2-Pyridinesulfonamide, N-[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]-3-(2,2,2-trifluoroethoxy)-, sodium salt (1:1)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6 May 1997 to 23 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 405, EU Method B.5 and EPA OPP 81-4 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 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye 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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately 18-24 weeks
- Weight at study initiation: 3660 - 4610 g
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

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

IN-LIFE DATES: From 6 May 1997 to 23 May 1997

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL test material, weighing approximately 66 mg

Duration of treatment / exposure:

- Duration of treatment: 24 hours

- Frequency of administration: One single dose

- Dose administration: Approximately 66 mg of the test material was applied into the conjunctival sac of the left eye of each rabbit by gently pulling the lower lid away from the eyeball. The lids were then gently held together for about 1 second. The right eye remained untreated and served as a control.

Observation period (in vivo):

Animals were observed up to 10 days post administration

Number of animals or in vitro replicates:

3 males and 3 females (6 animals in total)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Treated eyes were gently washed with distilled water for 1 minute after the reading at 24 hours post-treatment

SCORING SYSTEM:
The reactions observed were scored in line with the grading system in accordance with the OECD/EEC/MAFF scoring system outlined in the field “Any other information on materials and methods incl. Tables”.

TOOL USED TO ASSESS SCORE: To aid scoring, animals were examined using a portable, hand-held slit lamp.

OBSERVATIONS: Mortality and clinical signs were checked daily, and any remarkable findings were recorded. Bodyweights were measured and recorded immediately before dose administration, at the 72-hour examination, and on days 7 and 10.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 10 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.9

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritant / corrosive response data:

Scattered areas of corneal opacity were seen in a total of three animals, one at the 1-hour examination only, one at 1 and 24 hours, and one at 24, 48 and 72 hours. Moderate hyperemia of the iris was noted for five animals, only at the 1-hour reading. Diffuse, crimson-coloured conjunctival redness (scores of 2) was observed in the treated eyes of all animals after 1 hour, and diminished by day 7 to scores of 1 or were clear. Conjunctival redness was clear in all animals by day 10. All animals also exhibited above-normal swelling of the eyelids and nicitating membranes, or obvious swelling with partial eversion of the eyelids, beginning 1 hour after treatment. Conjunctival chemosis was reversed within 48 or 72 hours, or 7 days. All eye reactions were reversed by day 10.

Other effects:

There was no mortality during the test and no remarkable clinical signs were observed. Slight bodyweight losses were noted for one male and one female at day 3 and one female at day 7. However, these changes were not considered to be related to treatment.

Any other information on results incl. tables

Table 2: Irritation Scores

Animal no	Males			Females
	607	615	791	418	382	394
CORNEA
1 hour	1	0	0	0	0	1
1 day	1	0	1	0	0	0
2 days	0	0	1	0	0	0
3 days	0	0	1	0	0	0
7 days	0	0	0	0	0	0
10 days	0	0	0	0	0	0
IRIS
1 hour	1	1	1	0	1	1
1 day	0	0	0	0	0	0
2 days	0	0	0	0	0	0
3 days	0	0	0	0	0	0
7 days	0	0	0	0	0	0
10 days	0	0	0	0	0	0
CONJUNCTIVAL REDNESS
1 hour	2	2	2	2	2	2
1 day	2	2	2	1	2	2
2 days	2	2	2	1	2	1
3 days	1	1	1	1	1	1
7 days	1	1	1	0	1	0
10 days	0	0	0	0	0	0
CONJUNCTIVAL CHEMOSIS
1 hour	2	1	1	1	1	2
1 day	2	1	1	1	1	1
2 days	1	1	1	1	1	0
3 days	0	1	1	1	1	0
7 days	0	0	0	0	0	0
10 days	0	0	0	0	0	0

 

Table 3: Mean scores of the 24, 48 and 72 hours observations

Animal No.	607	615	791	418	382	394	Total (mean of 24, 48 and 72 hours)
Observation	Males			Females
Cornea	0.3	0	1	0	0	0	0.2
Iris	0	0	0	0	0	0	0
Conjunctival redness	1.7	2	2	1	2	1.3	1.7
Conjunctival chemosis	1	1	1	1	1	0.3	0.9

 

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 reactions, in any of the animals, during the course of the study indicating that the test material is not an eye irritant. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.

Executive summary:

The eye irritation potential of the test material was determined in accordance with standardised guidelines OECD 405, EU Method B.5 and EPA OPP 81-4. Approximately 66 mg of test material was instilled into the conjunctival sac of one eye of six rabbits; the second eye served as a control. The test eyes were gently washed with distilled water 24 hours after treatment. Eyes were examined for irritation at 1, 24, 48 and 72 hours and 7 and 10 days after treatment.

Scattered areas of corneal opacity were seen in a total of three animals, one at the 1-hour examination only, one at 1 and 24 hours, and one at 24, 48 and 72 hours. Moderate hyperemia of the iris was noted for five animals, only at the 1-hour reading. Diffuse, crimson-coloured conjunctival redness (scores of 2) was observed in the treated eyes of all animals after 1 hour, and diminished by day 7 to scores of 1 or were clear. Conjunctival redness was clear in all animals by day 10. All animals also exhibited above-normal swelling of the eyelids and nicitating membranes, or obvious swelling with partial eversion of the eyelids, beginning 1 hour after treatment. Conjunctival chemosis was reversed within 48 or 72 hours, or 7 days. All eye reactions were reversed by day 10. There was no mortality, and no remarkable clinical observations. Slight bodyweight losses were noted for one male and two females.

Under the conditions of the study, the test material does not require classification for eye irritation in line with Regulation No. 1272/2008.