2-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-(4-methoxy-3-(3-(4-methylpiperazin-1-yl)propoxy)phenylamino)acrylamide, compound with propan-2-ol (2:1)

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

other information

Study period:

14 July 2009-3 August 2009

Reliability:

1 (reliable without restriction)

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: ICH. Topic S2A Genotoxicity: Guidance on Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals; CPMP/ICH/141/95 Step 5 Guideline (Into Operation April 1996).

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: ICH. Topic S2B Genotoxicity: A Standard Battery for Genotoxicity Testing of Pharmaceuticals; CPMP/ICH/174/95 Step 5 Guideline (Into Operation March 1998).

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

(2E)-2-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-({4-methoxy-3-[3-(4-methylpiperazin-1-yl)propoxy]phenyl}amino)prop-2-enamide; propan-2-ol

EC Number:

700-456-7

Cas Number:

1333490-26-8

Molecular formula:

C26H31Cl2N5O4 · 1/2(C3H8O1)

IUPAC Name:

(2E)-2-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-({4-methoxy-3-[3-(4-methylpiperazin-1-yl)propoxy]phenyl}amino)prop-2-enamide; propan-2-ol

Details on test material:

Molecular formula C26H31Cl2N5O4
Molecular weight 548.46
Description Beige-yellow powder (determined at NOTOX)
Batch 09-002
Purity >92%
Composition 6.5% isopropanol as a hemi solvate

Method

Species / strain

Species / strain 1

Species / strain / cell type:

E. coli WP2 uvr A

Details on mammalian cell type (if applicable):

base-pair substitutions.

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 100

Details on mammalian cell type (if applicable):

Histidine mutation: hisG46/R-factor*
Mutation type: Base-pair substitutions

Species / strain 3

Species / strain / cell type:

S. typhimurium TA 1537

Details on mammalian cell type (if applicable):

Histidine mutation: hisC3076
Mutation type: Frameshift

Species / strain 4

Species / strain / cell type:

S. typhimurium TA 1535

Details on mammalian cell type (if applicable):

Histidine mutation: hisG46
Mutation type: Base-pair substitutions

Species / strain 5

Species / strain / cell type:

S. typhimurium TA 98

Details on mammalian cell type (if applicable):

Histidine mutation: hisD3052/R-factor*
Mutation type:Frameshift

Metabolic activation:

with and without

Metabolic activation system:

Rat liver microsomal enzymes were routinely prepared from adult male Wistar rats, which were obtained from Charles River, Sulzfeld, Germany.

Test concentrations with justification for top dose:

3, 10,33, 100, 333, 1000, 3330 and 5000 μg/plate

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

ETHANOL

Positive controls:

yes

Remarks:

with and without metabolic activation

Positive control substance:

other: 2-aminoanthracene

Results and discussion

Any other information on results incl. tables

Based on the results of this study it is concluded that WAY-189172 is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Based on the results of this study it is concluded that WAY-189172 is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.