3,7-bis(diethylamino)phenoxazin-5-ium tetrachlorozincate (2:1)

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from publication

Data source

Reference

Reference Type:

publication

Title:

Microbial mutagenic effects of the DNA minor groove binder pibenzimol (Hoechst 33258) and a series of mustard analogues

Author:

Lynnette R. Ferguson *, William A. Denny

Year:

1995

Bibliographic source:

Mutation Research 329 (1995) 19-27

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: As mentiuon below

Principles of method if other than guideline:

To evaluate the mutagenic potential of N,N-BIS(2-CHLOROETHYL)-4-(5-((5-(4-METHYL-1-PIPERAZINYL)-1H-BENZIMIDAZOL-2-YL)METHYL)-1H-BENZIMIDAZO L-2-YL)-BENZENAMINE in Salmonella strains TA98, TA100 and TA102 by bacterial reverse mutation assay.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

N,N-bis(2-chloroethyl)-4-[6-[[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]methyl]-1H-benzimidazol-2-yl]aniline

Cas Number:

166546-20-9

Molecular formula:

C30H33Cl2N7

IUPAC Name:

N,N-bis(2-chloroethyl)-4-[6-[[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]methyl]-1H-benzimidazol-2-yl]aniline

Details on test material:

Name of test material (as cited in study report): N,N-BIS(2-CHLOROETHYL)-4-(5-((5-(4-METHYL-1-PIPERAZINYL)-1H-BENZIMIDAZOL-2-YL)METHYL)-1H-BENZIMIDAZO L-2-YL)-BENZENAMINE
- Molecular weight : 562.546g/mol
- Substance type: Organic

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA98, TA100 and TA102

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

other: Other: All are deep rough derivatives of the LT2 subline of Salmonella typhimurium.

Cytokinesis block (if used):

not specified

Metabolic activation:

without

Metabolic activation system:

not specified

Test concentrations with justification for top dose:

0,4,10,20,40,80 and 120 µg/plate

Vehicle / solvent:

Vehicle
- Vehicle(s)/solvent(s) used: DMSO

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: TA98: daunomycin and cl-nitro-o-phenylene diamine TA100: sodium azide TA102: bleomycin

Details on test system and experimental conditions:

Details on test system and conditions
METHOD OF APPLICATION: plate incorporation assay

DURATION
- Preincubation period:
- Exposure duration: 3days

NUMBER OF REPLICATIONS: All assays were performed in triplicate,
and repeated at least once

Rationale for test conditions:

Characteristics of these strains and the rationale for their selection

Evaluation criteria:

Evaluation was done considering a dose dependent increase in the number of revertants/plate.

Statistics:

Mean± standard deviation was observed.

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA98, TA100 and TA102

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: No mutagenic effect were observed

Any other information on results incl. tables

Bacterial mutagenicity data for compounds 2

Compound	Concentration (µg/plate)	Bacterial strains^a
2	0	60±9	187±4	296±41
	4	70±3	196±23	406±20
	10	62±7	162±21	417±2
	20	67±9	172±13	442±62
	40	52±7	226±23	442±43
	80	65±3	207±12	(194±60)
	120	(53±39)	(155±39)	(82±48)

 

a Strains of S. typhimurium (Maron and Ames, 1983).

b Results are mean values (two experiments, plated in triplicate) f standard deviation.

c Square brackets denote toxicity was becoming apparent on visual inspection of the plates.

Applicant's summary and conclusion

Conclusions:

(N-(2-CHLOROETHYL)-N-ETHYL-4-(5-(4-METHYL-1-PIPERAZINYL)(2,5'-BI-1H-BENZIMIDAZOL)-2'-YL)-BENZENAMINE(166546-18-5) was tested for its mutagenic potential in Salmonella strains TA98, TA100 and TA102.The test result was considered to be negative both in the presence and absence of metabolic activation.

Executive summary:

In Vitro Genetoxicity study for (N-(2-CHLOROETHYL)-N-ETHYL-4-(5-(4-METHYL-1-PIPERAZINYL)(2,5'-BI-1H-BENZIMIDAZOL)-2'-YL)-BENZENAMINE was assessed for its mutagenic potential. For this purpose are Bacterial Reverse mutation assay was performed in Salmonella strains TA98, TA100 and TA102. The test material was exposed at the concentration of 0,4,10,20,40,80 and 120µg/plate in the presence and absence of metabolic activation. No mutagenic effects were observed. Therefore (N-(2-CHLOROETHYL) -N-ETHYL -4-(5- (4-METHYL-1-PIPERAZINYL)(2,5'-BI-1H-BENZIMIDAZOL)-2'-YL)-BENZENAMINE was considered to be non mutagenic in Salmonella strains TA98, TA100 and TA102 by bacterial reverse mutation assay. Hence the substance cannot be classified as gene mutant in vitro.