Quaternary ammonium compounds, di-C8-10-alkyldimethyl, chlorides

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 September 1986 - 20 January 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Read-across

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Version / remarks:

1984

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)

Version / remarks:

1984

GLP compliance:

yes

Type of assay:

other: Micronucleus assay

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

liquid

Specific details on test material used for the study:

Batch number: E06130085
Purity: 50.3%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CRL UK
- Assigned to test groups randomly: yes
- Fasting period before study: overnight prior to dosing
- Housing: plastic disposable cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Air changes (per hr): 30
- Photoperiod (hrs dark / hrs light): 12 hours artifical light/day

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

Sterile distilled water.

Details on exposure:

All animals in all groups were dosed by oral gavage with a standard volume of 20 ml/kg bw except that those receiving cyclophosphamide were dosed by IP injection.

Duration of treatment / exposure:

Single administration of dose.

Frequency of treatment:

Once.

Post exposure period:

48 hours

Doses / concentrations

Dose / conc.:

600 mg/kg bw/day (nominal)

No. of animals per sex per dose:

35/sex/dose

Control animals:

yes, concurrent vehicle

Positive control(s):

Cyclophosphamide
40 mg/kg bw/day
Prepared in a solution in sterile 0.9% saline at a concentration of 2.0 mg/ml.

Examinations

Tissues and cell types examined:

Both femurs were dissected from the animals and the proximal epiphysis was remoaved and the marrow eluted.

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: A preliminary toxicity test was conducted to evaluate the toxicity of the substance at various doses. The dose selcted for the main test was based on the lowest dose that did not result in any toxicity.

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Any other information on results incl. tables

Sampling time (hrs)	Treatment	Doseage (mg/kg bw)	Incidence of aberrant cells (%)
			Excluding gap damage	Including gap damage
6	Vehicle P0151	- 600	0 0	0 0
24	Vehicle P0151 Cyclophosphamide	- 600 40	0 0 5.6	0 0 5.6
48	Vehicle P0151	- 600	0 0	0 0

Applicant's summary and conclusion

Conclusions:

The substance was found to be negative for chromosomal damage in rat bone marrow in the in vivo cytogenetic test when administered orally by gavage.

Executive summary:

The substance was assessed for its potential to induce chromosomal damage in rats dosed by oral gavage at a dose of 600 mg/kg bw. The animals were observed for 48 hours for any signs of toxicity. Two hours prior to sacrifice the animals each received a dose of colchicine to arrest cells in the metaphase stage of cell division. At the end of the observation period the animals were terminated by cervical dislocation and the bone marrow from the femurs were removed for analysis. The substance was found to be negative for chromosomal damage in rat bone marrow in the in vivo cytogenetic test when administered orally by gavage.