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Description of key information

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:
1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Mellor rabbits, Chedderton heights, Chedderton UK
- Weight at study initiation: 2000-2620 g for males and 1775-2736 g for females
- Housing: The rabbits were housed individually in satinised aluminium sheet cages (605mm width x 490mm depth x 455mm height). The floor of each cage was made of perforated aluminium sheet and the door was made of polycarbonate (MAKROLON).
- Diet (e.g. ad libitum): The animals were allowed free access to food and were given access to unlimited water via an automatic system.
- Acclimation period: 6 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16°C
- Humidity (%): 50±10%
- Air changes (per hr): 20-30
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light and 12 hours of darkness.
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
other: Moistened with water
Controls:
not specified
Amount / concentration applied:
Approximately 500 mg moistened with water
Duration of treatment / exposure:
4 h
Observation period:
1, 24, 48 and 72 h
Number of animals:
6 males
Details on study design:
TEST SITE
- Area of exposure: left flank
- Type of wrap if used: The treated area was covered with a piece of surgical gauze (approximate size 25mm x 25mm; 8 ply) which was secured by two crossed strips of surgical tape (approximate size 12mm x 80mm). This was covered by a piece of impermeable rubber sheeting (approximate size 350mm x 135mm) wrapped once around the trunk of the animal and secured with adhesive impermeable polyethylene tape (75mm wide).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test sample using clean swabs of absorbent cotton wool soaked in clean warm water and was then dried gently with clean tissue paper.

OBSERVATION TIME POINTS
(indicate if minutes, hours or days)

1, 24, 48 and 72 h

SCORING SYSTEM:
- Method of calculation: Draise system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Due to red color of the substance erythema score cannot be calulated
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Due to red color of the substance erythema score cannot be calulated
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Due to red color of the substance erythema score cannot be calulated
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Due to red color of the substance erythema score cannot be calulated
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Due to red color of the substance erythema score cannot be calulated
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Due to red color of the substance erythema score cannot be calulated
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 3 d
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 3 d
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 3 d
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.75
Max. score:
4
Reversibility:
fully reversible within: 3 d
Remarks on result:
probability of mild irritation
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 3 d
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 3 d
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the substance was not irritating to rabbit skin.
Executive summary:

A study was conducted to determine the skin irritation potential of the test substance according to a method similar to OECD Guideline 404, in compliance with GLP. New-Zealand White rabbits were exposed for 4 h to 0.5 g of test substance wetted with water. The experiment consisted in an occlusive coverage on clipped skin free of fur. Following application, animals were observed after 1, 24, 48 and 72 h. The mean scores for oedema were between 0 and 0.1 and all effects were reversible within 3 d. The erythema score could not be calculated because of red coloration of the skin due to the test substance. Under the study conditions, the substance was not irritating to rabbit skin (Pemberton, 1987).

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:
1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Mellor rabbits, Chedderton heights, Chedderton UK
- Weight at study initiation: 2000-2620 g for males and 1775-2736 g for females
- Housing: The rabbits were housed individually in satinised aluminium sheet cages (605mm width x 490mm depth x 455mm height). The floor of each cage was made of perforated aluminium sheet and the door was made of polycarbonate (MAKROLON).
- Diet (e.g. ad libitum): The animals were allowed free access to food and were given access to unlimited water via an automatic system.
- Acclimation period: 6 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16°C
- Humidity (%): 50±10%
- Air changes (per hr): 20-30
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light and 12 hours of darkness.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
24 h
Observation period (in vivo):
21 d
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): fir three animals irrigation was done for 2 min
- Time after start of exposure: 1 minute

Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
80
Reversibility:
other: irreversible red colortion of cornea
Remarks on result:
probability of severe irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1-2 h
Score:
8
Max. score:
20
Reversibility:
fully reversible within: 7 d
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24 h
Score:
7.3
Max. score:
20
Reversibility:
fully reversible within: 7 d
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
48 h
Score:
3.3
Max. score:
20
Reversibility:
fully reversible within: 7 d
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
72 h
Score:
2.7
Max. score:
20
Reversibility:
fully reversible within: 7 d
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
20
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24 h
Score:
1.7
Max. score:
10
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
10
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.5
Max. score:
10
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
not measured/tested
Irritant / corrosive response data:
Initial Pain: Following application of 100mg of the test sample into the rabbit eye practically no initial pain reaction was seen in one animal and slight initial pain reactions were seen in the remaining animals (classes 1 and 2 on a 0-5 scale). One animal was holding its eye closed, as if in pain, 1-2 hours after application.

Irrigated Eyes: Approximately half the test sample was displaced from the conjunctival sac of one animal shortly after application.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Under the study conditions, the substance was severe irritating to rabbit eye.
Executive summary:

A study was conducted to determine the eye irritation potential of the test substance according to a method similar to OECD Guideline 405, in compliance with GLP. Six female rabbits were used for the study. 100 mg of test substance were loaded into the conjunctival sac of the left eye of the animals. Three animals were washed out with warm water after 1 minute of exposure to the test substance. One animal among the three of the washout group died after 24 h, however it was concluded that the death was not due to the test substance. In non-washout animals, up to at least 3 d after application, corneal opacity could not be assessed due to staining. In the two animals in which it was subsequently possible to assess, no signs of corneal opacity were seen. Iritis could not be assessed for up to 1 d after application in two of the animals. After this period, slight iritis was seen on Day 1 in one animal only. No iritis was seen in either of the other animals during the study. Due to staining, however, iritis could not be assessed in one of the animals until the third reading. Additional observations included corneal, iridial and conjunctival staining by the test sample, which persisted to the end of the study (21 days after application), dried secretion on the periorbital skin and three animals holding their eye closed 1-2 h after application. Due to the irreversible coloration of cornea, the test substance was considered to be a severe irritant (Pemberton, 1987).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation (in vivo):

A study was conducted to determine the skin irritation potential of the test substance according to a method similar to OECD Guideline 404, in compliance with GLP. New-Zealand White rabbits were exposed for 4 h to 0.5 g of test substance wetted with water. The experiment consisted in an occlusive coverage on clipped skin free of fur. Following application, animals were observed after 1, 24, 48 and 72 h. The mean scores for oedema were between 0 and 0.1 and all effects were reversible within 3 d. The erythema score could not be calculated because of red coloration of the skin due to the test substance. Under the study conditions, the substance was not irritating to rabbit skin (Pemberton, 1987).

Eye irritation (in vivo):

A study was conducted to determine the eye irritation potential of the test substance according to a method similar to OECD Guideline 405, in compliance with GLP. Six female rabbits were used for the study. 100 mg of test substance were loaded into the conjunctival sac of the left eye of the animals. Three animals were washed out with warm water after 1 minute of exposure to the test substance. One animal among the three of the washout group died after 24 h, however it was concluded that the death was not due to the test substance. In non-washout animals, up to at least 3 d after application, corneal opacity could not be assessed due to staining. In the two animals in which it was subsequently possible to assess, no signs of corneal opacity were seen. Iritis could not be assessed for up to 1 d after application in two of the animals. After this period, slight iritis was seen on Day 1 in one animal only. No iritis was seen in either of the other animals during the study. Due to staining, however, iritis could not be assessed in one of the animals until the third reading. Additional observations included corneal, iridial and conjunctival staining by the test sample, which persisted to the end of the study (21 days after application), dried secretion on the periorbital skin and three animals holding their eye closed 1-2 h after application. Due to the irreversible coloration of cornea, the test substance was considered to be a severe irritant (Pemberton, 1987).

Justification for classification or non-classification

Skin irritation:

Based on an in vivo skin irritation/corrosion study, the substance does not warrant classification for this endpoint according to CLP (EC 1272/2008) criteria.

Eye irritation:

Based on the results of an in vivo eye irritation study, the test substance is considered to cause serious damage to the eyes, with a classification as Eye Damage 1 - H318 (Causes serious eye damage) according to CLP (EC 1272/2008) criteria.