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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study reported in peer-reviewed journal article.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Version / remarks:
EPA/TSCA
GLP compliance:
yes
Type of assay:
mammalian germ cell cytogenetic assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Composition of test material, percentage of components: <1% C9, 22% C10, 43% C11, 35% C12, 1% C13, <1% C14; average C11.26
- Analytical purity: 98.5%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Frequency of treatment:
Single treatment
Post exposure period:
animals were sacrificed at 6, 12, 24, and 48 hrs after exposure (6 animals at each sacrifice)
Doses / concentrations
Remarks:
Doses / Concentrations:
2000, 6000, 12,700 mg/kg
Basis:
actual ingested
No. of animals per sex per dose:
18-24 male and female rats, negative control consisted of 24 male and 24 females
Control animals:
yes, concurrent vehicle
Positive control(s):
6 males and 6 females were given 40 mg/kg of cyclophosphamide and sacrificed at 24 hrs.

Examinations

Tissues and cell types examined:
bone marrow cells (60 cells per animal)
Details of tissue and slide preparation:
2 mg/kg colchicine was administered 2 hrs before termination. Immediately after termination, cells were collected and processed for slide preparation.
Statistics:
Kruskal-Wallis nonparametric analysis of variance

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
lowest dose producing toxicity = 6000 mg/kg
Additional information on results:
No effect on mitotic index or P/N ratio. Significant mean body weight loss in animals treated with 12,700 mg/kg bw. Significant weight loss was also seen in males at the 6000 mg/kg dose level.

Any other information on results incl. tables

Results of in vivo bone marrow assay

Concentration

Chromatid gaps

Chromosome gaps

Chromatid breaks

Chromosome breaks

Exchanges

% Aberrant cells

6-hrs

Corn oil

0

0

0

0

0

0

2,000 mg/kg

0

0

0

0

0

0

6,000 mg/kg

0

0

0

0

0

0

12,700 mg/kg

0

0

0

0

0

0

12 hrs

Corn oil

2

1

0

0

0

0.17

2,000 mg/kg

2

0

2

0

0

0.35

6,000 mg/kg

0

0

0

0

0

0

12,700 mg/kg

2

0

5

0

0

1.00

24 hrs

Corn oil

1

0

0

0

0

0

2,000 mg/kg

0

0

1

0

0

0.16

6,000 mg/kg

2

0

1

0

0

0.18

12,700 mg/kg

0

0

2

0

1

0.49

CP 40 mg/kg

6

1

68

3

9

14.80

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Alkylate 215 is not genotoxic in the rat bone marrow chromosome aberration assay.
Executive summary:

This study examined the potential of the test substance to cause chromosome aberrations in vivo. Groups of 18 -24 male and female rats were given doses of 2000, 6000, or 12,700 mg/kg of test substance. Negative control animals were given corn oil (vehicle) only. Positive control animals were given 40 mg/kg cyclophosphamide. Animals were sacrificed at 6, 12, 24, and 48 hrs after exposure. The bone marrow cells were then removed and examined for chromosome aberrations. The test substance was toxic (reduced body weight) at the 12,700 mg/kg dose in both males and females. Males in the 6000 mg/kg dose level also showed weight loss. No significant increase in chromosomal aberrations was seen in any treatment group. The test substance is not clastogenic.