tert-butyl {(1S)-1-[(2R)-oxiran-2-yl]-2-phenylethyl}carbamate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 Nov 1998 - 11 March 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: done under OECD method and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: EEC Directive 92/69/EEC, Method B12, OECD Guidelines for testing of Chemicals No. 474 "Micronucleus Test".

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Test animals

Species:

mouse

Strain:

CD-1

Remarks:

albino, (ICR)BR

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

Arachis oil

No. of animals per sex per dose:

Male: 1000 mg/kg; No. of animals: 7; Sacrifice time: 48 hours
Male: 1000 mg/kg; No. of animals: 7; Sacrifice time: 24 hours
Male: 500 mg/kg; No. of animals: 7; Sacrifice time: 24 hours
Male: 250 mg/kg; No. of animals: 7; Sacrifice time: 24 hours

Results and discussion

Additional information on results:

Doses producing toxicity:
In the range finding toxicity study, the toxicity observed at 2000 mg/kg was considered to be excessive, therefore, the maximum tolerated dose (MTD) of the test material, 1000 mg/kg, was selected for use in the main study, with 500 and 250 mg/kg as the lower dose levels. In animals dosed with the test material via the oral route one premature death occurred at 2000 mg/kg, and clinical signs were observed at and above 1000 mg/kg as follows: hunched posture, lethargy, ataxia, decreased respiratory rate, laboured respiration, tonic convulsions, increased salivation, splayed gait, pilo-erection, tiptoe gait, emaciation, ptosis and distended abdomen. These clinical signs indicate that systemic absorption had taken place.

Observations:
There was no evidence of a significant increase in the incidence of micronucleated polychromatic erythrocytes in animals dosed with the test material when compared to the concurrent vehicle control groups. No statistically significant decreases in the PCE/NCE ratio were observed in the 24 or 48-hour test material dose groups when compared to their concurrent control groups. However, the presence of clinical signs indicated that systemic absorption had occurred.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
The test material, BMS 217947-01, was considered to be non-genotoxic under the conditions of the test.

Executive summary:

An in vivo micronucleus assay was carried out on BMS 217947-01 according to EEC Directive 92/69/EEC, Method B12 and OECD Guidelines for testing of Chemicals No. 474 "Micronucleus Test". The test was carried out on albino, CD-1 (ICR)BR mice. The material was administered orally to groups of 7 rats at doses of 250, 500 and 1000 mg/kg, dispersed in arachis oil.

In the range finding toxicity study, the toxicity observed at 2000 mg/kg was considered to be excessive, therefore, the maximum tolerated dose (MTD) of the test material, 1000 mg/kg, was selected for use in the main study, with 500 and 250 mg/kg as the lower dose levels. In animals dosed with the test material via the oral route one premature death occurred at 2000 mg/kg, and clinical signs were observed at and above 1000 mg/kg as follows: hunched posture, lethargy, ataxia, decreased respiratory rate, laboured respiration, tonic convulsions, increased salivation, splayed gait, pilo-erection, tiptoe gait, emaciation, ptosis and distended abdomen. These clinical signs indicate that systemic absorption had taken place.

Observations:

There was no evidence of a significant increase in the incidence of micronucleated polychromatic erythrocytes in animals dosed with the test material when compared to the concurrent vehicle control groups. No statistically significant decreases in the PCE/NCE ratio were observed in the 24 or 48-hour test material dose groups when compared to their concurrent control groups. However, the presence of clinical signs indicated that systemic absorption had occurred.