Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 May 2011 to 23 May 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline and GLP compliant study.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): zinc 3,5-bis(α-methylbenzyl)salicylate
- Molecular formula (if other than submission substance): C46H42O6Zn
- Molecular weight (if other than submission substance): 756.21
- Physical state: White powder
- Analytical purity: 99.0%
- Lot/batch No.: 31205
- Expiration date of the lot/batch: December 2013
- Storage condition of test material: Room temperature (15-25°C)
- Other:
- Manufacture date: December 2003
- Safety precautions: Routine safety precautions (lab coat, gloves, goggles, face mask) for unknown materials will be applied to assure personnel health and safety

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: S&K-LAP Kft., 2173 Kartal, Császár út 135, Hungary
- Age at study initiation: ~16 weeks old (adult)
- Weight at beginning of life phase: 3834 - 4036 g
Weight at end of life phase: 3513 - 4299 g
- Housing: Rabbits were individually housed in AAALAC approved metal wire rabbit cages. Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages
- Diet (e.g. ad libitum): Animal received PURINA Base - Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum.
- Water (e.g. ad libitum): The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system.
- Acclimation period: 40 days

- Date of receipt of rabbits: 23 March 2011

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 24-67
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): Light 12 hours daily, from 6.00am to 6.00pm

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated right eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A single dose of 0.1 g of the solid test item zinc 3,5-bis(α-methylbenzyl)salicylate was administered to each animal
Duration of treatment / exposure:
The treated eye of the rabbits was rinsed at 1 hour after application with physiological saline solution.
Observation period (in vivo):
3 weeks
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye of the rabbits was rinsed with physiological saline solution.
- Time after start of exposure: 1 hour

SCORING SYSTEM:
- Scoring and Assessment of Local Reaction: The eye irritation scores were evaluated according to the scoring system by Draize (1977) and OECD 405 (24 April 2002) shown in Appendix 1 of attached report.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
1.9
Max. score:
4
Reversibility:
fully reversible within: 3 weeks
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
2.8
Max. score:
3
Reversibility:
not fully reversible within: 3 weeks
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
2.9
Max. score:
4
Reversibility:
fully reversible within: 2 weeks
Irritant / corrosive response data:
-Examination of eye-irritancy:
Initial Pain Reaction (IPR) (score 1 or 2) was observed in all animals.
 
One hour after the application, conjunctival redness (score 1 or 2) was observed in all animals, discharge (score 1 or 3) and chemosis (score 1 or 3) were seen in all rabbits. All animals showed corneal opacity (score 1, areas 2, 3 and 4).
 
At 24 hours after treatment conjunctival redness (score 3) was observed in all animals, discharge (score 3) and chemosis (score 2, 3 or 4) were seen in all rabbits. All animals showed corneal opacity (score 1, areas 2, 3 and 4).
 
At 48 hours after treatment, conjunctival redness (score 2 or 3) was observed in all animals, discharge (score 3) and chemosis (score 1 or 4) were seen in all rabbits. All animals showed corneal opacity (score 2 or 3, areas 2 and 3).
 
At 72 hours after treatment, conjunctival redness (score 2 or 3) was observed in all animals, discharge (score 2 or 3) and chemosis (score 1, 3 or 4) were seen in all rabbits. All animals showed corneal opacity (score 2 or 3, area 2 or 3).
 
At one week after treatment, conjunctival redness (score 1 or 2) was observed in all animals, discharge (score1 or 3) and chemosis (score 1) were seen in two rabbits. One animal showed corneal opacity (score 2, area 4) and iris was reactive in one animal (score 1).
 
At two weeks after treatment, conjunctival redness (score 1) was observed in all animals and discharge (score 1) was seen in two rabbits. One animal showed corneal opacity (score 1, area 1).
 
At three weeks after treatment, conjunctival redness (score 1) was observed in two animals and discharge (score 1) was seen in two rabbits. During the study, the control eye of all animals was symptom-free. The general state and behaviour of animals were normal throughout the study period. There were no notable body weight changes during the study period.
 
The animal’s individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows:
 
chemosis : 4.00, 3.00, 1.67
discharge : 3.00, 3.00, 2.67
redness : 3.00, 3.00, 2.33
cornea opacity : 2.33, 1.67, 1.67
iris: 0.00, 0.00, 0.00

Any other information on results incl. tables

-Mortality: There was no mortality observed during the study.

-Body weights: The mean body weight and the mean body weight change were considered to be normal with no indication of treatment related effect.

 

Clinical Observation:

-General daily examination: There were no clinical signs observed that could be related to treatment.

 

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item zinc 3,5-bis(α-methylbenzyl)salicylate (Batch No.: 31205), applied to rabbits’ eye mucosa, caused significant conjunctival and corneal irritant effects at one hour which were not reduced at 24 hours after application. The effects were not fully reversible within 3 weeks.

According to Regulation (EC) No 1272/2008, zinc 3,5-bis(α-methylbenzyl)salicylate requires classification as an eye irritant (Irreversible effects on the eye/serious damage to eyes (Category 1)).
Executive summary:

An acute eye irritation study of the test item zinc 3,5-bis(α-methylbenzyl)salicylate was performed in New Zealand White rabbits. The irritation effects of the test item were evaluated according to the Draize method (OECD No.: 405, 2002).

The test item was placed into the conjunctival sac of the left eye of each animal. The untreated right eye served as control. An amount of 0.1 g of the test item was administered as a single dose. The treated eye of the rabbits was rinsed at 1 hour after application with physiological saline solution.

 

The eyes were examined at 1, 24, 48, 72 hours and 1, 2 and 3 weeks after the application.

 

Initial Pain Reaction (IPR) (score 1 or 2) was observed in all animals.

 

One hour after the application, conjunctival redness (score 1 or 2) was observed in all animals, discharge (score 1 or 3) and chemosis (score 1 or 3) were seen in all rabbits. All animals showed corneal opacity (score 1, areas 2, 3 and 4).

 

At 24 hours after treatment conjunctival redness (score 3) was observed in all animals, discharge (score 3) and chemosis (score 2, 3 or 4) were seen in all rabbits. All animals showed corneal opacity (score 1, areas 2, 3 and 4).

 

At 48 hours after treatment, conjunctival redness (score 2 or 3) was observed in all animals, discharge (score 3) and chemosis (score 1or 4) were seen in all rabbits. All animals showed corneal opacity (score 2 or 3, areas 2 and 3).

 

At 72 hours after treatment, conjunctival redness (score 2 or 3) was observed in all animals, discharge (score 2 or 3) and chemosis (score 1, 3 or 4) were seen in all rabbits. All animals showed corneal opacity (score 2 or 3, area 2 or 3).

 

At one week after treatment, conjunctival redness (score 1 or 2) was observed in all animals, discharge (score1 or 3) and chemosis (score 1) were seen in two rabbits. One animal showed corneal opacity (score 2, area 4) and iris was reactive in one animal (score 1).

 

At two weeks after treatment, conjunctival redness (score 1) was observed in all animals and discharge (score 1) was seen in two rabbits. One animal showed corneal opacity (score 1, area 1).

 

At three weeks after treatment, conjunctival redness (score 1) was observed in two animals and discharge (score 1) was seen in two rabbits.

 

During the study, the control eye of all animals was symptom-free.

 

The general state and behaviour of animals were normal throughout the study period.

 

There were no notable body weight changes during the study period.

 

The animal’s individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows:

chemosis : 4.00, 3.00, 1.67

discharge : 3.00, 3.00, 2.67

redness : 3.00, 3.00, 2.33

cornea opacity : 2.33, 1.67, 1.67

iris : 0.00, 0.00, 0.00

 

According to Regulation (EC) No 1272/2008, zinc 3,5-bis(α-methylbenzyl)salicylate requires classification as an eye irritant (Irreversible effects on the eye/serious damage to eyes (Category 1)).