D-gluconic acid, compound with N,N''-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediamidine (2:1)

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:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

No official statement concerning GLP status, but study was controlled and signed by responsible study director. Only male mice were used. Cells from bone marrow were collected only once, at 6 h after the final treatment. Although there was no mortality at any dose, results were only reported for 6/10 treatment group. However, the presented results were consistent and clearly negative throughout. The positive control gave a positive response indicating the principle validity of the assay conditions. In summary, the results of the study are considered relevant as supportive data for the assessment of the genotoxicity of chlorhexidine digluconate.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1983

Reference 2

Reference Type:

publication

Title:

Final report on the safety assessment of chlorhexine/chlorhexidine diacetate/chlorhexidine dihydrochloride/chlorhexidine digluconate

Author:

Willis L

Year:

1993

Bibliographic source:

J Am Coll Toxicol 12, 201-223

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

no

Remarks:

No official statement concerning GLP status, but study was controlled and signed by responsible study director

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

D-gluconic acid, compound with N,N''-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediamidine (2:1)

EC Number:

242-354-0

EC Name:

D-gluconic acid, compound with N,N''-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediamidine (2:1)

Cas Number:

18472-51-0

Molecular formula:

C22H30Cl2N10.2C6H12O7

IUPAC Name:

N',N'''''-hexane-1,6-diylbis[N-(4-chlorophenyl)(imidodicarbonimidic diamide)] - D-gluconic acid (1:2)

Test animals

Species:

mouse

Strain:

Swiss

Sex:

male

Details on test animals or test system and environmental conditions:

Source: C.N.R.S, Orleans la Source
Age at study initiation: no data
Weight at study initiation: 30 g

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

Vehicle: DMSO/glycerol (1+4 v/v)
Concentration in vehicle: no data

Details on exposure:

Total volume applied: 10 or 20 mL/kg bw

Duration of treatment / exposure:

Number of applications: 2
Interval between applications: 24 h

Post exposure period:

6 h

Doses / concentrations

Remarks:

Doses / Concentrations:
2 * 10, 2 * 20 or 2 * 30 mg/kg bw
Basis:

No. of animals per sex per dose:

at least 5 m per dose and sampling time

Control animals:

yes, concurrent vehicle

Positive control(s):

Substance used as Positive Control: 2 * 2 mg/kg bw Mitomycin C (vehicle: water)

Examinations

Tissues and cell types examined:

Tissue: bone marrow

Details of tissue and slide preparation:

Maximum tolerable dose: 30 mg/kg bw
Number of animals: all animals
Number of cells: 2000
Time points: 6 h after last treatment
Type of cells: erythrocytes in bone marrow

Evaluation criteria:

Parameters: numbers and types of structural aberrations and ratio polychromatic/normochromatic erythrocytes

Statistics:

not further specified

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

pilorection, dyspnoea, ataxie, pain at injection site

Vehicle controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative

No increase of micronuclei in bone marrow cells at any dose above vehicle control. The positive control (Mitomycin) gave the expected positive response.

Executive summary:

Micronucleus test with male Swiss mice with intraperitoneal administration of chlorhexidine digluconate using three different dose levels and two treatments at 24 h interval. Assessment of micronuclei in bone marrow 6 h after the second treatment. Under the conditions of the assay, chlorhexidine digluconatedid not cause an increase in the frequency of micronuclei in bone marrow cells of male mice.