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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June 24-27 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
yes
Remarks:
the temperature exceeded the limit slightly - not judged to have any influence on the outcome.
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
liquid
Details on test material:
- Substance type: UVCB
- Physical state: liquid
- Lot/batch No.: PPA 6865
- Expiration date of the lot/batch: May 14 2004
- Stability under test conditions: Solutions in water are stable for at least 24 hours at room temperature or 4 degrees Celcius
- Storage condition of test material: -18 degrees of C

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Centre Lagro, France
- Age at study initiation: young adults
- Weight at study initiation: 2008-2210 g
- Housing: induvidually in stainless steel cages with perforated floor
- Diet (e.g. ad libitum): Standard diet ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23.9 C (target 17 - 23 C)
- Humidity (%): 30-70 %
- Air changes (per hr): ca 10 air changes per hr
- Photoperiod (hrs dark / hrs light): 12 hrs light/ 12 hrs dark cycle

IN-LIFE DATES: From: 24 June 2002 To: 27 June 2002

Test system

Vehicle:
other: Tested neat
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): Undiluted test material
Observation period (in vivo):
The reactions were judged 1, 24, 48 and 72 hours after treatment
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No washing


SCORING SYSTEM: According to OECD 405

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean 24-72h
Score:
ca. 0.7
Max. score:
1
Reversibility:
fully reversible within: 72 hrs
Remarks on result:
other: Small haemorrhage on the nictitating membrane at 1h reading, cleared at 24h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean 24-72h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean 24-72h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 72 hrs
Remarks on result:
other: Small haemorrhage on the nictitating membrane at 1h reading, cleared at 24h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean 24-72h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hrs
Remarks on result:
other: Discharge score 1 at 1 h, fully cleared at 24h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean 24-72h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 hrs
Remarks on result:
other: Small haemorrhage on the nictitating membrane at 1h reading, cleared at 24h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean 24-72h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48 hrs
Remarks on result:
other: Discharge score 2 at 1 h, fully cleared at 24h
Irritant / corrosive response data:
At the 1 hour reading, Subtilisin generally caused slight or moderate redness and slight or moderate swelling of the conjunctivae and slight or moderate ocular discharge in the rabbits. In addition, all rabbits showed a small haemorrhage on the nictitating membrane. After 24 hours, slight to moderate redness and swelling was observed in all treated rabbits. After 48 hours only slight redness was observed and 72 hours after treatment, all eye effects had cleared completely.

Applicant's summary and conclusion

Interpretation of results:
Category 2B (mildly irritating to eyes) based on GHS criteria
Conclusions:
According to EC-standards (as published in the Official Journal of the European Communities, L 110 A, volume 36, 4 May 1993), the test material is not irritating to eyes. However, due to the small haemorrhage on the nictitating membrane, the test material is regarded as a slight eye irritant.
Executive summary:

The study was carried out according to OECD guideline no. 405. Three rabbits were treated as follows: One rabbit was treated first and two more the following day. An amount of 0.1 ml of the undiluted test substance was instilled in the conjunctival cul-de-sac of one of the eyes of the rabbit. After administration, the upper and the lower eye lid were carefully closed and subsequently held together for at least one second before releasing to prevent loss of material. The other eye remained untreated and served as a control. The reactions of the eyes were judged at 1 h, 24 h, 48 h and 72 h after treatment.

At the 1 hour reading, Subtilisin generally caused slight or moderate redness and slight or moderate swelling of the conjunctivae and slight or moderate ocular discharge in the rabbits. In addition, all rabbits showed a small haemorrhage on the nictitating membrane. After 24 hours, slight to moderate redness and swelling was observed in all treated rabbits, while the haemorrhage on the nictitating membrane was no longer present. After 48 hours only slight redness was observed and 72 hours after treatment, all eye effects had cleared completely. According to EC-standards (as published in the Official Journal of the European Communities, L 110 A, volume 36, 4 May 1993), Subtilisin batch PPA 6865 is not irritating to eyes.