2-Pyridinesulfonamide, N-[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]-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:

29 April 1997 to 2 May 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed to GLP and in line with standardised guidelines OECD 404, EU Method B.4 and EPA OPP 81-5 with no deviations thought to impact on the reliability of the presented results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: J-MAFF 59 NohSan No. 4200

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

sodium 4,6-dimethoxy-N-({[3-(2,2,2-trifluoroethoxy)pyridin-2-yl]sulfonyl}carbamoyl)pyrimidin-2-aminide

EC Number:

688-332-8

Cas Number:

199119-58-9

Molecular formula:

C14H13F3N5O6SNa

IUPAC Name:

sodium 4,6-dimethoxy-N-({[3-(2,2,2-trifluoroethoxy)pyridin-2-yl]sulfonyl}carbamoyl)pyrimidin-2-aminide

Test material form:

solid: particulate/powder

Details on test material:

- Physical state: solid
- Storage condition of test material: room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately 18-24 weeks
- Weight at study initiation: 3790 - 4650 g
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): approximately 13-14 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

IN-LIFE DATES: From 29 April 1997 to 2 May 1997

Test system

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: test material moistened with 0.5% (w/v) carboxymethylcellulose in 0.1% (w/v) aqueous polysorbate 80

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g moistened with 0.5 % (w/v) carboxymethylcellulose in 0.1% (w/v) aqueous polysorbate 80 to allow good skin contact.

Duration of treatment / exposure:

4 hours

Observation period:

3 days post administration

Number of animals:

3 males, 3 females (6 animals in total)

Details on study design:

TEST SITE
- Area of exposure: On the day prior to application, an area approximately 10 cm wide from one flank to the other, of each animal, was shaved with an electric clipper. The test material was moistened with 0.5 % (w/v) carboxymethylcellulose in 0.1% (w/v) aqueous polysorbate 80 and applied to the test site by means of a gauze patch. A control patch, moistened with 0.5 % (w/v) carboxymethylcellulose in 0.1% (w/v) aqueous polysorbate 80, was applied to the other flank.
- Type of wrap if used: The treated area was covered with a gauze patch which was loosely covered with aluminium foil and held in place with adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing: At the end of the exposure period, the dressing was and the application site was cleansed with lukewarm water.
- Time after start of exposure: approximately 4 hours

SCORING SYSTEM:
The Draize scale (Draize 1959), was used to assess the degree of erythema and oedema at the application sites approximately 1 hour and 1, 2 and 3 days after the removal of the dressings. Any other clinical signs were also noted. Mortality was checked daily and bodyweigths were measured and recorded immediately before dose administration and at the 72 hour examination.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.2

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

Very slight erythema was observed in two male and two female animals 1 hour after patch removal and was still seen in one male and two females at the 24 hour observation. All skin reactions were fully reversible within 48 hours.

Other effects:

There were no signs of ill-health in any animal during the study and bodyweights were not affected by treatment.

Any other information on results incl. tables

Table 2: Erythema and Oedema Scores 

Animal No.	Erythema					Oedema
	Time after decontamination				Mean Score	Time after decontamination				Mean Score
	1 hour	1 day	2 days	3 days		1 hour	1 day	2 days	3 days
755 (M)	0	0	0	0	0	0	0	0	0	0
569 (M)	0	0	0	0	0	0	0	0	0	0
803 (M)	1	1	0	0	0.3	0	0	0	0	0
368 (F)	1	1	0	0	0.3	0	0	0	0	0
410 (F)	0	0	0	0	0	0	0	0	0	0
422 (F)	1	1	0	0	0.3	0	0	0	0	0

The mean values have been calculated using the day 1, 2 and 3 values.

 

Overall mean score(erythema) 24 - 72 hours = 0.2

Overall mean score(oedema) 24 - 72 hours = 0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study, the test material did not elicit any reaction in any of the animals during the course of the study that meant the test material required classification as a skin irritant. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.

Executive summary:

The skin irritation potential of the test material was determined in accordance with standardised guidelines OECD 404, EU Method B.4 and EPA OPP 81 -5. Six rabbits (3 male and 3 female) received a single four hour application of 0.5 g of the test material and were assessed for the following 3 days for any signs of skin irritation. Very slight erythema was observed in two male and two female animals 1 hour after patch removal and was still seen in one male and two females at the 24 hour observation. All skin reactions were fully reversible within 48 hours. There were no signs of ill-health in any animal during the study and bodyweights were not affected by treatment.

Under the conditions of the study, the test material was considered to be not-irritating to the skin in the albino rabbit. The test material does not require classification for skin irritation in line with Regulation No. 1272/2008.