Registration Dossier

A valid skin irritation/corrosion study and a valid eye irritation study are available. 2,2-dimethylpropane-1,3-diyl dibenzoate was slightly irritating to the skin and slightly irritating to the eyes,

which does not lead to classification or labelling.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Similar to the guideline of today, observation time 7 days, no GLP

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Observation period 7 days

GLP compliance:

no

Specific details on test material used for the study:

- yellowish white chunks

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2066-2380 g
- Housing: individually
- Diet ad libitum
- Water ad libitum
- Acclimation period: 9 days

ENVIRONMENTAL CONDITIONS
- temperature and humidity controlled quarters
- The animals were maintained in accordance with the recommendations contained in H.E.W. Publication No.74-23 (N.I.H.) entitled "Guide for the care and use of laboratory animals"

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped and 3/6 rabbits abraded

Vehicle:

not specified

Controls:

other: the opposite site of the back

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

24 hours

Observation period:

up to 72 hours

Number of animals:

6: 3/6 with intact skin and 3/6 with abraded skin

Details on study design:

3 male and 3 female rabbits were used for this study. The hair was removed from the back of each rabbit (20-30% of the body surface) with an electric clipper. The skin of 3 of the rabbits was abraded with a scalpel blade. 500 mg of the test material was applied to the back of each rabbit and covered by semiocclusive dressing. The opposite site of the treated area served as control. Following 24 hours of application the bandages were removed and the application sites were washed with tepid water and examined for skin irritation. These examinations were repeated at 72 hours.

Irritation parameter:

erythema score

Basis:

other: mean animals with intact skin

Time point:

other: 24 hours

Score:

ca. 0 - ca. 1

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: 1/3 animals showed erythema score 1 of max 4 at 24 hours.

Irritation parameter:

erythema score

Basis:

other: mean animals with intact skin

Time point:

other: 72 hours

Score:

ca. 0

Max. score:

4

Remarks on result:

other: No rabbit with intact skin showed erythema at 72 hours.

Irritation parameter:

edema score

Basis:

other: mean animals with intact skin

Time point:

other: 24 hours up to 72 hours

Score:

ca. 0

Max. score:

4

Reversibility:

other: N edema were observed.

Irritant / corrosive response data:

Animals with abraded skin showed erythema up to erythema score 2 at 24 hours and at 72 hours. 2/3 animals showed no erythema and 1/3 animals showed score 1 erythema. 1/3 animals with abraded skin showed edema up to 72 hours (score 1/4). 2/3 animals showed no edema.

Interpretation of results:

GHS criteria not met

Conclusions:

2,2-dimethylpropane-1,3-diyl dibenzoate has to be evaluated as minimal to slightly irritating to the skin of rabbits, which does not lead to classification or labelling.

Executive summary:

3 male and 3 female rabbits were used for a skin irritation study similar to the respective OECD guideline. The hair was removed from the back of each rabbit (20-30% of the body surface) with an electric clipper. The skin of 3 of the rabbits was abraded with a scalpel blade. 500 mg of the test material was applied to the back of each rabbit and covered by semiocclusive dressing. The opposite site of the treated area served as control. Following 24 hours of application the bandages were removed and the application sites were washed with tepid water and examined for skin irritation. These examinations were repeated at 72 hours.

Based on the available results the primary irritation score was calculated to be 0.6. Thus 2,2-dimethylpropane-1,3-diyl dibenzoate has to be evaluated as minimal to slightly irritating to the skin of rabbits, which does not lead to classification or labelling.

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Similar to the guideline of today, observation time 7 days, no GLP

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Observation period 7 days

GLP compliance:

no

Specific details on test material used for the study:

- yellowish white chunks

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2005-2676 g
- Housing: individually
- Diet ad libitum
- Water ad libitum
- Acclimation period: 9 days

ENVIRONMENTAL CONDITIONS
- temperature and humidity controlled quarters
- The animals were maintained in accordance with the recommendations contained in H.E.W. Publication No.74-23 (N.I.H.) entitled "Guide for the care and use of laboratory animals"

Vehicle:

unchanged (no vehicle)

Controls:

other: the left eye of each rabbit

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

not relevant

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6

Details on study design:

3 male and 3 female rabbits were used. Prior to test material administration the eyes of each rabbit were examined for corneal lesions with sodium fluorescein solution to exclude rabbits with lesions. The rabbits received 100 mg of the test material into the cupped conjunctival sac of the right eye of each rabbit and then the eyelids were gently held together for 1 second. The left eye served as the untreated control. None of the rabbits received a washout. The evaluation was done according to Draize at 1, 24, 48, 72 hours and at day 7 following installation including fluorescein staining of the cornea.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: from 1 hour up to 7 days

Score:

ca. 0

Max. score:

4

Remarks on result:

other: No effects on corneas of 6/6 rabbits were observed.

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 1hour up to 7 days

Score:

ca. 0

Max. score:

3

Remarks on result:

other: No effects were observed in the iris of 6/6 rabbits.

Irritation parameter:

other: conjunctiva score (includes redness, chemosis, discharge)

Basis:

animal #1

Time point:

other: 1 hour - 72 hour

Score:

ca. 0.2 - ca. 3.8

Max. score:

20

Irritation parameter:

other: conjunctiva score (includes redness, chemosis, discharge)

Basis:

animal #1

Time point:

other: 7 days

Score:

ca. 0

Max. score:

20

Reversibility:

fully reversible

Irritation parameter:

other: conjunctiva score (includes redness, chemosis, discharge)

Basis:

animal #2

Time point:

other: 1hour - 24 hour

Score:

ca. 3 - ca. 4

Max. score:

20

Irritation parameter:

other: conjunctiva score (includes redness, chemosis, discharge)

Basis:

animal #2

Time point:

other: 48 hour - 7 days

Score:

ca. 0

Max. score:

20

Reversibility:

fully reversible

Irritation parameter:

other: conjunctiva score (includes redness, chemosis, discharge)

Basis:

animal #3

Time point:

other: 1 hour - 24 hour

Score:

ca. 4 - ca. 6

Max. score:

20

Irritation parameter:

other: conjunctiva score (includes redness, chemosis, discharge)

Basis:

animal #3

Time point:

other: 48 hour - 7 days

Score:

ca. 0

Max. score:

20

Reversibility:

fully reversible

Irritation parameter:

other: conjunctiva score (includes redness, chemosis, discharge)

Basis:

animal #4

Time point:

other: 1 hour - 72 hour

Score:

ca. 1 - ca. 3

Max. score:

20

Irritation parameter:

other: conjunctiva score (includes redness, chemosis, discharge)

Basis:

animal #4

Time point:

other: 7 days

Score:

ca. 0

Max. score:

20

Reversibility:

fully reversible

Irritation parameter:

other: conjunctiva score (includes redness, chemosis, discharge)

Basis:

animal #5

Time point:

other: 1 hour

Score:

ca. 5

Max. score:

20

Irritation parameter:

other: conjunctiva score (includes redness, chemosis, discharge)

Basis:

animal #5

Time point:

other: 24 hour - 7 days

Score:

ca. 0

Max. score:

20

Reversibility:

fully reversible

Irritation parameter:

other: conjunctiva score (includes redness, chemosis, discharge)

Basis:

animal #6

Time point:

other: 1 hour

Score:

ca. 4

Max. score:

20

Irritation parameter:

other: conjunctiva score (includes redness, chemosis, discharge)

Basis:

animal #6

Time point:

other: 24 hour - 7 days

Score:

ca. 0

Max. score:

20

Reversibility:

fully reversible

Irritant / corrosive response data:

None of the animals showed corneal lesions or effects on the iris. Slight conjunctival redness was observed in all animals, but recovery occurred within 7 days. The very slight chemosis observed at 24 h and the very slight to slight discharge at 1 h disappeared within 48 hours.

Interpretation of results:

GHS criteria not met

Conclusions:

2,2-dimethylpropane-1,3-diyl dibenzoate has to be evaluated as mildly irritating to the eyes of rabbits, which does not lead to classification or labelling.

Executive summary:

3 male and 3 female rabbits were used. Prior to test material administration the eyes of each rabbit were examined for corneal lesions with sodium fluorescein solution to exclude rabbits with lesions. The rabbits received 100 mg of the test material into the cupped conjunctival sac of the right eye of each rabbit and then the eyelids were gently held together for 1 second. The left eye served as the untreated control. None of the rabbits received a washout. The evaluation was done according to Draize at 1, 24, 48, 72 hours and at day 7 following installation including fluorescein staining of the cornea.

None of the animals showed corneal lesions or effects on the iris. Slight conjunctival redness was observed in all animals, but recovery occurred within 7 days. The very slight chemosis observed at 24 h and the very slight to slight discharge at 1 h disappeared within 48 hours.

Thus 2,2-dimethylpropane-1,3-diyl dibenzoate is evaluated as mildly irritating to the eyes of rabbits.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin irritation

3 male and 3 female rabbits were used for a skin irritation study similar to the respective OECD guideline. The hair was removed from the back of each rabbit (20-30% of the body surface) with an electric clipper. The skin of 3 of the rabbits was abraded with a scalpel blade. 500 mg of the test material was applied to the back of each rabbit and covered by semiocclusive dressing. The opposite site of the treated area served as control. Following 24 hours of application the bandages were removed and the application sites were washed with tepid water and examined for skin irritation. These examinations were repeated at 72 hours.

Based on the available results the primary irritation score was calculated to be 0.6. Thus 2,2-dimethylpropane-1,3-diyl dibenzoate has to be evaluated as minimal to slightly irritating to the skin of rabbits, which does not lead to classification or labelling.

Eye irritation

3 male and 3 female rabbits were used. Prior to test material administration the eyes of each rabbit were examined for corneal lesions with sodium fluorescein solution to exclude rabbits with lesions. The rabbits received 100 mg of the test material into the cupped conjunctival sac of the right eye of each rabbit and then the eyelids were gently held together for 1 second. The left eye served as the untreated control. None of the rabbits received a washout. The evaluation was done according to Draize at 1, 24, 48, 72 hours and at day 7 following installation including fluorescein staining of the cornea.

None of the animals showed corneal lesions or effects on the iris. Slight conjunctival redness was observed in all animals, but recovery occurred within 7 days. The very slight chemosis observed at 24 h and the very slight to slight discharge at 1 h disappeared within 48 hours.

Thus 2,2-dimethylpropane-1,3-diyl dibenzoate is evaluated as mildly irritating to the eyes of rabbits.

Justification for selection of skin irritation / corrosion endpoint:
There is only one study available, which is performed similar to the guidelines of today.

Justification for selection of eye irritation endpoint:
There is only one study available, which is performed similar to the guideline of today.

Skin irritation

Based on the available data 2,2-dimethylpropane-1,3-diyl dibenzoate is evaluated as slightly irritating to the skin, which does not lead to classification or labelling.

Eye irritation

Based on the available data 2,2-dimethylpropane-1,3-diyl dibenzoate is evaluated as slightly irritating to the eyes, which does not lead to classification or labelling.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.