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Administrative data

Description of key information

The above results triggered classification under the CLP Regulation (EC No 1272/2008) as Eye Damage Category 1.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1 November 2000 - 15 November 2000
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Performed according to GLP, OECD Guideline followed and no deviations reported. Read-across study therefore it is categorised as Klimisch 2 study.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK.
- Age at study initiation: 12 to 16 weeks old
- Weight at study initiation: 2.89 to 3.01 kg
- Housing: The animals were individually housed in suspended metal cages.
- Diet (e.g. ad libitum): Free access to food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK)
- Water (e.g. ad libitum): Free access to mains drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): at least 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light (06:00 to 18:00) and 12 hours darkness

IN-LIFE DATES: From 1 November 2000 to 15 November 2000
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hour
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 mL of the test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin.
- Type of wrap if used: The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): any residual test material removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.
- Time after start of exposure: 4 hours

SCORING SYSTEM: See attached report for scoring system.

Additional observations were made on Days 7 and 14 to assess the reversibility of skin reactions.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.77
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.11
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
- Very slight erythema was noted at all treated skin sites at the 24-hour observation and persisted at two treated skin sites at the 48 and 72-hour observations.
- Very slight oedema was noted at one treated skin site at the 72-hour observation.
- (See Table 1 of attached report for the individual scores for erythema/eschar and oedema).
Other effects:
Moderate desquamation was noted at two treated skin sites at the 7-day observation.
- One treated skin site appeared normal at the 48-hour observation and the two remaining treated skin sites appeared normal at the 14-day observation.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material produced a primary irritation index of 1.0 and was classified as a MILD IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. The test material did not meet the criteria for classification as irritant or corrosive according to the CLP Regulation.
Executive summary:

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight erythema and an isolated incident of very slight oedema. Moderate desquamation was also noted. One treated skin site appeared normal at the 48-hour observation and the two remaining treated skin sites appeared normal at the 14-day observation.

Conclusion: The test material produced a primary irritation index of 1.0 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test material did not meet the criteria for classification as irritant or corrosive according to the CLP Regulation.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
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.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
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
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.
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

-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.

 

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)).

 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In the key study, the mixture containing zinc 3,5-bis(alpha-methylbenzyl)salicylate, produced a primary irritation index of 1.0 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. In a supporting study, daily application of the mixture to the skin of rabbits at concentrations up to 20% in ointment caused only minimal irritation to the skin and did not cause any severe changes. In both studies, the criteria for classification as irritant or corrosive according to the CLP Regulation were not fulfilled.

Justification for read-across

The two skin irritation studies were conducted using a mixture containing 30.2% zinc 3,5-bis(alpha-methylbenzyl)salicylate.

The remaining substances present in the mixture include:

-         5.5% PSMS-11

-         1.1% PVA

-         0.7% DIBLAME

-         < 1% Other

-         Remainder: water

PSMS-11 and PVA are not considered to be hazardous substances. DIBLAME is classified as H315: Causes skin irritation, H317: May cause an allergic skin reaction and H411: Toxic to aquatic life with long lasting effects. However, the concentration of DIBLAME in mixture is below that which triggers classification of the mixture for these hazards. Therefore, it is considered justified to read-across from this mixture to zinc 3,5-bis(α-methylbenzyl)salicylate.

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.


Justification for selection of skin irritation / corrosion endpoint:
Only study that was conducted in accordance with GLP and recognised guideline.

Justification for selection of eye irritation endpoint:
Only 1 study is available.

Effects on eye irritation: corrosive

Justification for classification or non-classification

The above studies have been ranked reliability 1 or 2 according to the Klimisch et al system. This ranking was deemed appropriate because the studies were conducted according to recognised test methods. Sufficient dose ranges and numbers are detailed; hence they are appropriate for use based on reliability and animal welfare grounds.

The above results triggered classification under the CLP Regulation (EC No 1272/2008) as Eye Damage Category 1.