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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
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 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
yes
Remarks:
: lack of cytotoxicity data
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test

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.

Method

Target gene:
Not applicable.
Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Details on mammalian cell type (if applicable):
no data
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254-induced rat liver S9 mix + cofactors
Test concentrations with justification for top dose:
0, 1600, 3000, 5000 µg/mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Chinese hamster ovary cells were incubated with study compound or solvent (dimethylsulfoxide).
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
Migrated to IUCLID6: mitomycin C (-9); cyclophosphamide (+S9)
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium;

DURATION
- Exposure duration: 10 h without S9, 2 h with S9

SPINDLE INHIBITOR (cytogenetic assays): colcemid
STAIN (for cytogenetic assays): Giemsa

Cells were arrested in first metaphase by addition of colcemid and harvested by mitotic shake off, fixed, and stained
in 6% Giemsa.

In the absence of S9, cells were incubated with study compound or solvent for 10 h at 37°C. Cells were then
washed and fresh medium containing colcemid was added for an additional 3 h followed by harvest.

In the presence of S9, cells were incubated with study compound or solvent for 2 h at 37°C. Cells were then
washed, medium without test compound was added, and incubation was continued for 10 h. Colcemid was added
for the last 3 h of incubation before harvest. S9 was from the livers of Aroclor 1254-induced male Sprague Dawley
rats.

Results and discussion

Test results
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
Castor oil did not induce chromosome aberrations in Chinese hamster ovary cells treated with concentrations up to 5000 mg/mL with and without S9 mix.

Any other information on results incl. tables

Table 1:Summary of results of the chromosome aberration study with Castor oil*

 

 

S9

Harvest time

(h)

Conc.

in μg/mL

Cells scored

No of aberrations

Aberrations /Cell

Percent Cells with aberrations

DMSO

-

12

 

200

2

0.01

1.0

Test item

-

12

1600

200

1

0.01

0.5

Test item

-

12

3000

200

2

0.01

1.0

Test item

-

12

5000

200

1

0.01

0.5

Pos. control

(MMC)

-

12

0.0625

200

48

0.24

15.5

DMSO

+

13

 

200

3

0.02

1.5

Test item

+

13

1600

200

4

0.02

2.0

Test item

+

13

3000

200

4

0.02

2.0

Test item

+

13

5000

200

3

0.02

1.5

Pos. control

(CP)

+

13

2.5

200

44

0.22

16.0

MMC = Mitomycin C

CP = Cyclophosphamide

*In the absence of S9, cells were incubated with study compound or solvent for 10 h at 37°C. Cells were then washed and fresh medium containing colcemid was added for an additional 3 h followed by harvest. In the presence of S9, cells were incubated with study compound or solvent for 2 h at 37°C. Cells were then washed, medium without test compound was added, and incubation was continued for 10 h. Colcemid was added for the last 3 h of incubation before harvest.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative Castor oil did not induce chromosome aberrations in vitro in Chinese Hamster Ovary cells.