-5.
34. Handbook of Proton NMR Spectra and Data (1985). Vol. 3 (Asahi Research Center Co., Ed.). Academic Press, New York.
35. Haworth, S., Lawlor, T., Mortelmans, K., Speck, W., and Zeiger, E. (1983). Salmonella mutagenicity test results for 250 chemicals. Environ. Mutagen. 5, 3-142.
36. Hollander, M., and Wolfe, D.A. (1973). Nonparametric Statistical Methods, pp. 120-123. John Wiley and Sons, New York.
37. Hollstein, M., Marion, M.J., Lehman, T., Welsh, J., Harris, C.C., Martel-Planch, G., Kusters, I., and Montesano, R. (1994). p53 mutations at A:T base pairs in angiosarcomas of vinyl chloride-exposed factory workers. Carcinogenesis 15, 1-3.
38. Hong, H.-H.L., Devereux, T.R., Melnick, R.L., Moomaw, C.R., Boorman, G.A., and Sills, R.C. (2000). Mutations of ras protooncogenes and p53 tumor suppressor gene in cardiac hemangiosarcomas from B6C3F1 mice exposed to 1,3-butadiene for 2 years. Toxicol. Pathol. 28, 529-534.
39. 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.
40. International Agency for Research on Cancer (IARC) (1996). IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man: Printing Processes and Printing Inks, Carbon Black and Some Nitro Compounds, Vol. 65. IARC, Lyon, France.
41. Jones, M.A., Young, R.H., and Scully, R.E. (1995). Malignant mesothelioma of the tunica vaginalis: A clinicopathologic analysis of 11 cases with review of the literature. Am. J. Surg. Pathol. 19, 815-825.
42. Kaplan, E.L., and Meier, P. (1958). Nonparametric estimation from incomplete observations. J. Am. Stat. Assoc. 53, 457-481.
43. Kawai, A., Goto, S., Matsumoto, Y., and Matsushita, H. (1987). Mutagenicity of aliphatic and aromatic nitro compounds: Industrial materials and related compounds. Jpn. J. Ind. Health 29, 34-54.
44. Kedderis, G.L., Dyroff, M.C., and Rickert, D.E. (1984). Hepatic macromolecular covalent binding of the hepatocarcinogen 2,6-dinitrotoluene and its 2,4-isomer in vivo: Modulation by the sulfotransferase inhibitors pentachlorophenol and 2,6-dichloro-4-nitrophenol. Carcinogenesis 5, 1199-1204.
45. Kirk-Othmer Encyclopedia of Chemical Technology (1981). 3rd ed. (M. Grayson and D. Eckroth, Eds.), Vol. 15, pp. 925-933. John Wiley and Sons, New York.
46. 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.
47. 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.
48. Marion, M.J., Froment, O., and Trepo, C. (1991). Activation of Ki-ras gene by point mutation in human liver angiosarcoma associated with vinyl chloride exposure. Mol. Carcinog. 4, 450-454.
49. 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.
50. Marques, M.M., Mourato, L.L.G., Amorim, M.T., Santos, M.A., Melchior, W.B., Jr., and Beland, F.A. (1997). Effect of substitution site upon the oxidation potentials of alkylanilines, the mutagenicities of n-hydroxyalkylanilines, and the conformations of alkylaniline-DNA adducts. Chem. Res. Toxicol. 10, 1266-1274.
51. Marrogi, A., Pass, H.I., Khan, M., Metheny-Barlow, L.J., Harris, C.C., and Gerwin, B.I. (2000). Human mesothelioma samples overexpress both cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (NOS2): In vitro antiproliferative effects of a COX-2 inhibitor. Cancer Res. 60, 3696-3700.
52. Melnick, R.L., and Kohn, M.C. (1995). Mechanistic data indicate that 1,3-butadiene is a human carcinogen. Carcinogenesis 16, 157-163.
53. The Merck Index (1996). 12th ed., p. 1141. Merck and Company, Inc., Whitehouse Station, NJ.
54. 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.
55. Miller, R.G., Jr. (1960). Simultaneous Statistical Inference. McGraw Hill, New York.
56. Mirsalis, J.C., and Butterworth, B.E. (1980). Detection of unscheduled DNA synthesis in hepatocytes isolated from rats treated with genotoxic agents: An in vivoin vitro assay for potential carcinogens and mutagens. Carcinogenesis 1, 621-625.
57. Mirsalis, J.C., Tyson, C.K., and Butterworth, B.E. (1982a). Detection of genotoxic carcinogens in the in vivo-in vitro hepatocyte DNA repair assay. Environ. Mutagen. 4, 553-562.
58. Mirsalis, J.C., Hamm, T.E., Jr., Sherrill, J.M., and Butterworth, B.E. (1982b). Role of gut flora in the genotoxicity of dinitrotoluene. Nature 295, 322-323.
59. Mirsalis, J.C., Tyson, C.K., Steinmetz, K.L., Loh, E.N., Hamilton, C.M., Bakke, J.P., and Spaldin, J.W. (1989). Measurement of unscheduled DNA synthesis and S-phase synthesis in rodent hepatocytes following in vivo treatment: Testing of 24 compounds. Environ. Mol. Mutagen. 14, 155-164.
60. Miyata, R., Nohmi, T., Yoshikawa, K., and Ishidate, M., Jr. (1981). Metabolic activation of nitrotoluene and trichlorethylene by rat-liver S9 or mouse-liver S9 fractions in Salmonella typhimurium strains. Eisei Shikenji Jokoku 99, 60-65.
61. Mor, O., Yaron, P., Huszar, M., Yellin, A., Jakobovitz, O., Brok-Simoni, F., Rechavi, G., and Reichert, N. (1997). Absence of p53 mutations in malignant mesotheliomas. Am. J. Respir. Cell Mol. Biol. 16, 9-13.
62. National Cancer Institute (NCI) (1978a). Bioassay of Acronycine for Possible Carcinogenicity (CAS No. 7008-42-6). Technical Report Series No. 49. NIH Publication No. 78-849. U.S. Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health, Bethesda, MD.
63. National Cancer Institute (NCI) (1978b). Bioassay of Phenoxybenzamine Hydrochloride for Possible Carcinogenicity (CAS No. 63-92-3). Technical Report Series No. 72. NIH Publication No. 78-1322. U.S. Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health, Bethesda, MD.
64. National Cancer Institute (NCI) (1978c). Bioassay of o-Anisidine Hydrochloride for Possible Carcinogenicity (CAS No. 134-29-0). Technical Report Series No. 89. NIH Publication No. 78-1339. U.S. Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health, Bethesda, MD.
65. National Cancer Institute (NCI) (1978d). Bioassay of p-Anisidine Hydrochloride for Possible Carcinogenicity (CAS No. 20265-97-8). Technical Report Series No. 116. NIH Publication No. 78-1371. U.S. Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health, Bethesda, MD.
66. National Cancer Institute (NCI) (1979). Bioassay of o-Toluidine Hydrochloride for Possible Carcinogenicity (CAS No. 636-21-5). Technical Report Series No. 153. NIH Publication No. 79-1709. U.S. Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health, Bethesda, MD.
67. National Institute for Occupational Safety and Health (NIOSH) (1990). National Occupational Exposure Survey (1981-1983), unpublished provisional data as of July 1, 1990. NIOSH, Cincinnati, OH.
68. National Institute for Occupational Safety and Health (NIOSH) (1997). NIOSH Pocket Guide to Chemical Hazards. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, Washington, D.C.
69. National Toxicology Program (NTP) (1981). Carcinogenesis Bioassay of Cytembena (CAS No. 21739-91-3). Technical Report Series No. 207. NIH Publication No. 81-1763. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC, and Bethesda, MD.
70. 1 Mice (Inhalation Study). Technical Report Series No. 210. NIH Publication No. 82-1766. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC, and Bethesda, MD.
71. 1 Mice (Inhalation Studies). Technical Report Series No. 288. NIH Publication No. 84-2544. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
72. 1 Mice (Inhalation Studies). (CAS No. 75-56-9). Technical Report Series No. 267. NIH Publication No. 85-2527. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
73. 1 Mice (Feed Studies). Technical Report Series No. 349. NIH Publication No. 89-2804. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
74. National Toxicology Program (NTP) (1990a). Toxicology and Carcinogenesis Studies of 3,3N-Dimethoxybenzidine Dihydrochloride (CAS No. 20325-40-0) in F344/N Rats (Drinking Water Studies). Technical Report Series No. 372. NIH Publication No. 90-2827. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
75. 1 Mice (Gavage Studies). Technical Report Series No. 374. NIH Publication No. 90-2829. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
76. National Toxicology Program (NTP) (1991). Toxicology and Carcinogenesis Studies of 3,3N-Dimethylbenzidine Dihydrochloride (CAS No. 612-82-8) in F344/N Rats (Drinking Water Studies). Technical Report Series No. 390. NIH Publication No. 91-2845. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
77. 1 Mice. Toxicity Report Series No. 23. NIH Publication No. 93-3346. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
78. National Toxicology Program (NTP) (1993). Toxicology and Carcinogenesis Studies of 2,3-Dibromo1-propanol (CAS No. 96-13-9) in F344/N Rats and B6C3F1 Mice (Dermal Studies). Technical Report Series No. 400. NIH Publication No. 94-2855. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
79. National Toxicology Program (NTP) (1996). NTP Technical Report on Comparative Toxicity and Carcinogenicity Studies of o-Nitrotoluene and o-Toluidine Hydrochloride (CAS Nos. 88-72-2 and 63621-5) Administered in Feed to Male F344/N Rats. Toxicity Report Series No. 44. NIH Publication No. 96-3936. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
80. 1 Mice (Inhalation Studies). Technical Report Series No. 450. NIH Publication No. 97-3366. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
81. 1 Mice (Inhalation Studies). Technical Report Series No. 467. NIH Publication No. 98-3957. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
82. National Toxicology Program (NTP) (1999). Toxicology and Carcinogenesis Studies of Pentachlorophenol (CAS No. 87-86-5) in F344/N Rats (Feed Studies). Technical Report Series No. 483. NIH Publication No. 99-3973. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
83. 1 Mice (Feed Studies). Technical Report Series No. 498. NIH Publication No. 02-4432. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC.
84. Nishiyama, Y., Suwa, H., Okamoto, K., Fukumoto, M., Hiai, H., and Toyokuni, S. (1995). Low incidence of point mutations in H-, K- and N-ras oncogenes and p53 tumor suppressor gene in renal cell carcinoma and peritoneal mesothelioma of Wistar rats induced by ferric nitrilotriacetate. Jpn. J. Cancer Res. 86, 1150-1158.
85. NIST Standard Reference Database. NBS/EPA/MSDC Mass Spectral Database, PC Version (Database 1-A). National Institute of Standards and Technology, Gaithersburg, MD.
86. Ohuchida, A., Furukawa, A., and Yoshida, R. (1989). Micronucleus test of polyploidy inducers. Mutat. Res. 216, 371-372.
87. Parton, J.W., Yount, D.J., and Garriott, M.L. (1995). Improved sensitivity of the unscheduled DNA synthesis assay in primary rat hepatocytes following culture in serum-free defined media. Environ. Mol. Mutagen. 26, 147-154.
88. PATHCO, Inc. (2000). Pathology report on selected organs in the rat 90-day subchronic o-nitrotoluene study. PATHCO, Inc., Frederick, MD.
89. Piegorsch, W.W., and Bailer, A.J. (1997). Statistics for Environmental Biology and Toxicology, Section 6.3.2. Chapman and Hall, London.
90. 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.
91. Portier, C.J., Hedges, J.C., and Hoel, D.G. (1986). Agespecific models of mortality and tumor onset for historical control animals in the National Toxicology Program's carcinogenicity experiments. Cancer Res. 46, 4372-4378.
92. Ramael, M., Lemmens, G., Eerdekens, C., Buysse, C., Deblier, I., Werner, J., and Van Marck, E. (1992). Immunoreactivity for p53 protein in malignant mesothelioma and non-neoplastic mesothelium. J. Pathol. 168, 371-375.
93. Ramael, M., Deblier, I., Eerdekens, C., Lemmens, G., Jacobs, W., and Van Marck, E. (1993). Immunohistochemical staining of ras oncogene product in neoplastic and non-neoplastic mesothelial tissues: Immunoreactivity for N-ras and lack of immunohistochemical staining for Ha-ras and K-ras. J. Pathol. 169, 421-424.
94. 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.
95. 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.
96. Rao, G.N., and Knapka, J.J. (1988). Animal diets in safety evaluation studies. In Nutrition and Chemical Toxicity (C. Ioannides, Ed.), pp. 345-374. Wiley, New York.
97. 14C]ortho-Toluidine (OTL) in Rats and Mice. Project Report No. 06/13, NIEHS Contract No. N01-ES-15329. Research Triangle Park, NC.
98. 1 Mice. Project Report No. 16P, NIEHS Contract No. N01-ES-15329.
99. 14C]m-Nitrotoluene (MNT) in Rats and Mice. Project Report No. 17, NIEHS Contract No. N01-ES-15329. Research Triangle Park, NC.
100. Rickert, D.E. (1987). Metabolism of nitroaromatic compounds. Drug. Metab. Rev. 18, 23-53.
101. Rickert, D.E., and Long, R.M. (1981). Metabolism and excretion of 2,4-dinitrotoluene in male and female Fischer 344 rats after different doses. Drug Metab. Dispos. 9, 226-232.
102. Rickert, D.E., Butterworth, B.E., and Popp, J.A. (1984a). Dinitrotoluene: Acute toxicity, oncogenicity, genotoxicity, and metabolism. CRC Crit. Rev. Toxicol. 13, 217-234.
103. Rickert, D.E., Long, R.M., Dyroff, M.C., and Kedderis, G.L. (1984b). Hepatic macromolecular covalent binding of mononitrotoluenes in Fischer 344 rats. Chem. Biol. Interact. 52, 131-139.
104. Rickert, D.E., DeBethizy, J.D., Glover, M.R., and Kedderis, G.L. (1985). Kinetics of conjugation and oxidation of nitrobenzyl alcohols by rat hepatic enzymes. Biochem. Pharmacol. 34, 4163-4168.
105. The Sadtler Handbook of Ultraviolet Spectra (1979). Spectrum No. 1042 (W. Simons, Ed.). Sadtler Research Laboratories, Philadelphia.
106. Shelby, M.D. (1988). The genetic toxicity of human carcinogens and its implications. Mutat. Res. 204, 3-15.
107. 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.
108. 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.
109. 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.
110. Shimizu, M., and Yano, E. (1986). Mutagenicity of mono-nitrobenzene derivatives in the Ames test and rec assay. Mutat. Res. 170, 11-22.
111. Singer, B. (1996). DNA damage: Chemistry, repair, and mutagenic potential. Regul. Toxicol. Pharmacol. 23, 2-13.
112. 14C]toluidine in the F344 rat. Xenobiotica 10, 457-468.
113. Spain, J.C. (1995). Biodegradation of nitroaromatic compounds. Annu. Rev. Microbiol. 49, 523-555.
114. Spanggord, R.J., Mortelmans, K.E., Griffin, A.F., and Simmon, V.F. (1982). Mutagenicity in Salmonella typhimurium and structure-activity relationships of wastewater components emanating from the manufacture of trinitrotoluene. Environ. Mutagen. 4, 163-179.
115. Straus, D.S. (1981). Somatic mutation, cellular differentiation, and cancer causation. JNCI 67, 233-241.
116. Suzuki, J., Koyama, T., and Suzuki, S. (1983). Mutagenicities of mono-nitrobenzene derivatives in the presence of norharman. Mutat. Res. 120, 105-110.
117. Tarone, R.E. (1975). Tests for trend in life table analysis. Biometrika 62, 679-682.
118. Tennant, R.W., and Ashby, J. (1991). Classification according to chemical structure, mutagenicity to Salmonella and level of carcinogenicity of a further 39 chemicals tested for carcinogenicity by the U.S. National Toxicology Program. Mutat. Res. 257, 209-227.
119. 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.
120. U.S. Environmental Protection Agency (USEPA) (1976). Frequency of organic compounds identified in water. EPA-600/4-76-062. USEPA, Athens, GA.
121. U.S. Environmental Protection Agency (USEPA) (1999). Office of Pollution Prevention and Toxics High Production Volume Chemicals. Retrieved 30 March 1999 from the World Wide Web:
122. Verschueren, K. (1983). Handbook of Environmental Data on Organic Chemicals, 2nd ed. Van Nostrand Reinhold Company, New York.
123. Walker, C., Everitt, J., and Barrett, J.C. (1992). Possible cellular and molecular mechanisms for asbestos carcinogenicity. Am. J. Ind. Med. 21, 253-273.
124. Ward, E., Carpenter, A., Markowitz, S., Roberts, D., and Halperin, W. (1991). Excess number of bladder cancers in workers exposed to ortho-toluidine and aniline. J. Natl. Cancer Inst. 83, 501-506.
125. Ward, J.M., Mann, P.C., Morishima, H., and Frith, C.H. (1999). Thymus, spleen, and lymph nodes. In Pathology of the Mouse (R.R. Maronpot, Ed.), pp. 333-360. Cache River Press, Vienna, IL.
126. Weisburger, E.K., Russfield, A.B., Homburger F., Weisburger, J.H., Boger, E., Van Dongen, C.G., and Chu, K.C. (1978). Testing of twenty-one environmental aromatic amines or derivatives for long-term toxicity or carcinogenicity. J. Environ. Pathol. Toxicol. 2, 325-356.
127. White, A., Handler, P., Smith, E.L., Hill, R.L., and Lehman, I.R. (1978). Principles of Biochemistry, 6th ed., p. 751. McGraw-Hill Book Company, New York.
128. 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.
129. Williams, D.A. (1972). The comparison of several dose levels with a zero dose control. Biometrics 28, 519-531.
130. 1 mice from short-term, prechronic, and chronic studies of the NTP Carcinogenesis Bioassay Program. Environ. Mol. Mutagen. 36, 163-194.
131. Working, P.K., and Butterworth, B.E. (1984). An assay to detect chemically induced DNA repair in rat spermatocytes. Environ. Mutagen. 6, 273-286.
132. Xiao, S., Li, D., Vijg, J., Sugarbaker, D.J., Corson, J.M., and Fletcher, J.A. (1995). Codeletion of p15 and p16 in primary malignant mesothelioma. Oncogene 11, 511-515.
133. 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.