Propylene carbonate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro DNA damage and/or repair study

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 15, 1985 - August 13, 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 482 (Genetic Toxicology: DNA Damage and Repair, Unscheduled DNA Synthesis in Mammalian Cells In Vitro)

GLP compliance:

yes (incl. QA statement)

Type of assay:

DNA damage and repair assay, unscheduled DNA synthesis in mammalian cells in vitro

Test material

Test material information

Constituent 1

Reference substance name:

Propylene carbonate

EC Number:

203-572-1

EC Name:

Propylene carbonate

Cas Number:

108-32-7

Molecular formula:

C4H6O3

IUPAC Name:

4-methyl-1,3-dioxolan-2-one

Test material form:

liquid

Method

Species / strain

Species / strain / cell type:

hepatocytes: Adult male F344 rats

Details on mammalian cell type (if applicable):

- Type and identity of media: WME

Metabolic activation:

without

Test concentrations with justification for top dose:

40, 133, 400, 1333, 4000 ug/well

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water

Controls

Untreated negative controls:

yes

Remarks:

untreated WME only

Negative solvent / vehicle controls:

yes

Remarks:

water

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-acetylaminofluorene

Remarks:

final concentration of 1 x 10 E-5 M

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium


DURATION
- Exposure duration: Cells were exposed to test substance in 10 uCi/ml 3[H] thymidine-WME for 18 to 20 hours.
- Fixation time (start of exposure up to fixation or harvest of cells): Cells were fixed 18 to 20 hours after inititation of exposure to test substance.


NUMBER OF REPLICATIONS: 3


NUMBER OF CELLS EVALUATED: a total of 60 cells per dose point were counted

DETERMINATION OF CYTOTOXICITY
- Method: unscheduled DNA repair synthesis is evidenced by a net increase in black silver grains over the nucleus. This is quantified by determining nuclear and cytoplasmic grain counts (Artek 880 automated colony counter with microscopic / video camera attachment)

Evaluation criteria:

The test substance is reported positive when the minimum net grain count of 5 per nucleus was consistently observed in triplicate wells. Where possible, a dose response profile should be observed.

Results and discussion

Test results

Species / strain:

hepatocytes: Adult male F344 rats

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES:
following doses were tested: 0.13, 0.4, 1.3, 4.0, 13, 40, 133, 400, 1333 and 4000 ug/well.
The test article was nontoxic.

COMPARISON WITH HISTORICAL CONTROL DATA:
The negative and positive control values were within the acceptable range of mean historical data

ADDITIONAL INFORMATION ON CYTOTOXICITY:
no cytotoxicity observed.

Remarks on result:

other: all strains/cell types tested

Any other information on results incl. tables

None of the treated cultures produced net nuclear grain counts that were substantially greater than the solvent control (water).

Applicant's summary and conclusion

Conclusions:

Result of the test: negative without metabolic activation
Under the conditions of this study, the test substance was not genotoxic in the hepatocyte primary culture/DNA repair test. This conclusion is based upon the finding of the inability of the test substance to produce a mean nuclear grain count of 5 or greater than the vehicle control mean net nuclear grain count at any level of concentration.