Propanoic acid, 2-[(ethoxythioxomethyl)thio]-, methyl ester

Eye irritation

Administrative data

Endpoint:

eye 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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

The relative humidity and temperature of the animal room exceeded the limits mentioned in the guidelines. The body weigbt range ordered was 2000-2500 g instead of 1500-1900 g. These deviations had no impact on the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

The relative humidity and temperature of the animal room exceeded the limits mentioned in the guidelines. The body weigbt range ordered was 2000-2500 g instead of 1500-1900 g. These deviations had no impact on the study.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Test material form:

liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Remarks:

SPF bred

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Centre Lagro, France
- Age at study initiation: young adult
- Weight at study initiation: 3243-3421 g
- Housing: individually in stainless steel cages with perforated floor
- Diet (e.g. ad libitum): standard laboratory rabbit diet ad libitum. Each batch of this diet is analyzed by the supplier (SDS Special Diets services, Whitham, England) for the nutrients and contaminants and the results are available upon request.
- Water (e.g. ad libitum): Tap water (N.V. Waterleidingbedrijf Midden-Nederland) ad libitum. Results of routine physical, chemical and microbiological examination of drinking water as conducted by the supplier are available upon request.
- Acclimation period: 49 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C. (On 13 June, the temperature was up to 26.2°C for a very short period of time due to a malfunction).
- Humidity (%): 58-80 % (incidentally the upper limit was higher !han 70%, because of wet cleaning of the animal room and/or meteorological circumstances).
- Air changes (per hr): ca 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark cycle

IN-LIFE DATES: From: 25 April 2000 To: 16 June 2000

OTHERS
The non-GLP Chicken Enucleated Eye Test showed no signs of initation. Therefore, it was decided to proceed with the in vivo test, which was immediately started with three rabbits. Both eyes of the rabbits selected were examined just before testing. Only rabbits without observable eye defects were used.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml

VEHICLE
No

Observation period (in vivo):

24, 48, and 72 h

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

An amount of ca 0.1 ml of the test substance was instilled in the conjonctival cul-de-sac of the right eye. After administration, the upper and lower eye lid were carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material. The left eye remaining untreated, served as a control. The reactions of the test eyes were judged at circa one, 24, 48, and 72 h after treatment using the scoring scale.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 9

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible

Results 10

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 12

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible

Irritant / corrosive response data:

One rabbit (no. 77) screamed for a very short period immediately after dosing. At I h after treatment, the eye effects observed in the three rabbits consisted of slight or moderate redness with or without slight swelling of the conjunctivae.
In addition, one rabbit showed moderate ocular discharge. At 24 h after treatment one rabbit still showed slight redness and slight swelling of the conjunctivae and slight ocular discharge.
At 48 and 72 h after treatment, no signs of eye irritation were observed in any of the three rabbits.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of the study, RHODIXAN A-1 was considered to be slight irritant to the eyes.

Executive summary:

RHODIXAN A-1 was tested for acute eye irritation on 3 male New Zealand White albino rabbits, according to O.E.C.D. guideline Nb.405/EEC method B.5, and in compliance with Good Laboratory Practice. The test article, a liquid, was instillated as such, in a single dose of 0.1 ml into the conjunctival sac of the right eye of each animal. The left eye remained untreated and served as a control. The eyes were not rinsed. Ocular examinations were performed 1, 24, 48 and 72 hours after the instillation.

 

No corneal opacity or iritis was observed throughout the study.

Slight to moderate conjunctival redness was observed in all of the 3 animals,hour, which persisted at 24 hour in 1 animal. In addition, 1 animal displayed also slight chemosis and ocular dischargehour and 24 hours after instillation. Mean scores (24-48-72 hours) calculated for each animal were 0.0 - 0.0 - 0.3 for conjunctival redness, and 0.0 - 0.0 - 0.3 for chemosis. In addition, slight ocular discharge was observed in one animal and 24 hours.

Based on these results, RHODIXAN A-1 is not classified as an eye irritant according to CLP and GHS criteria.