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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:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to established published methodology under the GLP regulations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Principles of method if other than guideline:
Petzold GL, Swenberg JA. Detection of DNA damage induced in vivo following exposure of rats to carcinogens. Cancer Res. 1978 Jun;38(6):1589-94.
GLP compliance:
yes
Type of assay:
other: Alkaline elution detection of DNA single breaks.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Liquid at room temperature.
Details on test material:
As per IUCLID5 Sections 1.1, 1.2. and 1.4..

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Male and female albino Wistar strain rats (6—8 weeks of age) were obtained from the Rodent Breeding unit of the Shell Toxicology Laboratory (Tunstall). The animals were individually housed during the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Test substance was dosed neat. DMSO was the vehicle for the positive control methyl methane sulphonate.
Details on exposure:
2,3-Epoxypropyl neodecanoate was administered without solvent carrier, to pairs of rats of both sexes (body wt. ranges: female, 200—250gm; male, 350—470gm), by the oral gavage route.
Duration of treatment / exposure:
6 hr
Frequency of treatment:
Once
Post exposure period:
None
Doses / concentrations
Remarks:
Doses / Concentrations:
Approximately 4850 mg/kg of body weight.
Basis:
nominal conc.
No. of animals per sex per dose:
2
Control animals:
yes, concurrent vehicle
Positive control(s):
Methyl Methanesulphonate at 300 mg/kg of body weight in DMSO.

Examinations

Tissues and cell types examined:
Liver cells
Details of tissue and slide preparation:
A 2gm sample of the liver from each animal was placed in a small beaker containing 2 ml of ice—cold homogenising medium (0.023M Na3 EDTA; 0.075M NaC1; pH 7.5). The tissue was gently squashed using the blunt end of a spatula (Cox et al., 1972) and the resultant cell suspension centrifuged (200 rpm, 1 mm) to sediment large pieces of liver.
Evaluation criteria:
No data
Statistics:
No data

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
Alkaline elution profiles of rat liver DNA, derived from solvent control animals, showed that the bulk of the DNA (greater than 90%) was retained on the membrane filter demonstrating little or no DNA damage. Treatment of the rats with a single oral dose of methyl methanesulphonate (300 mg/kg) gave single—strand damage which was manifested as a reduction in single strand molecular weight and observed as an increase in rate of elution of radioactivity upto seven-fold the solvent control value. 2,3-Epoxypropyl neodecanoate was administered to rats at a single oral dose level of approximately 4850 mg/kg and failed to produce any detectable DNA single—strand damage under these experimental conditions

Any other information on results incl. tables

Summary Data Tables of radioactivity and Alkaline Elution Profile figures are attached below.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Treatment of rats by oral gavage with 2,3-epoxypropyl neodecanoate at a dose level of approximately 4850 mg/kg of body weight did not result in the detection of DNA single strand breaks in the rat liver cells. DNA single strand breaks are the manifestaion of premutagenic and preclastogenic DNA lesions (Petzold and Swenberg, 1978; Fornace AJ et. al. 1980a; Fornace AJ Jr. et. al. 1980b; Bootsma and Hoeijmakers, 1994). Therefore, 2,3-epoxypropyl neodecanoate did not induce DNA damage that could result in gene-mutation and/or chromosome damage in vivo under the conditions of this study.
Executive summary:

When 2,3 -epoxypropyl neodecanoate was assessed in a rat oral gavage liver alkaline elution DNA damage study at a dose level of approximately 4850 mg/kg of body weight, no evidence of DNA single strand break formation was observed. Therefore, 2,3 -epoxypropyl neodecanoate did not cause DNA damage in rat liver cells and is not genotoxic in vivo under the conditions of this study. .