BMS 233110-01

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4th - 22nd May 1998

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:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation 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

Method

Species / strain

Species / strain / cell type:

bacteria, other: TA98, TA100, TA1535, TA1537, E Coli WP2uvrA

Metabolic activation system:

Aroclor 1254 induced rat liver S-9 fraction

Test concentrations with justification for top dose:

Concentration range in the main test (with metabolic activation): 33.3 ... 5000 µg/plate
Concentration range in the main test (without metabolic activation): 33.3 ... 5000 µg/plate

Vehicle / solvent:

Solvent: DMSO

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

without

Genotoxicity:

other: no data

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

(> 5000 µg/plate)

Test results 2

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

( <=5000 µg/plate)

Test results 3

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

<=5000 µg/plate)

Test results 4

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

(> 5000 µg/plate)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

(> 5000 µg/plate)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 6

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 7

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 8

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Observations: There was no indication of toxicity in either experiments.There was also no observed increase in revertant strains except for weak response in the presence of S-9 in TA-98 in both experiments

Applicant's summary and conclusion

Conclusions:

positive with metabolic activation
negative without metabolic activation

The results of the salmonella-escherichia coli / Mammalian-Microsome Reverse Mutation Assay with a Confirmatory Assay indicate that under the conditions of this study, BMS 233110-01 caused a positive increase in the mean number of revertants per plate with tester strain TA98 (3.1-fold in the inital assay and 2.8-fold in the confirmatory assay) in the presence of S9 mix. No positive increases were observed with any of the remaining tester strain/activation conditions combinations.