Methanethiol

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Methanethiol

EC Number:

200-822-1

EC Name:

Methanethiol

Cas Number:

74-93-1

Molecular formula:

CH4S

IUPAC Name:

methanethiol

Test animals

Species:

mouse

Strain:

Swiss Webster

Sex:

male/female

Administration / exposure

Route of administration:

inhalation

Duration of treatment / exposure:

6 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 114, 258 and 512 ppm
Basis:

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Any other information on results incl. tables

DOSE RANGE FINDING EXPERIMENT
No significant differences as observed between terminal and
pre-exposure body weights of each of the treatment groups at
each of the sacrifice times.
Clinical signs observed included shallow breathing at the
fourth hour of exposure at 112 ppm, shallow breathing at the
third hour of exposure at 374 and 570 ppm with hypoactivity
at the mid and high dose levels in all mice when observed
after completion of exposure. Two male mice were found dead
near the end of the second hour and during the sixth hour of
exposure at 570 ppm. Any mouse showing clinical signs
appeared normal on Day 2. Surviving mice were sacrificed
approximately 72 hours after the inhalation exposure, and
cytotoxicity was determined based on the ratio of
RNA-positive erythrocytes (PCEs) to total red blood cells
(RBCs) in both peripheral blood and bone marrow smears. No
significant PCE suppression was observed in any of the
methyl mercaptan treatment groups when compared to the air
control group in either peripheral blood or bone marrow.

DEFINITIVE EXPERIMENT
Clinical observations in this experiment included shallow
breathing and hypoactivity at the fourth and fifth hours,
respectively, of exposure at 258 ppm in all mice. All mice
at 258 ppm appeared normal on Day 2 and on all subsequent
experiment days. Shallow breathing at the third and fourth
hours of exposure, and hypoactivity at the fifth hour of
exposure were observed at 512 ppm in all mice. One female
mouse was found dead after 2 hours of exposure at 512 ppm,
and two female and two male mice were found dead at 512 ppm
on Day 2. All surviving mice at 512 ppm appeared normal on
Day 2 and on all subsequent experiment days. Mice treated
with 114 ppm methyl mercaptan, air control, or urethane
appeared normal throughout the experiment.
The percentages of PCEs among RBCs in groups treated with
methyl mercaptan did not differ significantly from those of
the air control groups in any of the dose groups for either
sex.
In male mice (Table 1), none of the individual dose groups
had a statistically significant increase in MN frequency. Using
the Cochran-Armitage test for a trend in binomial
proportions, a statistically significant upward trend in
micronucleus (MN) frequency was observed in female mice
(Table 2) sacrificed at 24 hr after exposure to the methyl mercaptan.
However, the MN frequency in the control group was lower
than the laboratory historical value (0.21%) for females of
this strain of mice, and none of the individual dose groups
had a statistically significant increase in MN frequency.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative

Executive summary:

A mouse micronucleus assay was conducted with methanethiol inhalation exposure to male and female Swiss Webster mice according to the OECD 474 Guideline. The mice (15/sex/group) were exposed (nose-only) to methanethiol via inhalation at 0, 114, 258 and 512 ppm for 6 hours. A positive control group of male mice was exposed to urethane concurrently with the treated groups. Five mice/sex were sacrificed at 24, 48 and 72 hours after the single exposure and bone marrow was evaluated for cytotoxicity and micronucleus formation. One female mouse was found dead after 2 hours of 512 ppm exposure and 4 mice (2 males and 2 females) in the 512 ppm were found dead on Day 2. At 24 hours, there was a statistically-significant upward trend in micronuclei in females, but comparison of individual doses to controls did not yield statistically-significant differences and the control group value was lower than the laboratory historical mean The mean average value for the historical controls was determined on 11 studies performed between 1990 and 1994 and using in total 120 male and 120 female mice. It was concluded that methanethiol did not induce chromosome mutations under the conditions of this study.