Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 January 1997 to 26 March 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline compliant study conducted without deviation to extant GLP requirements
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):Ro 31-9232 (PTH-Decahydroamide)
- Physical state: white powder
- Lot/batch No.: #5020230CU1
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: standard room temperature and humidity

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source:Ace Animals, Boyertown, PA, USA
- Age at study initiation: circa 10-12 weeks
- Weight at study initiation: 2.0-2.2 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): Purina Rabbit Chow, Diet #5321 adlibitum
- Water (e.g. ad libitum): potable water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: From: 28 January 1997 To: 4 February 1997

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 81 mg (equivalent weight to a 0.1 mL volume of test material)
- Concentration (if solution): Not applicable

Duration of treatment / exposure:
Following instillation of the test material into the conjunctival sac, the eyelids were held together for appproximately one second to prevent immediate ejection of the material. The eyes were not rinsed to remove the material however after 24 hours fluorescein dye was used to aid examinations and this was flushed out of the eye and consequently any test material was removed at the first rinsing after fluorescein usage.
Observation period (in vivo):
Eyes were examined 1, 24, 48 and 72 hours after instillation and then on Day 7.
Number of animals or in vitro replicates:
Three
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Eyes were not rinsed but the post-fluorescein application involves rinsing away excess dye. This was completed at 24 hours after instillation and again at each subsequent evaluation

SCORING SYSTEM: Standard Draize assessment, evaluated using the method of Kay& Calandra

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72 hours
Score:
0.89
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Corneal opacity observed in 2 of 3 rabbits, scores did not exceed 2, mean scores was lower than EU classification threshold. Reactions resolved within 72 hours
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 hours
Score:
0.44
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Only two rabbits showed iritis, the degree of reaction did not exceed 1. The mean score did not exceed classification thresholds and all reactions resolved within 7 days.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24-72 hours
Score:
1.56
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Reactions in all three treated rabbits did not exceed a diffuse crimson redness but persisted for at least 72 hours although all reactions had resolved by Day 7. The mean score of 1.56 did not exceed the classification threshold.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-72 hours
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Obvious swelling with partial eversion of the eyelids was sustained in two of the three treated rabbits. Although reactions resolved by Day 7, the mean score of 2.0 in at least two animals requires classification as R36, Irritating to eyes.
Irritant / corrosive response data:
The slight to moderate reactions observed in two of the three rabbits were sufficient to classifiy the test substance on the basis of persistent moderate chemosis.
Classification according to Commission Regulation (EC) No. 1272/2008 requires the Signal word "Warning", appropriate GHS pictogram and classification as "Category 2: Eye irritant with the hazard statement 'H319: causes serious eye irritation'.
Precautionary statements P264 and P280 for prevention and P305 +P351 +P338 and P337 +P313 for response should be considered.
Other effects:
None

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Corneal opacity generally resolved by Day 3 having been noted in two of the treated eyes. Iritis, also noted in two animals was slight in degree but persisted through the 72 hour assessment and had resolved by Day 7. Conjunctival irritation, redness and swelling, was observed in all three treated eyes but was only moderate or marked in two animals. The degree of response in these two rabbits was sufficient to require classification of Ro 31-9373 (PTH-Decahydroamide) as R36, Irritating to eyes.
Classification according to Commission Regulation (EC) No. 1272/2008 requires the Signal word "Warning", appropriate GHS pictogram and classification as "Category 2: Eye irritant with the hazard statement 'H319: causes serious eye irritation'.
Precautionary statements P264 and P280 for prevention and P305 +P351 +P338 and P337 +P313 for response should be considered.
Executive summary:

The irritation potential to rabbit eye of Ro 31 -9373 (PTH-decahydroamide) was investigated using a standard protocol based on OECD Test Guideline 405.

Ro 31 -9373 (PTH-decahydroamide) was instilled into the conjunctival sac of three New Zealand White rabbits, as 81 mg of powder (weight equivalent to the volume of 0.1 ml). The eyes were examined at 1, 24, 48 and 72 hours after dosing and then on day 7, and reactions scored using the standard Draize assessment method.

Corneal opacity generally resolved by Day 3 having been noted in two of the treated eyes. Iritis, also noted in two animals was slight in degree but persisted through the 72 hour assessment and had resolved by Day 7. Conjunctival irritation, redness and swelling, was observed in all three treated eyes but was only moderate or marked in two animals. The degree of response in these two rabbits was sufficient to require classification as R36, Irritating to eyes.

Classification according to Commission Regulation (EC) No. 1272/2008 requires the Signal word "Warning", appropriate GHS pictogram and classification as "Category 2: Eye irritant with the hazard statement 'H319: causes serious eye irritation'.

Precautionary statements P264 and P280 for prevention and P305 +P351 +P338 and P337 +P313 for response should be considered.