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Description of key information

Two in vivo skin irritation studies are available, both studies were conducted before GLP principles were in place (Klimisch 2 studies). Both studies represent worst case situations, as exposure was done occlusively for 24 hours (with sufficient amount of test material).

Two in vivo eye irritation studies are available, both studies were conducted before GLP principles were in place (Klimisch 2 studies).

The available data do not indicate corrosive or irritant effects on skin or eyes.

In addition, a study summary of an in vivo skin and eye irritancy test is available. The information is not sufficient for final conclusion on classification (Klimisch 4 study). However, the results do not contradict the other studies, so the information is used as supportive data.

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Study design unknown, available as short abstract, limitations in reporting
Qualifier:
according to guideline
Guideline:
other: Federal Register 38, No. 187, §1500.41 (Haut), S. 27019
Version / remarks:
September 27, 1973
Principles of method if other than guideline:
assessment of results according to: Draize, J.H. (1959): Dermal Toxicity. In: FDA appraisal of the Safety of the Chemicals in Foods, Drugs and Cosmetics
GLP compliance:
no
Remarks:
Study performed before GLP principles were in place.
Species:
rabbit
Type of coverage:
not specified
Preparation of test site:
other: scarification
Irritation parameter:
primary dermal irritation index (PDII)
Score:
0.3
Max. score:
5
Reversibility:
fully reversible within: 3 days
Interpretation of results:
study cannot be used for classification
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
other: "Hazardous Substances Regulations" under the U.S. Federal Hazardous Substances Labelling Act Sect. 191.11
Version / remarks:
February 1965
GLP compliance:
no
Remarks:
Study performed before GLP principles were in place.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: bred on the premises
- Age at study initiation: 3-4 months
- Weight at study initiation: male 2.54 kg and female 2.46 kg
- Housing: single
- Diet: a commercial irradiated diet (Styles-Oxoid) ad libitum
- Water: sterile filtered water was available at al times
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±1
- Humidity (%): 50-70
- Photoperiod (hrs dark / hrs light): 10 hours artificial light (08.00-18.00h)
Type of coverage:
occlusive
Preparation of test site:
other: left shaved; right shaved+abraded
Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g

VEHICLE
- Amount applied: 0.5 mL
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2 test sites of 2.5 cm2
- % coverage: 10%
- Type of wrap if used: Gauze pad covered with aluminium foil secured with "Sleek" adhesive tape. The test sites were then enclosed by a 6" wide "Coban"-self adhesive bandage the edges of which were fixed to the skin by strips of "Sleek" in order to retain the test substance in close contact with the skin.

REMOVAL OF TEST SUBSTANCE
- Washing: No
- Time after start of exposure: 24 hours

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: intact and abraded skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: intact and abraded skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: intact and abraded skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: intact and abraded skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: intact and abraded skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: intact and abraded skin
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
ca. 1.17
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: intact and abraded skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: intact and abraded skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: intact and abraded skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
72 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: intact and abraded skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
72 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: intact and abraded skin
Irritation parameter:
edema score
Basis:
animal #5
Time point:
72 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: intact and abraded skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
72 h
Score:
ca. 0
Max. score:
4
Reversibility:
fully reversible within: 72h
Remarks on result:
other: intact and abraded skin
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of an in vivo test, in which 6 New Zealand White rabbits (3 male, 3 female) were occlusively exposed to 0.5 g of the test substance in 0.5 mL water for 24 hours, it is concluded that the test substance is not corrosive and not irritant to the skin.
Executive summary:

In a skin irritation test, 6 New Zealand White rabbits (3 male, 3 female) were exposed to 0.5 g of the test substance in 0.5 mL water. Twenty-four hours prior to the dermal application, the backs of the rabbits were shaved over an area consisting of at least 10% of the total body surface. Two test sites lateral to the mid line of the back were used on each rabbit. Immediately before the application of the test compound, the right hand site was abraded. The application site was covered with aluminium foil secured with adhesive tape. The test sites were then enclosed by a self adhesive bandage the edges of which were fixed to the skin. After 24 hours, the dressing was removed and the intact and abraded application sites were assessed for oedema and erythema. A further assessment was made at 72 hours. Mild to moderate oedema was seen at the test sites in 3/6 rabbits 24 hours after application of the test compound. There was no difference between intact and abraded sites. This reaction had subsided by 72 hours. The primary irritation score was 0.6. The substance is not considered to be corrosive and/or irritating to rabbit skin.

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

Eye irritation

Link to relevant study records

Referenceopen allclose all

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: see 'Remark'
Remarks:
Non-GLP non-guideline study, available as unpublished report, predates implementation of GLP and/or development of study guidelines, notable limitations in design and/or reporting. After application eye lids were held open for a few seconds instead of closed.
Qualifier:
according to guideline
Guideline:
other: "Hazardous Substances Regulations" under the U.S.A. Federal Hazardous Substances Labelling Act Sect. 191.12
Version / remarks:
February 1965
GLP compliance:
no
Remarks:
Study performed before GLP principles were implemented.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: bred on the premises
- Age at study initiation: 3-4 months
- Weight at study initiation: male 2.54 kg and female 2.46 kg
- Housing: single
- Diet: a commercial irradiated diet (Styles-Oxoid) was fed ad libitum
- Water: sterile filtered water was available at all times
- Acclimation period: one week prior to the start of the trial

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±1
- Humidity (%): 50-70
- Photoperiod (hrs dark / hrs light): artificial light for 10 hours daily from 08.00 - 18.00 hours
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits with warm water for 1 minute.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: the eyes of three of the rabbits with warm water
- Time after start of exposure: 30 seconds

SCORING SYSTEM: Draize
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
24 h
Score:
0.17
Max. score:
3
Reversibility:
fully reversible within: 2 days
Irritant / corrosive response data:
The mean score for redness at one and six hours after instillation was 1 (maximum 3). The mean score for chemosis at one and six hours after instillation was 0.17 (maximum 4). The mean score for discharge at one hour after instillation was 1 (maximum 3) and 0.17 after six hours. This was fully reversed after 2 days.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of an in vivo eye irritancy study study with 6 New Zealand White rabbits, the substance is found to be not irritating to eyes.
Executive summary:

In an eye irritation test 6 New Zealand White rabbits received 100 mg of the test substance into the conjunctival sac of the left eye with a spatula. After application, the eyelids were held closed for one second. The right eye served as a control. After 30 seconds the treated eyes of three rabbits were each rinsed with warm water for 1 minute after treatment. The rabbits were examined 1, 6, 24, 48 and 72 hours after application. A minimal conjunctival reaction was seen in all eyes one hour after treatment. From 6 hours onwards this regressed and all eyes were normal by 48 hours. Based on these results, the substance does not have to be lassified for eye irritant properties.

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: Non-GLP non-guideline study, available as unpublished report, predates implementation of GLP and/or development of study guidelines, minor restrictions in design and/or reporting but otherwise adequate for assessment.
Qualifier:
according to guideline
Guideline:
other: Federal Register 38 No. 187 paragraph 1500.42 (eye) page 27019
Version / remarks:
September 27, 1973
GLP compliance:
no
Remarks:
Study performed before GLP principles were implemented.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3-4 kg
- Housing: single, in stainless steel cages
- Diet: standard rabbit pellet feed, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2;
- Humidity (%): 55±10;
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 light from 7.00-19.00h;
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
one instillation
Observation period (in vivo):
up to 7 days
Number of animals or in vitro replicates:
6
Details on study design:
SCORING SYSTEM: Draize
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.89
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours, 7 days
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hours, 7 days
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24 hours
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 48 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 72 hours
Score:
0.17
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 7 days
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 hours
Score:
0.17
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 48, 72 hours, 7 days
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
mean
Time point:
other: 24, 48, 72 hours, 7 days
Score:
0
Max. score:
3
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of an in vivo eye irritancy study, the substance is found to be not irritating to eyes.
Executive summary:

In an eye irritation test 6 New Zealand White rabbits received 100 mg of the test substance into the conjunctival sac of one eye. The other eye served as a control. The rabbits were examined 1, 24, 48 and 72 hours after application. When irritation was observed the observation period would be extended to 7 days. A minimal conjunctival reaction was seen from one hour to 72 hours after the application of the compound. Based on the results of this study, the substance is found to be not irritating to eyes.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In a skin irritation test, 6 New Zealand White rabbits were exposed to 0.5 g of the test substance in a 22% solution of lutrol:water (15:20). Two to 16 hours prior to the dermal application, the backs of the rabbits were shaved. Two test sites lateral to the mid line of the back were used on each rabbit. Immediately before the application of the test compound, the left hand site was scarified. The application site was covered with gauze and an elastic bandage. The trunk of the animal was thereafter covered with plastic foil fixed with adhesive tape. After 24 hours the dressing was removed and the skin was washed with warm water or a lutrol-water mixture. The rabbits were examined 24 and 72 hours after application. A very slight erythema and oedema was present on the scarified skin 24 and 72 hours after application of the compound. All sites were clear by 7 days. Based on the results of this study, the substance is found to be not irritating to skin.

In a skin irritation test 6 New Zealand White rabbits (3 male, 3 female) were exposed to 0.5 g of the test substance in 0.5 mL water. Twenty-four hours prior to the dermal application, the backs of the rabbits were shaved over an area consisting of at least 10% of the total body surface. Two test sites lateral to the mid line of the back were used on each rabbit. Immediately before the application of the test compound, the right hand site was abraded. The application site was covered with aluminium foil secured with adhesive tape. The test sites were then enclosed by a self adhesive bandage the edges of which were fixed to the skin by strips of adhesive tape. After 24 hours the dressing was removed and the intact and abraded application sites were assessed for oedema and erythema. A further assessment was made at 72 hours. Mild to moderate oedema was seen at the test sites in 3/6 rabbits 24 hours after application of the test compound. There was no difference between intact and abraded sites. This reaction had subsided by 72 hours. The primary irritation score was 0.6. The substance is not considered to be irritating to rabbit skin.

Eye irritation

In an eye irritation test 6 New Zealand White rabbits received 100 mg of the test substance into the conjunctival sac of one eye. The other eye served as a control. The rabbits were examined 1, 24, 48 and 72 hours after application. When irritation was observed the observation period would be extended to 7 days. A minimal conjunctival reaction was seen from one hour to 72 hours after the application of the compound. Based on the results of this study, the substance is found to be not irritating to eyes.

In an eye irritation test 6 New Zealand White rabbits received 100 mg of the test substance into the conjunctival sac of the left eye with a spatula. After application, the eyelids were held closed for one second. The right eye served as a control. After 30 seconds the treated eyes of three rabbits were each rinsed with warm water for 1 minute after treatment. The rabbits were examined 1, 6, 24, 48 and 72 hours after application. A minimal conjunctival reaction was seen in all eyes one hour after treatment. From 6 hours onwards this regressed and all eyes were normal by 48 hours. Based on these results the substance is a minimal eye irritant.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes. As a result the substance is not classified for skin and eye irritation under Regulation (EC) No. 1272/2008.