BMS 233110-01

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9th November 1998 - 1st March 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

other: micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

429-080-9

EC Name:

-

Cas Number:

198904-85-7

Molecular formula:

C17 H21 N3 O2

IUPAC Name:

Tert-butyl 2-[4-(2-pyridinyl) phenylmethyl] hydrazine carboxylate

Test material form:

solid: bulk

Specific details on test material used for the study:

Identity of test material same as for substance defined in section 1

Test animals

Species:

mouse

Strain:

other: Crl:CD-1(ICR)BR

Sex:

male

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

Carboxymethylcellulose solution

No. of animals per sex per dose:

Male: 200 mg/kg; No. of animals: 7; Sacrifice time: 24 hours
Male: 400 mg/kg; No. of animals: 7; Sacrifice time: 24 hours
Male: 800 mg/kg; No. of animals: 7; Sacrifice time: 24 hours
Male: 800 mg/kg; No. of animals: 7; Sacrifice time: 48 hours

Results and discussion

Test results

Key result

Sex:

male

Genotoxicity:

negative

Remarks:

up to 800 mg/kg

Toxicity:

yes

Remarks:

at 1000 and 2000 mg/kg

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

Doses producing toxicity:
In a range finding study, male and female mice were treated by the oral and intraperitoneal routes. The IP route gave deaths at 500 and 1000 mg/kg, although an absence of a clear dose related response suggested problems with this method of administration. The IP route was not used in the main study.

Oral administration caused 1/4 deaths in males at 1000 mg/kg and 7/13 deaths in males at 2000 mg/kg. There was no mortality with females. Only males were used in the main study.

Observations:
There was no mortality in the main study, but at 800 mg/kg, clinical signs included hunched posture, lethargy and ptosis.

There were no indications of a positive response.

Any other information on results incl. tables

Systemic toxicity inidcated that absorption took place. Subsequent toxicity testing on rats demonstrated systemic effects following oral adminstration.

Applicant's summary and conclusion

Conclusions:

Negative.

BMS 233110-01 is considered to be non-genotoxic under the conditions of the test