Naphtha (Fischer-Tropsch), light, C4-10-branched and linear

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:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
[Describe why the read-across can be performed (e.g. common functional group(s), common precursor(s)/breakdown product(s) or common mechanism(s) of action]

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
[Provide here, if relevant, additional information to that included in the Test material section of the source and target records]

3. ANALOGUE APPROACH JUSTIFICATION
[Summarise here based on available experimental data how these results verify that the read-across is justified]

4. DATA MATRIX

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

not applicable

GLP compliance:

yes

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Naphtha (petroleum), light alkylate

EC Number:

265-068-8

EC Name:

Naphtha (petroleum), light alkylate

Cas Number:

64741-66-8

IUPAC Name:

Naphtha (petroleum), light alkylate

Details on test material:

- Name of test material (as cited in study report): Naphtha (petroleum), light alkylate [CAS 64741-66-8]
- Test substance is closely related to Naphtha (Fischer-Tropsch), light, C4-10 - branched and linear; it is defined as : 'A complex combination of hydrocarbons produced by the distillation of the reaction products of isobutane with monoolefinic hydrocarbons usually ranging in carbon numbers from C3 through C5. It consists of predominantly branched chain saturated hydrocarbons having carbon numbers predominantly in the range of C7-C10 and boiling in the range 90-160°C (194-320°F).'

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle used: corn oil

Frequency of treatment:

single treatment

Post exposure period:

6, 24 and 48 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.3, 1.0, 3.0 g/kg
Basis: nominal conc.

No. of animals per sex per dose:

5/sex/dose

Control animals:

yes

Positive control(s):

- Positive control group: 500 µg/kg of triethylenemelamine (TEM), group exposed for 24 hours.
- Negative control group: corn oil (5 ml/kg body weight).

Examinations

Tissues and cell types examined:

bone marrow

Details of tissue and slide preparation:

Immediately after sacrifice bone marrow was obtained from the femurs of the animals. The marrow was washed and the cells were fixed before being spread on slides (at least 3 from each animal) for examination. Slides were scored for chromosomal aberrations. Where possible, a minimum of 50 metaphase cells from each animal were examined and scored for chromatid and chromosome gaps and breaks, fragments, structural rearrangements and ploidy (1-3). A mitotic index (= No. of cells in mitosis/500 counted X 100) was calculated and recorded.

Evaluation criteria:

The data were evaluated according to the following criteria:
For the test to be considered to be valid, the % of cells in the negative control group demonstrating aberrations of any type, other than gaps, must not exceed 4%. The % of cells with aberrations in the positive control group must be statistically increased (p=0.05) relative to the vehicle control using Chi-square statistics.
The test material is considered positive when the % of cells with aberrations in any treatment group is significantly increased (p = 0.05) relative to the vehicle control using Chi-square analysis and the number of aberrations per cell is also significantly increasd (p =0.05) relative to the vehicle control using t-test statistics.

Statistics:

see "Evaluation criteria"

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

In the cytogenetics assay, 5 of 18 males and 4 of 18 females receiving 3 g/kg Light Alkylate Naphtha died within 3 days. At this dose level, there was a weight loss of 10% and 9% in males and females respectively within 48 hours of administration. Other signs of toxicity included piloerection, crusty eyes and noses and excess lacrimation. No sex-related differences were noted in the study and therefore the data for males and females were combined for the cytogenetics evaluation.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Naphtha (petroleum), light alkylate (EC 265-068-8) did not induce bone marrow chromosomal aberrations in male or female Sprague-Dawley rats.

Executive summary:

Naphtha (petroleum), light alkylate (EC 265-068-8) was tested in a Sprague Dawley rat chromosome aberration assay [15/sex/group] at doses of 0.3, 1.0, and 3.0 g/kg in corn oil, administered intraperitoneally in a single dose. Two to four hours prior to sacrifice the rats were given a single intraperitoneal dose of colchicine (1 mg/kg). Animals [5/sex/group/time] were sacrificed at 6, 24 and 48 hrs post dose. A group of 5 animals of each sex to be used as positive controls was dosed with triethylenemelamine (TEM) at a level of 0.5 mg/kg and these animals were killed at 24 hours postdose. Deaths occurred in both male [5/18] and females [4/18] in the highest dose group and a 9-10% body weight loss was observed in surviving rats of both sexes. Other signs of toxicity included piloerection, crusty eyes and noses and excess lacrimation. Bone marrow was harvested from the femurs of treated rats, processed and stained for cytogenetic examination [a minimum of 50 metaphase spreads per animal]. No chromosome aberrations, rearrangements, or cell cycle disruption were observed in any dose group.