Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
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 guideline study with acceptable restrictions. Report does not contain all study details.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
exposure duration 13 weeks
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
- Synonyms: Ricinus Oil, oil of Palma Christi, tangantangan oil, phorboyl, Neoloid
- Composition of test material, percentage of components: Triglyceride of fatty acids. Fatty acid composition is approximately 87% ricinoleic,
7% oleic, 3% linoleic, 2% palmitic, 1% stearic, and trace amounts of dihydroxystearic.
- Analytical grade: USP AA grade
- Source: Cas Chemical, Inc. (Bayonne, NJ, USA)
- Stability: The stability of the study material during the toxicology studies was monitored by determination of peroxide content and by high performance liquid chromatography. No deterioration of the castor oil study material was observed over the course of the studies.

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Simonsen Laboratories (Gilroy, CA, USA)
- Age at study initiation: 6 weeks
- Weight at study initiation: males: 22.6 - 23.0 g, females 17.2 - 17.7 g
- Fasting period before study:
- Housing: rats: 5 per cage, mice individually in Polycarbonate cages lined with heat-treated hardwood chips, covered with polyester filter sheets.
- Diet (e.g. ad libitum): Control feed (NIH 07) or diet formulations of castor oil were available ad libitum; feeders were changed twice per week throughout the study.
- Water (e.g. ad libitum): automatic watering system
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-76°F
- Humidity (%): 42% to 72%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: feed
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
Formulated diets were prepared by blending the appropriate amount of castor oil with a small quantity of feed to prepare a premix. The premix then was layered between the required amount of feed in a twin-shell blender and blended for 15 minutes to achieve a uniform mix. The homogeneity of castor oil in feed at 10% (100 mg/g) was determined by gravimetric analysis, and blends at 0.5% (5 mg/g) were determined by HPLC analysis. These concentrations of chemical in feed were found to be homogeneously distributed by this mixing procedure. The stability of the 0.5% dose level was determined using HPLC; it was found to be stable for at least 21 days when stored in the dark at 5°C and for 3 days when stored open to air and light in a rodent cage. During the studies, formulated diets were stored for no longer than 3 weeks at 5°C; feed hoppers in the animal cages were changed twice weekly.
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily
Post exposure period:
none
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 0.62, 1.25, 2.50, 5.00, 10.0 % (w/w)
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
0, 917, 2022, 3800, 7823, 15017 mg/kg bw/day
Basis:
other: actual ingested: male animals
Remarks:
Doses / Concentrations:
0, 1153, 2282, 5009, 9627, 16786 mg/ kg bw/day
Basis:
other: actual ingested: female mice
No. of animals per sex per dose:
10
Control animals:
yes, plain diet
Positive control(s):
- Route of administration: Male mice treated for 4 weeks with urethane in the drinking water (0.2%).
- Doses / concentrations: 0.2 %
These animals were not part of the 13-week study, but were added as a measure of quality control for the assay.

Examinations

Tissues and cell types examined:
Peripheral erythrocytes

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
No significant elevation in the frequency of micronucleated erythrocytes was observed in either male or female mice administered castor oil in dosed feed.

Any other information on results incl. tables

Table 1:Frequency of Micronuclei in Peripheral Blood Erythrocytes of B6C3F1 Mice Exposed to Castor Oil in Dosed Feed for 13 Weeks

 

sex

% in feed

% Normochromatic erythrocytes with micronuclei

(mean values)

% Polychromatic erythrocytes with micronuclei

(mean values)

Number of mice

f

0

0.11

1.20

10

f

0.6

0.13

1.18

10

f

1.3

0.11

1.16

10

f

2.5

0.13

1.24

10

f

5.0

0.09

1.40

9

f

10.0

0.09

1.21

10

m

0

0.10

1.18

10

m

0.6

0.09

1.21

10

m

1.3

0.07

1.11

9

m

2.5

0.09

1.11

10

m

5.0

0.09

1.49

10

m

10.0

0.06

1.00

10

m

Urethane 0.2 %

1.68

1.71

3

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative Castor oil did was not found to be genotoxic in this in vivo micronucleus assay in mice.