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Description of key information

Skin irritation: not irritating, EPA OPP 81-5, Glaza 1995
Eye irritation: not irritating, EPA OPP 81-4, Glaza 1995

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to guideline; under GLP conditions.
Qualifier:
according to guideline
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: Hra:(NZW)SPF
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: not reported
- Weight at study initiation: 2.719 - 3.119 kg
- Housing: Test animals were individually housed in screen-bottomed stainless steel cages
- Diet (e.g. ad libitum): Certified rabbit diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 50 +/- 20
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark

IN-LIFE DATES: From: To: 1995-07-07 to 1995-07-10
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- No vehicle used, the test material was administered as received.
Duration of treatment / exposure:
4 hours
Observation period:
72 hours (observations made at 30 minutes, 24h, 48h and 72h).
Number of animals:
6 females
Details on study design:
TEST SITE
- Area of exposure: The test material was applied to the intact skin site on each animal's back (approximate exposure area of 6.25 cm2).
- % coverage: not reported.
- Type of wrap if used: The area of application was covered with a 2.5-cm X 2.5-cm gauze patch secured with paper tape, loosely overwrapped with Saran Wrap® and secured with Elastoplast® tape to provide a semiocclusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): patches were removed and the test sites were washed using tap water and disposable paper towels. The test material was removed from the test sites as thoroughly as possible without irritating the skin.
- Time after start of exposure: After the 4-hour exposure period.

SCORING SYSTEM: based pn the method of Draize.;
- Erythema and Eschar Formation
No erythema 0; Very slight erythema {barely perceptible) 1; Well-defined erythema 2; Moderate to severe erythema 3; Severe erythema {beet redness) to slight eschar formation (injuries in depth) 4
- Edema Formation
Very slight edema (barely perceptible) 0; Slight edema (edges are well defined by definite raising) 1; Moderate edema (raised approximately 1 mm) 2; Severe edema (raised approximately 1 mm and extending beyond area of exposure) 4

Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 4h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 48h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Irritant / corrosive response data:
No dermal irritation was observed.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the test material produced no dermal irritation effects. The test material is considered to be non-irritating to the skin.
Executive summary:

The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The study was performed to GLP and followed the EPA guideline 81-5. The test substance was evaluated in 6 female New Zealand white rabbits. A dose of 0.5 g test substance, moistened with 0.5 mL distilled water, was applied to the intact shorn dorsal skin site under a semi-occlusive dressing for 4 hours. The patch was then removed and the application site was washed to remove residual test material. Skin observations were made 30 minutes, 24, 48 and 72 hours after patch removal.

A single 4-hour, semi-occluded application of the test material to the intact skin produced no irritation effects. The test material produced a primary irritation index (PII) of 0 and is considered to be non-irritating to skin.

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:
1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to guideline; under GLP conditions.
Qualifier:
according to guideline
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: Hra:(NZW)SPF
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Recognised animal supplier.
- Age at study initiation: Not reported.
- Weight at study initiation: 2553 - 2948 g
- Housing: housed in screen-bottom stainless steel cages
- Diet (e.g. ad libitum): Certified rabbit diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23
- Humidity (%): 50 +/- 20
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12h light/12h dark

IN-LIFE DATES: From: To: 1995-07-11 to 1995-07-15
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 61 mg (0.1 ml weight equivalent).

VEHICLE
- Amount(s) applied (volume or weight with unit): The test material was administered as received.
- Concentration (if solution): n/a
- Lot/batch no. (if required): n/a
- Purity: n/a
Duration of treatment / exposure:
The eyes of the rabbits in Group 1 remained unflushed immediately after treatment while the treated eyes of the rabbits in Group 2 were flushed with lukewarm tap water for 1 minute starting 30 seconds after test material instillation.
Observation period (in vivo):
The treated eyes of both groups were observed for ocular irritation at 1, 24, 48, and 72 hours after treatment. Additional observations were made at 96 hours after treatment for the animals in Group 1. Irritation was graded and scored according to the Draize technique using a penlight as the source of illumination. A sodium fluorescein examination was used to aid in revealing possible corneal injury at 24 hours.
Number of animals or in vitro replicates:
Five male and four female rabbits were used in total. The rabbits were divided into two groups consisting of six rabbits in Group 1 and three rabbits
in Group 2.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes of the rabbits in Group 1 remained unflushed immediately after treatment while the treated eyes of the rabbits in Group 2 were flushed with lukewarm tap water for 1 minute starting 30 seconds after test material instillation.

SCORING SYSTEM: Draize scoring system and ocular irritation scoring scale (based on the method of Draize).

TOOL USED TO ASSESS SCORE: penlight and fluorescein
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 1h
Score:
9.7
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
other: Group 1
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 24h
Score:
4
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
other: Group 1
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 48h
Score:
2.7
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
other: Group 1
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 72h
Score:
0.3
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
other: Group 1
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 96h
Score:
0
Max. score:
110
Remarks on result:
other: Group 1
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 1h
Score:
7.7
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
other: Group 2
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 24h
Score:
2.7
Max. score:
110
Reversibility:
fully reversible
Remarks on result:
other: Group 2
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 48h
Score:
0
Max. score:
110
Remarks on result:
other: Group 2
Irritation parameter:
other: Average Primary eye irritation score
Basis:
mean
Time point:
other: 72h
Score:
0
Max. score:
110
Remarks on result:
other: Group 2
Irritant / corrosive response data:
All unwashed treated eyes (Group 1) had returned to a normal appearance by 96 hours after treatment. In the treated eyes receiving a washout approximately 30 seconds after instillation (Group 2), the test material produced iridal involvement and slight to moderate conjunctival irritation. All treated eyes in this group returned to a normal appearance by 48 hours after treatment.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the test material produced very mild eye irritating effects which fully reversed by 96h.
Executive summary:

The study was performed to assess the irritancy potential of the test material to the eye following a single application in the New Zealand White rabbit. The study was performed to GLP and the method was designed to meet the requirements of EPA Guideline 81 -4. A total of 9 animals were used and split into two groups with group 1 containing 6 animals and group 2 containing 3 animals. A volume of 0.1 ml (61mg) of the test material was placed into the conjunctival sac of the right eye of all 9 animals. The left eye remained untreated and was used for control purposes. The eyes of the rabbits in Group 1 remained unflushed immediately after treatment while the treated eyes of the rabbits in Group 2 were flushed with lukewarm tap water for 1 minute starting 30 seconds after test material instillation. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. Additional observations were made at 96 hours after treatment for the animals in Group 1. Irritation was graded and scored according to the Draize technique using a penlight as the source of illumination. A sodium fluorescein examination was used to aid in revealing possible corneal injury at 24 hours.

In the group 1 test animals, no corneal effects (opacity) were noted during the study. Iridial inflammation (grade 1) was noted for four animals at one hour. Minimal to moderate (grade 1 to 2) conjunctival irritation was noted for all animals one hour after treatment and at the 24 to 72 -hour observations. All treated eyes appeared normal at the 96h observation. In the group 2 test animals, no corneal effects (opacity) were noted during the study. Iridial inflammation (grade 1) was noted in 1 animal at one hour. Minimal to moderate (grade 1 to 2) conjunctival irritation was noted for all animals one hour after treatment and at the 24 -hour observations. All treated eyes appeared normal at the 48h observation. The test material produced a maximum group mean score of 9.7. Based on these results and according to the classification scheme of Kay and Calandra (1962), the test material is mildly irritating to eyes unwashed immediately after treatment and minimally irritating to eyes receiving a washout after treatment. The test material is considered to be non irritating according to the Commission Directive 93/21/EEC.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion

EPA OPP 81-5, Glaza 1995d: The test substance was evaluated in 6 female New Zealand white rabbits. A dose of 0.5 g test substance, moistened with 0.5 mL distilled water, was applied to the intact shorn dorsal skin site under a semi-occlusive dressing for 4 hours. The patch was then removed and the application site was washed to remove residual test material. Skin observations were made 30 minutes, 24, 48 and 72 hours after patch removal. A single 4-hour, semi-occluded application of the test material to the intact skin produced no irritation effects. The test material produced a primary irritation index (PII) of 0 and is considered to be non-irritating to skin.

 

Eye irritation:

EPA OPP 81-4, Glaza 1995e: The test substance was evaluated in 9 (4 male:5 female) New Zealand white rabbits. A volume of 0.1 ml (61mg) of the substance was placed into the conjunctival sac of 9 animals. The eyes of the rabbits in Group 1 remained unflushed immediately after treatment while the treated eyes of the rabbits in Group 2 were flushed with lukewarm tap water for 1 minute starting 30 seconds after test material installation. The left eye remained untreated. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, additional observations were made at 96 hours after treatment. Irritation was graded and scored according to the Draize technique using a penlight as the source of illumination. A sodium fluorescein examination was used to aid in revealing possible corneal injury at 24 hours. In the group 1 test animals, no corneal effects (opacity) were noted during the study. Iridial inflammation (grade 1) was noted for four animals at one hour. Minimal to moderate (grade 1 to 2) conjunctival irritation was noted for all animals one hour after treatment and at the 24 to 72 -hour observations. All treated eyes appeared normal at the 96h observation. In the group 2 test animals, no corneal effects (opacity) were noted during the study. Iridial inflammation (grade 1) was noted in 1 animal at one hour. Minimal to moderate (grade 1 to 2) conjunctival irritation was noted for all animals one hour after treatment and at the 24 -hour observations. All treated eyes appeared normal at the 48h observation. The test material produced a maximum group mean score of 9.7. Based on these results and according to the classification scheme of Kay and Calandra (1962), the test material is mildly irritating to eyes unwashed immediately after treatment and minimally irritating to eyes receiving a washout after treatment. The test material is considered to be non-irritating according to the Commission Directive 93/21/EEC and CLP Regulation 1272/2008.


Justification for selection of skin irritation / corrosion endpoint:
Robust study summary selected has lowest dose descriptor relevant for this endpoint.

Justification for selection of eye irritation endpoint:
Robust study summary selected has lowest dose descriptor relevant for this endpoint.

Justification for classification or non-classification

The substance does not meet classification criteria under EU Directive 67/548/EEC for dermal and eye irritation.

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for dermal and eye irritation.