Analysis of chloroethane toxicity and carcinogenicity including a comparison with bromoethane

Toxicology and Industrial Health

Volumn 24, Issue 10, 2008, Pages 655-675

  Holder, Jw ^a  

^a U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

Author keywords

bromoethane; cancer risk; carcinogenicity; chloroethane; chlorohydrocarbons; colonization; endometrium; ethyl bromide; ethyl chloride; halohydrocarbons; malignancy; metastasis; uterus

Indexed keywords

ACETALDEHYDE; CARCINOGEN; CHLOROETHANE; CORTICOSTEROID; CYTOCHROME P450 2E1; DEOXYCYTIDINE KINASE; ESTROGEN; ETHANE; ETHYL BROMIDE; GLUTATHIONE; GLUTATHIONE TRANSFERASE; HYDROCARBON; PROGESTERONE; STEROID; UNCLASSIFIED DRUG;

ADRENAL GLAND; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BIOASSAY; CANCER INCIDENCE; CANCER RISK; CARCINOGENESIS; CARCINOGENICITY; CONJUGATION; CONTROLLED STUDY; ENDOMETRIUM CANCER; ENDOMETRIUM CELL; ESTRUS CYCLE; EXTRAVASATION; FEEDBACK SYSTEM; FEMALE; FISCHER 344 RAT; GOOD LABORATORY PRACTICE; HUMAN; HUMAN CELL; HYPERKINESIA; HYPOTHALAMUS; HYPOTHALAMUS HYPOPHYSIS SYSTEM; MALE; METASTASIS; MOUSE; MYOMETRIUM; NONHUMAN; RAT; STEROIDOGENESIS; STRESS; TOXICITY;

ANIMALS; CARCINOGENICITY TESTS; CARCINOGENS; ECOTOXICOLOGY; ESTROUS CYCLE; ETHYL CHLORIDE; FEMALE; HYDROCARBONS, BROMINATED; HYPERPLASIA; MALE; MICE; MUTAGENICITY TESTS; NEOPLASM METASTASIS; NEOPLASMS; RATS; RATS, INBRED F344; UTERINE NEOPLASMS; UTERUS;

ANIMALIA; MURINAE; MUS; RATTUS; RODENTIA;

EID: 60149086794     PISSN: 07482337     EISSN: None     Source Type: Journal    
DOI: 10.1177/0748233708100371     Document Type: Article

References (88)

1. Anisman H, Merali Z (1999) Understanding stress: characteristics and caveats. Alcohol Res Health 23: 241–249.
2. Apter SJ, Eriksson CJ (2006) The role of social isolation in the effects of alcohol on corticosterone and testosterone levels of alcohol-preferring and non-preferring rats. Alcohol Alcohol 41: 33–38.
3. Araki A, Noguchi T, Kato F, Matsushima T (1994) Improved method for mutagenicity testing of gaseous compounds by using a gas sampling bag. Mutat Res 307: 335–344.
4. ATSDR (Agency for Toxic Substances and Disease Registry) (1997) Toxicological Profile for Chloroethane. Public Comment Draft. U.S. Department of Health and Human Services. Atlanta, GA: Agency for Toxic Substances and Disease Registry.
5. Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow. Lancet 357: 539–545.
6. Behrens UJ, Hoerner M, Lasker JM, Lieber CS (1988) Formation of acetaldehyde adducts with ethanol-inducible P-450IIE1 in vivo. Biochem Biophys Res Commun 154: 584–590.
7. Boussard LA, Boussard AK, Pittman TS, Lirette DK (2000) Death due to inhalation of ethyl chloride. [chloroethane]J Forensic Sci 45: 223–225.
8. Boutwell RK (1989) Model systems for defining initiation, promotion, and progression of skin neoplasms. Prog Clin Biol Res 298: 3–15.
9. Breslin WJ; Berdasco NM; Phillips JE; Johnson KA; (1988) Ethyl Chloride (EtCl): Effects on Estrous Cycling in B6C3F1 Mice. Final Report with cover letter dated 11/21/88. Dow Chemical Company. This study has been submitted to OPPTS/US EPA and may recovered by written request to OPPTS referring to: EPA Document no. 86-890000040.
10. Bucher JR, Morgan DL, Adkins B, Travlos GS, Davis BJ, Morris R (1995) Early changes in sex hormones are not evident in mice exposed to the uterine carcinogens chloroethane and bromoethane. Toxicol Appl Pharmacol 130: 169–173.
11. Carmel-Harel O, Storz G (2000) Roles of the glutathione- and thioredoxin-dependent reduction systems in the Escherichia coli and saccharomyces cerevisiae responses to oxidative stress. Annu Rev Microbiol 54: 439–461.
12. Cassarett LJ, Doull J (2001) Cassarett and Doull's Toxicology: the basic science of poisons, sixth ed. In: C Klaussen (ed), McGraw-Hill. New York, NY: Medical Publishing Division.
13. Cole WH (1956) Ethyl chloride as a gaseous anesthetic. Analgesia 11: 156.
14. Cole WH (1967) A re-evaluation of the pharmacology of ethyl chloride. Med J Aust 1: 853–855.
15. Davidson BM (1976) Studies of intoxication. V. The action of ethyl chloride. J Pharmacol Exp Ther 26: 37–42.
16. DeHaan JB, Crack PJ, Flentjar N, Iannello RC, Hertzog PJ, Kola I (2003) An imbalance in antioxidant defense affects cellular function: the pathophysiological consequences of a reduction in antioxidant defense in the glutathione peroxidase-1 (Gpx1) knockout mouse. Redox Rep 8: 69–79.
17. Dobkin AB, Byles PH (1971) The pharmacodynamics of divinyl ether, ethylchloride, fluroxene, nitrous oxide and trichloroethylene. In: LR Soma (ed), Textbook of Veterinary Anesthesia. Baltimore, MD: Williams & Wilkins, pp. 94–104.
18. Ebert R, Fedtke N, Certa H, Wiegand HJ, Régnier JF, Marshall R (1994) Genotoxicity studies with chloroethane. Mutat Res 322: 33–44.
19. Elliot SJ (1995) Pyschosocial stress, women and hearth health: a critical review. Soc Sci Med 40: 105–115.
20. Eriksson, CJ (2001) The role of acetaldhyde in the actions of alcohol (update 2000). Alcohol Clin Exp Res 25(Suppl. ISBRA): 15S–32S.
21. Fedtke N, Certa H, Ebert R, Wiegand HJ (1994a) Species differences in the biotransformation of ethyl chloride. I. Cytochrome P450-dependent metabolism. Arch Toxicol 68: 158–166.
22. Fedtke N, Certa H, Ebert R, Wiegand HJ (1994b) Species differences in the biotransformation of ethyl chloride. II. GSH-dependent metabolism. Arch Toxicol 68: 217–223.
23. Feinberg AP (2007) Phenotypic plasticity and the epigenetics of human disease. Nature 447: 433–440.
24. Feinberg AP, Ohlsson R, Henikoff S (2006) The epigenetic progenitor origin of human cancer. Nat Rev Genet 7: 21–33.
25. Gargas ML, Sweeney LS, Himmelstein MW, Pottenger LH, Bus JS, Holder JW (2008) Physiologically based pharmacokinetic modeling of chloroethane disposition in mice, rats, and women. Toxicol Sci 104: 54–66.
26. Gold LS, Zeiger E (1997) Handbook of Carcinogenic Potency and Genotoxicity Data Bases. Boca Raton, FL: CRC Press, Inc., pp. 1–754.
27. Greenlee RT, Hill-Harmon MB, Murray T, Thun M (2001) Cancer statistics, 2001. CA Cancer J Clin 51: 15–37.
28. Griesemer RA, Eustis SL (1994) Gender differences in animal bioassays for carcinogenicity. J Occup Med 36: 855–859.
29. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 11: 57–70.
30. Haseman JK (1984) Statistical issues in the design, analysis and interpretation of animal carcinogenicity studies. Environ Health Perspect 58: 385–392.
31. Haseman JK (1990) Use of statistical decision rules for evaluating laboratory animal carcinogenicty studies. Fundam Appl Toxicol 14: 637–648.
32. Haseman JK, Huff J, Boorman GA (1984) Use of historical control data in carcinogenicity studies in rodents. Toxicol Pathol 12: 126–135.
33. Hes JP, Cohn DF, Streifler M (1979) Ethyl chloride sniffing and cerebellar dysfunction (case report). Isr Ann Psychiatr Relat Discip 17: 122–125.
34. Holder JW; (2002) Chloroethane toxicity compared to structurally-related chlorohydrocarbons, Presented to: Society of Toxicology, in Nashville, TN. The Toxicilogist. Poster no. 904, 3/12/2002. Copies available from: holder_james@yahoo.com.
35. Holliday R (1987) The inheritance of epigenetic defects. Science 238: 163–170.
36. Huff JE (1992) Chemical toxicity and chemical carcinogenesis. Is there a causal connection? A comparative morphological evaluation of 1500 experiments. IARC Sci Publ 116: 437–475.
37. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100: 57–70.
38. Ivanetich KM, Van Den Honert LH (1981) Chloroethanes: their metabolism by hepatic cytochrome P-450 in vitro. Carcinogenesis 2: 697–702.
39. Jablonka E (2004) Epigenetic epidemiology. Int J Epidemiol 33: 929–935.
40. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57: 43–66.
41. Khan S, O'Brien PJ (1991) 1-Bromoalkanes as new potent nontoxic glutathione depletors in isolated rat hepatocytes. Biochem Biophys Res Commun 179: 436–441.
42. Kim JY, Tavaré S, Shibata D (2005) Counting human somatic cell replications: methylation mirrors endometrial stem cell divisions. Proc Natl Acad Sci U S A 102: 17739–17744.
43. Konietzko H (1984) Chlorinated ethanes: sources, distribution, environmental impact and health effects. Hazard Assess Chem Curr Dev 3: 407–410.
44. Kornbrust DJ, Bus JS (1982) Metabolism of methyl chloride to formate in rats. Toxicol Appl Pharmacol 65: 135–143.
45. Kornbrust DJ, Bus JS (1983) The role of glutathione and cytochrome P-450 in the metabolism of methyl chloride. Toxicol Appl Pharmacol 67: 246–256.
46. Kornbrust DJ, Bus JS (1984) Glutathione depletion by methyl chloride and association with lipid peroxidation in mice and rats. Toxicol Appl Pharmacol 72: 388–399.
47. Kornbrust DJ, Bus JS, Doerjer G, Swenberg JA (1982) Association of inhaled [14C]methyl chloride with macromolecules from various rat tissues. Toxicol Appl Pharmacol 65: 122–134.
48. Landry TD, Ayres JA, Johnson KA, Wall JM (1982) Ethyl chloride: a two-week inhalation toxicity study and effects on liver non-protein sulfhydryl concentrations. Fundam Appl Toxicol 2: 230–234.
49. Landry TD, Johnson KA, Phillips JE, Weiss SK (1989) Ethyl chloride - 11-day continuous exposure inhalation toxicity study in B6C3F1 mice. Fundam Appl Toxicol 13: 516–522.
50. Lawson JI (1965) Ethyl chloride. Br J Anaesth 37: 667–670.
51. Lieber CS (1999) Microsomal ethanol-oxidizing system (MEOS): the first 30 years (1968–1998)–a review. Alcohol Clin Exp Res 23: 991–1007.
52. Linton E woodman, J, Asboth, G, Glynn, B, Plested, C, Bernal, A (2001) Corticotropin releasing hormone: it's potential for a role in human myometrium. Exp Physiol 86: 273–281.
53. Lucas WE (1974) Causal relationships between endrocrine-metabolic variables in patients with endometrial carcinoma. Obstet Gynecol Surv 29: 507–528.
54. MacEwen J; Vernot E; (1972) Annual Technical Report. AMRL-TR-72-62, (Nation Technical Information Service AD755-358) Wright-Patterson Air Force Base (OH): Aerospace Medical Research Laboratory, Toxic Hazards Research Unit.
55. Marks F, Furstenberger G, Muller-Decker K (2007) Tumor promotion as a target of cancer prevention. Recent Results Cancer Res 174: 37–47.
56. McCardie WJ (1903) Ethyl chloride as a general anesthetic. Lancet 1: 952–955.
57. Mollerstrom G, Carstrom K, Largrelius A, Einhorn N (1993) Is there an altered steroid profile in patients with endometrial carcinoma. Cancer 72: 173–181.
58. Morris JB (1997) Dosimetry, toxicity and carcinogenicity of inspired acetaldehyde in the rat. IV. Progression and regression of nasal lesions after discontinuation of exposure. Mutat Res Fundam Mol Mech Mutagen 380: 113–124.
59. Murakami S, Noguchi T, Takeda K, Ichijo H (2007) Stress signaling in cancer. Cancer Sci 98: 1521–1527.
60. NTP (National Toxicology Program) (1978) Bioassay of 1,2-Dichloroethane for Possible Carcinogenicity. CAS. NO. 107-06-2. Research Triangle Park, NC: U.S. Department of Health and Human Services, National Institutes of Health, NTP TR No. 55. Report available at http://ntp-server.niehs.nih.gov/.
61. NTP (National Toxicology Program) (2005) Sixth Annual Report on Carcinogens. National Institute of Environmental Health Sciences (NIEHS), US Public Service, Report on acetaldehyde. CAS No. 75-07-0. Report available at http://ntp-server.niehs.nih.gov/.
62. Peto R, Gray R, Brantom P, Grasso P (1991) Effects on 4080 rats of chronic ingestion of N-nitrosodiethylamine or N-nitrosodimethylamine: a detailed dose-response study. Cancer Res 51: 6415–6451.
63. Peto R, Gray R, Brantom P, Grasso P (1993) Effects on 4080 rats of chronic ingestion of N-nitrosodiethylamine or N-nitrosodimethylamine: a detailed dose-response study. Cancer Res 53: 4107–4108.
64. Picut CA, Aoyama H, Holder JW, Gold LS, Maronpot RR, Dixon D (2003) Bromoethane, chloroethane and ethylene oxide induced uterine neoplasms in B6C3F1 mice from 2-year NTP inhalation bioassays: pathology and incidence data revisited. Exp Toxicol Pathol 55: 1–9.
65. Pottenger LH; Gilbert JR; Bus JS; (1993) Disposition and Metabolism of Female F344 rats and B6C3F1 Mice Following Inhalation Exposure: Part B. Dow Chemical Co. R & D Report, accessed 6-10-05 EPA document no. 86-930000120.
66. Pottenger LH; Landry TD; Bus JS; (1991) Species-specific and dose-dependent non-protein sulfhydyls (NPSH) depletion in female mice and rats after inhalation exposure to ethyl chloride. The Toxicologist (Poster: Society of Toxicology Annual Publication) 11: 348.
67. Pottenger LH; Nieusma JL; Landry TD; (1992) Ethyl chloride: disposition and metabolism in female Fischer 344 rats and B6C3F1 mice following inhalation exposure: Part A. Dow Chemical Co. R & D Report. Report accessible from OPPTS/ US EPA. EPA document no. 86-930000120.
68. Rakoff-Nahoum S (2006) Why cancer and inflammation. Yale J Biol Med 79: 123–130.
69. Reiche EM, Nunes SO, Morimoto HK (2004) Stress, depression, the immune system, and cancer. Lancet Oncol 5: 617–625.
70. Reinhardt CF, Azar A, Maxfield ME, Smith PE, Mullin LS (1971) Cardiac arrhythmias and aerosol “sniffing. Arch Environ Health 22: 265–279.
71. Riveros-Rosas H, Julian-Sanchez A, Pina E (1997) Enzymology of ethanol and acetaldehyde metabolism in mammals. Arch Med Res 28: 453–471.
72. Ryan E, Rajan B, Evans S, Widdowson E (1997) Bromoethane Risk Assessment Document EH 72/3. Sudbury, Suffolk, United Kingdom: HSE Books.
73. Scheel C, Onder T, Karnoub A, Weinberg RA (2007) Adaption versus selection: the origins of metastatic behavior. Cancer Res 67: 11476–11480.
74. Sills RC, Hailey JR, Neal J, Boorman GA, Haseman JK, Melnick RL (1999) Examination of low-incidence brain tumor responses in F-344 rats following chemical exposures in the National Toxicology Program carcinogenicity studies. Toxicol Pathol 25: 589–599.
75. Sivridis E, Giatromanolaki A, Kourkourakis M, Anastasiadis P (2001) Endometrial carcinoma: association of steroid receptor expression with low angiogenesis and bcl-2 expression. Virchows Arch 438: 470–477.
76. Soult TA, Walker JS (1993) Ethyl chloride intoxication. Am J Emerg Med 11: 313–315.
77. Steckler T (2001) The molecular neurobiology of stress–evidence from genetic and epigenetic models. Behav Pharmacol 12: 381–427.
78. Szyf S (2007) The dynamic episome and its implications in toxicology. Toxicol Sci 100: 7–23.
79. The Sapphire Group (2006) Evaluation of chloroethane Pharmacokinetics in the Females of the Rat, Mouse, and Human. Phase 1-3 reports, respectively. Phase 4 report compares PBPK among the three species. Reports submitted to the U.S. EPA final on September 8, 2006. Authors: Michael Gargas and Lisa Sweeney, Dayton, Ohio. Copies of these reports can be requested at: EPA at (703)347-8561, or the Author at holder_james@yahoo.com.
80. Thier R, Wiebel FA, Bolt HM (1999) Differential substrate behaviors of ethylene oxide and propylene oxide towards human glutathione transferase theta hGSTT1-1. Arch Toxicol 73: 489–492.
81. Troshina MN (1966) Determination of maximum permissible concentration of ethyl chloride in the atmosphere of work premises. Gig Tr Prof Zabol 10: 37–42[in Russian with English abstract].
82. U.S. EPA (U.S. Environmental Protection Agency) (2008) Toxicological review of chloroethane (ToxR). Draft Author: James W. Holder of the National Center for Environmental Assessment-W (NCEA-W), Final Draft Technical Support Document (ToxR) of Chloroethane complete Toxicology information prepared for the Integrated Risk Information System (IRIS).
83. van Kempen LC, de Visser KE, Coussens LM (2006) Inflammation, proteases and cancer. Eur J Cancer 42: 728–734.
84. Westhorpe R (1994) Ethyl chloride. Anaesth Intensive Care 22: 3.
85. Wu G, Fang YZ, Yang S, Lupton JR, Turner ND (2004) Glutathione metabolism and its implications for health. J Nutr 134: 489–492.
86. Yacoub I, Robinson CA, Simmons GT, Hall M (1993) Death attributed to ethyl chloride (case report). J Anal Toxicol 17: 384–385.
87. Yang J, Mani SA, Weinberg RA (2006) Exploring a new twist on tumor metastasis. Cancer Res 66: 4549–4552.
88. Zeise L, Crouch EA, Wilson R (1985) On the relationship of toxicity and carcinogenicity. Risk Anal 5: 265–270.