2,5-diphenyloxazole

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian cell study: DNA damage and/or repair

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Not specified

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Data source

Reference

Reference Type:

publication

Title:

Gentoxic and radioprotective properties of 2,5-Diphenyloxazole derivatives on mouse DNA structure

Author:

Zhizhina et al

Year:

2005

Bibliographic source:

Russian Academy of Sciences, Radiation Biology Radioecology, 45(1), 56-62

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The study was primarily conducted on Balb/c female mice. each control or experimental group consisted of 8-10 animals. The mice were exposed to a 12 cGy X-ray in a RUM-17 X-ray unit (210 kV voltage, 15 mA current) with a dose rate of 44 cGy/min. To study the genotoxic properties of the compounds, they were administered intraperitoneally to the animals in one of four concentrations 30 minutes prior to sacrificing the animals and removing the spleen. To study the radioprotective properties of the compounds, they were administered to the animals in the same doses 30 minutes prior to a 12cGy irradiation dose, and the mice were sacrificed and the spleen removed 60 min after irradiation. Measurement of the DNA characteristics was therefore regarded as corresponding to 30 and 90 min after administration of the compounds.Since all the compounds are hydrophobic, they were administered as a suspension in a mixture: Tween 80 – acetone-water = 0.3 : 1.0 : 8.7.
DNA was extracted from the spleen by the Marmur method and enzymatically purified from RNA and protein impurities by incubation with RNAase (100 μg/ml) 60 min and pronase E (150 μg/ml) 90 min at 37°C.. Final RNA and protein impurity content did not exceed 1-2%.
Standard conditions were used for 0.7% agarose gel electrophoresis in a neutral buffer. The gels, stained with ethidium bromide (0.5 μg/ml, Serva), were photographed in ultraviolet light.

GLP compliance:

not specified

Type of assay:

mammalian comet assay

Test material

Test material information

1

Reference substance name:

2,5-diphenyloxazole

EC Number:

202-181-3

EC Name:

2,5-diphenyloxazole

Cas Number:

92-71-7

Molecular formula:

C15H11NO

IUPAC Name:

2,5-diphenyl-1,3-oxazole

Test material form:

solid: crystalline

Details on test material:

Expiry date:01 February 2021
Storage conditions: Room temperature in the dark
Batch 21-16131

Test animals

Species:

mouse

Strain:

Balb/c

Sex:

female

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

Tween 80 – acetone-water = 0.3 : 1.0 : 8.7.

Duration of treatment / exposure:

Administered intraperitoneally to the animals in one of four concentrations (Table 1) 30 minutes prior to sacrificing the animals and removing the spleen.

Frequency of treatment:

Single exposure.

Post exposure period:

30 minutes and 90 minutes.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

1 mg/kg bw/day

Doses / concentrations 2

Dose / conc.:

10 mg/kg bw/day

Doses / concentrations 3

Dose / conc.:

30 mg/kg bw/day

Doses / concentrations 4

Dose / conc.:

60 mg/kg bw/day

No. of animals per sex per dose:

8 - 10 animals/dose.

Control animals:

yes

Examinations

Tissues and cell types examined:

Spleen cells.

Results and discussion

Test results

Key result

Sex:

female

Genotoxicity:

positive

Toxicity:

not examined

Vehicle controls validity:

valid

Negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

The substance affected the structural characteristics of mouse spleen DNA. The dose-dependence of these characteristics was nonlinear (often extreme).

Any other information on results incl. tables

Dose (mg/kg bw)	Number of double strand breaks
0	0.03±0.02
1	0.40±0.05
10	0.54±0.06
30	0.45±0.04
60	0.90±0.09

Applicant's summary and conclusion

Conclusions:

The substance has been shown to cause DNA double strand breaks and DNA damage (as evidenced by binding of DNA to nitrocellulose membrane) in mice administered intraperitoneal doses of 1, 10, 30 and 60 mg/kg bw/day. Therefore, the substance is expected to be a genotoxin.

Executive summary:

The substance was administered as a single dose of 1, 10, 30 or 60 mg/kg bw/day to mice via intraperitoneal injection. The animals were sacrificed 30 minutes post-exposure and the spleen was removed for examination. DNA extracted from the spleen was run on agarose gel under electrophoresis to assess DNA strand breaks. To evaluate the conformational state of DNA the solutions were filtered through nitrocellulose filters to provide inforamtion about the extent of DNA damage caused by the substance. The substance affected the structural characteristics of mouse spleen DNA in a dose-dependent manner, however the dose-dependency was non-linear. The substance was shown to cause DNA double strand breaks at all doses administered. Therefore, the substance is expected to be a genotoxin.