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Toxicological information

Genetic toxicity: in vivo

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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 guidelineopen allclose all
Qualifier:
no guideline followed
Qualifier:
equivalent or similar to
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

Reference
Name:
Unnamed
Type:
Constituent
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 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.