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

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

There are no studies available for the assessment of in vitro genotoxicity of the substance. However, there is a reliable in vitro studies available for a structurally similar substance. The substance (at concentrations up to 50 µg/plate) was found to be negative for mutagenicity in the reverse mutation assay (Ames) employing Salmonella typhimurium strains TA1535, TA1537, TA98, TA102 and TA100 in the presence and absence of a metabolic activation system.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 March 2001 - 22 March 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not specified

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Metabolic activation system:

10% liver S9 in standard co-factors.

Test concentrations with justification for top dose:

Doses were selected based on a range finder study.
using 0.05 to 15 µg/plate without S9.
Dose range finder using 0.15 to 50 µg/plate with S9.

Vehicle / solvent:

Dimethyl sulphoxide.

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Vehicle

Positive controls:

yes

Positive control substance:

2-acetylaminofluorene

4-nitroquinoline-N-oxide

9-aminoacridine

N-ethyl-N-nitro-N-nitrosoguanidine

benzo(a)pyrene

other: 1,8-Dihydroxyanthraquinone

Evaluation criteria:

The test material should have induced a reproducible, dose-related and statistically (Dunnett's method of linear regression) significant increase in the revertant count in at least one strain of bacteria.

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Conclusions:

The substance (at concentrations up to 50 µg/plate) was found to be negative for mutagenicity in the reverse mutation assay employing Salmonella typhimurium strains TA1535, TA1537, TA98, TA102 and TA100 in the presence and absence of a metabolic activation system.

Executive summary:

In the in vitro genotoxicity study (Ames test) the substance was tested for mutagenicity in Salmonella typhimurium strains TA1535, TA1537, TA98, TA102 and TA100. Concentrations of up to 50 μg/plate were tested. No evidence of mutagenic activity was seen at any concentration of the substance in the presence and absence of a metabolic activation system. It was concluded that the substance showed no evidence of mutagenic activity in this bacterial system under the test conditions employed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

There are no studies available for the assessment of in vivo genotoxicity of the substance. However, there is a reliable in vivo study available for a structurally similar substance. 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.

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Version / remarks:

1984

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

Specific details on test material used for the study:

Batch number: E06130085
Purity: 50.3%

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

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

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.

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.

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Justification for classification or non-classification

Based on the findings of three reliable in vitro and one reliable in vivo genotoxicity studies conducted on a structurally similar substance, classification of the substance is not justified.