Fuel oil, residual

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian cell study: DNA damage and/or repair

Remarks:

Type of genotoxicity: DNA damage and/or repair

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: Near-guideline, GLP-compliant study. Adequate for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

no guideline followed

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OTS 798.5915 (In Vivo Sister Chromatid Exchange Assay)

Principles of method if other than guideline:

Sister chromatid exchange in mouse bone marrow cells was determined 4 hr after a single i.p. injection of test substance.

GLP compliance:

yes

Type of assay:

sister chromatid exchange assay

Test material

Test material information

Constituent 1

Reference substance name:

64741-62-4

Cas Number:

64741-62-4

IUPAC Name:

64741-62-4

Test material form:

other: Viscous hydrocarbon liquid

Details on test material:

Catalytic cracked clarified oil (CCCO), API 81-15, CAS No. 64741-62-4.
Dark brown viscous liquid

Data below taken from American Petroleum Institute (1985d). In-vivo sister chromatid exchange (SCE) assay. Catalytic cracked clarified oil, API Sample 81-15, CAS No. 64741-62-4. Testing laboratory: Microbiological Associates Inc., 5221 River Road, Bethesda, MD 20816, USA. Owner company: American Petroleum Institute, 2101 L Street, Northwest, Washington, DC 20037, USA. Study number: 32-32754. Report date: 1985-11-25.

Gravity API: 0.1
Specific gravity: 1.0753
Viscosity in SUS @ 210 °F: 56.1
Flash Point °F: 396
Sulfur wt %: 1.1
Pour Pt °F: 35
Asphaltenes % (MN 596): 4.2
Carbon residue wt %: 4.6
Ash wt %: 0.05

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Frederick Cancer Research Facility, Frederick, MD, USA.
- Age at study initiation: 9-10 wk
- Weight at study initiation: males 20-25 g, females 16-21 g

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

corn oil

Details on exposure:

Single i.p. injection in corn oil, 10 mg/Kg bw

Duration of treatment / exposure:

Bone marrow collected 20-22 hr post-treatment

Frequency of treatment:

Single treatment

Post exposure period:

20-22 hr

Doses / concentrations

Remarks:

Doses / Concentrations:
0.4, 2.0 and 4.0 g/Kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

5/sex/dose level

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide, 10 mg/Kg bw

Examinations

Tissues and cell types examined:

femural bone marrow cells

Details of tissue and slide preparation:

TREATMENT AND SAMPLING TIMES:
BRdU pellets implanted subcutaneously in lower abdomen 4 hr prior to treatment
Animals sacrificed 20-22 hr post-treatment.
Colchicine (1 mg/kg i.p.) given 2-4 hr prior to sacrifice.

DETAILS OF SLIDE PREPARATION:
Air-dried preparations of femural bone marrow cells stained with Hoechst 33258/Giemsa and mounted for microscopic examination.

METHOD OF ANALYSIS:
A minimum of 50 second-division metaphase spreads examined blind under oil immersion and scored for SCEs and chromosome number. The percentage cells in of first, second and third-division metaphase (100 cells) and the mitotic index (500 cells) were also determined.

Evaluation criteria:

Results were considered positive if a statistically significant dose-related increase in SCE was present

Statistics:

Results analysed by ANOVA and the Students Range Test.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

positive

Toxicity:

yes

Remarks:

>4 g/Kg bw

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY
- Dose range: 0, 1, 2, 4, 6, 8
- Mortality: 0/10, 0/10, 0/10, 1/10, 2/10, 9/10
An upper dose of 4 g/Kg bw selected (- low level of mortality, minimal effect on body weight)

Any other information on results incl. tables

Results were positive.

The test substance produced a small but significant dose-dependent increase in mouse bone marrow SCEs compared with the corn oil control.

The positive control group gave the expected results.

 

Treatment	Mean (SD) SCE/cell/mouse
	male	female
0.0	5.43 (0.60)	6.73 (0.68)
0.4	7.43 (1.00)	7.22 (1.17)
3.0	8.43 (1.15) *	8.06 (1.36)
4.0	8.83 (1.60) *	9.26 (0.95) *
+ve control	24.61 (7.39) *	31.60 (7.24) *

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): positive
The test substance induced SCE in mouse bone marrow following single i.p. injection.

Executive summary:

The potential of catalytic cracked clarified oil to induce sister chromatid exchanges in mouse bone marrow was investigated in vivo in a GLP-compliant study. Animals received a single i.p. treatment of 0 (corn oil), 0.4, 2.0 or 4.0 g test substance /Kg bw/d 20-22 hr prior to sacrifice, with positive controls given a single i.p. treatment of 0 or 10 mg/Kg cyclophosphamide. Microscopic examination of a minimum of 50 second-division metaphase spreads under oil immersion revealed a significant and dose-related increase in SCEs per metaphase in both sexes; a satisfactory response was obtained in the positive control group.

The results demonstrated that test substance had a clear potential to induce SCEs in femoral bone marrow in vivo.