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RECORD NUMBER: 4 OF 4

Main Title Support: Bone Marrow Micronucleus Assay in Male and Female Swiss-Webster Mice Following Acute Nose-Only Inhalation Exposure to Methyl Mercaptain with Cover Letter dated 07/12/1996.
CORP Author SRI International, Menlo Park, CA.; Elf Atochem North America, Philadelphia, PA.; Environmental Protection Agency, Washington, DC. Office of Toxic Substances.
Year Published 1996
Report Number 8EHQ-0796-13576
Stock Number OTS0558450-1
Additional Subjects Toxicology ; Health effects ; Toxic substances ; Methyl mercaptan ; Genotoxicity ; Chromosomal effects ; Mammals ; Mice ; Inhalation ; CAS No 74-93-1
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NTIS  OTS0558450-1 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 101p
Abstract
The genoroxic potential of mose-only inhalation exposure of methyl mercaptan to induce micronucleus formation in bone marrow erythrocytes was determined in Swiss-Webster nnce. A dose range finding experiment was performed at doses of I12, 374, or 570 ppm methyl mercaptan for a single 6 hour nose-only inhalation exposure, and sacrificed approximately 72 hours after exposure. Clinical signs observed included shallow breathing at 112 ppm, and shallow breathing and hypoactivity at 374 and 570 ppm. Two male mice were found dead at 570 ppm during the exposure period. No statistically significant polychromatic erythrocyte (PCE) suppression was observed in any dose group in either bone marrow or peripheral blood. Based on the data, the following target exposure concentrations of methyl mercaptan were chosen for the definitive experiment for both sexes: 125, 250, and 500 ppm. In the definitive experiment, 15 mice per sex per treatment group were exposed to methyl mercaptan by nose-only inhalation at 114, 258, or 512 ppm. Five mice per sex per group were sacrificed 24, 48, and 72 hours after the single 6 hour exposure and bone marrow was evaluated for cytotoxicity and micronucleus formation. An air-exposed control group of male and female mice and a urethane positive control group of male mice were treated similarly and evaluated concurrently with the methyl mercantan-treated groups. Clinical observations included shallow breathing and hypoactivity at 258 and 512 ppm in all mice. Three female and two male mice were immd dead at 512 ppm methyl mercaptan. A statistically significant increase in micronucleated PCE was observed in male mice at 24 br after exposure to 512 ppm of methyl mercaptan. Although statistically significant, the biological significance of this increase is equivocal since the control group had a micronucleus frequency lower than the SRI historical mean (0.08% vs. the laboratory mean historical frequency of 0.21%). Using the Cochran-Armitage test for a trend in binomial proportions, statistically significant increases in micronucleated PCE were observed in male mice at 24 and 48 hr and in female mice at 48 hr after exposure to methyl mercaptan. In conclusion, although the increases in micronucleated frequencies observed are weak, methyl mercaptan meets the criteria established in the protocol for a positive response in the mouse bone marrow erythrocyte micronucleus assay.