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Administrative data

Description of key information

Skin irritation in vivo (OECD TG 404): not irritating (reference 7.3.1-1).

Eye irritation in vivo (OECD TG 405): not irritating (reference 7.3.2-1).

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:
05.03.1990 to 12.03.1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: SAVO-Ivanovas, Kisslegg
- Age at study initiation: 16 - 17 weeks
- Weight at study initiation: 3.10 (3.04 - 3.21) kg
- Housing: KK 017 (floor area: 75 x 54.5 = 4087 cm2, height: 38 cm; manufacturer: Hulskamp)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 24
- Humidity (%):41 to 56
- Air changes (per hr): not specified but, air-conditioned room
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 05.03.1990 until 12.0.3.1990
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
0.5 g test item, were moistened with water (aqua pro injectione) and were spread onto 4 cm 2 patches.
Duration of treatment / exposure:
4 h
Observation period:
The rabbits were examined for skin alterations, behaviour and general condition 1 hour after removal of the patches, after 24, 48 and 72 hours, and then daily up to experimental day 8.
Number of animals:
3 (2 female, 1 male)
Details on study design:
TEST SITE
- Area of exposure: left side of animal's back
- Type of wrap if used: polyethylene foil which was kept in place by a leather sleeve.

REMOVAL OF TEST SUBSTANCE
- Washing: Yes
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
1 hour, 24, 48, 72 hours and then daily up to experimental day 8 after patch removal

SCORING SYSTEM:
- Method of calculation: Draize scheme
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
No skin irritating potential could be detected.
Other effects:
- Other adverse local effects: none
- Other adverse systemic effects: No signs of clinical toxicity were detected. All animals survived the observation period. Body weight development of the treated rabbits was inconspicuous.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item is considered to be not irritating to skin.
Executive summary:

The skin irritation potential of the test item was investigated according to OECD Guideline 404 under GLP conditions. An amount of 0.5 g of the test material was mixed with several drops of Aqua pro injectione to ensure good skin contact. The initial test with one animal and the confirmatory test with two further animals showed no signs of irritation at the treated areas following single application to the intact dorsal skin of rabbits for 4 hours under occlusive conditions. No signs of clinical toxicity were detected. All animals survived the observation period. Body weight development of the treated rabbits was inconspicuous. Under the conditions of the present study no signs of irritation were seen.

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:
05.03.1990 to 12.03.1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: SAVO-Ivanovas, Kisslegg
- Age at study initiation: 16 - 17 weeks
- Weight at study initiation: 3.10 (3.04 - 3.21) kg
- Housing: KK 017 (floor area: 75 x 54.5 = 4087 cm2, height: 38 cm; manufacturer: Hulskamp)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 24
- Humidity (%):41 to 56
- Air changes (per hr): not specified but, air-conditioned room
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 05.03.1990 until 12.0.3.1990
Vehicle:
water
Controls:
no
Amount / concentration applied:
0.1 g test item, were instilled into the conjunctival sac of the left eye of all animals.
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM:
CORNEA
Opacity: degree of density (area most dense taken for reading)
0 no ulceration or opacity
1 scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible
2 easily discernible translucent area, details of iris slightly obscured
3 nacreous areas, no details of iris visible, size of pupil barely discernible
4 Opaque cornea, iris not discernible through the opacity

IRIS
0 normal
1 markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2 no reaction to light, haemorrhage, gross destruction (any or all of these)

CONJUNCTIVAE
Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)
0 blood vessels normal
1 some blood vessels definitely hyperaemic (injected)
2 diffuse, crimson colour, individual vessels not easily discernible
3 diffuse beefy red

Chemosis: lids and/or nictitating membrane
0 no swelling
1 any swelling above normal (including nictitating membranes)
2 obvious swelling with partial eversion of lids
3 swelling with lids about half-closed
4 swelling with lids more than half-closed
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 3 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 3 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 3 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritant / corrosive response data:
Reversibility of any observed effect: Changes fully reversible within 3 days.
Interpretation of results:
GHS criteria not met
Conclusions:
According to the conducted study, the test substance is not regarded as irritant to the eyes.
Executive summary:

In a primary eye irritation study in accordance with OECD guideline 405 and EU method B.5, 0.1 g of the undiluted test substance was instilled into the conjunctival sac of the right eye of three female New Zealand White rabbits. The eyes were not washed. Animals were then observed for up to 8 days. Irritation was scored by the method of Draize.

 

 

Mean score

(24, 48, and 72 hours)

Maximum value
(2d, 48, or 72 hours)

Animal No.

 

1

2

3

1

2

3

Cornea

A

0

0

0.3

0

0

1

 

B

0

0

1.3

0

0

4

Iris

A

0

0

0

0

0

0

Conjunctivae

A

1.3

0.6

1.3

2

1

2

 

B

0.3

0

0.6

1

0

2

Discharge

 

 

 

 

 

 

 

 

After single instillation of 0.1 g test item, into the conjunctival sac of the left eye, without rinsing, in 1 animal opacity of cornea (score 1) was seen on day 2. Redness and chemosis of conjunctivae were observed in all 3 animals up to day 3 of the study (mean 1.1). The rabbits showed discharge at the first and second reading. No signs of irritation were observed the iris. The untreated eyes were unchanged. Based on the above results the test substance was non-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

The skin irritation potential of the test item was investigated according to OECD Guideline 404 under GLP conditions. An amount of 0.5 g of the test material was mixed with several drops of Aqua pro injectione to ensure good skin contact. The initial test with one animal and the confirmatory test with two further animals showed no signs of irritation at the treated areas following single application to the intact dorsal skin of rabbits for 4 hours under occlusive conditions. No signs of clinical toxicity were detected. All animals survived the observation period. Body weight development of the treated rabbits was inconspicuous. Under the conditions of the present study no signs of irritation were seen.

Eye irritation

In a primary eye irritation study in accordance with OECD guideline 405 and EU method B.5, 0.1 g of the undiluted test substance was instilled into the conjunctival sac of the right eye of three female New Zealand White rabbits. The eyes were not washed. Animals were then observed for up to 8 days. Irritation was scored by the method of Draize.

 

 

Mean score

(24, 48, and 72 hours)

Maximum value
(2d, 48, or 72 hours)

Animal No.

 

1

2

3

1

2

3

Cornea

A

0

0

0.3

0

0

1

 

B

0

0

1.3

0

0

4

Iris

A

0

0

0

0

0

0

Conjunctivae

A

1.3

0.6

1.3

2

1

2

 

B

0.3

0

0.6

1

0

2

Discharge

 

 

 

 

 

 

 

 

After single instillation of 0.1 g test item, into the conjunctival sac of the left eye, without rinsing, in 1 animal opacity of cornea (score 1) was seen on day 2. Redness and chemosis of conjunctivae were observed in all 3 animals up to day 3 of the study (mean 1.1). The rabbits showed discharge at the first and second reading. No signs of irritation were observed the iris. The untreated eyes were unchanged. Based on the above results the test substance was non-irritating to eyes.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered not to be classified for eye or skin irritation under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) No 2019/521.

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