Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: DNA damage and/or repair
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP complaint, guideline study with minor restrictions, adequate for assessment. For read across justification see Section 13.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Principles of method if other than guideline:
Smears were prepared from peripheral blood samples obtained by cardiac puncture of dosed and control animals at the termination of the 13 week study. Slides were stained with Hoechst 33258/pyronin Y (MacGregor et al., 1983). At least 2000 PCE and 10000 NCE from each animal were scored for micronuclei.
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Castor oil
- Lot/batch No.: L-5G30-01
- Molecular formula (if other than submission substance): C55 H100 O9
- Molecular weight (if other than submission substance): 905.41
- Smiles notation (if other than submission substance): O=C(CCCCCCC=CCC(CCCCCC)O)OC(COC(=O)(CCCCCCCC=CCC(O)CCCCCC))C(=O)(OCCCCCCCC=CCC(O)CCCCCC)

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Simonsen Laboratories, Gilroy, CA
- Age at study initiation: 6 weeks
- Weight at study initiation: No data
- Assigned to test groups randomly: Yes, weight randomised
- Fasting period before study: No
- Housing: Individually caged
- Diet (e.g. ad libitum): Yes, NIH 07 standard rodent diet, ad libitum
- Water (e.g. ad libitum): Yes, ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 42 - 72
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light):

IN-LIFE DATES: From: April 1988 To: July 1988

Administration / exposure

Route of administration:
oral: feed
Vehicle:
Not applicable
Details on exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): No data but no longer than 21 days (limit of stability)
- Mixing appropriate amounts with (Type of food): A premix of the substance and powdered diet was prepared for each dosed feed formulation. Additional portions of feed were added and the premix stirred after each addition. For the final preparation, the premix and additional feed were layered in a twin-shell blender and blended for 15 minutes
- Storage temperature of food: 5 deg C, in the dark
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
Continuous (via diet)
Post exposure period:
None
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.00, 0.62, 1.25, 2.50, 5.00 and 10.00%
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
0, 1035, 2152, 4404, 8725 and 15901 mg/kg body weight/day
Basis:
other: average of individual consumption values
No. of animals per sex per dose:
10 males / 10 females
Control animals:
yes, plain diet
Positive control(s):
Male mice treated for 4 weeks with urethane in the drinking water (0.2%).

Examinations

Tissues and cell types examined:
Erythrocytes
Details of tissue and slide preparation:
TREATMENT AND SAMPLING TIMES: Following 13 weeks exposure

DETAILS OF SLIDE PREPARATION: Slides stained with Hoechst 33258/pyronin Y

METHOD OF ANALYSIS: Microscopic examination of stained slides, at least 2000 PCE and 10000 NCE from each animal scored for micronuclei.
Statistics:
Significance of any difference from controls assessed using Shirley's test

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
not specified
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
No induction of micronuclei was observed in peripheral blood erythrocytes of male and female B6C3F1 mice sampled on termination of a 13-week repeated dose toxicity study following administration of the substance in the diet at concentrations of up to 10%.
Executive summary:

No induction of micronuclei was observed in peripheral blood erythrocytes of male and female B6C3F1mice sampled on termination of a 13-week repeated dose toxicity study following administration of the substance in the diet at concentrations of up to 10%.