CHLOROFORM: EXPOSURE ESTIMATION, HAZARD CHARACTERIZATION, AND EXPOSURE-RESPONSE ANALYSIS

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. , Kubic , V. L and Anders , M. W. 1977 . Metabolism of haloforms to carbon monoxide: I. In vitro studies . Drug Metab. Dispos. , 5 ( 2 ) : 198 – 204 .
   PubMedGoogle Scholar
• Reitz , R. H. , Mendrala , A. L , Corley , R. A. , Quast , J. F. , Gargas , M. L. , Andersen , M. E. , Staats , D. A. and Conolly , R. B. 1990 . Estimating the risk of liver cancer associated with human exposures to chloroform using physiologically based pharmacokinetic modeling . Toxicol. Appl. Pharmacol. , 105 : 443 – 459 .
   PubMed Web of Science ®Google Scholar
• Robbiano , L. , Mereto , E. , Morando , A. M. , Pastore , P. and Brambilla , G. 1998 . Increased frequency of micronucleated kidney cells in rats exposed to halogenated anaesthetics . Mutat. Res. , 413 ( 1 ) : 1 – 6 .
   PubMedGoogle Scholar
• Roe , F. J. C. , Palmer , A. K. , Worden , A. N. and Van Abbé , N. J. 1979 . Safety evaluation of toothpaste containing chloroform. I. Long-term studies in mice . J. Environ. Pathol. Toxicol. , 2 : 799 – 819 .
   PubMed Web of Science ®Google Scholar
• Sasaki, T., Suzuki, M., Noda, K., Noguchi, T., Ishida, R., Oda, H., Araki, A., and Matsushima, T. 1998. Mutagenicity study of carbon tetrachloride and chloroform with microbial mutagenicity test and rat liver micronucleus test. J. Toxicol. Sci. 23(Suppl. ll):305 (abstr. P-OI8).
   Google Scholar
• Shimokura , G. H. , Savitz , D. A. and Symanski , E. 1998 . Assessment of water use for estimating exposure to tap water contaminants . Environ. Health Perspect. , 106 ( 2 ) : 55 – 59 .
   PubMedGoogle Scholar
• Smith , J. H. and Hook , J. B. 1983 . Mechanism of chloroform 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 chloroform nephrotoxicity: III. Renal and hepatic microsomal 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 chloroforminduced nephrotoxicity in rats . Toxicol. Appl. Pharmacol. , 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 in the rat liver lobule . Biochem.J. , 182 : 103 – 108 .
   PubMed Web of Science ®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
• Taylor , D. C , Brown , D. M. , Kebble , R. and Langley , P. F. 1974 . Metabolism of chloroform: II. A sex difference in the metabolism of [14C]chloroform in mice . Xenobiotica , 4 ( 3 ) : 165 – 174 .
   Web of Science ®Google Scholar
• Templin , M. V. , Jamison , K. C , Wolf , D. C , Morgan , K. Y. and Butterworth , B. E. 1996a . Comparison of chloroform-induced toxicity in the kidneys, liver, and nasal passages of male Osborne-Mendd and F-344 rats . Cancer Lett. , 104 : 71 – 78 .
   PubMed 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. 1996b . 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. 1996c . Chloroform-induced cytotoxicity and regenerative cell proliferation in the kidneys and liver of BDF1 mice . Cancer Lett. , 108 : 225 – 231 .
   PubMedGoogle Scholar
• Templin , M. V. , Constan , A. A. , Wolf , D. C , Wong , B. A. and Butterworth , B. E. 1998 . Patterns of chloroform-induced regenerative cell proliferation in BDF1 mice correlate with organ specificity and dose-response of tumor formation . Carcinogenesis , 19 ( 1 ) : 187 – 193 .
   PubMedGoogle Scholar
• Testai , E. and Vittozzi , L . 1986 . Biochemical alterations elicited in rat liver microsomes by oxidation and reduction products of chloroform metabolism . Chem. Biol. Interact. , 59 : 157 – 171 .
   PubMed Web of Science ®Google Scholar
• Testai , E. , Di Marzio , S. and Vittozzi , L. 1990 . Multiple activation of chloroform in hepatic microsomes from uninduced B6C3F1 mice . Toxicol. Appl. Pharmacol. , 104 : 496 – 503 .
   PubMed Web of Science ®Google Scholar
• Testai , E. , Gemma , S. and Vittozzi , L. 1992 . Bioactivation of chloroform in hepatic microsomes from rodent strains susceptible or resistant to CHCl3, carcinogenicity . Toxicol. Appl. Pharmacol. , 114 : 197 – 203 .
   PubMed Web of Science ®Google Scholar
• Tomasi , A. , Albano , E. , Biasi , F. , Slater , T. F. , Vannini , V. and Dianzani , M. U. 1985 . Activation of chloroform and related trihalomethanes to free radical intermediates in isolated hepatocytes and in the rat in vivo as detected by the ESR-spin-trapping technique . Chem. Biol. Interact. , 55 : 303316
   Google Scholar
• Tomatis , L. 1993 . Cell proliferation and carcinogenesis: A brief history and current view based on an IARC workshop report . Environ. Health Perspect. , 101 ( suppl. 5 ) : 149 – 152 .
   PubMedGoogle Scholar
• Tsutsumi , M. , Lasker , J. M. , Shimizu , M. , Rosman , A. S. and Lieber , C. S. 1989 . The intralobular distribution of ethanol-inducible P450IIE1 in rat and human liver . Hepatology , 10 ( 4 ) : 437 – 446 .
   PubMedGoogle Scholar
• Tumasonis , C. F. , McMartin , D. N. and Bush , B. 1985 . Lifetime toxicity of chloroform and bromodichloromethane when administered over a lifetime in rats . Ecotoxicol. Environ. Safety , 9 : 233240
   Google Scholar
• Tumasonis , C. F. , McMartin , D. N. and Bush , B. 1987 . Toxicity of chloroform and bromodichloromethane when administered over a lifetime in rats . J. Environ. Pathol. Toxicol. Oncol. , 7 ( 4 ) : 55 – 64 .
   PubMedGoogle Scholar
• Tyson , C. A. , Hawk-Prather , K. , Story , D. L. and Could , 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
• Uehleke , H. and Werner , T. 1975 . A comparative study on the irreversible binding of labeled halothane trichlorofluoromethanc chloroform, and carbon tetrachloride to hepatic protein and lipids in vitro and in vivo . Arch. Toxicol. , 34 ( 4 ) : 289 – 308 .
   PubMed Web of Science ®Google Scholar
• U.S. Environmental Protection Agency. (1996a). Review of Jorgenson/SRI tumor incidence data for rats and mice exposed to chloroform in drinking water. Implications for chloroform risk assessment. Report No. NCEA-W-0079; NTIS Publication No. PB96-169909. National Center for Environmental Assessment.
   Google Scholar
• Environmental Protection Agency. , U.S. 1996b . Proposed guidelines for carcinogen risk assessment; notice . Fed. Regist. , 61 : 17960 – 18011 .
   Google Scholar
• U.S. Environmental Protection Agency. 1997. Exposure factors handbook. Vol. III. Activity factors. EPA/ 600/P-95/002Fc. Washington, DC: Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment, August.
   Google Scholar
• Varma , M. M. , Ampy , F. R. , Verma , K. and Talbot , W. W. 1988 . In vitro mutagenicity of water contaminants in complex mixtures . J. Appl. Toxicol. , 8 ( 4 ) : 243 – 248 .
   PubMed Web of Science ®Google Scholar
• Vittozzi , L. , Testai , E. and De Biasi , A. 1991 . “ Multiple bioactivation of chloroform: A comparison between man and experimental animals ” . In Biological reactive intermediates. IV. Molecular and cellular effects and their impacts on human health. 4th International Symposium, Tucson, AZ (Advances in Experimental Medicine and Biology , Edited by: Witmer , C. M. Vol. 283 , 665 – 667 . New York : Plenum .
   Google Scholar
• Weisel , C. P. and Chen , W. J. 1994 . Exposure to chlorination by-products from hot water uses . Risk Anal. , 14 ( 1 ) : 101 – 106 .
   PubMed Web of Science ®Google Scholar
• Wilkes , C. R. , Small , M. J. , Andelman , J. B. , Giardino , N. J. and Marshall , J. 1992 . Inhalation exposure model for volatile chemicals from indoor uses of water . Atmos. Environ. , 26(A) ( 12 ) : 2227 – 2236 .
   Google Scholar
• Williams, D. T., Lebel, G. L., and Benoit, F. M. 1995. A national survey of chlorinated disinfection byproducts in Canadian drinking water. Report 95-EHD-197; Catalogue H46-2/95-197E; ISBN O662-24295-5. Ottawa, Ontario: Health Canada, Environmental Health Directorate.
   Google Scholar
• Ames , B. N. and Gold , L S. 1990 . Chemical carcinogenesis: 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 division: three factors in mutagenesis and carcinogenesis . Environ. Health Perspect. , 101 ( suppl. 5 ) : 3544
   Google Scholar
• Yuan , J. 1993 . Modeling blood/plasma concentrations in dosed feed and dosed drinking water toxicology studies . Toxicol. Appl. Pharmacol. , 119 : 131 – 141 .
   PubMedGoogle 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 kidney microsomes . Biochem. Pharmacol. , 53 : 765771
   Google Scholar
• Anders , M. W. , Stevens , J. L. , Sprague , R. W. , Shaath , Z. and Ahmed , A. E. 1978 . Metabolism of haloforms to carbon monoxide: II . In vitro studies. Drug Metab. Dispos. , 6 ( 5 ) : 556 – 560 .
   PubMedGoogle Scholar
• Benoit, F. M., Nicolidakis, H., Cardinall, C, Alleyne, C, and Mori, B. 1997. Characterization of chloroform levels in the breathing zone of showers by GC/MS. Presented at the 45th American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics, Palm Springs, CA.
   Google Scholar
• Benoit, F. M., Nicolidakis, H., Cardinall, C., Alleyne, C., and Mori, B. 1998. Characterization of human exposure to chloroform in an experimental shower by breath analysis. Presented at the 46th American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics, Orlando, FU 31 May-4 June 1998.
   Google Scholar
• Blancato , J. N. and Chiu , N. 1994 . “ Use of pharmacokinetic models to estimate internal doses from exposure ” . In Drinking water contaminants and health: Integration of exposure assessment, toxicology, and risk assessment , Edited by: Wang , R. 217 – 239 . New York : Marcel Dekker .
   Google Scholar
• Brady , J. F. , Li , D. , Ishizaki , H. , Lee , M. , Ning , S. M. , Xiao , F. and Yang , C. S. 1989 . Induction of cytochromes P450IIE1 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: Chloroform, halothane and glutathione . Anesthesiology , 41 ( 6 ) : 554 – 561 .
   PubMedGoogle Scholar
• Brown , D. M. , Langley , P. F. , Smith , D. and Taylor , D. C. 1974 . Metabolism of chloroform. I. The metabolism of 14C-chloroform by different species . Xenobiotica , 4 ( 3 ) : 151 – 163 .
   Web of Science ®Google Scholar
• Brown , R. P. , DeIp , M. D. , Lindstedt , S. L. , Rhomber , L. R. and BeIiles , R. P. 1997 . Physiological parameter values for physiologically based pharmacokinetic models . Toxicol. Ind. Health , 13 : 407484
   Google Scholar
• Buhler , R. , Lindros , K. , Nord , I , ing , A. , Johansson , I. and Ingelman-Sundberg , M. 1992 . Zonation of cytochrome P450 isozyme expression and induction in rat liver, Eur . J. Biochem. , 204 : 407 – 412 .
   Google Scholar
• Butler , T. C. 1961 . Reduction of carbon tetrachloride in vivo and reduction of carbon tetrachloride and chloroform in vitro by tissues and tissue constituents . J. Pharmacol. Exp. Ther. , 134 : 311 – 319 .
   PubMed Web of Science ®Google Scholar
• Butterworth, B. E. 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. 56:4270-4272.
   Google Scholar
• Butterworth , B. E. , Templin , M. V. , Constan , A. A. , Sprankle , C. S. , Wong , B. A. , Pluta , L. J. , Everitt , J. I. and Redo , L. 1998 . Long-term mutagenicity studies with chloroform and dimethylnitrosamine in female lacl transgenic B6C3F1 mice . Environ. MoI. Mutagen. , 31 ( 3 ) : 248 – 256 .
   PubMedGoogle Scholar
• Clemens , T. L. , Hill , R. N. , Bullock , L. P. , Johnson , W. D. , Sultatos , L. G. and Vesseli , E. S. 1979 . Chloroform toxicity in the mouse: Role of genetic factors and steroids . Toxicol. Appl. Pharmacol. , 48 : 117 – 130 .
   PubMed Web of Science ®Google Scholar
• Cohen , S. M. 1995 . Role of cell proliferation in regenerative and neoplastic disease . Toxicol. Lett. , 82/ 83 : 15 – 21 .
   Google Scholar
• Cohen , S. M. and Ellwein , LB. 1990 . Cell proliferation in carcinogenesis . Science , 249 : 1007 – 1011 .
   PubMed Web of Science ®Google Scholar
• Cohen , S. M. and Ellwein , L. 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
• Colacci , A. , Bartoli , S. , Bonora , B. , Guidotti , L. , Lattanzi , G. , Mazzullo , M. , Niero , A. , Perocco , P. , Silingardi , P. and Grilli , S. 1991 . Chloroform bioactivation leading to nucleic acids binding . Tumori , 77 : 285 – 290 .
   PubMedGoogle Scholar
• Concord Environmental Corporation. 1992. Results of a national pilot survey of airborne volatile organic compounds in Canadian residences. Vois. 1 and 2. CE J2431. Downsview, Ontario.
   Google 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 chloroform by cytochrome P450 2E1 is required for induction of toxicity in the liver, kidney, and nose of male mice . Toxicol. Appl. Pharmacol. , 160 : 120 – 126 .
   PubMed Web of Science ®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 physiologically 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 chloroform by rat and human liver microsomes: In vitro effect on some enzyme activities and mechanisms of irreversible binding to macromolecules . Chem. BhI. Interact. , 24 : 153 – 165 .
   PubMed Web of Science ®Google Scholar
• Cunningham , M. L. and Matthews , H. B. 1995 . Cell proliferation as a determining factor for the carcinogenicity of chemicals: Studies with mutagenic carcinogens and m u ta genie noncarcinogens . Toxicol. Lett. , 82/83 : 9 – 14 .
   Google Scholar
• Daft , J. L . 1988a . Rapid determination of fumigant and industrial chemical residues in food . J. Assoc. Off. Anal. Chem. , 71 ( 4 ) : 748 – 760 .
   PubMedGoogle Scholar
• Daft , J. L. 1988b . Fumigant contamination during large-scale food sampling for analysis . Arch. Environ. Contam. Toxicol. , 17 : 177 – 188 .
   PubMedGoogle Scholar
• De Biasi , A. , Sbraccia , M. , Keizer , J. , Testai , E. and Vittozzi , L . 1992 . The regioselective binding of CHCI3, reactive intermediates to microsomal phospholipids . Chem. Biol. Interact. , 85 ( 2-3 ) : 229242
   Google Scholar
• Decisioneering, Inc. 1996. Crystal Ball version 4.Oc. User manual. Denver, CO.
   Google Scholar
• de Groot , H. and Noll , T. 1989 . Halomethane hepatotoxicity: Induction of lipid peroxidation and inactivation of cytochrome P-450 in rat liver microsomes under low oxygen partial pressure . Toxicol. Appl. Pharmacol. , 97 : 530 – 537 .
   PubMedGoogle Scholar
• Dicker , E. , McHugh , T. and Cederbaum , A. I. 1991 . Increased catalytic activity of cytochrome P450IlE1 in pericentral hepatocytes compared to peri porta I hepatocytes isolated from pyrazoletreated rats . Biochim. Biophys.Acta , 1073 : 316 – 323 .
   PubMedGoogle Scholar
• Dix, K., and Borghoff, S. J. 1995. Comparison of gavage vehicle-dependent chloroform (CHCI3) tissue dosimetry in mice and rats. Toxicologist 15:268 (abstr.).
   Google Scholar
• Dix, K., Murphy, J. E., and Borghoff, S. J. 1994. Vehicle dependence of chloroform (CHCI3) tissue dosimetry following oral gavage in male F344 rats. Toxicologist14:275 (abstr.).
   Google Scholar
• Dorman , D. C. , Miller , K. L. , D'Antonio , A. , James , R. A. and Morgan , K. L. 1997 . Chloroform-induced olfactory mucosal degeneration and osseous ethmoid hyperplasia are not associated with olfactory deficits in Fischer 344 rats . Toxicology , 122 ( 1-2 ) : 39 – 50 .
   PubMedGoogle Scholar
• Environmental Health Directorate. 1998. Exposure factors for assessing total daily intake of Priority Substances by the general population of Canada. Unpublished report. Ottawa, Ontario: Health Canada, Environmental Health Directorate, Priority Substances Section.
   Google Scholar
• Farber, E. 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 [reply to letter to editor]. Cancer Res. 56:4272-4274.
   Google Scholar
• Fry , B. J. , Taylor , T. and Hathway , D. E. 1972 . Pulmonary elimination of chloroform and its metabolite in man . Arch. Int. Pharmacodyn. , 196 : 98 – 111 .
   PubMedGoogle Scholar
• Fujie , K. , Aoki , T. and Wada , M. 1990 . Acute and subacute cytogenetic effects of the trihalomethanes on rat bone marrow cells in vivo . Mutat. Res. , 242 : 111 – 119 .
   PubMedGoogle Scholar
• World Health Organization. 1994. Environmental Health Criteria 163: Chloroform. ISBN 92 4 157163 2. Geneva: World Health Organization, International Programme on Chemical Safety.
   Google Scholar
• Wolf , C. R. , Mansuy , D. , Nastainczyk , W. , Deutschmann , G. and Ullrich , V. 1977 . The reduction of polyhalogenated methanes by liver microsomal cytochrome P-450 . MoI. Pharmacol. , 13 : 698 – 705 .
   PubMed Web of Science ®Google Scholar
• Yamamoto, S. 1996. Carcinogenesis study of chloroform (inhalation). Unpublished study, Division of Experimental Toxicology, Japan Bioassay Research Center, Hirasawa Hadano Kanagawa, Japan.
   Google Scholar
• Gearhart , J. M. , Seckel , C and Vinegar , A. 1993 . In vivo metabolism of chloroform in B6C3F1 mice determined by the method of gas uptake: The effects of body temperature on tissue partition coefficients and metabolism . Toxicol. Appl. Pharmacol. , 119 : 258 – 266 .
   PubMedGoogle Scholar
• Gollapudi, B. B., Yano, B. L., Day, S. J., Linscombe, V. A., Jackson, K. M., and Bus, J. S. 1999. Response of the transgenic p53+/- mouse 26-wk carcinogenicity assay to chloroform. Toxicologist 48(1S):369 (abstr. 1740).
   Google Scholar
• Guengerich , F. P. , Kirn , D. H. and Iwasaki , M. 1991 . Role of human cytochrome P-450 MEI in the oxidation of many low molecular weight cancer suspects . Chem. Res. Toxicol. , 4 : 168 – 179 .
   PubMed Web of Science ®Google Scholar
• Hard, G. C, and Wolf, D. C. 1999. Re-evaluation of the chloroform 2-year drinking water bioassay in Osborne-Mendd rats indicates that sustained renal tubule injury is associated with renal tumor development. Toxicologist 48(1 -S):30 (abstr. 140).
   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 . Toxicol. Sci. , 53 ( 2 ) : 237 – 244 .
   PubMedGoogle Scholar
• Health Canada. 1994. Canadian Environmental Protection Act. Human health risk assessment for Priority Substances. Catalogue No. En40-215/41E; ISBN 0-662-22126-5. Ottawa, Ontario: Minister of Supply and Services Canada.
   Google Scholar
• Health Canada. 1999. Canadian Environmental Protection Act supporting documentation for chloroform. Human exposure assessment. November 1999. Ottawa, Ontario: Health Canada, Environmental Health Directorate, Priority Substances Section.
   Google Scholar
• Heikes , D. L. 1987 . Purge and trap method for determination of volatile halocarbons and carbon disulfide in table-ready foods . J. Assoc. Off. Anal. Chem. , 70 ( 2 ) : 215 – 226 .
   PubMedGoogle Scholar
• Heikes , D. L , Jensen , S. R. and Fleming-Jones , M. E. 1995 . Purge and trap extraction with GC-MS determination of volatile organic compounds in table-ready foods . J. Agric. Food Chem. , 43 : 2869 – 2875 .
   Web of Science ®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
• Heywood , R. , Sortwell , R. J. , Noel , P. R. B. , Street , A. E. , Prentice , D. E. , Roe , F. J. C , Wadsworth , P. F. , Worden , A. N. and Van Abbß , N. J. 1979 . Safety evaluation of toothpaste containing chloroform. III. Long-term study in beagle dogs . J. Environ. Pathol. Toxicol. , 2 : 835 – 851 .
   PubMed Web of Science ®Google Scholar
• Hoechst. 1987. Chloroform. Detection of gene mutations in somatic cells in culture. HCPRT-test with V79 cells. Project ID 86.1085; Hoechst Report No. 87.0692; TSCA Document No. FYI-OTS-09880635; Microfiche No. OTS0000635. Pharma Research Toxicology and Pathology, Hoechst Aktiengesellschaft Laboratory.
   Google Scholar
• Hong , J. Y. , Pan , J. , Ning , S. M. and Yang , C. S. 1989 . Molecular basis for the sex-related difference in renal N-nitrosodimethylaminedemethylase in C3H/HeJ mice . Cancer Res. , 49 : 2973 – 2979 .
   PubMed Web of Science ®Google Scholar
• Howe , R. B. 1995 . THRESH: A computer program to compute a reference dose from quanta! animal toxicity data using the benchmark dose method , Ruston, LA : ICF Kaiser Engineers, Inc .
   Google Scholar
• ICF Kaiser . 1999 . Development of a PBPK model for chloroform for human health risk assessment. Contract report for Health Canada , Ruston, LA : The K. S. Crump Group, Inc., ICF Kaiser .
   Google Scholar
• llett , K. E. , Reid , W. D. , Sipes , I. G. and Krishna , G. 1973 . Chloroform toxicity in mice: Correlation of renal and hepatic necrosis with covalent binding of metabolites to tissue macromolecules . Exp. MoI. Pathol. , 19 : 215 – 229 .
   PubMed Web of Science ®Google Scholar
• Ingelman-Sundberg , M. , Johansson , I. , Penttilä , K. E. , Glaumann , H. and Lindros , K. O. 1988 . Centrilobular expression of ethanol-inducible cytochrome P-450 (llE1 ) in rat liver . Biochem. Biophys. Res. Commun. 15 , 7 ( 1 ) : 55 – 60 .
   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 evaluation of EPA's proposed guidelines for carcinogen risk assessment using chloroform and dichloroacetate as case studies: Report of an expert panel. ISBN 1-57881 -002-70. Washington, DC: ILSI Health and Environmental Institute.
   Google Scholar
• Johansson , I. , Lindros , K. O. , Eriksson , H. and Ingelman-Sundberg , M. 1990 . Transcriptional control of CYP2E1 in the perivenous liver region and during 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
• Kluwe , W. M. 1981 . “ The nephrotoxicity of low molecular weight halogenated alkane solvents, pesticides, and chemical intermediates ” . In Toxicology of the kidney , Edited by: Hook , J. B. 179 – 226 . New York : Raven Press .
   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 proliferation 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 proliferation in the liver, kidneys and nasal passages of female F-344 rats, induced by chloroform administered 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
• Larson , J. L , Templin , M. V. , Wolf , D. C. , Jamison , K. C. , Leininger , J. R. , Mery , A. , Morgan , K. T. , Wong , B. A. , Conolly , R. B. and Butterworth , B. E. 1996 . A 90-day chloroform inhalation study in female and male B6C3F1 mice: Implications for cancer risk assessment . Fundam. Appl. Toxicol. , 30 ( 1 ) : 118 – 137 .
   PubMedGoogle Scholar
• Lebel , G. L. and Williams , D. T. 1995 . Differences in chloroform levels from drinking water samples analyzed using various sampling and analytical techniques . Int. J. Environ. Anal. Chem. , 60 : 213220
   Google Scholar
• Lilly, P. D. 1996. A physiologically-based toxicity model of orally-administered bromodichloromethane. PhD thesis. Chapel Hill: University of North Carolina.
   Google Scholar
• öfberg , L , Tjälve , B. and H. 1986 . Tracing tissues with chloroform-metabolizing capacity in rats . Toxicology , 39 : 13 – 35 .
   PubMedGoogle Scholar
• Mansuy , D. , Beaune , P. , Cresteil , T. , Lange , M. and Leroux , J. P. 1977 . Evidence for phosgene formation during liver microsomal oxidation of chloroform . Biochem. Biophys. Res. Commun. , 79 : 513517
   Google Scholar
• McNeal , T. P. , Hollifield , H. C and Diachenko , G. W. 1995 . Survey of trihalomethanes and other volatile chemical contaminants in processed foods by purge-and-trap capillary gas chromatography with mass selective detection . J. Assoc. Off. Anal. Chem. Int. , 78 ( 2 ) : 391 – 397 .
   Google Scholar
• Meek , M. E. , Newhook , R. , Liteplo , R. G. and Armstrong , V. C. 1994 . Approach to assessment of risk to human health for Priority Substances under the Canadian Environmental Protection Act . J. Environ. Sd. Health , C12 ( 2 ) : 105 – 134 .
   Google Scholar
• Melnick , R. L. 1992 . Does chemically-induced hepatocyte proliferation predict liver carcinogenesis? . FASEB J. , 6 : 2698 – 2706 .
   PubMed Web of Science ®Google Scholar
• Melnick , R. L. , Kohn , M. C , Dunnick , J. K. and Leininger , J. R. 1998 . Regenerative hyperplasia is not required for liver tumor induction in female B6C3F1 mice exposed to trihalomethanes . Toxicol. Appl. Pharmacol. , 148 ( 1 ) : 137 – 147 .
   PubMedGoogle Scholar
• Mery , S. , Larson , J. L , Butterworth , B. E. , Wolf , D. C , Harden , R. and Morgan , K. T. 1994 . Nasal toxic-ity of chloroform in male F-344 rats and female B6C3F1 mice following a 1-week inhalation exposure . Toxicol. Appl. Pharmacol. , 125 ( 2 ) : 214 – 227 .
   PubMedGoogle Scholar
• Microsoft Corporation. 1997. Microsoft Excel 97 SR-1 for Windows 95. Version 4.0.
   Google Scholar
• Miller , L. J. and Uhler , A. D. 1988 . Volatile halocarbons in butter: elevated tetrachloroethylene levels in samples obtained in close proximity to dry-cleaning establishments . Bull. Environ. Contam. Toxicol. , 41 : 469 – 474 .
   PubMedGoogle Scholar
• Mohla , S. , Ahir , S. and Ampy , F. R. 1988 . Tissue specific regulation of renal N-nitrosodimethylaminedemethylase activity by testosterone in BALB/c mice . Biochem. Pharmacol. , 37 ( 13 ) : 2697 – 2702 .
   PubMedGoogle Scholar
• Morimoto , K. and Koizumi , A. 1983 . Trihalomethanes induce sister chromatid exchanges in human lymphocytes in vitro and mouse bone marrow cells in vivo . Environ. Res. , 32 : 72 – 79 .
   PubMed Web of Science ®Google Scholar
• Morita , T. , Asano , N. , Awogi , T. , Sasaki , Y. F. , Sato , S. I. , Shimada , H. , Surou , S. , Suzuki , T. , Wakata , A. , Sofuni , T. and Hayashi , M. 1997 . Evaluation of the rodent micronucleus assay in the screening of the IARC carcinogens (Groups 1, 2A and 2B). The summary report of the 6th collaborative study by CSGMT/JEMS-MMS . Mutat. Res. , 389 : 3 – 122 .
   PubMed Web of Science ®Google Scholar
• Nagano , K. , Nishizawa , T. , Yamamoto , S. and Matsushima , T. 1998 . “ Inhalation carcinogenesis studies of six halogenated hydrocarbons in rats and mice ” . In Advances in the prevention of occupational respiratory diseases , Edited by: Chiyotani , K. , Hosoda , Y. and Aizawa , Y. 741 – 746 . Amsterdam : Elsevier .
   Google Scholar
• Nakajima , T. , Elovaara , D. , Engstrom , K. , Park , S. S. , Gelboin , H. V. and Vainio , H. 1991 . Metabolism of inhaled styrene in acetone-, phenobarbital- and 3-methylcholanthene-pretreated rats: Stimulation and stereochemical effects by induction of cytochromes P450IIE1, P450IIB and P450IA . Xenobiotica , 21 ( 5 ) : 651 – 661 .
   PubMedGoogle Scholar
• Nakajima , T. , Elovaara , E. , Park , S. S. , Gelboin , H. and Vainio , H. 1995a . lmmunochemical detection of cytochrome P450 isozymes induced in rat liver by n-hexane, 2-hexanone and acetonyl acetone . Arch. Toxicol. , 55 : 542 – 547 .
   Google Scholar
• Nakajima , T. , Elovaara , E. , Okino , T. , Gelboin , H. , Klockars , M. , Riihimäki , V. , Aoyama , T. and Vainio , H. 1995b . Different contributions of cytochrome P450 2E1 and P450 2B1/2 to chloroform hepatotoxicity in rat . Toxicol. Appl. Pharmacol. , 133 : 215 – 222 .
   PubMed Web of Science ®Google Scholar
• National Cancer Institute. 1976. Report on carcinogenesis bioassay of chloroform. NTIS Publication No. PB-264 018. Bethesda, MD.
   Google Scholar
• Page , B. D. and Lacroix , G. M. 1995 . On-line steam distillatioin/purge and trap analysis of halogenated, nonpolar, volatile contaminants in foods . J. Assoc. Off. Anal. Chem. Int. , 78 ( 6 ) : 1416 – 1428 .
   Google Scholar
• Palmer , A. K. , Street , A. E. , Roe , F. J. C , Worden , A. N. and Van Abbé , N. J. 1979 . Safety evaluation of toothpaste containing chloroform. II. Long term studies in rats . J. Environ. Pathol. Toxicol. , 2 : 821833
   Google Scholar
• Pegram , R. A. , Andersen , M. E. , Warren , S. H. , Ross , T. M. and Claxton , L. D. 1997 . Glutathione Stransferase-mediated mutagenicity of trihalomethanes in Salmonella typhimurium: Contrasting results with bromodichloromethaneand chloroform . Toxicol. Appl. Pharmacol. , 144 : 183 – 188 .
   PubMed Web of Science ®Google Scholar
• Pereira , M. A. 1994 . Route of administration determines whether chloroform enhances or inhibits cell proliferation in the liver of B6C3F1 mice . Fundam. Appl. Toxicol. , 23 : 87 – 92 .
   PubMedGoogle Scholar
• Pereira , M. A. , Lin , L C , Lippitt , J. M. and Herren , S. L. 1982 . Trihalomethanes as initiators and promoters of carcinogenesis . Environ. Health Perspect. , 46 : 151 – 156 .
   PubMed Web of Science ®Google Scholar
• Pohl , L R. 1979 . Biochemical toxicology of chloroform . Rev. Biochem. Toxicol. , 1 : 79 – 107 .
   Google Scholar
• Pohl , L. R. and Krishna , G. 1978 . Deuterium isotope effect in bioactivation and hepatotoxicity of chloroform . Life Sci. , 23 : 1067 – 1072 .
   PubMed Web of Science ®Google Scholar
• Pohl , L R. , Bhooshan , B. , Whittaker , N. F. and Krishna , G. 1977 . Phosgene: A metabolite of chloroform . Biochem. Biophys. Res. Commun. , 79 : 684 – 691 .
   PubMed Web of Science ®Google Scholar
• Pohl , L. R. , Martin , J. L. and George , J. W. 1980 . Mechanism of metabolic activation of chloroform by rat liver microsomes . Biochem. Pharmacol. , 29 : 3271 – 3276 .
   PubMed Web of Science ®Google Scholar
• Pohl , L R. , Branchflower , R. V. , Highet , R. J. , Martin , J. L , Nunn , D. S. , Monks , T. J. , George , J. W. and Hinson , J. A. 1981 . The formation of diglutathionyl dithiocarbonate as a metabolite of chloroform, bromotrichloromethane, and carbon tetrachloride . DrugMetab. Dispos. , 9 : 334 – 339 .
   PubMed Web of Science ®Google Scholar
• Pohl , L. R. , George , J. W. and Satoh , H. 1984 . Strain and sex differences in chloroform-induced nephrotoxicity. Different rates of metabolism of chloroform to phosgene by the mouse kidney . DrugMetab. Dispos. , 12 ( 3 ) : 304 – 308 .
   PubMedGoogle Scholar
• Preston-Martin , S. , Pike , M. C. , Ross , R. K. , Jones , P. A. and Henderson , B. E. 1990 . Increased cell division as a cause of human cancer . Cancer Res. , 50 : 7415 – 7421 .
   PubMed Web of Science ®Google Scholar