2-Pyridinesulfonamide, 3-(2,2,2-trifluoroethoxy)-, sodium salt (1:1)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to internationally accepted test guidance and good laboratory practices guidance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

The study was performed in accordance with Study Protocol No. 20698 TAL and subsequent amendments, with the following deviations from the agreed Study Protocol:
- the relative humidity recorded in the animal room was sometimes outside of the target ranges specified in the protocol,
- during the study, the animals had free access to 110 pelleted diet instead of 112 C pelleted diet,
- since the signed Study Specific Supplement was received at CIT after the end of the study, it was not audited by the CIT Quality Assurance Unit. Nevertheless, the standard Novartis protocol had been previously audited.
These minor deviations were not considered to have compromised the validity or integrity of the study.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

sodium 2-(azanidylsulfonyl)-3-(2,2,2-trifluoroethoxy)pyridine

EC Number:

700-926-1

Cas Number:

227605-94-9

Molecular formula:

C7H6F3N2NaO3S

IUPAC Name:

sodium 2-(azanidylsulfonyl)-3-(2,2,2-trifluoroethoxy)pyridine

Constituent 2

Reference substance name:

Sodium {[3-(2,2,2-trifluoroethoxy)-2-pyridinyl]sulfonyl}azanide

IUPAC Name:

Sodium {[3-(2,2,2-trifluoroethoxy)-2-pyridinyl]sulfonyl}azanide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): CA 3105 A (intermediate of CGA 362622)
- Substance type: Organic mono constituent substance
- Physical state: White powder
- Analytical purity: 93.9%
- Lot/batch No.: EZ001002
- Expiration date of the lot/batch: July 2002 (reanalysis date)
- Storage condition of test material: Room temperature
- Other: The pH of the test substance at the concentration of 10% in purified water, measured at CIT, was approximately 10.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France.
- Age at study initiation: No data provided.
- Weight at study initiation: On the day of treatment, the animals weighed 2.7, 2.8 and 2.7 kg, respectively.
- Housing: The animals were housed individually in polystyrene cages ( 48.2 cm x 58 cm x 36.5 cm). Each cage was equipped with a food container and a water bottle.
- Diet (e.g. ad libitum): During the study, the animals had free access to 110 pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France). Food is analysed regularly by the supplier for composition and contaminant levels.
- Water (e.g. ad libitum): Drinking water filtered by a FG Millipare membrane (0.22 micron) was provided ad libitum.
Bacteriological and chemical analyses of water are performed regularly by external laboratories.
These analyses include the detection of possible contaminants (pesticides, heavy metals and nitrosamines). No contaminants were known to have been present in the diet or drinking water at levels which may be expected to have interfered with or prejudiced the outcome of the study. The results of the appropriate diet and water analyses are maintained in the test facility archive.
- Acclimation period: At least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): Approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 19 September 2000 (experimental starting date first animal) To: 24 September 2000 (end of the observation period)

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: Purified water (prepared at CIT by reverse osmosis) was used in order to moisten the pad and ensure a good contact with the skin.

Controls:

other: The untreated skin served as control.

Amount / concentration applied:

- Amount(s) applied (volume or weight with unit): 500 mg

Duration of treatment / exposure:

As possible irritant effects were anticipated, the test substance was first evaluated on a single animal (No. 874). The duration of exposure was 3 minutes on one flank (left flank) and 4 hours on the other flank (right flank). Since the test substance was not irritant on this first animal, it was then applied for 4 hours to two other animals (Nos. 884 and 885).

Observation period:

The skin was examined approximately 1 hour, 24, 48 and 72 hours after removal of the dressing.
Following the OECD and EC guidelines, because there was no evidence of dermal irritation after 72 hours, the study was ended.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: flank
- % coverage: No data provided.
- Type of wrap if used: Doses of 500 mg of the test substance were placed on a moistened gauze pad, which was then applied to the right flank (application for 4 hours) or the left flank (application for 3 minutes) of the animals. The test substance and the gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage. The untreated skin served as control.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: After removal of the dressing (after 3 minutes or after 4 hours), any residual test substance was wiped off by means of a moistened gauze pad (water).


SCORING SYSTEM:
The skin was examined approximately 1 hour, 24, 48 and 72 hours after removal of the dressing.
Following the OECD and EC guidelines, because there was no evidence of dermal irritation after 72 hours, the study was ended.

Erythema and eschar formation:
. no erythema : 0
. very slight erythema (barely perceptible): 1
. well-defined erythema : 2
. moderate to severe erythema : 3
. severe erythema (beet redness) to slight eschar formation (injuries in depth) : 4

Oedema formation
. no oedema: 0
. very slight oedema (barely perceptible): 1
. slight oedema (edges of area well-defined by definite raising): 2
. moderate oedema (raised approximately 1 millimetre): 3
. severe oedema (raised more than 1 millimetre and extending beyond area
of exposure): 4

Any other lesions were noted.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 7

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under our experimental conditions, the test substance is non-irritant when applied topically to rabbits.
According to the classification criteria laid down in Commission Directive 93/21/EEC, CA 3105 A (Intermediate of CGA 362622) is not required to be classified as irritating to the skin.

Executive summary:

The potential of the test substance CA 3105 A (Intermediate of CGA 362622) to induce skin irritation was evaluated in rabbits according to OECD (No. 404, 17th July 1992) and EC (92/69/EEC, B.4, 31 st July 1992) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

 

The test substance was first applied for periods of 3 minutes and 4 hours to a single male New Zealand White rabbit. Since the test substance was not irritant on the first animal, it was then applied for 4 hours to two other animals. A single dose of 500 mg of the test substance in its original form was applied to the closely-clipped skin of one flank. The test substance was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing.

After a 3-minute exposure (one animal), no cutaneous reactions were observed. After a 4-hour exposure (three animals), a very slight erythema was noted in 2/3 animals on day 1; it persisted up to day 2 in one of them.

Mean scores over 24, 48 and 72 hours for each animal were 0, 0.3 and 0 for erythema and 0, 0 and 0 for oedema. Mean scores for the three animals were 0.1 for erythema and 0 for oedema.

Under our experimental conditions, the test substance is non-irritant when applied topically to rabbits.

According to the classification criteria laid down in Commission Directive 93/21/EEC, CA 3105 A (Intermediate of CGA 362622) is not required to be classified as irritating to the skin.