Zinc 3,5-bis(α-methylbenzyl)salicylate

Eye irritation

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-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

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

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Zinc 3,5-bis(α-methylbenzyl)salicylate

EC Number:

258-753-8

EC Name:

Zinc 3,5-bis(α-methylbenzyl)salicylate

Cas Number:

53770-52-8

Molecular formula:

C46H42O6Zn

IUPAC Name:

zinc 3,5-bis(α-methylbenzyl)salicylate

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

Results

Results 1

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

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

2

Results 3

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

Results 4

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)).