A Framework for Human Relevance Analysis of Information on Carcinogenic Modes of Action

References

• Ade, P., Guastadisegni, C., Testai, E., and Vittozzi, L. (1994). Multiple activation of chloroform in kidney microsomes from male and female DBA/2J mice. J. Biochem. Toxicol. 9(6):289–295.
   PubMedGoogle Scholar
• Ahmed, A.E., Abdel-Aziz, A.H., Abdel-Rahman, S.Z., Haque, A.K., Nouraldeen, A.M., and Shouman, S.A. (1992a). Pulmonary toxicity of acrylonitrile: Covalent interaction and effect on replicative and unscheduled DNA synthesis in the lung. Toxicol- ogy 76(1):1–14.
   PubMed Web of Science ®Google Scholar
• Ahmed, A.E., Abdel-Rahman, S.Z., and Nour-Al Deen, A.M. (1992b). Acrylonitrile interaction with testic- ular DNA in rats. J. Biochem. Toxicol. 7(1):5–11.
   PubMedGoogle Scholar
• Ahmed, A.E., and Nouraldeen, A.M. (1996). Effects of acrylonitrile (VCN) on reactive oxygen i.e. ies mediated strand breaks in pBluescript plas- mid in vitro. Toxicologist 30(1 part 2):332 (Abstr. 1706).
   Google Scholar
• Ahmed, A.E., El-zahaby, M.H., and Mohamadin, A.M. (1996). A role of reactive oxygen species in the pathogenesis of acrylonitrile induced gastric mu- cosal cell damage. Toxicologist 30(1 part 2):238 (Abstr. 1221).
   Google Scholar
• Ames, B.N., and Gold, L.S. (1990). Chemical carcino- genesis: Too many rodent carcinogens. Proc. Natl. Acad. Sci. USA 87:7772–7776.
   PubMed Web of Science ®Google Scholar
• Ames, B.N., and Gold, L.S. (1996). Correspondence re: E. Farber, Cell proliferation as a major risk factor for cancer: A concept of doubtful validity. Cancer Res. 55: 3759–3762,1995 [letter to editor]. Cancer Res. 56:4267–4269.
   Google Scholar
• Ames, B.N., Shigenaga, M.K., and Gold, L.S. (1993). DNA lesions, inducible DNA repair, and cell divi- sion: Three factors in mutagenesis and carcinogen- esis. Environ. Health Perspect. 101(Suppl. 5):35– 44.
   Google Scholar
• Amet, Y., Berthou, F., Fournier, G., Dreano, Y., Bardou, L., Cledes, J., and Menez, J.-F. (1997). Cytochrome P450 4A and 2E1 expression in human kid- ney microsomes. Biochem. Pharmacol. 53:765– 771.
   Google Scholar
• Aschheim, P. (1976). Aging in the hypothalamic- hypophyseal ovarian axis in the rat. In: Hypothala- mus, Pituitary and Aging, A.V. Everitt and J.A. Burgess, eds., pp. 376–418. Charles C. Thomas Company, Springfield, IL.
   Google Scholar
• Banerjee, S.K., De, A., and Sarkar, D.K. (1994). Colocal- ization of prolactin and proliferating cell nuclear antigen in the anterior pituitary during estrogen- induced pituitary tumors. Cancer Lett. 87(2):139– 144.
   PubMed Web of Science ®Google Scholar
• Basler, A., von der Hude, W., and Seelbach, A. (1989). Genotoxicity of epoxides. I. Investi- gations with the OSOC Chromotest and the Salmonella/mammalian microsome test. Mutage- nesis 4:313–314.
   Google Scholar
• Benn, T., and Osborne, K. (1998). Mortality of United Kingdom acrylonitrile workers—An extended and updated study. Scand. J. Work Environ. Health 24(Suppl. 2):17–24.
   Google Scholar
• Beyer-Boon, M.E., Cuypers, L.H.R.I., de Voogt, H.J., and Brussee, J.A.M. (1978). Cytological changes due to urinary calculi. A consideration of the relationship between calculi and the development of urothelial carcinoma. Br. J. Urol. 50:81–89.
   Google Scholar
• Bio/Dynamics, Inc. (1980a). A twenty-four month oral toxicity/carcinogenicity study of acrylonitrile ad- ministered to Spartan rats in the drinking water. Fi- nal report. Two volumes. Division of Biology and Safety Evaluation. Submitted to Monsanto Com- pany, St. Louis, MO (Project No. 77-1745; BDN- 77-28).
   Google Scholar
• Bio/Dynamics, Inc. (1980b). A twenty-four month oral toxicity/carcinogenicity study of acrylonitrile ad- ministered in the drinking water to Fischer 344 rats. Final report. Four volumes. Submitted to Monsanto Company, St. Louis, MO (Project No. 77-1744; BDN-77-27).
   Google Scholar
• Bio/Dynamics, Inc. (1980c). A twenty-four month oral toxicity/carcinogenicity study of acrylonitrile ad- ministered by intubation to Spartan rats. Final re- port. Two volumes. Submitted to Monsanto Com- pany, St. Louis, MO (Project No. 77-1746; BDN- 77-29).
   Google Scholar
• Blair, A., Stewart, P., Zaebst, D., Pottern, L., Zey, J., Bloom, T., Miller, B., Ward, E., and Lubin, J. (1998). Mortality study of industrial workers ex- posed to acrylonitrile. Scand. J. Work Environ. Health 24(Suppl. 2):25–41.
   Google Scholar
• Borak, J. (1992). Acute acrylonitrile toxicity: Reconsid- eration of mechanisms and antidotes. The OEM Report 6(3):19–21.
   Google Scholar
• Borba, H., Monteiro, M., Proenca, M.J., Chaveca, T., Pereira, V., Lynce, N., and Rueff, J. (1996). Eval- uation of some biomonitoring markers in occupa- tionally exposed populations to acrylonitrile. Ter- atogen. Carcinogen. Mutagen. 16(4):205–218.
   PubMedGoogle Scholar
• Borghoff, S.J., and Lagarde, W.H. (1993). Assessment of binding of 2,4,4-trimethy-2-pentanol to low molecular weight proteins isolated from kidneys of male rats and humans. Toxicol. Appl. Pharma- col. 119:228–235.
   PubMed Web of Science ®Google Scholar
• Borghoff, S.J., Short, B.G., and Swenberg, J.A. (1990). Biochemical mechanisms and pathobiology of α2µ-globulin nephropathy. Annu. Rev. Pharmacol. Toxicol. 30:349–267.
   PubMed Web of Science ®Google Scholar
• Brady, J.F., Li, D., Ishizaki, H., Lee, M., Ning, S.M., Xiao, F., and Yan, C.S. (1989). Induction of cytochromes P450IIE 1 and P450IIB1 by secondary ketones and the role of P450IIE1 in chloroform metabolism. Toxicol. Appl. Pharmacol. 100:342–349.
   PubMed Web of Science ®Google Scholar
• Brown, B.R., Sipes, I.G., and Sagalyn, M.A. (1974). Mechanisms of acute hepatic toxicity: Chloro- form, halothane and glutathione. Anesthesiology 41(6):554–561.
   PubMedGoogle Scholar
• Brown, C., Asgharian, B., Turner, M., and Fennell, T. (1998). Ethylene oxide dosimetry in the mouse. Toxicol. Appl. Pharmacol. 148:215–221.
   PubMed Web of Science ®Google Scholar
• Brown, C.D., Wong, B.A., and Fennel, T.R. (1996). In vivo and in vitro kinetics of ethylene oxide metabolism in rats and mice. Toxicol. Appl. Phar- macol. 136:8–19.
   PubMed Web of Science ®Google Scholar
• Brown, R.P., Delp, M.D., Lindstedt, S.L., Rhomberg, L.R., and Beliles, R.P. (1997). Physiological pa- rameter values for physiologically based pharma- cokinetic models. Toxicol. Ind. Health 13:407– 484.
   Google Scholar
• Brugnone, F., Perbellini, L., Faccini, G.B., Pasini, F., Bartolucci, G.B., and DeRosa, E. (1986). Ethylene oxide exposure. Biological monitoring by analysis of alveolar air and blood. Int. Arch. Occup. Environ. Health 58:105–112.
   Google Scholar
• Brusick, D.J. (1994). An assessment of the genetic toxicity of atrazine: Relevance to health and effects. Mut. Res. 317:133–144.
   PubMedGoogle Scholar
• Bryan, G.T. (1969). Pellet implantation studies of carcino- genic compounds. J. Natl. Cancer Inst. 43:255– 261.
   Google Scholar
• Buhler, R., Lindros, K., Nordling, A., Johansson, I., and Ingelman-Sundberg, M. (1992). Zonation of cytochrome P450 isozyme expression and in- duction in rat liver. Eur. J. Biochem. 204:407– 412.
   Google Scholar
• Burin, G.J., Gibb, H.J., and Hill, R.N. (1995). Human bladder cancer: Evidence for a potential irritation- induced mechanism. Food Chem. Toxicol. 33:785– 795.
   Google Scholar
• Butterworth, B.E. (1996). Correspondence re: E. Farber, Cell proliferation as a major risk factor for can- cer: A concept of doubtful validity. Cancer Res. 55: 3759–3762,1995 [letter to editor]. Cancer Res. 56:4270–4272.
   Google Scholar
• California Air Resources Board. (1994). Toxic volatile organic compounds in environmental tobacco smoke: Emission factors for modeling exposures of California populations. Prepared by Lawrence Berkeley Laboratory, Berkeley, California (Na- tional Technical Information Services Publication No. NTIS/DE95006717).
   Google Scholar
• Capen, C.C. (2001). Toxic responses of the endocrine sys- tem. In: Toxicology: The Basic Science of Poisons,
   Google Scholar
• C. D. Klaassen, ed., pp. 711–759. McGraw-Hill, New York.
   Google Scholar
• Clayson, D.B. (1979). Bladder Carcinogenesis in Rats and Mice: Possibility of Artifacts. National Can- cer Institute Monograph 52, pp. 519–524. National Cancer Institute, Bethesda, MD.
   Google Scholar
• Clayson, D.B., Fishbein, L., and Cohen, S.M. (1995). Ef- fects of stones and other physical factors on the induction of rodent bladder cancer. Food Chem. Toxicol. 33:771–784.
   PubMed Web of Science ®Google Scholar
• Clemens, T.L., Hill, R.N., Bullock, L.P., Johnson, W.D., Sultatos, L.G., and Vessell, E.S. (1979). Chloro- form toxicity in the mouse: Role of genetic factors and steroids. Toxicol. Appl. Pharmacol. 48:117– 130.
   Google Scholar
• Clinton, S.K., Li, P.S., Mulloy, A.L., Imrey, P.B., Nand- kumar, S., and Visek, W.J. (1995). The combined effects of dietary fat and estrogen on survival, 7,12-dimethylbenz [a] anthracene-induced breast cancer and prolactin metabolism in rats. J. Nutr. 125(5):1192–1204.
   Google Scholar
• Cohen, S.M. (1995a). Role of cell proliferation in re- generative and neoplastic disease. Toxicol. Lett. 82/83:15–21.
   Google Scholar
• Cohen, S.M. (1995b). The role of urinary physiology and chemistry in bladder carcinogenesis. Food Chem. Toxicol. 33:715–730.
   PubMed Web of Science ®Google Scholar
• Cohen, S.M., and Ellwein, L.B. (1990). Cell proliferation in carcinogenesis. Science 249:1007–1011.
   PubMed Web of Science ®Google Scholar
• Cohen, S.M., and Ellwein, S.B. (1991). Genetic errors, cell proliferation, and carcinogenesis. Cancer Res. 51:6493–6505.
   PubMed Web of Science ®Google Scholar
• Cohen, S.M., and Ellwein, L.B. (1996). Correspondence re: E. Farber, Cell proliferation as a major risk factor for cancer: A concept of doubtful validity. Cancer Res. 55: 3759–3762,1995 [letter to editor]. Cancer Res. 56:4269–4270.
   Google Scholar
• Connor, K., Howell, J., Chen, I., Liu, H., Berhane, K., Sciarretta, C., Safe, S., and Zacharewski, T. (1996). Failure of chloro-s-triazine-derived compounds to induce estrogen receptor-mediated responses in vivo and in vitro. Fund. Appl. Toxicol. 30:93–101.
   PubMedGoogle Scholar
• Constan, A.A., Sprankle, C.S., Peters, J.M., Kedderis, G.L., Everitt, J.I., Wong, B.A., Gonzalez, F.L., and Butterworth, B.E. (1999). Metabolism of chloro- form by cytochrome P450 2E1 is required for in- duction of toxicity in the liver, kidney, and nose of male mice. Toxicol. Appl. Pharmacol. 160:120– 126.
   Google Scholar
• Cooper, R.L., Parrish, M.B., McElroy, W.K., Rehnberg, G.L., Hein, J.F., Goldman, J.M., Stoker, J.M., and Tyrey, L. (1995). Effects of atrazine on the hor- monal control of the ovary. Toxicologist 15 (1):Abstr. 1572.
   Google Scholar
• Cooper, R.L., Stoker, T.E., Goldman, J.M., Hein, J., and Tyrey, G. (1996). Atrazine disrupts hypothalamic control of pituitary–ovarian function. Toxicologist 30(1):66.
   Google Scholar
• Corley, R.A., Mendrala, A.L., Smith, F.A., Staats, D.A., Gargas, M.L., Conolly, R.B., Andersen, M.E., and Reitz, R.H. (1990). Development of a physiologi- cally based pharmacokinetic model for chloroform. Toxicol. Appl. Pharmacol. 103:512–527.
   PubMed Web of Science ®Google Scholar
• Cresteil, T., Beaune, P., Leroux, J.P., Lange, M., and Mansuy, D. (1979). Biotransformation of chloro- form by rat and human liver microsomes: In vitro effect on some enzyme activities and mechanisms of irreversible binding to macromolecules. Chem. Biol. Interact. 24:153–165.
   PubMed Web of Science ®Google Scholar
• Cunningham, M.L., and Matthews, H.B. (1995). Cell pro- liferation as a determining factor for the carcino- genicity of chemicals: Studies with mutagenic car- cinogens and mutagenic noncarcinogens. Toxicol. Lett. 82/83:9–14.
   Google Scholar
• Curran, P.G., and DeGroot, L. J. (1991). The effect of hep- atic enzyme-inducing drugs on thyroid hormones and the thyroid gland. Endocr. Rev. 12:135–150.
   PubMed Web of Science ®Google Scholar
• Cutts, H.J., and Noble, R.L. (1964). Estrone-induced mammary tumors in the rat. Cancer Research 24:1116–1123.
   Google Scholar
• deSandro, V., Chevrier, M., Boddaert, A., Melcion, C., Cordier, A., and Richert, L. (1991). Com- parison of the effects of propylthiouracil, amio- darone, diphenylhydantoin, phenobarbital, and 3-methylcholanthrene on hepatic and renal T4 metabolism and thyroid gland function in rats. Tox- icol. Appl. Pharmacol. 111:263–278.
   PubMed Web of Science ®Google Scholar
• Dicker, E., McHugh, T., and Cederbaum, A.I. (1991). In- creased catalytic activity of cytochrome P-450IIE1 in pericentral hepatocytes compared to peripor- tal hepatocytes isolated from pyrazole-treated rats. Biochim. Biophys. Acta 1073:316–323.
   PubMedGoogle Scholar
• Dietrich, D.R., and Swenberg, J. A. (1991a). NCI Black Reiter (NBR) male rats fail to develop renal dis- ease following exposure to agents that induce α2µ-globulin nephropathy. Fundam. Appl. Toxi- col. 16:749–762.
   PubMedGoogle Scholar
• Dietrich, D.R., and Swenberg, J.A (1991b). The presence of α2µ-globulin is necessary for d-limonene pro- motion of male rat kidney tumors. Cancer Res. 51:3512–3521.
   PubMed Web of Science ®Google Scholar
• Dohler, K.D., Wong, C.C., and Von Zur Muhlen, A. (1979). The rat as a model for the study of drug ef- fects on thyroid function: Consideration of method- ological problems. Pharmacol. Ther. 5:305–318.
   PubMed Web of Science ®Google Scholar
• Dunkelberg, H. (1981). Carcinogenic activity of ethylene oxide and its reaction products 2-chloro-ethanol, 2 romoethanol, ethylene glycol and diethylene gly- col. I. Carcinogenicity of ethylene oxide in compar- ison with 1,2-propylene oxide after subcutaneous administration in mice. Zbl. Bakt. Hyg. I. Abt. Orig. B 174: 383–404(in German).
   Google Scholar
• Dunkelberg, H. (1982). Carcinogenicity of ethylene oxide and 1,2-propylene oxide upon intragastric admin- istration to rats. Br. J. Cancer 46:924–933.
   PubMed Web of Science ®Google Scholar
• Dybing, E., and Sanner, T. (1999). Species differences in chemical carcinogenesis of the thyroid gland, kid- ney and urinary bladder. In: Species Differences in Thyroid Gland, Kidney and Urinary Bladder Car- cinogenesis, C. C. Capen, E. Dybing, J. M. Rice and J. D. Wilbourn, eds, pp. 15–32. IARC Scien- tific Publications No. 147, Lyon, France.
   Google Scholar
• Eldridge J.C., McConnell, R.F., Wetzel. L.T., and Tis- del, M.O. (1998). Appearance of mammary tumors in atrazine-treated female rats: Probable mode of action involving strain-related control of ovula- tion and estrous cycling. In: Triazine Herbicides Risk Assessment, L. Balantine, J.E. McFarland, and D. Hackett, eds., pp. 414–423. ACS Symposium Series No. 683, Washington, DC.
   Google Scholar
• Elson, C.E., Maltzman, T.H., Boston, J.L., Tanner, M.A., and Gould, M. N. (1988). Anti-carcinogenic ac- tivity of d-limonene during initiation and pro- motion/progression states of DMBA-induced rat mammary carcinogenesis. Carcinogenesis 9:332– 332.
   Google Scholar
• El-zahaby, M.H., Mohamadin, A.M., and Ahmed, A.E. (1996). Acrylonitrile bioactivation; role of iron/hypoxanthine/xanthine oxidase system in vitro. Toxicologist 30(1 part 2):283(Abstr. 1449).
   Google Scholar
• Farber, E. (1996). Correspondence re: E. Farber, Cell pro- liferation as a major risk factor for cancer: A con- cept of doubtful validity. Cancer Res. 55:3759– 3762, 1995 [reply to letter to editor]. Cancer Res. 56:4272–4274.
   Google Scholar
• Farooqui, M.Y.H., and Ahmed, A.E. (1983). In vivo in- teractions of acrylonitrile with macromolecules in rats. Chem. Biol. Interact. 47:363–371.
   PubMed Web of Science ®Google Scholar
• Fennell, T.R., and Brown, C.D. (2001). A physiologically based pharmacokinetic model for ethylene oxide in mouse, rat and human. Toxicol. Appl. Pharmacol. 173:161–175.
   PubMed Web of Science ®Google Scholar
• Fennell, T.R., Kedderis, G.L., and Sumner, S.C.J. (1991). Urinary metabolites of [1,2,3-13C] acrylonitrile in rats and mice detected by 13C nuclear mag- netic resonance spectroscopy. Chem. Res. Toxicol. 4(6):678–687.
   PubMed Web of Science ®Google Scholar
• Fennell, T.R., and Sumner, S.C.J. (1994). Identification of metabolites of carcinogens by 13C NMR spec- troscopy. Drug Metab. Rev. 26:(1&2)469–481.
   Google Scholar
• Filser, J.G. (1992). The closed chamber technique-uptake, endogenous production, excretion, steady-state ki-netics and rates of metabolism of gases and vapors. Arch. Toxicol. 66:1–10.
   PubMed Web of Science ®Google Scholar
• Filser, J.G., and Bolt, H.M. (1984). Inhalation pharma- cokinetics based on gas uptake studies. VI. Com- parative evaluation of ethylene oxide and butadi- ene monoxide as exhaled reactive metabolites of ethylene and 1,3-butadiene in rats. Arch. Toxicol. 55:219–223.
   PubMed Web of Science ®Google Scholar
• Flower, D.R., North, A.C., and Attwood, T.K. (1993). Structure and sequence relationships in the lip- calins and related proteins. Protein Sci. 2:753–761.
   PubMed Web of Science ®Google Scholar
• Fry, B.J., Taylor, T., and Hathway, D.E. (1972). Pul- monary elimination of chloroform and its metabo- lite in man. Arch. int. Pharmacodyn. 196:98–111.
   PubMedGoogle Scholar
• Fukushima, S., Tanaka, H., Asakawa, E., Kagawa, M., Yamamoto, A., and Shirai, T. (1992). Carcino- genicity of uracil, a nongenotoxic chemical, in rats and mice and its rationale. Cancer Res. 52:1675– 1680.
   Google Scholar
• Fuchs, J., Wullenweber, U., Hengstler, J., Bienfait, H., Hiltl, G., and Oesch, F. (1994). Genotoxic risks for humans due to work place exposure to ethy- lene oxide: Remarkable individual differences in susceptibility. Arch. Toxicol. 68(6):343–348.
   Google Scholar
• Gargas, M.L., Andersen, M.E., Teo, S.K.O., Batra, R., Fennell, T.R., and Kedderis, G.L. (1995). A physi- ologically based dosimetry description of acryloni- trile and cyanoethylene oxide in the rat. Toxicol. Appl. Pharmacol. 134:185–194.
   PubMed Web of Science ®Google Scholar
• Garman, R.H., Snellings, W.M., and Maronpot, R.R. (1985). Brain tumors in F344 rats associated with chronic inhalation exposure to ethylene oxide. Neurotoxicology 6:117–138.
   PubMed Web of Science ®Google Scholar
• Garman, R.H., Snellings, W.M., and Maronpot, R.R. (1986). Frequency, size and location of brain tu- mors in F344 rats chronically exposed to ethylene oxide. Food Chem. Toxicol. 24:145–153.
   PubMed Web of Science ®Google Scholar
• Generoso, W.M., Kain, K.T., Cornett, C.V., Cacherio, N.T.L., and Hughes, L.A. (1990). Concentration- response curves for ethylene oxide-induced herita- ble translocations and dominant lethal mutations. Environ. Mol. Mutagen 16:126–131.
   PubMed Web of Science ®Google Scholar
• Goldstein, J.A., and Taurog, A. (1968). Enhanced biliary excretion of thyroxin glucuronide in rats pretreated with benzopyrene. Biochem. Pharmacol. 17:1049– 1065.
   Google Scholar
• Goodman, R.L., and Knobil, E. (1981). The sites of action of ovarian steroids in the regulation of LH secre- tion. Neuroendocrinology 32:57–63.
   PubMed Web of Science ®Google Scholar
• Graumann, K., Briethofer, A., and Jungbaur, A. (1999). Monitoring of estrogen mimics by recombinant yeast assay: Synergy between natural and synthetic compounds? Sci. Tot. Environ. 225:69–79.
   PubMedGoogle Scholar
• Guengerich, F.P., Geiger, L.E., Hogy, L.L., and Wright, P.L. (1981). In vitro metabolism of acrylonitrile to 2-cyanoethylene oxide, reaction with glutathione, and irreversible binding to proteins and nucleic acids. Cancer Res. 41:4925–4933.
   PubMed Web of Science ®Google Scholar
• Guengerich, F.P., Kim, D.H., and Iwasaki, M. (1991). Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem. Res. Toxicol. 4:168–179.
   PubMed Web of Science ®Google Scholar
• Gullino, P.M., Pettigrew, H.M., and Grantham, F.H. (1975). N-Nitrosmethylurea and mammary gland carcinogen in rats. J. Nat. Cancer Inst. 54(20):401– 414.
   PubMed Web of Science ®Google Scholar
• Hagmar, L., Welinder, H., Linde´n, K., Attewell, R., Osterman-Golkar, S., and To¨rnqvist, M. (1991). An epidemiological study of cancer risk among work- ers exposed to ethylene oxide using hemoglobin adducts to validate environmental exposure assess- ments. Int. Arch. Occup. Environ. Health 63:271– 277.
   Google Scholar
• Hagmar, L., Mikoczy, Z., and Welinder, H. (1995). Cancer incidence in Swedish sterilant workers exposed to ethylene oxide. Occup. Environ. Med. 52(3):154– 156.
   PubMed Web of Science ®Google Scholar
• Hard, G.C., Boorman, G.A., and Wolf, D.C. (2000). Re- evaluation of the 2-year chloroform drinking water carcinogenicity bioassay in Osborne-Mendel rats supports chronic renal tubule injury as the mode of action underlying the renal tumor response. Toxi- col. Sci. 53(2):159–172.
   Google Scholar
• Hazelette, J.R., and Green, J.D. (1987). 18-Month Onco- genicity Study of Atrazine Technical in Mice. Project No. MIN 842120. Ciba-Geigy Pharma- ceuticals SEF, October 30, 1987. MRID No. 40431302.
   Google Scholar
• Health Canada. (1994). Canadian Environmental Protec- tion Act. Human health risk assessment for Prior- ity Substances. Minister of Supply and Services Canada, Ottawa, Ontario. 36 pp. (Catalogue No. En40-215/41E; ISBN 0-662-22126-5).
   Google Scholar
• Health Canada. (2002). http://www.hc-sc.gc.ca/exsd Heck, H.d’A., and Tyl, R.W. (1985). The induction of bladder stones by terephthalic acid, dimethyl terephthalate, and melamine (2,4,5-triamino-s- triazine) and its relevance to risk assessment. Regul. Toxicol. Pharmacol. 5:294–313.
   Google Scholar
• Henderson, C.J., Scott, A.R., Yang, C.S., and Wolf, R.C. (1989). Testosterone-mediated regulation of mouse renal cytochrome P-450 isoenzymes. Biochem. J. 278:499–503.
   Google Scholar
• Hiatt, R.A., Dales, L.G., Friedman, G.D., and Hunkeler, E.M. (1982). Frequency of nephrolithiasis in a prepaid medical care program. Am. J. Epidemiol. 115:226–265.
   Google Scholar
• Highman, W., and Wilson, E (1982). Urine cytology in patients with calculi. J. Clin. Pathol. 35:350– 356.
   Google Scholar
• Hogy, L.L., and Guengerich, F.P. (1986). In vivo inter- action of acrylonitrile and 2-cyanoethylene oxide with DNA in rats. Cancer Res. 46:3932–3938.
   PubMed Web of Science ®Google Scholar
• Hong, J.Y., Pan, J.M., Ning, S.M., and Yang, C.S. (1989). Molecular basis for the sex-related differ- ence in renal N-nitrosodimethylamine demethy- lase in C3H/HeJ mice. Cancer Res. 49:2973– 2979.
   Google Scholar
• Hood, A., and Klaassen, C.D. (2000). Differential effects of microsomal enzyme inducers on in vitro thryox- ine (T4) and triiodothyronine (T3) glucuronidation. Toxicol. Sci. 55:78–84.
   PubMed Web of Science ®Google Scholar
• Hood, A., Liu, Y.P., Gattone, V.H. II., and Klaassen, C.D. (1999). Sensitivity to thyroid gland growth to thy- roid stimulating hormone (TSH) in rats treated with antithyroid drugs. Toxicol. Sci. 49:263–271.
   PubMed Web of Science ®Google Scholar
• ICF Kaiser. (1999). Development of a PBPK model for chloroform for human health risk assessment. Con- tract report for Health Canada. The K.S. Crump Group, Inc., ICF Kaiser, Ruston, Louisiana.
   Google Scholar
• Igimi, H., Hisatsugu, T., and Nashimura, M. (1976). The use of d-limonene preparation as a dis- solving agent of gallstones. Dig. Dis. 21:926– 939.
   Google Scholar
• Ilett, K.E., Reid, W.D., Sipes, I.G., and Krishan, G. (1973). Chloroform toxicity in mice: Correlation of re- nal and hepatic necrosis with covalent binding of metabolites to tissue macromolecules. Exp. Mol. Pathol. 19:215–229.
   PubMed Web of Science ®Google Scholar
• Ingelman-Sundberg, M., Johansson, I., Penttila¨, K.E., Glaumann, H., and Lindros, K.O. (1988). Cen- trilobular expression of ethanol-inducible cy- tochrome P-450 (IIE1) in rat liver. Biochem. Bio- phys. Res. Commun. 157(1):55–60.
   PubMed Web of Science ®Google Scholar
• Innes, J.R., Ulland, B.M., Valerio, M.G., Petrucelli, L., Fishbein, L., Hart, E.R., Pallotta, A.J., Batts, R.R., Falk, H.L., Gart, J.J., Klein, M., Mitchell, I., and Peters, J. (1969). Chronic bioassay of pes- ticides and industrial chemicals for tumorigenicity in mice: A preliminary note. J. Natl. Canc. Inst. 42:1101–1114.
   PubMed Web of Science ®Google Scholar
• Interagency Regulatory Liaison Group. (1979). Scientific bases for identification of potential carcinogens and estimation of risks. J. Natl Cancer Inst. 63:241– 268.
   Google Scholar
• International Agency for Research on Cancer. (1992). Occupational exposures to mists and vapors from strong inorganic acids; and other industrial chem- icals. Preamble. IARC Monogr. Eval. Carcinogen. Risks Hum. 54:13–32.
   Google Scholar
• International Agency for Research on Cancer. (1994). Some industrial chemicals. IARC Monogr. Eval. Carcinogen. Risks Hum. 60:73–159.
   Google Scholar
• International Agency for Research on Cancer. (1999a). Some chemicals that cause tumours of the kid- ney or urinary bladder in rodents and some other substances. IARC Monogr. Eval. Carcinogen. Risks Hum. 73:329–338.
   Google Scholar
• International Agency for Research on Cancer. (1999b). Consensus report. In: Species Differences in Thy- roid, Kidney and Urinary Bladder Carcinogene- sis, C.C. Capen, E. Dybing, J.M. Rice, and J.D. Wilbourn, eds., pp. 1–14. IARC Scientific Publi- cations No. 147, Lyon, France.
   Google Scholar
• International Commission on Radiological Protection. (1992). Report of the Task Group on Reference Man. (Report No. 23). New York: Pergamon Press.
   Google Scholar
• International Life Sciences Institute. (1997). An evalua- tion of EPA’s proposed guidelines for carcinogen risk assessment using chloroform and dichloroac- etate as case studies: Report of an expert panel. (ISBN 1-57881-002-70). ILSI Health and Environ- mental Sciences Institute, Washington, DC.
   Google Scholar
• Jiang, J., Xu, Y., and Klaunig, J.E. (1997). Induction of oxidative stress in rat brain by acrylonitrile. Toxi- cologist 36(1 part 2):94(Abstr. 481).
   Google Scholar
• Jiang, J., Xu, Y., and Klaunig, J.E. (1998). Induction of oxidative stress in rat astrocytes. Toxicologist 42(1- S):179 (Abstr. 883).
   Google Scholar
• Johansson, I., Lindros, K.O., Eriksson, H., and Ingelman- Sundberg, M. (1990). Transcriptional control of CYP2E1 in the perivenous liver region and dur- ing starvation. Biochem. Biophys. Res. Commun. 173(1):331–338.
   PubMedGoogle Scholar
• Jorgenson, T.A., Meierhenry, E.F., Rushbrook, C.J., Bull, R.J., and Robinson, M. (1985). Carcinogenicity of chloroform in drinking water to male Osborne- Mendel rats and female B6C3F1 mice. Fundam. Appl. Toxicol. 5:760–769.
   PubMedGoogle Scholar
• Jull, J.W. (1979). The effect of time on the incidence of carcinomas obtained by the implantation of paraf- fin wax pellets into mouse bladder. Cancer Lett. 6:21–25.
   PubMed Web of Science ®Google Scholar
• Kagawa, M., Yamamoto, A., Ogawa, K., Shitai, T., and Fukushima, S. (1992). Uracil-induced urolithiasis in the urinary tract is irritation dependent. Toxicol. Lett. 61:21–26.
   Google Scholar
• Kamendulis, L.M., Jiang, J., Zhang, H., deFeijter-Rupp, H., Trosko, J.R., and Klaunig, J.E. (1999a). The ef- fect of acrylonitrile on gap junctional intercellular communication in rat astrocytes. Cell Biol. Toxicol. 15:173–183.
   PubMed Web of Science ®Google Scholar
• Kamendulis, L.M., Jiang, J., Zhang, H., Xu, Y., and Klaunig, J.E. (1999b). Induction of oxidative stress and oxidative damage in rat glial cells by acryloni- trile. Carcinogenesis 20:1555–1560.
   PubMed Web of Science ®Google Scholar
• Kedderis, G.L. (1997). Development of a physiologi- cally based dosimetry description for acrylonitrile (ACN) in humans. Toxicologist 36(1 part 2):31 (Abstr. 158).
   Google Scholar
• Kedderis, G.L., and Batra, R. (1991). Metabolism of acry- lonitrile (ACN) and 2-cyanoethylene oxide (CEO) by rodent brain enzymes. Toxicologist 11 (1):229(Abstr. 863).
   Google Scholar
• Kedderis, G.L., and Batra, R. (1993). Species differ- ences in the hydrolysis of 2-cyanoethylene oxide, the epoxide metabolite of acrylonitrile. Carcino- genesis 14(4):685–689.
   PubMed Web of Science ®Google Scholar
• Kedderis, G.L., and Held, S.D. (1998). Refinement of the human dosimetry description for acry- lonitrile (ACN). Toxicologist 42(1-S):142 (Abstr. 700).
   Google Scholar
• Kedderis, G.L., Sumner, S.C.J., Held, S.D., Batra, R., Turner, M.J., Roberts, A.E., and Fennell, T.R. (1993a). Dose-dependent urinary excretion of acrylonitrile metabolites by rats and mice. Toxicol. Appl. Pharmacol. 120:288–297.
   PubMed Web of Science ®Google Scholar
• Kedderis, G.L., Batra, R., Held, S.D., Loos, M.A., and Teo, S.K.O. (1993b). Rodent tissue distribution of 2-cyanoethylene oxide, the epoxide metabolite of acrylonitrile. Toxicol. Lett. 69:25–30.
   PubMedGoogle Scholar
• Kedderis, G.L., Batra, R., and Koop, D.R. (1993c). Epoxidation of acrylonitrile by rat and human cytochromes P450. Chem. Res. Toxicol. 6:866– 871.
   Google Scholar
• Kedderis, G.L., Batra, R., and Turner, M.J. (1995). Conju- gation of acrylonitrile and 2-cyanoethylene oxide with hepatic glutathione. Toxicol. Appl. Pharma- col. 135:9–17.
   PubMed Web of Science ®Google Scholar
• Kedderis, G.L., Teo, S.K.O., Batra, R., Held, S.D., and Gargas, M.L. (1996). Refinement and verification of the physiologically based dosimetry description for acrylonitrile in rats. Toxicol. Appl. Pharmacol. 140(2):422–435.
   PubMedGoogle Scholar
• Kim, S., Kedderis, G., Batra, R., and Novak, R. (1993). Induction of rat liver microsomal epoxide hydro- lase by thiazole and pyrazine: Hydrolysis of 2- cyanoethylene oxide. Carcinogenesis 14(8):1665– 1670.
   PubMedGoogle Scholar
• Kirk, R.E., Othmer, D.F., Grayson, M., and Eckroth, D. (1983). Acrylonitrile. In: Kirk–Othmer Ency- clopaedia of Chemical Technology, Vol. 1, 3rd ed., pp. 414–426. John Wiley and Sons, New York.
   Google Scholar
• Kluwe, W.M. (1981). The nephrotoxicity of low molecu- lar weight halogenated alkane solvents, pesticides, and chemical intermediates. In: Toxicology of the Kidney, J.B. Hook, ed., pp. 179–226. Raven Press, New York.
   Google Scholar
• Knobil, E. (1974). On the control of gonadotrophin secre- tion in the rhesus monkey. Recent Prog. Hormone Res. 30:1–36.
   PubMedGoogle Scholar
• Koga, M., Hori, H., Tanaka, I., Akiyama, T., and Inoue, N. (1985). Quantitative analysis of urinary ethy- lene glycol in rats exposed to ethylene oxide. J. UOEH (Sangyo Ika Daigaku Zasshi) 7: 45–49(in Japanese). Koga, M., Hori, H., Tanaka, I., Akiyama, T., and Inoue, N. (1987). Analysis of urinary metabolites of rats exposed to ethylene oxide. J. UOEH (Sangyo Ika Daigaku Zasshi) 9: 167–170(in Japanese).
   Google Scholar
• Krey, L.C., Butler, W.R., and Knobil, E. (1975). Surgi- cal disconnection of the medial basal hypothala- mus and pituitary function in the rhesus monkey. I. Gonadotropin secretion. Endocrinology 96:1073– 1087.
   Google Scholar
• Krishnan, K., Gargas, M.L., Fennell, T.R., and Andersen, M.E. (1992). A physiologically based description of ethylene oxide dosimetry in the rat. Toxicol. Ind. Health 8:121–140.
   PubMed Web of Science ®Google Scholar
• Larson, J.L., Wolf, D.C., and Butterworth, B.E. (1994a). Induced cytotoxicity and cell proliferation in the hepatocarcinogenicity of chloroform in female B6C3F1 mice: Comparison of administration by gavage in corn oil vs ad libitum in drinking water. Fundam. Appl. Toxicol. 22:90–102.
   PubMedGoogle Scholar
• Larson, J.L., Wolf, D.C., and Butterworth, B.E. (1994b). Induced cytolethality and regenerative cell prolif- eration in the livers and kidneys of male B6C3F1 mice given chloroform by gavage. Fundam. Appl. Toxicol. 23(4):537–543.
   PubMedGoogle Scholar
• Larson, J.L., Wolf, D.C., Mery, S., Morgan, K.T., and Butterworth. B.E. (1995a). Toxicity and cell pro- liferation in the liver, kidneys and nasal passages of female F-344 rats, induced by chloroform admin- istered by gavage. Food Chem. Toxicol. 33(6):443– 456.
   PubMed Web of Science ®Google Scholar
• Larson, J.L., Wolf, D.C., and Butterworth, B.E. (1995b). Induced regenerative cell proliferation in livers and kidneys of male F-344 rats given chloroform in corn oil by gavage or ad libitum in drinking water. Toxicology 95:73–86.
   PubMed Web of Science ®Google Scholar
• Lehman-McKeeman, L.D. (1997). α2µ-Globulin nephropathy. In: Comprehensive Toxicology, R.S. Goldstein, ed., Vol. 7, pp. 677–692. Elsevier Science, New York.
   Google Scholar
• Lehman-McKeeman, L.D., and Caudill, D. (1992a). α2µ- Globulin is the only member of the lipocalin protein superfamily that binds to hyaline droplet inducing agents. Toxicol. Appl. Pharmacol. 116:170–176.
   PubMed Web of Science ®Google Scholar
• Lehman-McKeeman, L.D., and Caudill, D. (1992b). Bio- chemical basis for mouse resistance to hyaline droplet nephropathy: Lack of relevance of the α2µ-globulin protein superfamily in this male rat-specific syndrome. Toxicol. Appl. Pharmacol. 112:214–221.
   PubMed Web of Science ®Google Scholar
• Lehman-McKeeman, L.D., and Caudill, D. (1994). D- Limonene-induced hyaline droplet nephropathy in α2µ-globulin transgenic mice. Fundam. Appl. Tox- icol. 23:562–568.
   PubMedGoogle Scholar
• Litton Bionetics, Inc. (1980). Three-generation re- production study of rats receiving acrylonitrile in drinking water. Submission to Office of Toxic Substances, U.S. Environmental Protection Agency (TSCATS Accession No. 44131; Doc- ument I.D. No. 88-920002178; Microfiche No. OTS0536313).
   Google Scholar
• Liu, J., Liu, Y., Barter, R.A., and Klaassen, C.D. (1995). Alteration of thyroid hormone homeostasis by UDP-glucuronosyltransferase inducers in rats: A dose-response study. J. Pharmacol. Exp. Ther. 273:977–985.
   PubMed Web of Science ®Google Scholar
• Lo¨fberg, B., and Tja¨lve, H. (1986). Tracing tissues with chloroform-metabolizing capacity in rats. Toxicol- ogy 39:13–35.
   PubMed Web of Science ®Google Scholar
• Loosli, R. (1995). Epidemiology of atrazine. Reviews of environmental contamination and toxicology. Toxicology 143:47–57.
   Google Scholar
• Lynch, D.W., Lewis, T.R., Moorman, W.J., Burg, J.R., Groth, D.H., Khan, A., Ackerman, L.J., and Cockrell, B.Y. (1984). Carcinogenic and toxico- logical effects of inhaled ethylene oxide and propy- lene oxide in F344 rats. Toxicol. Appl. Pharmacol. 76:69–84.
   PubMed Web of Science ®Google Scholar
• Mast, R.W., Jeffcoat, A.R., Sadler, B.M., Kraska, R.C., and Friedman, M.A. (1983). Metabolism, disposi- tion and excretion of [14C]melamine in male Fis- cher 344 rats. Food Chem. Toxicol. 21:807–810.
   PubMed Web of Science ®Google Scholar
• Mastrangelo, G., Serena, R., and Marzia, V. (1993). Mor- tality from tumors in workers in an acrylic fibre factory. Occup. Med. 43(3):155–158.
   Google Scholar
• Masubuchi, N., Hakusui, H., and Okazaki, O. (1997). Effect of proton pump inhibitors on thyroid hormone metabolism in rats. Biochem. Pharmacol. 54:1225–1231.
   PubMedGoogle Scholar
• Mazzaferri, E.L. (2000). Thyroid cancer and Graves’ disease: The controversy ten years later. Endocr. Pract. 6:221–225.
   PubMedGoogle Scholar
• McClain, R.M. (1992). Thyroid gland neoplasia: Non- genotoxic mechanisms. Toxicol. Lett. 64/65:397– 408.
   Google Scholar
• McClain, R.M. (1995). The use of mechanistic data in cancer risk assessment: Case example— Sulfonamides. In: Low-Dose Extrapolation of Can- cer Risks, S. Olin, W. Farland, C. Park, L. Rhomberg, R. Scheuplein, T. Starr, and J. Wilson, eds., pp. 163–173. ILSI Press, Washington, DC.
   Google Scholar
• McClain, R.M., Levin, A.A., Posch, R., and Downing, J.C. (1989). The effect of phenobarbital on the metabolism and excretion of thyroxin in rats. Tox- icol. Appl. Pharmacol. 99:216–228.
   PubMed Web of Science ®Google Scholar
• McClain, R.M., and Rice, J.M. (1999). A mechanis- tic relationship between thyroid follicular cell tu- mors and hepatocellular neoplasms in rodents. In: Species Differences in Thyroid Gland, Kidney and Urinary Bladder Carcinogenesis, C. C. Capen, E. Dybing, J. M. Rice and J. D. Wilbourn, eds., pp. 61–68. IARC Scientific Publications No. 147, Lyon, France.
   Google Scholar
• McConnell, R.F. (1989). Comparative aspects of contra- ceptive steroids: Effects observed in rats. Toxicol Pathol. 17(2):385–388.
   Google Scholar
• McConnell, R.F. (1995). A histomorphologic reevalu- ation of the ovaries, uterus, vagina, Mammary gland, and pituitary gland from Spraque-Dawley and Fischer 344 female rats treated with atrazine. Unpublished U.S. EPA MRID Report 43598622. Washington, DC, USA.
   Google Scholar
• Meites, J. (1972). Relation of prolactin and estrogen to mammary tumorigenesis in the rat. J National Can- cer Institute 48(4):1217–1224.
   PubMedGoogle Scholar
• Meites, J., Huang, H.H., and Simpkins, J.W. (1978). Re- cent studies on neuroendocrine control of repro- ductive senescence in rats. In: The Aging Repro- ductive System, E.L. Scheider, ed., pp. 213–235. Raven Press, New York.
   Google Scholar
• Melnick, R.L. (1992). Does chemically-induced hepa- tocyte proliferation predict liver carcinogenesis? FASEB J. 6:2698–2706.
   PubMed Web of Science ®Google Scholar
• Melnick, R.L., Boorman, G.A., Haseman, J.K., Montall, R.J., and Huff, J. (1984). Urolithiasis and bladder carcinogenicity of melamine in rodents. Toxicol. Appl. Pharmacol 72:292–303.
   PubMed Web of Science ®Google Scholar
• Melnick, R.L., Kohn, M.C., Dunnick, J.K., and Leininger, J.R. (1998). Regenerative hyperplasia is not re-quired for liver tumor induction in female B6C3F1 mice exposed to trihalomethanes. Toxicol. Appl. Pharmacol. 148(1):137–147.
   PubMedGoogle Scholar
• Mohamadin, A.M., El-zahaby, M.H., and Ahmed, A.E. (1996). Acrylonitrile oxidation and cyanide release in cell free system catalyzed by Fenton-like reac- tion. Toxicologist 30(1 part 2):238 (Abstr. 1220).
   Google Scholar
• Mohla, S., Ahir, S., and Ampy, F.R. (1988). Tissue spe- cific regulation of renal N -nitrosodimethylamine- demethylase activity by testosterone in BALB/c mice. Biochem. Pharmacol. 37(13):2697–2702.
   PubMedGoogle Scholar
• Morseth, S.L. (1996a). Evaluation of the luteinizing hormone (LH) surge in atrazine-exposed female Sprague-Dawley rats—Interim report, Rep. No. CHV 2386-111, January 25, 1996a. Corning Hazleton, Inc., Vienna, VA.
   Google Scholar
• Morseth, S.L. (1996b). Evaluation of the luteinizing hormone (LH) surge in atrazine-exposed female Sprague-Dawley rats—6-Months report. Rep. No. CHV 2386-111, October 25, 1996b. Corning Hazleton, Inc., Vienna, VA.
   Google Scholar
• Morseth, S.L. (1998). Chronic (12–24 month) study in rats with atrazine technical. Covance Laboratory Study 2386-108. April 15.
   Google Scholar
• National Cancer Advisory Board. (1977). General cri- teria for assessing the evidence for carcino- genicity of chemical substances: Report of the subcommittee on Environmental Carcinogenesis, National Cancer Advisory Board. J Natl Cancer Inst. 58:461–465.
   Google Scholar
• National Cancer Institute. (1976). Report on carcinogen- esis bioassay of chloroform (NTIS Publication No. PB-264 018). Springfield, VA, USA.
   Google Scholar
• National Institute for Occupational Safety and Health. (1998). National occupational exposure survey (1981-83). National Institute for Occupational Safety and Health, Cincinnati, OH.
   Google Scholar
• National Library of Medicine. (1998). Toxic chemical re- lease inventory 1987 (TRI87). National Library of Medicine, Bethesda, MD.
   Google Scholar
• National Research Council. (1983). Risk Assessment in the Federal Government: Managing the Pro- cess. Natural Research Council. National Academy Press, Washington, DC.
   Google Scholar
• National Research Council. (1994). Science and Judg- ment in Risk Assessment. National Academy Press, Washington, DC.
   Google Scholar
• National Toxicology Program. (1983). Carcinogenesis bioassay of melamine (CAS No. 108-78-1) in F344/N rats and B6C3F1 mice (feed study). Technical Report No. 245). National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC.
   Google Scholar
• National Toxicology Program. (1987). Technical Report Series No. 326. Toxicology and Carcinogenesis Studies of Ethylene Oxide (CAS No. 75-21-8) in B6C3F1 Mice (Inhalation Studies). NIH Publica- tion No. 88-2582, 60 pp. National Toxicology Pro- gram, Research Triangle Park, NC.
   Google Scholar
• National Toxicology Program. (1990). Toxicology and Carcinogenesis Studies of d-Limonene in F344/N Rats and B6C3F1 Mice (Gavage Study). NTP Technical Report 347. U.S. Department of Health and Human Services, Public Health Service, Na- tional Institutes of Health, Bethesda, MD.
   Google Scholar
• National Toxicology Program. (1998). Introduction. Re- port on Carcinogens, 8 edition. National Toxicol- ogy Program. National Institute of Environmental Health Sciences, Research Triangle Park, NC.
   Google Scholar
• National Toxicology Program. (2001). Toxicology and Carcinogenesis Studies on Acrylonitrile in B6C3F1 Mice. NIH Publication No. 01-4440. TR 506.
   Google Scholar
• Nestmann, E.R., Bryant, D.W., and Carr, C.J. (1996). Tox- icological significance of DNA adducts: Summary of discussions with an expert panel. Regul. Toxicol. Pharmacol. 24(1):9–18.
   Google Scholar
• Neuberger, J.S. (1996). Atrazine and/or triazine herbi- cides exposure and cancer: An epidemiologic re- view. J. Agromed. 3:9–30.
   Google Scholar
• Nims, R.W., Lubet, R.A., Jones, C.R., Mellini, C.W., and Thomas, P.E. (1993). Comparative pharmacody- namics of CYP2B induction by phenobarbital in the male and female F344/NCr rat. Biochem. Phar- macol. 45:521–526.
   PubMed Web of Science ®Google Scholar
• Norman, S., Berlin, J., Soper, K., Middendorf, B., and Stolley, P. (1995). Cancer incidence in a group of workers potentially exposed to ethylene oxide. Int. J. Epidemiol. 24(2):276–284.
   PubMed Web of Science ®Google Scholar
• Oesch, F., Hengstler, J., Arand, M., and Fuchs, J. (1995). Detection of primary DNA damage: Applicabil- ity to biomonitoring of genotoxic occupational ex- posure and in clinical therapy. Pharmacogenetics 5:S118–S122.
   Google Scholar
• Office of Science and Technology Policy. (1985). Chemical carcinogens: A review of the science and its principles. Fed. Reg. 50: 10371–10442.(Also pub- lished in Environ. <i>Health Perspect. 67:201–282).
   Google Scholar
• Ogasawara, H., Imaida, K., Ishiwata, H., Toyoda, K., Kawanishi, T., Uneyama, C., Hayashi, S., Taka- hashi, M., and Hayashi, Y. (1995). Urinary blad- der carcinogenesis induced by melamine in F344 male rats: Correlation between carcinogenicity and urolith formation. Carcinogenesis 16:2773–2777.
   PubMed Web of Science ®Google Scholar
• Ohnhaus, E.E., Burgi, H., Burger, A., and Studer, A. (1981). The effect of antipyrine, phenobarbital and rifampicin on thyroid hormone metabolism in man. Eur. J. Clin. Invest. 11:381–387.
   PubMed Web of Science ®Google Scholar
• Ohnhaus, E.E., and Studer, A. (1983). A link between liver microsomal enzyme activity and thyroid hormone metabolism in man. Br. J. Clin. Pharm. 15:71–76.
   PubMed Web of Science ®Google Scholar
• Olsen, G.W., Lacy, S.E., Bodner, K.M., Chau, M., Arceneaux, T.G., Cartmill, J.B., Ramlow, J.M., and Boswell, J.M. (1997). Mortality from pancre- atic and lymphopoietic cancer among workers in ethylene and propylene chlorohydrin production. Occup. Environ. Med. 54:592–598.
   PubMed Web of Science ®Google Scholar
• Olsen, J.H., Wallin, H., Boice, J.D., Rask, K., Schulgen, G., and Fraumen, J.F., Jr. (1993). Phenobarbital, drug metabolism and human cancer. Cancer Epi- demiol. Biomarkers Prev. 5:449–452.
   Google Scholar
• Ordog, T., Goldsmith, J.R., Chen, M.D., Connaughton, M.A., Hotchkiss, J., and Knobil, E. (1998). On the mechanism of the positive feedback action of estra- diol on luteinizing hormone secretion in the rhe- sus monkey. J. Clin. Endocrinol. Metab. 83:4047– 4053.
   Google Scholar
• Osterman-Golkar, S., Farmer, P.B., Segerba¨ck, D., Bailey, E., Calleman, C.J., Svensson, K., and Ehrenberg, L. (1983). Dosimetry of ethylene oxide in the rat by quantitation of alkylated histidine in hemoglobin. Teratogen. Carcinogen. Mutagen. 3:395–405.
   PubMedGoogle Scholar
• Otori, K., Yano, Y., Takada, N., Lee, C.C.R., Hayashi, S., Otani, S., and Fukushima, S. (1997). Reversibility and apoptosis in rat urinary bladder papillomatosis induced by uracil. Carcinogenesis, 18:1485–1489.
   Google Scholar
• Oyasu, R. (1995). Epithelial tumors of the lower urinary tract in humans and rodents. Food Chem. Toxicol. 33:747–755.
   PubMed Web of Science ®Google Scholar
• Pegram, R.A., Andersen, M.E., Warren, S.H., Ross, T.M., and Claxton, L.D. (1997). Glutathione S-transferase-mediated mutagenicity of tri- halomethanes in Salmonella typhimurium: Contrasting results with bromodichloromethane and chloroform. Toxicol. Appl. Pharmacol. 144: 183–188[cited in ILSI, 1997].
   Google Scholar
• Pereira, M.A. (1994). Route of administration determines whether chloroform enhances or inhibits cell pro- liferation in the liver of B6C3F1 mice. Fundam. Appl. Toxicol. 23:87–92.
   PubMedGoogle Scholar
• Peter, H., Appel, K.E., Berg, R., and Bolt, H.M. (1983). Ir- reversible binding of acrylonitrile to nucleic acids. Xenobiotica 13(1):19–25.
   PubMed Web of Science ®Google Scholar
• Pitot, H.C., and Dragan, Y.P. (2001). Chemical Carcino- genesis. In: Casarett & Doull’s Toxicology, The Basic Science of Poisons, C.D. Klaassen, ed., 6th ed., pp. 241–320. McGraw-Hill, New York.
   Google Scholar
• Pohl, C.R., and Knobil, E. (1982). The role of the central nervous system in the control of ovarian function in higher primates. Annu. Rev. Physiol. 44:583–593.
   PubMedGoogle Scholar
• Pohl, L.R., Martin, J.L., and George, J.W. (1980). Mech- anism of metabolic activation of chloroform by rat liver microsomes. Biochem. Pharmacol. 29:3271– 3276.
   Google Scholar
• Pohl, L.R., George, J.W., and Satoh, H. (1984). Strain and sex differences in chloroform-induced nephrotox- icity. Different rates of metabolism of chloroform to phosgene by the mouse kidney. Drug. Metab. Dispos. 12(3):304–308.
   PubMedGoogle Scholar
• Popp, W., Vahrenholz, C., Przygoda, H., Brauksiepe, A., Goch, S., Mueller, G., Schell, C., and Norpoth, K. (1994). DNA-protein cross-links and sister chro- matid exchange frequencies in lymphocytes and hydoxyethyl mercapturic acid in urine of ethylene oxide-exposed workers. Int. Arch. Occup. Environ. Health 66(5):325–332.
   Google Scholar
• Preston, R.J. (1999). Cytogenetic effects of ethylene ox- ide, with an emphasis on population monitoring. Crit. Rev. Toxicol. 29:263–282.
   PubMed Web of Science ®Google Scholar
• Preston-Martin, S., Pike, M.C., Ross, R.K., Jones, P.A., and Henderson, B.E. (1990). Increased cell divi- sion as a cause of human cancer. Cancer Res. 50:7415–7421.
   PubMed Web of Science ®Google Scholar
• Prokopczyk, B., Bertinato, P., and Hoffmann, D. (1988). Cyanoethylation of DNA in vivo by 3-(methylnitrosamino) propionitrile, an Areca- derived carcinogen. Cancer Res. 48:6780–6784.
   PubMed Web of Science ®Google Scholar
• Prow, T.W., Zhang, H., Jiang, J., and Klaunig, J.E. (1997). The effects of acrylonitrile on gap junctional inter- cellular communication in DI TNCI rat astrocytes. Toxicologist 36(1 part 2):59 (Abstr. 303).
   Google Scholar
• Quast, J.F., Schuetz, D.J., Balmer, M.F., Gushow, T.S., Park, C.N., and McKenna, M.J. (1980a). A two- year toxicity and oncogenicity study with acryloni- trile following inhalation exposure of rats. Tox- icology Research Laboratory, Health and Envi- ronmental Sciences, Dow Chemical USA, Mid- land, MI (TSCATS Accession No. 45647; Doc- ument I.D. No. 88-920002471; Microfiche No. OTS0537281).
   Google Scholar
• Quast, J.F., Wade, C.E., Humiston, C.G., Carreon, R.M., Hermann, E.A., Park, C.N., and Schwetz, B.A. (1980b). A two-year toxicity and oncogenicity study with acrylonitrile incorporated in the drink- ing water of rats. Toxicology Research Labora- tory, Health and Environmental Sciences, Dow Chemical USA, Midland, MI (TSCATS Accession No. 48306; Document I.D. No. 88-920003736; Microfiche No. OTS0540235).
   Google Scholar
• Ribeiro, L., Salvadori, D., Rios, A., Costa, S., Tates, A., To¨rnqvist, M., and Natarajan, A. (1994). Biological monitoring of workers occupationally exposed to ethylene oxide. Mutat. Res. 313:81–87.
   PubMed Web of Science ®Google Scholar
• Roberts, A.E., Lacy, S.A., Pilon, D., Turner, M.J., and Rickert, D.E. (1989). Metabolism of acrylonitrile to 2-cyanoethylene oxide in F-344 rat liver mi- crosomes, lung microsomes, and lung cells. Drug Metab. Dispos. 17(5):481–486.
   PubMedGoogle Scholar
• Rodent Bladder Carcinogenesis Working Group. (1995). Urinary bladder carcinogenesis: Implications for risk assessment. Fd. Chem. Toxicol. 33:797–802.
   PubMed Web of Science ®Google Scholar
• Roe, F.J.C., Palmer, A.K., Worden, A.N., and Van Abbe´, N.J. (1979). Safety evaluation of toothpaste con- taining chloroform. I. Long-term studies in mice. J. Environ. Pathol. Toxicol. 2:799–819.
   PubMed Web of Science ®Google Scholar
• Ron, E., Kleinerman, R.A., Boice, J.D., LiVolsi, V.A., Flannery, J.T., and Fraumeni, J.F., Jr. (1987). A population-based case-control study of thyroid cancer. J. Natl. Cancer Inst. 79:1–12.
   PubMed Web of Science ®Google Scholar
• Roy, A.K., McMinn, D.M., and Biswas, N.M. (1975). Estrogenic inhibition of the hepatic synthesis of α2µ-globulin in the rat. Endocrinology 97:1501– 1508.
   Google Scholar
• Sarkar, D.K., Gottschall, P.E., and Meites, J. (1982). Dam- age to hypothalamic dopaminergic neurons is as- sociated with development of prolactin-secreting pituitary tumors. Science 12:218 (4573):684–686.
   Google Scholar
• Sathiakumar, N., and Delzell, E. (1997). A review of epi- demiologic studies of triazine herbicides and can- cer. Crit. Rev. Toxicol. 27:599–612.
   PubMed Web of Science ®Google Scholar
• Sawyer, C.H. (1975). First Geoffrey Harris Memorial Lec- ture. Some recent developments in brain–pituitary– ovarian physiology. Neuroendocrinology 17:97– 124.
   Google Scholar
• Schiff, I., and Wilson, E. (1978). Clinical Aspects of aging of the female reproductive system. In: The Aging Reproductive System, E.L. Scheider, ed., pp. 9–28. Raven Press, New York.
   Google Scholar
• Schulte, P., Walker, J., Boeniger, M., Tsuchiya, Y., and Halperin, W. (1995). Molecular, cytogenetic, and hematologic effects of ethylene oxide on fe- male hospital workers. J. Occup. Environ. Med. 37(3):313–320.
   PubMed Web of Science ®Google Scholar
• Sega, G.A., Brimer, P.A., and Generoso, E.E. (1991). Ethylene oxide inhalation at different exposure rates affects binding levels in mouse germ cells and hemoglobin. Possible explanation for effect. Mutat. Res. 249:339–349.
   Google Scholar
• Segerba¨ck, D. (1990). Reaction products in hemoglobin and DNA after in vitro treatment with ethylene oxide and N -(2-hydroxyethyl)-N -nitrosourea. Carcinogenesis 11:307–312.
   PubMed Web of Science ®Google Scholar
• Shirai, T., Fukushima, S., Tagawa, Y., Okumura, M., and Ito, N. (1989). Cell proliferation induced by uracil- calculi and subsequent development of reversible papillomatosis in the rat urinary bladder. Cancer Res. 49:378–383.
   PubMed Web of Science ®Google Scholar
• Shore, R.E., Gardner, M.J., and Pannett, B. (1993). Ethy- lene oxide: An assessment of the epidemiologic ev- idence on carcinogenicity. Br. J. ind. Med. 50:971– 997.
   Google Scholar
• Sielken, R.L., Valdez-Flores, C., and Holden, L. (1999). Palpable tumors in Sprague-Dawley rats: Time to tumor analyses. Unpublished report, JSC Sielken, October 27, 1999, pp. 1–54.
   Google Scholar
• Simpkins, J.W., Advis, J.P., Hodson, C.A., and Meites, J. (1979a). Blockade of steroid induced LH release by selective depletion of anterior hypothalamic nore- pinephrine activity. Endocrinology 104:506–509.
   PubMedGoogle Scholar
• Simpkins, J.W., Huang, H.H., Advis, J.P., and Meites, J. (1979b). Evaluation of changes in NE and DA turnover during progesterone induced LH and pro- lactin surges in ovariectomized, estrogen primed rats. Biol. Reprod. 20:625–632.
   PubMedGoogle Scholar
• Simpkins, J.W., Millard, W.J., Gabriel, S.M., and Soltis, E.E. (1985). Noradrenergic methods in Neu- roendocrinology. In: Handbook of Pharmacologic Methodologies for the Study of the Neuroendocrine System, R.W. Steger and A. Johns, eds., pp. 1–63. CRC Press, Boca Raton, FL.
   Google Scholar
• Simpkins, J.W., Eldridge, J.C., and Wetzel, L.T. (1998). Role of strain-specific reproductive patterns in the appearance of mammary tumors in atrazine-treated rats. In: Triazine Herbicides Risk Assessment,
   Google Scholar
• L. Ballantine, J.E McFarland, and D. Hackett, eds., pp. 399–413. ACS Symposium Series No. 683, ACS.
   Google Scholar
• Sisk, S.C., Pluta, L.J., Meyer, K.G., Wong, B.C., and Recio, L. (1997). Assessment of the in vivo muta- genicity of ethylene oxide in the tissues of B6C3F1 lacI transgenic mice following inhalation exposure. Mutat. Res. 391:153–164.
   PubMed Web of Science ®Google Scholar
• Smith, J.H., and Hook, J.B. (1983). Mechanism of chloro- form nephrotoxicity. II. In vitro evidence for renal metabolism of chloroform in mice. Toxicol. Appl. Pharmacol. 70:480–485.
   PubMed Web of Science ®Google Scholar
• Smith, J.H., and Hook, J.B. (1984). Mechanism of chloro- form nephrotoxicity: III. Renal and hepatic micro- somal metabolism of chloroform in mice. Toxicol. Appl. Pharmacol. 73:511–524.
   PubMed Web of Science ®Google Scholar
• Smith, J.H., Maita, K., Sleight, S.D., and Hook, J.B. (1984). Effect of sex hormone status on chloroform nephrotoxicity and renal mixed function oxidase in mice. Toxicology 30:305–316.
   PubMed Web of Science ®Google Scholar
• Smith, J.H., Hewitt, W.R., and Hook, J.B. (1985). Role of intrarenal biotransformation in chloroform- induced nephrotoxicity in rats. Toxicol. Appl. Phar- macol. 79:166–174.
   PubMed Web of Science ®Google Scholar
• Smith, M.T., Loveridge, N., Wills, E.D., and Chayen, J. (1979). The distribution of glutathione is the rat liver lobule. Biochem. J. 182:103– 108.
   Google Scholar
• Snellings, W.M., Weil, C.S., and Maronpot, R.R. (1984). A two-year inhalation study of the carcinogenic potential of ethylene oxide in Fischer 344 rats. Toxicol. Appl. Pharmacol. 75:105–117.
   PubMed Web of Science ®Google Scholar
• Solomon, J.J., and Segal, A. (1989). DNA adducts of propylene oxide and acrylonitrile epoxide: Hy- drolytic deamination of 3-alkyl-dCyd to 3-alkyl- dUrd. Environ. Health Perspect. 81:19–22.
   PubMedGoogle Scholar
• Solomon, J.J., Cote, I.L., Wortman, M., Decker, K., and Segal, A. (1984). In vitro alkylation of calf thy- mus DNA by acrylonitrile. Isolation of cyanoethyl- adducts of guanine and thymine and carboxyethyl- adducts of adenine and cytosine. Chem. Biol. Interact. 51:167–190.
   PubMed Web of Science ®Google Scholar
• Solomon, J.J., Singh, U.S., and Segal, A. (1993). In vitro reactions of 2-cyanoethylene oxide with calf thy- mus DNA. Chem. Biol. Interact. 88:115–135.
   PubMed Web of Science ®Google Scholar
• Sonich-Mullin, C., Fielder, R., Wiltse, J., Baetcke, K., Dempsey, J., Fenner-Crisp, P., Grant, D., Hartley, M., Knaap, A., Kroese, D., Mangelsdorf, I., Meek, E., Rice, J.M., and Younes, M. (2001). IPCS con- ceptual framework for evaluating a MOA for chem- ical carcinogenesis. Regul. Toxicol. Pharmacol. 34:146–152.
   PubMed Web of Science ®Google Scholar
• Stayner, L., Steenland, K., Greife, A., Hornung, R., Hayes, R.B., Nowlin, S., Morawetz, J., Ringenburg, V., Elliot, L., and Halperin, W. (1993). Exposure- response analysis of cancer mortality in a cohort of workers exposed to ethylene oxide. Am. J. Epi- demiol. 138:787–798.
   PubMed Web of Science ®Google Scholar
• Steenland, K., Stayner, L., Greife, A., Halperin, W., Hayes, R., Hornung, R., and Nowlin, S. (1991). Mortality among workers exposed to ethylene ox- ide N. Engl. J. Med. 324:1402–1407.
   Google Scholar
• Stemmermann, G.N., Noffsinger, A., and Fenoglio- Preiser, C.M. (1996). Correspondence re: E. Farber, Cell proliferation as a major risk factor for cancer: A concept of doubtful validity. Cancer Res. 55: 3759–3762,1995 [letter to editor]. Cancer Res. 56:4267–4274.
   Google Scholar
• Stevens, J.L., and Anders, M.W. (1981). Metabolism of haloforms to carbon monoxide. IV. Studies on the reaction mechanism In vivo. Chem. Biol. Interact. 37:365–374.
   PubMed Web of Science ®Google Scholar
• Stevens, J.T., Breckenridge, C.B., Wetzel, L., Gilles, J.H., Luempert, L. III, and Eldridge, J.C. (1994). Hy- pothesis for mammary tumorigenesis in Sprague- Dawley rats exposed to certain triazine herbicides. J. Toxicol. Environ. Health 43:139–153.
   PubMed Web of Science ®Google Scholar
• Sumner, D.D. (1981). Carcinogenicity Study with Atrazine Technical in Albino Mice. Project No. 8580-8906. Industrial Bio-Test Laboratories, June 30, 1981. Unpublished U.S. EPA MRID No. 00085399. Washington, DC, USA.
   Google Scholar
• Sumner, S.C., Fennell, T.R., Moore, T.A., Chanas, B., Gonzalez, F., and Ghanayem, D.I. (1999). Role of cytochrome P450 2E1 in the metabolism of acrylamide and acrylonitrile in mice. Chem. Res. Toxicol. 12:1110–1116.
   PubMed Web of Science ®Google Scholar
• Swaen, G., Bloemen, L., Twisk, J., Scheffers, T., Slangen, J., Collins, J., ten Berge, W., and Sturmans, D. (1998). Mortality update of workers exposed to acrylonitrile in the Netherlands. Scand. J. Work Environ. Health 24(Suppl. 2):10–16.
   Google Scholar
• Swenberg, J.A., and Lehman-McKeeman, L.D. (1999). α2 Urinary-globulin-associated nephropathy as a mechanism of renal tubule cell carcinogenesis in male rats. In: Species Differences in Thyroid, Kidney and Urinary Bladder Carcinogenesis, C. Capen, E. Dybing, J. Rice, and J. Wilbourne, eds., pp. 95–118. IARC Scientific Publications No. 147, Lyon, France.
   Google Scholar
• Tates, A., Boogaard, P., Darroudi, F., Natarajan, A., Caubo, M., and Sittert, N. (1995). Biological ef- fect monitoring in industrial workers following in- cidental exposure to high concentrations of ethy- lene oxide. Mutat. Res. 329:63–77.
   PubMed Web of Science ®Google Scholar
• Taylor, D.C., Brown, D.M., Kebble, R., and Langley, P.F. (1974). Metabolism of chloroform: II. A sex dif- ference in the metabolism of [14C]chloroform in mice. Xenobiotica 4(3):165–174.
   Web of Science ®Google Scholar
• Templin, M.V., Larson, J.L., Butterworth, B.E., Jamison, K.C., Leininger, J.R., Mery, S., Morgan, K.T., Wong, B.A., and Wolf, D.C. (1996a). A 90-day chloroform inhalation study in F-344 rats: Profile of toxicity and relevance to cancer studies. Fundam. Appl. Toxicol. 32:109–125.
   PubMedGoogle Scholar
• Templin, M.V., Jamison, K.C., Sprankle, C.S., Wolf, D.C., Wong, B.A., and Butterworth, B.E. (1996b). Chloroform-induced cytotoxicity and regenerative cell proliferation in the kidneys and liver of BDF1 mice. Cancer Lett. 108:225–231.
   PubMedGoogle Scholar
• Tennant, M.K., Hill, S.D., Eldridge, J.C.H., Wetzel, T.L., Breckenridge, C.B., and Stevens, T.J. (1994). Pos- sible antiestrogenic properties of chloro-s-triazines in rat uterus. J. Toxicol. Environ. Health 43(2):183– 196.
   PubMed Web of Science ®Google Scholar
• Thakur, A.K. (1991a). Determination of hormone levels in Sprague-Dawley rats treated with atrazine tech- nical. Hazleton Laboratories, Vienna, VA, Project No. 483-278. Hazleton Washington, October 17, 1991a. MRID No. 42085001.
   Google Scholar
• Thakur, A.K. (1991b). Determination of Hormone Levels in Fischer-344 Rats Treated with Atrazine Tech- nical. Project No. 483-279. Hazleton Washington, November 8, 1991b. MRID No. 42146101.
   Google Scholar
• Thakur, A. K. (1992). Oncogenicity Study in Fischer-344 Rats with Atrazine Technical. Project No. 483-277. Hazleton Washington, February 18, 1992. MRID No. 42227001.
   Google Scholar
• Thiess, A.M., Frentzel-Beyme, R., Link, R., and Wild, H. (1980). Mortalitats-studie bei chemiefachar- beitern verschiedener produktionsbetriebe mit ex- position auch gegenuber acrylonitrile. Zentralbl. Arbeitsmed. 30:259–267.
   Google Scholar
• Thomas, G.A., and Williams, E.D. (1999). Thyroid stimu- lating hormone (TSH)-associated follicular hyper- trophy and hyperplasia as a mechanism of thyroid carcinogenesis in mice and rats. In: Species Dif- ferences in Thyroid Gland, Kidney and Urinary Bladder Carcinogenesis, C.C. Capen, E. Dybing, J.M. Rice, and J.D. Wilbourn, eds., pp. 45– 59. IARC Scientific Publications No. 147, Lyon, France.
   Google Scholar
• Tomatis, L. (1993). Cell proliferation and carcinogene- sis: A brief history and current view based on an IARC workshop report. Environ. Health Perspect. 101(Suppl. 5):149–152.
   Google Scholar
• Tran, D.Q., Kow, K.Y., McLachlan, J.A., and Arnold, S.F. (1996). The inhibition of estrogen receptor- mediated responses by chloro-s-triazine-derived compounds is dependent on estradiol concentra- tion in yeast. Biochem. Biophys. Res. Commun. 227:140–146.
   PubMed Web of Science ®Google Scholar
• Tsutsumi, M., Lasker, J.M., Shimizu, M., Rosman, A.S., and Lieber, C.S. (1989). The intralobular distri- bution of ethanol-inducible P450IIE1 in rat and human liver. Hepatology 10 (4):437–446[cited in ILSI, 1997].
   Google Scholar
• Tyrey, L., Stoker, T., Hein, J., and Cooper, R. (1996). Atrazine suppression of luteinizing hormone secre- tion in the rat. Program of the U.S. Environmental Protection Agency Symposium on Susceptibility and Risk, Durham, NC.
   Google Scholar
• Tyson, C.A., Hawk-Prather, K., Story, D.L., and Gould, D.H. (1983). Correlations of in vitro and in vivo hepatotoxicity for five haloalkanes. Toxicol. Appl. Pharmacol. 70:289–302.
   PubMed Web of Science ®Google Scholar
• U.S. Environmental Protection Agency. (1984). Cyro- mazine; Proposed tolerance. Fed. Reg. 49:18120– 18125.
   Google Scholar
• U.S. Environmental Protection Agency. (1986). Guide- lines for Carcinogen Risk Assessment. Fed. Reg. 51(185):33992–34003. Available from http:// www.epa.gov/ncea/raf/
   Google Scholar
• U.S. Environmental Protection Agency. (1988). Melamine; Toxic chemical release reporting; Community right-to-know. Fed. Reg. 53:23128– 23133.
   Google Scholar
• U.S. Environmental Protection Agency. (1991). Alpha 2µ-globulin: Association with chemically-induced renal toxicity and neoplasia in the male rat. EPA/625/3-91/019F. Cincinnati, OH, USA.
   Google Scholar
• U.S. Environmental Protection Agency. (1996). Proposed guidelines for carcinogen risk assessment; notice. Fed. Reg. 61:17960–18011.
   Google Scholar
• U.S. Environmental Protection Agency. (1998). [OPPTS-42206; FRL-6021-3]Endocrine Dis- ruptor Screening Program: Environmental Pro- tection Agency (EPA). Fed. Reg. 63 (154):42852–42855.
   Google Scholar
• U.S. Environmental Protection Agency. (1999). Guide- lines for carcinogen risk assessment. Risk As- sessment Forum. SAB review draft. U.S. Envi- ronmental Protection Agency, Washington, DC. (www.epa.gov/ncea/raf/crasab.htm)
   Google Scholar
• U.S. Environmental Protection Agency. (2000). http:// www.epa.gov/scipoly/sap/2000/june27/finalparta atz.pdf (atrazine).
   Google Scholar
• U.S. Environmental Protection Agency. (2002a). http:// www.epa.gov/oppsrrd1/reregistration/vinclozolin/ ra 2.pdf (vinclozolin).
   Google Scholar
• U.S. Environmental Protection Agency. (2002b). http:// www.epa.gov/opprd001/factsheets/mesotrione.pdf
   Google Scholar
• U.S. Environmental Protection Agency. (2003). Draft Final Guidelines for Carcinogen Risk Assess- ment. Risk Assessment Forum. U.S. Environ- mental Protection Agency, Washington, DC. (www.epa.gov/ncea/raf/cancer2003.htm)
   Google Scholar
• Vainio, H., Magee, P.N., McGregor, D.B., and McMichael, A.J. (1992). Mechanisms of carcino- genesis in risk identification. IARC Scientific Pub- lications No. 116. International Agency for Re- search on Cancer, Lyon, France.
   Google Scholar
• Van Duuren, B.L., Orris, L., and Nelson, N. (1965). Carcinogenicity of epoxides, lactones, and peroxy compounds. Part II. J. Natl. Cancer Inst. 35:707– 717.
   Google Scholar
• Vansell, N.R., and Klaassen, C.D. (2001). Increased bil- iary excretion of thyroxin by microsomal enzyme inducers. Toxicol. Appl. Pharmacol. 176:187–194.
   PubMed Web of Science ®Google Scholar
• Vansell, N.R., and Klaassen, C.D. (2002). Effect of mi- crosomal enzyme inducers on the biliary excretion of triiodothyroine (T3) and its metabolites. Toxicol. Sci. 65:184–191.
   PubMed Web of Science ®Google Scholar
• Vigushin, D.M., Poon, G.K., Boddy, A., English, J., Halbert, G.W., Pagonis, C., Jarman, M., and Coombes, R.C. (1998). Phase I and pharmacoki- netic study of d-limonene in patients with advanced cancer. Cancer Chemother. Pharmacol. 42:111– 117.
   Google Scholar
• Walker, V.E., Fennell, T.R., Upton, P.B., Skopek, T.R., Prevost, V., Shuker, D.E.G., and Swenberg, J.A. (1992). Molecular dosimetry of ethylene oxide: Formation and persistence of 7-(2-hydroxyethyl)guanine in DNA following repeated exposures of rats and mice. Cancer Res. 52:4328–4334.
   PubMed Web of Science ®Google Scholar
• Walker, V.E., Sisk, S.C., Upton, P.B., Wong, B.A., and Recio, L. (1997). In vivo mutagenicity of ethy- lene oxide at the hprt locus in T-lymphocytes of B6C3F1 lacI transgenic mice following inhalation exposure. Mutat. Res. 392:211–222.
   PubMed Web of Science ®Google Scholar
• Walker, V.E., Wu, K.Y., Upton, P.B., Ranasinghe, A., Scheller, N., Cho, M.H., Vergenes, J.S., Skopek, T.R., and Swenberg, J.A. (2000). Biomarkers of exposure and effect as indicators of potential car- cinogenic risk arising from in vivo metabolism of ethylene oxide. Carcinogenesis 21:1661–1669.
   PubMed Web of Science ®Google Scholar
• Waxman, D.J., and Azaroff, L. (1992). Phenobarbital induction of cytochrome P450 gene expression. Biochem. J. 281:577–592.
   PubMed Web of Science ®Google Scholar
• Weiss, G., Schmidt, C., Kleinberg, D.L., and Ganguly, M. (1977). Positive feedback effects of oestrogen on LH secretion in women in neuroleptic drugs. Clin. Endocrinol. 7:423–427.
   Google Scholar
• Wester, R., Hartway, T., Serranzana, S., and Maibach, H. (1997). Human skin in vitro percutaneous absorp- tion of gaseous ethylene oxide from fabric. Food Chem. Toxicol. 35(5):513–516.
   Google Scholar
• Whysner, J., Steward, R.E., Chen, D., Richie, J.P., Ali, N., and Williams, G.M. (1997). Mechanistic stud- ies in brain tumor development in rats exposed to acrylonitrile. Toxicologist 36(1 part 2):94 (Abstr.480).
   Google Scholar
• Whysner, J., Steward, R.E., Chen, D., Conaway, C.C., Verna, L.K., Richie, J.P., Ali, N., and Williams, G.M. (1998a). Formation of 8-oxodeoxyguanosine in brain DNA of rats exposed to acrylonitrile. Arch. Toxicol. 72:429–438.
   PubMed Web of Science ®Google Scholar
• Whysner, J., Chen, D., and Steward, R.E. (1998b). Acrylonitrile exposure effects on levels of 8- oxodeoxyguanosine and immunohistochemical markers in rat brain. Toxicologist 42(1-S):179 (Abstr. 882).
   Google Scholar
• Wise, P.M., Kashon, M.L., Krajnak, K.M., Rosewell, K.L., Cai, A., Scarbrough, K., Harney, J.P., McShane, T., Lloyd, J.M., and Weiland, N.G. (1997). Aging of the female reproductive system: A window into brain aging. Recent Prog. Horm. Res. 52:279–303.
   PubMedGoogle Scholar
• Wood, S.M., Buffler, P.A., Burau, K., and Krivanek, N. (1998). Mortality and morbidity of workers ex- posed to acrylonitrile in fiber production. Scand. J. Work Environ. Health 24(Suppl. 2):54–62.
   Google Scholar
• World Health Organization. (1983). Environmental Health Criteria 28: Acrylonitrile. International Pro- gramme on Chemical Safety, Geneva.
   Google Scholar
• World Health Organization. (1994). Environmental Health Criteria 163: Chloroform. International Pro- gramme on Chemical Safety, Geneva.
   Google Scholar
• World Health Organization. (2000). Environmental Health Criteria 216: Disinfectants and Disinfectant By-Products. International Programme on Chemi- cal Safety, Geneva.
   Google Scholar
• Worzalla, J., Kaiman, B.D., Johnson, B.M., Ramirez, G., and Bryan, G.T. (1974). Metabolism of hexamethylmelamine-ring-14C in rats and man. Cancer Res. 34:2669–2674.
   PubMed Web of Science ®Google Scholar
• Wu, K.Y., Renasinghe, A., Upton, P.B., Walker, V.E., and Swenberg, J.A. (1999). Molecular dosimetry of endogenous and ethylene oxide-induced N7 (2- hydroxyethyl) guanine formation in tissues of ro- dents. Carcinogenesis 20(9):1787–1792.
   Google Scholar
• Yamamoto, S. (1996). Carcinogenesis study of chloro- form (inhalation). Unpublished study by Division of Experimental Toxicology, Japan Bioassay Re- search Center. Kauagawa, Japan.
   Google Scholar
• Yates, J.M., Sumner, S.C.J., Turner, M.J., Recio, L., and Fennell, T.R. (1993). Characterization of an adduct and its degradation product produced by the re- action of cyanoethylene oxide with deoxythymi- dine and DNA. Carcinogenesis 14(7):1363– 1369.
   PubMed Web of Science ®Google Scholar
• Yates, J.M., Fennell, T.R., Turner, M.J., Recio, L., and Sumner, S.C.J. (1994). Characterization of phos- phodiester adducts produced by the reaction of cyanoethylene oxide with nucleotides. Carcinogenesis 15(2):277–283.
   PubMed Web of Science ®Google Scholar
• Yong, L.C., Schulte, P.A., Wiencke, J.K., Boeniger, N.F., Conally, L.B., Walker, J.T., Whelan, E.A., and Ward, E.M. (2001). Hemoglobin adducts and sis- ter chromatid exchanges in hospital workers ex- posed to ethylene oxide: Effects of glutathione S- transferase T1 and M1 geneotypes. Cancer Epi- demiol Biomarkers Prev. 10:539–550.
   PubMed Web of Science ®Google Scholar
• Yoshida, H., Suzuki, M., Okugawa, K., Wada, S., Fukunsiii, R., Okamoto, S., and Matsumoto, K. (1982). Mammary carcinoma induced by a series of intragastric intubations of 7,12- dimethylbenz[a]anthracene in gonadectomized fe- male and male Sprague-Dawley rats. Gann 73:539–542.
   Google Scholar
• Zhang, H., Wang, Y., Jiang, J., Xu, Y., and Klaunig, J.E. (1998). Prevention of acrylonitrile induced morphological transformation in Syrian hamster embryo (SHE) cells by antioxidants. Toxicologist 42(1-S):76 (Abstr. 374).
   Google Scholar
• Zhang, H., Xu, Y., Kamendulis, L.M., and Klaunig, J.E. (2000a). Acrylonitrile-induced morphological transformation in Syrian hamster embryo (SHE) cells. Carcinogenesis 21(4):722–733.
   Google Scholar
• Zhang, H., Xu, Y., Kamendulis, L.M., and Klaunig, J.E. (2000b). The role of 8-hydroxy-2t-deoxyguanosine in morphological transformation of Syrian hamster embryo (SHE) cells. Toxicological Sci. 56:303– 312.
   Google Scholar
• Zhang, H., Kamendulis, L.M., and Klaunig, J.E. (2002). Mechanisms for the induction of oxidative stress in Syrian hamster embryo cells by acrylontrile. Toxi- col. Sci. 67(2):247–255.
   PubMed Web of Science ®Google Scholar
• Zhou, B., and Wang, T. (1991). Historical cohort study of causes of death in a chemical fiber factory. J. Chin. Med. Univ. 20: 35–37(in Chinese) [cited in Rothman, 1994].
   Google Scholar