Benzene, C15-16-alkyl derivs.

Genetic toxicity: in vivo

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

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

Test material information

Constituent 1

Reference substance name:

Alkylate 215

IUPAC Name:

Alkylate 215

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:

In cases where no data were available on the target substance, Benzene, C15 -16 -alkyl derivs., data were read across from a structurally related material (the test substance).

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.