Potassium 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulphonate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Data source

Reference

Reference Type:

other: National Toxicology Program (NTP) Database

Title:

Unnamed

Year:

2012

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

not specified

Type of assay:

mammalian germ cell cytogenetic assay

Test material

Test material information

Constituent 1

Reference substance name:

Potassium 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulphonate

EC Number:

249-616-3

EC Name:

Potassium 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulphonate

Cas Number:

29420-49-3

Molecular formula:

C4HF9O3S.K

IUPAC Name:

potassium 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonate

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Not specified
- Expiration date of the lot/batch:
- Purity test date:

RADIOLABELLING INFORMATION (if applicable)
- Radiochemical purity:
- Specific activity:
- Locations of the label:
- Expiration date of radiochemical substance:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
- Stability under test conditions:
- Solubility and stability of the test substance in the solvent/vehicle:
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
- Preliminary purification step (if any):
- Final dilution of a dissolved solid, stock liquid or gel:
- Final preparation of a solid:

FORM AS APPLIED IN THE TEST (if different from that of starting material)

OTHER SPECIFICS:

Test animals

Species:

rat

Strain:

other: Harlan Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Labs
- Age at study initiation: No data
- Weight at study initiation: No data
- Assigned to test groups randomly: No data
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS: No data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: Deionized water with 2% Tween 80
- Justification for choice of solvent/vehicle: No data
- Concentration of test material in vehicle: Dose formulations were prepared to deliver 0 (vehicle control), 31.3, 62.5, 125, or 250 mg/kg test article.
- Amount of vehicle (if gavage or dermal): No data

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: Dose formulations were prepared to deliver 0 (vehicle control), 31.3, 62.5, 125, or 250 mg/kg test article.

Duration of treatment / exposure:

28 days

Frequency of treatment:

Daily

Post exposure period:

Blood samples were collected 24 hours after the last dose was adminstered.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (actual dose received)

Remarks:

Vehicle Control (Deionized water with 2% Tween 80)

Doses / concentrations 2

Dose / conc.:

31.3 mg/kg bw/day (actual dose received)

Doses / concentrations 3

Dose / conc.:

62.5 mg/kg bw/day (actual dose received)

Doses / concentrations 4

Dose / conc.:

125 mg/kg bw/day (actual dose received)

Doses / concentrations 5

Dose / conc.:

250 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

None

Examinations

Tissues and cell types examined:

Blood samples were examined via flow cytometry to measure the number of micronucleated polychromatic and normochromatic erythrocytes.

Evaluation criteria:

The micronucleus data were tabulated as the mean frequency of the micronucleated erythrocytes per 1000 cells per animal, plus or minus the standard error of the mean amoung animals within a treatment group. The frequency of micronucleated cells among Polychromatic erythrocytes (PCE) and Normochromatic erythrocytes (NCE). Pairwise comparisons were analyzed between each exposure group and control group using an unadjusted one-tailed Pearson X^2 test. A test was considered positive if the trend test P value was 0.025 or less or the P value for any single exposure group was 0.025/N or less where N is the number of treatment groups. Trend test P values between 0.025 and 0.05 were considered to be equivocal if accompanied by a monotonic increase in the frequency of micronuclei over the dose range investigated. All other responses were considered to be negative.

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Positive controls validity:

not examined

Remarks on result:

other:

Remarks:

Treatment with the test article up to 250 mg/kg/day for 28 days did not induce a statistically significant increase in the frequency of micronucleated erythrocytes per 1000 cells per animal in polychromatic or normochramtic erythrocytes.

Applicant's summary and conclusion

Conclusions:

Based on the results of the study, the test article is negative in the mammalian micronucleus test in male and female rats.

Executive summary:

The genotoxic potential of the test article was evaluated in Harlan Sprague-Dawley rats. Rats (5/sex/group) were administered 0 (vehicle control: Deionized water with 2% Tween 80), 31.3, 62.5, 125, or 250 mg/kg test article via oral gavage for 28 days. Peripheral blood samples were collected from each animal 24 hours after administration of the final dose. Blood samples were examined via flow cytometry to measure the number of micronucleated polychromatic and normochromatic erythrocytes. The micronucleus data were tabulated as the mean frequency of the micronucleated erythrocytes per 1000 cells per animal, plus or minus the standard error of the mean amoung animals within a treatment group.  The frequency of micronucleated cells among Polychromatic erythrocytes (PCE) and Normochromatic erythrocytes (NCE).  Pairwise comparisons were analyzed between each exposure group and control group using an unadjusted one-tailed Pearson X^2 test.  A test was considered positive if the trend test P value was 0.025 or less or the P value for any single exposure group was 0.025/N or less where N is the number of treatment groups.  Trend test P values between 0.025 and 0.05 were considered to be equivocal if accompanied by a monotonic increase in the frequency of micronuclei over the dose range investigated.  All other responses were considered to be negative. Treatment with the test article up to 250 mg/kg/day for 28 days did not induce a statistically significant increase in the frequency of micronucleated erythrocytes per 1000 cells per animal in polychromatic or normochramtic erythrocytes. Based on the results of the study, the test article is negative in the mammalian micronucleus test in male and female rats.