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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Principles of method if other than guideline:
The test substance was evaluated, using autoradiographic technique, for its ability to induce unscheduled DNA synthesis (UDS) in the liver of rats. A single 6-hour exposure via whole-body inhalation was given to male rats at concentrations of 1000 and 1500 ppm. Hepatocytes were isolated at the end of the 6 hour exposure period and were assessed for the induction of UDS following autoradiography.
GLP compliance:
yes
Type of assay:
unscheduled DNA synthesis

Test material

Constituent 1
Chemical structure
Reference substance name:
Hexafluoropropene
EC Number:
204-127-4
EC Name:
Hexafluoropropene
Cas Number:
116-15-4
Molecular formula:
C3F6
IUPAC Name:
1,1,2,3,3,3-hexafluoroprop-1-ene
Details on test material:
- Purity: 99.99%

Test animals

Species:
rat
Strain:
other: Alpk:APSD
Sex:
male
Details on test animals or test system and environmental conditions:
Report available to DuPont was incomplete therefore some information noted as "not reported" may actually be available in the full report.

TEST ANIMALS
- Age at study initiation: 7-8 weeks of age (Phase I and II)
- Weight at study initiation: Not reported
- Assigned to test groups randomly: Not reported
- Fasting period before study: None
- Housing: Housed up to 5 per cage on mobile rat cage racks
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 40-70
- Air changes (per hr): 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: gas
Vehicle:
Vehicle was dried filtered air.
Details on exposure:
TYPE OF INHALATION EXPOSURE: whole body

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Test atmospheres were generated by passing liquid hexafluoropropylene through a copper coil immersed in a water bath maintained at 40°C. The resultant vapor was then metered to individual exposure chambers where it was diluted with dried filtered air to achieve the required concentrations.
- Exposure apparatus: Not reported
- Method of holding animals in test chamber: Not reported
- Source and rate of air: Not reported
- Method of conditioning air: Not reported
- System of generating particulates/aerosols: Not reported
- Temperature, humidity, pressure in air chamber: Not reported
- Air flow rate: Not reported
- Air change rate: Not reported
- Method of particle size determination: Not reported
- Treatment of exhaust air: Not reported

TEST ATMOSPHERE
- Brief description of analytical method used: Not reported
- Samples taken from breathing zone: Not reported
Duration of treatment / exposure:
Single 6-hour exposure
Frequency of treatment:
Once
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 1000, 1500 ppm (Phase II)
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
0, 878, 1412 ppm (Phase II)
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
0, 1000, 1500, 2000 ppm (Phase I)
Basis:

No. of animals per sex per dose:
Control and positive control: 2 animals
1000 and 1500 ppm HFP: 5 animals
Control animals:
other: Filtered air
Positive control(s):
1,2-dimethylhydrazine dihydrochloride (30 mg/kg)

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative

Any other information on results incl. tables

Nominal Concentration

Mean nuclear grain count (N)

Mean cytoplasmic grain count (C)

Mean (N-C)

Mean % cells in repair

0 ppm

1.7

3.5

-1.7

0

1000 ppm

1.9

3.7

-1.7

0

1500 ppm

1.9

3.8

-1.9

0

Positive control

(30 mg/kg DNH.2HCl)

14.5

2.1

12.4

87

Applicant's summary and conclusion

Conclusions:
The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
Executive summary:

The test substance was evaluated using an autoradiographic technique, for its ability to induce unscheduled DNS synthesis (UDS) in the liver of rats. A single 6-hour exposure via whole body inhalation was given to groups of male rats at target concentrations of 1000 and 1500 ppm. The latter concentration represents the maximum tolerated concentration for male rats based on patterns of clinical signs and lethalities over a four day observation period. Hepatocytes were isolated at the end of the 6-hour exposure period and were assessed for the induction of UDS following autoradiography.

The values recorded for the mean net grain counts and the percentage of cells in repair clearly show that the test substance did not induce DNA repair, as measured by UDS at either atmospheric concentration investigated.

 

Under the conditions of the test, the test substance did not induce DNA repair (as measured by unscheduled DNA synthesis) in the rat liver in vivo.