2,2-dichloro-1,1,1-trifluoroethane

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: High because a scientifically defensible and guideline method was used. Critical study for SIDS endpoint. Only study summary reviewed from secondary source.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

HCFC-123 was evaluated for genotoxic activity in an chromosome aberration study with
peripheral blood lymphocytes from male Sprague-Dawley rats that had been exposed (6 h/d, 7 d/wk) over a period of 14 weeks to HCFC-123 concentrations of 300, 1,000 or 5,000 ppm HCFC-123. Chromosome aberrations were determined in the high dose group.

GLP compliance:

yes

Type of assay:

mammalian germ cell chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

2,2-dichloro-1,1,1-trifluoroethane

EC Number:

206-190-3

EC Name:

2,2-dichloro-1,1,1-trifluoroethane

Cas Number:

306-83-2

Molecular formula:

C2HCl2F3

IUPAC Name:

2,2-dichloro-1,1,1-trifluoroethane

Constituent 2

Reference substance name:

Ethane,2,2-dichloro-1,1,1-trifluoro-

IUPAC Name:

Ethane,2,2-dichloro-1,1,1-trifluoro-

Details on test material:

- Name of test material (as cited in study report): Ethane,2,2-dichloro-1,1,1-trifluoroethane- HCFC-123
- Purity: not specified

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Administration / exposure

Route of administration:

inhalation

Details on exposure:

Male rats (10/exposure level), housed at Huntingdon Research Centre (HRC), were bled following exposure to the test chemical or negative control agent. Blood was taken from each rat and dispensed into a culture tube containing sodium heparin. Tubes were agitated for at least 1 minute, then held at ambient temperature prior to collection, during transportation to Hazelton Microtest, and prior to establishment in culture.

Duration of treatment / exposure:

14 weeks

Frequency of treatment:

6 hours/day, 7 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 300, 1000, 5000 ppm
Basis:
no data

No. of animals per sex per dose:

10 per exposure level

Control animals:

yes, concurrent no treatment

other: positive control 5 rats received a single i.p. injection of 10 ml/kg cyclophosphamide

Positive control(s):

A concurrent positive control group of 5 male rats were dosed intraperitoneally with 20 mg/kg cyclophosphamide (CPA) at Hazelton Microtest. These animals were bled 6 hours later on the same day that animals were sampled at HRC.

Examinations

Tissues and cell types examined:

Two blood cultures were established for each animal from all treatment and control groups.

Details of tissue and slide preparation:

Cultures contained 1 mL of washed blood, Hepes-buffered medium containing fetal calf serum, and gentamycin. Phytohaemagglutinin was included in the culture medium to stimulate the lymphocytes to divide. Cultures were rocked continuously during incubation, and harvested 49 hours following initiation. Colchicine was added 1.5 hours prior to harvest to arrest dividing cells in metaphase. Slides were prepared and stained with Giemsa stain. Fifty metaphases were analyzed per culture for negative and positive control animals and animals receiving 5000 ppm HCFC-123. Mitotic indices based on a total of 500 cells per culture were determined.

Evaluation criteria:

The test chemical was considered to be clearly positive if statistically significant increases in the proportion of cells with structural aberrations occurred at 1 (or more) concentration(s). Cells with exchange aberrations or cells with greater than 1 aberration occur very infrequently in negative control cultures. Their appearance was therefore to be considered of biological significance.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

When the data from all animals in each group were pooled, fewer cells with aberrations were apparent in the group receiving 5000 ppm HCFC-123 than in the concurrent negative control group. The decrease was small, but statistically significant.

There was no evidence of a reduction in mitotic index in any 5000 ppm HCFC-123-treated animal.

A clear statistically significant increase in cells with aberrations was seen in cultures from rats receiving CPA.

Applicant's summary and conclusion

Conclusions:

It is concluded that peripheral blood cultured from animals treated with HCFC 123 at 5000 ppm did not have increased frequencies of lymphocytes with chromosome aberrations when compared with blood from concurrent negative control animals.