Evaluation of possible modes of action for acute effects of methyl iodide in laboratory animals

Inhalation Toxicology

Volumn 21, Issue 6, 2009, Pages 537-551

  Kirman, Christopher R ^a   Sweeney, Lisa M ^b   Gargas, Michael L ^b   Kinzell, John H ^c  

^a Sapphire Group Inc   (United States)

^b Sapphire Group   (United States)

^c ARYSTA LIFESCIENCE CORPORATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLUTATHIONE; IODINE; METHYL IODIDE; THYROID HORMONE;

ACUTE TOXICITY; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DNA METHYLATION; EXPERIMENTAL RABBIT; FEMALE; HORMONE ACTION; NEUROTOXICITY; NONHUMAN; NOSE MUCOSA; OLFACTORY EPITHELIUM; PRIORITY JOURNAL; RISK ASSESSMENT;

ANIMALS; DRUG EVALUATION, PRECLINICAL; FEMALE; HUMANS; HYDROCARBONS, IODINATED; MALE; MODELS, ANIMAL; PREGNANCY; RABBITS; RATS; TISSUE DISTRIBUTION;

ANIMALIA; RATTUS;

EID: 70350576870     PISSN: 08958378     EISSN: 10917691     Source Type: Journal    
DOI: 10.1080/08958370802601510     Document Type: Article

References (101)

1. Aboul-Khair, S.A., Buchanan, T.J., Crooks, J., and Turnbull, A.C. 1966. Structural and functional development of the human foetal thyroid. Clin. Sci. 31:415-424.
2. Aceto, A., Di Ilio, C., Angelucci, S., Longo, V., Gervasi, P.G., and Federici, G. 1989. Glutathione transferases in human nasal mucosa. Arch. Toxicol. 63:427-431.
3. Arrington, L.R., Taylor, R.N., Jr., Ammerman, C.B., and Shirley, R.L. 1965. Effects of excess dietary iodine upon rabbits, hamsters, rats and swine. J. Nutr. 87:394-398.
4. Ballard, P.L., Benson, B.J., Brehier, A., Carter, J.P., Kriz, B.M., and Jorgensen, E.C. 1980. Transplacental stimulation of lung development in the fetal rabbit by 3,5-dimethyl-3'-isopropyl-L-thyronine. J. Clin. Invest. 65:1407-1417. (Pubitemid 10122383)
5. Biaglow, J.E., Varnes, M.E., Roizen-Towle, L., Clark, E.P., Epp, E.R., Astor, M.B., and Hall, E.J. 1986. Biochemistry of reduction of nitro heterocycles. Biochem. Pharmacol. 35:77-90.
6. Bolt, H.M., and Gansewendt, B. 1993. Mechanisms of carcinogenicity of methyl halides. Crit. Rev. Toxicol. 23:237-253.
7. Bonnefoi, M.S., Davenport, C.J., and Morgan, K.T. 1991. Metabolism and toxicity of methyl iodide in primary dissociated neural cell cultures. Neurotoxicology 12:33-46.
8. Bonnefoi, M.S. 1992. Mitochondrial glutathione and methyl iodide-induced neurotoxicity in primary neural cell cultures. Neurotoxicology 13:401-412.
9. Byrd, R.A., and Francis, P.C. 1998. The selective estrogen receptor modulator, raloxifene: Segment II studies in rats and rabbits. Reprod. Toxicol. 12:261-270.
10. Chamberlain, M.P., Lock, E.A., and Reed, C.J. 1998a. Investigations of the pathways of toxicity of methyl iodide in the rat nasal cavity. Toxicology 129:169-181.
11. Chamberlain, M.P., Lock, E.A., Gaskell, B.A., and Reed, C.J. 1998b. The role of glutathione S-transferase and cytochrome P450-dependent metabolism in the olfactory toxicity of methyl iodide in the rat. Arch. Toxicol. 72:420-428.
12. Chamberlain, M.P., Sturgess, N.C., Lock, E.A., and Reed, C.J. 1999. Methyl iodide toxicity in rat cerebellar granule cells in vitro: The role of glutathione. Toxicology 139:27-37.
13. Chellman, G.J., White, R.D., Norton, R.M., and Bus, J.S. 1986. Inhibition of the acute toxicity of methyl chloride in male B6C3F1 mice by glutathione depletion. Toxicol. Appl. Pharmacol. 86:93-104.
14. Chiou, J.-S., Ma, S.-M., Kamaya, H., and Ueda, I. 1990. Anæsthesia cutoff phenomenon: Interfacial hydrogen bonding. Science 248:583-585.
15. Clewell, R.A., Merrill, E.A., Yu, K.O., Mahle, D.A., Sterner, T.R., Mattie, D.R., Robinson, P.J., Fisher, J.W., and Gearhart, J.M. 2003. Predicting fetal perchlorate dose and inhibition of iodide kinetics during gestation: a physiologically-based pharmacokinetic analysis of perchlorate and iodide kinetics in the rat. Toxicol. Sci. 73:235-255.
16. Conolly, R.B., Lilly, P.D., and Kimbell, J.S. 2000. Simulation modeling of the tissue disposition of formaldehyde to predict nasal DNA-protein crosslinks in Fischer 344 rats, rhesus monkeys, and humans. Environ. Health Perspect. 108(suppl. 5):919-924.
17. Cottino, F., Zoppetti, G., Favero, A., Lombardi, M., Cenderelli, G., and Costa, A. 1972. Placental tissue and maternal and cord serum iodine following pharmacological loading. Folia Endocrinol. 25:278-285.
18. Crone, M., and Waago, G. 1961. Transfer of radioactive iodide between mother and foetus in the rabbit. Acta Physiol. Scand. 51:84-93.
19. Curry, S., Lieb, W.R. and Franks, N.P. 1990. Effects of general anæsthetics on the bacterial luciferase enzyme from Vibrio harveyi: An anæsthetic target site with differential sensitivity. Biochemistry 29:4641-4652.
20. Davenport, C.J., Ali, S.F., Miller, F.J., Lipe, G.W., Morgan, K.T., and Bonnefoi, M.S. 1992. Effect of methyl bromide on regional brain glutathione, glutathione-S-transferases, monoamines, and amino acids in F344 rats. Toxicol. Appl. Pharmacol. 112:120-127.
21. Devaskar, U.P., Devaskar, S.U., Sadiq, H.F. and Chechani, V. 1986. Ontogeny of plasma-free thyroxine and triiodothyronine concentrations during the perinatal period and maternofetal transfer of thyroid hormones in the rabbit. Dev. Pharmacol. Ther. 9:115-123.
22. Di Simplicio, P., Dolara, P., and Lodovici, M. 1984. Blood glutathione as a measure of exposure to toxic compounds. J. Appl. Toxicol. 4:227-229.
23. Dickinson, R., Franks, N.P. and Lieb, W.R. 1993. Thermodynamics of anæsthetic/protein interactions. Temperature studies on firefly luciferase. Biophys. J. 64:1264-1271.
24. Dorman, D.C., Moulin, F.J., McManus, B.E., Mahle, K.C., James, R.A., and Struve, M.F. 2002. Cytochrome oxidase inhibition induced by acute hydrogen sulfide inhalation: Correlation with tissue sulfide concentrations in the rat brain, liver, lung, and nasal epithelium. Toxicol. Sci. 65:18-25.
25. Eustis, S.L., Haber, S.B., Drew, R.T., and Yang, R.S. 1988. Toxicology and pathology of methyl bromide in F344 rats and B6C3F1 mice following repeated inhalation exposure. Fundam. Appl. Toxicol. 11:594-610.
26. Franks, N.P., and Lieb, W.R. 1994. Molecular and cellular mechanisms of general anæsthesia. Nature 367:607-614.
27. Frederick, C.B., Potter, D.W., Chang-Mateu, M.I., and Andersen, M.E. 1992. A physiologically based pharmacokinetic and pharmacodynamic model to describe the oral dosing of rats with ethyl acrylate and its implications for risk assessment. Toxicol. Appl. Pharmacol. 114:246-260.
28. Gandy, J., Millner, G.C., Bates, H.K., Casciano, D.A., and Harbison, R.D. 1990. Effects of selected chemicals on the glutathione status in the male reproductive system of rats. J. Toxicol. Environ. Health 29:45-57.
29. Gansewendt, B., Xu, D., Foest, U., Hallier, E., Bolt, H.M., and Peter, H. 1991. DNA binding of methyl iodide in male and female F344 rats. Carcinogenesis 12:463-467
30. Ghosh, N., and Bhattacharya, S. 1992. Thyrotoxicity of the chlorides of cadmium and mercury in rabbit. Biomed. Environ. Sci. 5:236-240.
31. Hallier, E., Deutschmann, S., Reichel, C., Bolt, H.M., and Peter, H. 1990. A comparative investigation of the metabolism of methyl bromide and methyl iodide in human erythrocytes. Int. Arch. Occup. Environ. Health 62:221-225.
32. Hansen, J.M., Carney, E.W., and Harris, C. 1999. Differential alteration by thalidomide of the glutathione content of rat vs. rabbit conceptuses in vitro. Reprod. Toxicol. 13:547-554.
33. Hermouet, C., Garnier, R., Efthymiou, M., and Fournier, P. 1996. Methyl iodide poisoning: report of two cases. Am. J. Ind. Med. 30:759-764.
34. Himmelstein, M.W., et al. 2005. Iodomethane: In vivo 2-day inhalation mechanistic toxicity study in the rat. Unpublished report, DuPont Haskell Laboratory
35. Honma, T., Miyagawa, M., Sato, M., and Hasegawa, H. 1985. Neurotoxicity and metabolism of methyl bromide in rats. Toxicol. Appl. Pharmacol. 81:183-191.
36. Howdeshell, K.L. 2002. A model of the development of the brain as a construct of the thyroid system. Environ. Health Perspect. 110(suppl. 3):337-348.
37. Hudson, D.G., and Hull, D. 1975. Growth of adipose tissue in the fetal rabbit. Biol. Neonate 27:71-79.
38. Janes, N., Hsu, J.W.,Rubin, E., and Taraschi, T.F. 1992. Nature of alcohol and anæsthetic action on cooperative membrane equilibria. Biochemistry 31:9467-9472.
39. Janoff, A.S., and Miller, K.W. 1982. A critical assessment of the lipid theories of general anæsthetic action. In Biological membranes, ed. Chapman D., pp. 417-476. London:Academic Press.
40. Kaneda, M., Hatakenaka, N., Teramoto, S., and Maita, K. 1993. A twogeneration reproduction study in rats with methyl bromide-fumigated diets. Food Chem. Toxicol. 31:533-542.
41. Kaneda, M., Hojo, H., Teramoto, S., and Maita, K. 1998. Oral teratogenicity studies of methyl bromide in rats and rabbits. Food Chem. Toxicol. 36:421-427.
42. Kirkpatrick, D.T. 2002. A 13-week inhalation toxicity study (with a 4-week interim necropsy) of iodomethane in albino rats, WIL-418015. Wildlife International Ltd., Maryland, January 28.
43. Kirkpatrick, D.T. 2003. A 24-month inhalation combined chronic toxicity/ carcinogenicity study of iodomethane in rats, interim report (chronic, one-year toxicity assessment), WIL-418019. Wildlife International Ltd., Maryland, December 2.
44. Klein, A.H., Jenkins, J.J., Reviczky, A., and Fisher, D.A. 1981. Thyroid hormonesensitive brown adipose tissue respiration in the newborn rabbit. Am. J. Physiol. 241:E449-E453.
45. Kornbrust, D.J., and Bus, J.S. 1984. Glutathione depletion by methyl chloride and association with lipid peroxidation in mice and rats. Toxicol. Appl. Pharmacol. 72:388-399.
46. Lampe, L., Kertesz, L., Vachter, J., and Dzvonyar, J. 1967. Maternal-foetal iodine metabolism in the rabbit. II. Distribution of 131I administered to the mother in placenta, and maternal and foetal blood. Acta Physiol. Acad. Sci. Hung. 31:303-308.
47. Landry, T.D., Gushow, T.S., Langvardt, P.W., Wall, J.M., and McKenna, M.J. 1983. Pharmacokinetics and metabolism of inhaled methyl chloride in the rat and dog. Toxicol. Appl. Pharmacol. 68:473-486.
48. Lee, M.S., Faller, T.H., Kreuzer, P.E., Kessler, W., Csanady, G.A., Putz, C., Rios-Blanco, M.N., Pottenger, L.H., Segerback, D., Osterman-Golkar, S., Swenberg, J.A., and Filser, J.G. 2005. Propylene oxide in blood and soluble nonprotein thiols in nasal mucosa and other tissues of male Fischer 344/N rats exposed to propylene oxide vapors-relevance of glutathione depletion for propylene oxide-induced rat nasal tumors. Toxicol. Sci. 83:177-189.
49. Liberman, C.S., Pino, S.C., Fang, S.L., Braverman, L.E., and Emerson, C.H. 1998. Circulating iodide concentrations during and after pregnancy. J. Clin. Endocrinol. Metab. 83:3545-3549.
50. Logothetopoulos, J., and Scott, R.F. 1956. Active iodide transport across the placenta of the guinea pig, rabbit and rat. J. Physiol. 132:365-371.
51. Maruyama, T., Kozai, S., and Sasaki, F. 2000. Method for the synthesis of uric acid derivatives. Nucleosides Nucleotides Nucleic Acids 19:1193-1203.
52. Mathison, B.H., Taylor, M.L., and Bogdanffy, M.S. 1995. Dimethyl sulfate uptake and methylation of DNA in rat respiratory tissues following acute inhalation. Fundam. Appl. Toxicol. 28:255-263.
53. Matsui, H., Wada, O., Manabe, S., Ushijima, Y., Komatsu, S., and Ono, T. 1982. Pathogenesis of hyperlipidemia induced in rabbits by methyl iodide. Toxicol. Appl. Pharmacol. 65:245-249.
54. McCarver, D.G., and Hines, R.N. 2002. The ontogeny of human drugmetabolizing enzymes: phase II conjugation enzymes and regulatory mechanisms. J. Pharmacol. Exp. Ther. 300:361-366.
55. Messaoudi, S., Lee, K.-H., Beaulieu, D., Baribeau, J., and Boucher, F. 1992. Equilibria between multiple spectral forms of bacteriorhodopsin effect of delipidation, anæsthetics and solvents on their pH dependance. Biochim. Biophys. Acta 1140:45-52.
56. Muller, M., Voss, M., Heise, C., Schulz, T., Bunger, J., and Hallier, E. 2001. High-performance liquid chromatography/fluorescence detection of S-methylglutathione formed by glutathione-S-transferase T1 in vitro. Arch. Toxicol. 74:760-767.
57. National Toxicology Program. 1992. NTP toxicology and carcinogenesis studies of methyl bromide (CAS 74-83-9) in B6C3F1 mice (inhalation studies). Natl. Toxicol. Program Tech. Rep. Ser. 385:1-212.
58. Nemec, M.D. 2002a. An inhalation prenatal developmental toxicity study of iodomethane in rabbits, WIL-418002. Wildlife International Ltd., Maryland, January 28.
59. Nemec, M.D. 2002b. An inhalation two-generation reproductive toxicity study of iodomethane in rats, WIL-418004. Wildlife International Ltd., Maryland, June 28.
60. Nemec, M.D. 2003. A phased-exposure prenatal developmental toxicity study of iodomethane in rabbits, WIL-418023. Wildlife International Ltd., Maryland, February 3.
61. Nishida, Y. 1991. Inhibition of lipid peroxidation by methylated analogues of uric acid. J. Pharm. Pharmacol. 43:885-887.
62. Nour, B.M., Boudreaux, J.P., and Rowe, M.I. 1984. An experimental model to study thermogenesis in the neonatal surgical patient. J. Pediatr. Surg. 19:764-770.
63. Ozolins, T.R., and Gupta, U. 2004. Embryo/fetal toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in rats and rabbits. Birth Defects Res. Part B Dev. Reprod. Toxicol. 71:161-170. (Pubitemid 39031156)
64. Pancetti, F., Oyarce, M., Aranda, M., Parodi, J., Aguayo, L.G., Morales, B., Westphal, G., Muller, M., Hallier, E., and Zeise, M.L. 2004. S-methylcysteine may be a causal factor in monohalomethane neurotoxicity. Neurotoxicology 25:817-823.
65. Pennington, J.A.T. 1990. A review of iodine toxicity reports. J. Am. Diet. Assoc. 90:1571-1580.
66. Peter, H., Laib, R.J., Ottenwalder, H., Topp, H., Rupprich, N., and Bolt, H.M. 1985. DNA-binding assay of methyl chloride. Arch. Toxicol. 57:84-87.
67. Plopper, C.G., Van Winkle, L.S., Fanucchi, M.V., Malburg, S.R., Nishio, S.J., Chang, A., and Buckpitt, A.R. 2001. Early events in naphthalene-induced acute Clara cell toxicity. II. Comparison of glutathione depletion and histopathology by airway location. Am. J. Respir. Cell. Mol. Biol. 24:272-281.
68. Price, D.J., and Sherwin, J.R. 1986. Autoregulation of iodide transport in the rabbit: Absence of autoregulation in fetal tissue and comparison of maternal and fetal thyroid iodination products. Endocrinology 119:2547-2552.
69. Pringle, M.J., Brown, K.B., and Miller, K.W. 1981. Can the lipid theories of anæsthesia account for the cutoff in anæsthetic potency in homologous series of alcohols. Mol. Pharmacol. 19:49-55.
70. Raijmakers, M.T., Steegers, E.A., and Peters, W.H. 2001. Glutathione S-transferases and thiol concentrations in embryonic and early fetal tissues. Hum. Reprod. 16:2445-2450.
71. Rayburn, W., Robinson, A., Braverman, L., et al. 2007. Iodide concentrations in matched maternal plasma, cord plasma and amniotic fluid from term and pre-term human pregnancies. Unpublished study prepared by The Sapphire Group, Technology Sciences Group Inc., and New Mexico St. University.
72. Reed, C.J., Gaskell, B.A., Banger, K.K., and Lock, E.A. 1995. Olfactory toxicity of methyl iodide in the rat. Arch. Toxicol. 70:51-56.
73. Richards, C.D., Martin, K., Gregory, S., Keightley, C.A., Hesketh, T.R., Smith, G.A., Warren, G.B., and Metcalfe, J.C. 1978. Degenerate perturbations of protein structure as the mechanism of anæsthetic action. Nature 276:775-779.
74. Robinson, D.A., Foster, J.R., Nash, J.A., and Reed, C.J. 2003. Three-dimensional mapping of the lesions induced by beta-beta'- iminodiproprionitrile, methyl iodide and methyl methacrylate in the rat nasal cavity. Toxicol. Pathol. 31:340-347.
75. Roemer, E., Anton, H.J., and Kindt, R. 1993. Cell proliferation in the respiratory tract of the rat after acute inhalation of formaldehyde or acrolein. J. Appl. Toxicol. 13:103-107.
76. Roti, E., Gnudi, A., and Braverman, L.E. 1983. The placental transport, synthesis, and metabolism of hormones and drugs which affect thyroid function. Endocr. Rev. 4:131-149.
77. Roti, E., and Vagenakis, A.G. 2004. Effect of excess iodine: Clinical aspects. In Werner & Ingbar's The thyroid, a fundamental and clinical text, 9th ed., eds. Braverman and Utiger, , pp. 288-305. Lippincott Williams & Wilkins.
78. Sannolo, N., Mamone, G., Ferranti, P., Basile, A., and Malorni, A. 1999. Biomonitoring of human exposure to methyl bromide by isotope dilution mass spectrometry of peptide adducts. J. Mass Spectrom. 34:1028-1032.
79. Schaefer, G.J. 2002. An acute neurotoxicity study of iodomethane in rats, WIL- 418008. WIL Research Laboratories, Ashland, OH, January 7.
80. Sherratt, P.J., Pulford, D.J., Harrison, D.J., Green, T., and Hayes, J.D. 1997. Evidence that human class Theta glutathione S-transferase T1-1 can catalyse the activation of dichloromethane, a liver and lung carcinogen in the mouse. Comparison of the tissue distribution of GST T1-1 with that of classes Alpha, Mu and Pi GST in human. Biochem. J. 326(Pt 3):837-846.
81. Sherratt, P.J., Williams, S., Foster, J., Kernohan, N., Green, T., and Hayes, J.D. 2002. Direct comparison of the nature of mouse and human GST T1-1 and the implications on dichloromethane carcinogenicity. Toxicol. Appl. Pharmacol. 179:89-97.
82. Shokeer, A., Larsson, A.K., and Mannervik, B. 2005. Residue 234 in glutathione transferase T1-1 plays a pivotal role in the catalytic activity and the selectivity against alternative substrates. Biochem. J. 388:387-392.
83. Singh, M.M., and Kamboj, V.P. 1992. Fetal resorption in rats treated with an antiestrogen in relation to luteal phase nidatory estrogen secretion. Acta Endocrinol. (Copenh.) 126:444-450.
84. Slater, S.J., Cox, K.J.A., Lombardi, J.V., Ho, C., Kelly, M.B., Rubin, E., and Stubbs, C.D. 1993. Inhibition of protein kinase C by alcohols and anæsthetics. Nature 364:82-84.
85. Slebodzinski, A.B. 1988. Hyperiodothyroninaemia of neonates, its significance for thermogenesis. Acta Physiol. Pol. 39:364-379.
86. Sloter, E.D., Nemec, M., Stump, D., Holson, J., Kirkpatrick, D., Gargas, M., and Kinzell, J. 2007. Methyl iodide induced fetal hypothyroidism implicated in late-stage fetal death in rabbits. Submitted.
87. Snyder, J.W., Safir, E.F., Summerville, G.P., and Middleberg, R.A. 1995. Occupational fatality and persistent neurological sequelae after mass exposure to hydrogen sulfide. Am. J. Emerg. Med. 13:199-203.
88. Snyder, R., and Andrews, L.S. 1996. Toxic effects of solvents and vapors. In Casarett and Doull's Toxicology: The basic science of poisons, 5th ed., ed. Klassen, C.D. pp.New York: McGraw-Hill.
89. Solnyshkova, T.G., Shakhlamov, V.A., and Volodina, E.P. 2004. Cerebral cortex ultrastructure during exposure to hydrogen sulfide gas. Neurosci. Behav. Physiol. 34:343-345.
90. Steele, R.E., and Wekstein, D.R. 1972. Influence of thyroid hormone on homeothermic development of the rat. Am. J. Physiol. 222:1528-1533.
91. Sweeney, L.M., Kirman, C.R., and Gargas, M.L. 2005. Derivation of human toxicity reference values for methyl iodide using physiologically based pharmacokinetic (PBPK) modeling. Submitted.
92. Takahashi, K., and Kawazoe, Y. 1987. Potent induction of the adaptive response by a weak mutagen, methyl iodide, in Escherichia coli. Mutat. Res. 180:163-169. (Pubitemid 18022074)
93. Thier, R., Bruning, T., Roos, P.H., Rihs, H.P., Golka, K., Ko, Y., and Bolt, H.M. 2003. Markers of genetic susceptibility in human environmental hygiene and toxicology: The role of selected CYP, NAT and GST genes. Int. J. Hyg. Environ. Health 206:149-171.
94. Trevor, A.J., and White, P.F. 2004. General anesthetics. In Basic and clinical pharmacology, 9th ed., ed. Katzung B. G., pp. New York: Lange Medical Books, McGraw-Hill.
95. US EPA. 2005. Guidelines for carcinogen risk assessment, EPA/630/P-03/001F. Washington, DC: US Environmental Protection Agency. Utiger, , pp. 1013-1028. Lippincott Williams & Wilkins.
96. Vorhees, C.V., Butcher, R.E., and Brunner, R.L. 1984. Developmental toxicity and psychotoxicity of potassium iodide in rats: a case for the inclusion of behaviour in toxicological assessment. Food Chem. Toxicol. 22:963-970.
97. Warenycia, M.W., Goodwin, L.R., Benishin, C.G., Reiffenstein, R.J., Francom, D.M., Taylor, J.D., and Dieken, F.P. 1989. Acute hydrogen sulfide poisoning. Demonstration of selective uptake of sulfide by the brainstem by measurement of brain sulfide levels. Biochem. Pharmacol. 38:973-981.
98. Westerveld, G.J., Dekker, I., Voss, H.P., Bast, A., and Scheeren, R.A. 1997. Antioxidant levels in the nasal mucosa of patients with chronic sinusitis and healthy controls. Arch. Otolaryngol. Head Neck Surg. 123:201-204.
99. Wolkowski-Tyl, R., Phelps, M., and Davis, J.K. 1983. Structural teratogenicity evaluation of methyl chloride in rats and mice after inhalation exposure. Teratology 27:181-195.
100. Working, P.K., Bus, J.S., and Hamm, T.E., Jr. 1985. Reproductive effects of inhaled methyl chloride in the male Fischer 344 rat. I. Mating performance and dominant lethal assay. Toxicol. Appl. Pharmacol. 77:133-143.
101. Zwart, A., Woutersen, R.A., Wilmer, J.W., Spit, B.J., and Feron, V.J. 1988. Cytotoxic and adaptive effects in rat nasal epithelium after 3-day and 13- week exposure to low concentrations of formaldehyde vapour. Toxicology 51:87-99.