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Administrative data

Description of key information

Two studies in rabbits were performed to evaluate irritating or corrosive properties of the test material to skin or eyes (OECD guideline 404 and 405). Application of the test substance did not provoke skin irritation. Treatment of rabbits eyes caused slight to minimal conjuctival irritation. All reaction on skin and eyes has resolved within 8 days or were below threshold of regulation. Therefore, the substance is not considered to be irritating.

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:
From Sep. 14, 1981 to Sep. 21, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Deviations:
yes
Remarks:
-protocol with occlusive application for 24h, which is more stringent than the OECD guideline 404, and observation period should be up to 14 days to determine reversibility effects
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Bred and raised rabbits on the premises (Ciba-Geigy Ltd. - Exp. Toxicology Sisseln GU 2.1)
- Age at study initiation: Adults
- Weight at study initiation: 2 to 3 kg
- Housing: Housed individually in metal cages
- Diet (e.g. ad libitum): ad libitum, standard rabbit food (NAFAG No. 814, Gossau SG)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
other: polyethylene glycol (PAG 400) + saline (70:30 parts)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): 50%

VEHICLE
- Amount(s) applied (volume or weight with unit): Not reported
- Concentration (if solution): 70:30 parts of polyethylene glycol (PAG 400) + saline
Duration of treatment / exposure:
24 hours
Observation period:
7 days
Number of animals:
3 males and 3 females
Details on study design:
TEST SITE
- Area of exposure: Before treatment, the entire back and flank of the rabbits were shaved and immediately before treatment the shaven skin on one side was slightly scarified. The test material was applied to the prepared abraded and intact skin.
- % coverage: 2.5 cm x 2.5 cm
- Type of wrap if used: The patches were covered with an impermeable material and were fastened to the body of the rabbit with adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not reported
- Time after start of exposure: 24 hours
The dressings were removed after a 24 hour application.

SCORING SYSTEM: The skin reaction was appraised upon removal and during an observation period of 7 days on the basis of the following evaluation scheme.

Score for skin irritation in rabbits
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
Total possible erythema score - 4

Edema formation
No edema - 0
Very slight edema (barely perceptible) - 1
Slight edema (edges of area well defined by definite raising) - 2
Moderate edema (raised approximately 1 mm) - 3
Severe edema (raised more than 1 mm and extending beyond area of exposure) - 4
Total possible edema score - 4

Assessment of irritation:
0
0.1-1.0 = minimal
1.1-2.0 = slight
2.1-4.0 = moderate
4.1-6.0 = marked
6.1-8.0 = extreme
Irritation parameter:
overall irritation score
Remarks:
intact skin
Basis:
mean
Time point:
24 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
overall irritation score
Remarks:
intact skin
Basis:
mean
Time point:
48 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
overall irritation score
Remarks:
intact skin
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
overall irritation score
Remarks:
intact skin
Basis:
mean
Time point:
other: 4 days
Score:
0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
overall irritation score
Remarks:
intact skin
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
overall irritation score
Remarks:
abraded skin
Basis:
mean
Time point:
24 h
Score:
1.7
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
overall irritation score
Remarks:
abraded skin
Basis:
mean
Time point:
48 h
Score:
1.2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
overall irritation score
Remarks:
abraded skin
Basis:
mean
Time point:
72 h
Score:
0.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
overall irritation score
Remarks:
abraded skin
Basis:
mean
Time point:
other: 4 days
Score:
0.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
overall irritation score
Remarks:
abraded skin
Basis:
mean
Time point:
7 d
Score:
0.2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24 h
Score:
0.8
Max. score:
8
Reversibility:
not specified
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
72 h
Score:
0.8
Max. score:
8
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
0.3
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Irritant / corrosive response data:
The test item was found to cause a minimal irritation when applied to intact and abraded rabbit skin.
The primary irritation index was 1.3//0.3 for erythema/edema at 24h and 0.0/0. for erythema/oedema at 72h for intact skin. No further findings on intact skin appeared until the last day of the observation period (day 7). Findings on abraded skin were still observed in one animal on day 7

Table 1. Primary Irritation Score

Time after exposure (hours)

Mean reaction score

Erythema

Edema

Intact skin

Abraded skin

Intact skin

Abraded skin

24

1.0

1.3

0.3

0.3

72

0

0.3

0

0

Total

1.0

1.6

0.3

0.3

The scores read after 24 and 72 hours for erythema and edema for the intact as well as for the abraded skin were summed up and divided by 4.

Total = 1.0 + 1.6 + 0.3 + 0.3 = 3.2

Primary irritation index = 3.2 / 4 = 0.8

Interpretation of results:
GHS criteria not met
Conclusions:
The test item was found to be not irritant to the skin under the test conditions.
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:
From Sep. 14, 1981 to Sep. 21, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
-comparable to OECD 405, at the last time point of 7 days, one animal still had a redness of conjunctivae score of 1 (observation period should be up to 21 days)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Bred and raised rabbits on the premises (Ciba-Geigy Ltd. - Exp. Toxicology Sisseln GU 2.1)
- Age at study initiation: Not reported
- Weight at study initiation: 2 to 3 kg
- Housing: Housed individually in metal cages
- Diet (e.g. ad libitum): ad libitum, standard rabbit food
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:
Single exposure
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 males and 3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 mL of physiological saline.
- Time after start of exposure: Approximately 30 seconds after treatment in 3 of the 6 rabbits

SCORING SYSTEM: Same scale as the one provided in the OECD guideline, with the exception of 1 criteria (changes related to discharge were included in addition to the other parameters evaluated)

TOOL USED TO ASSESS SCORE: slit lamp

The eye irritation was appraised with a slit-lamp on day 1, 2, 3, 4, and 7 and was scored for each individual rabbit. The mean reaction scores for cornea, iris and conjunctiva observed after 1, 2, 3, 4, and 7 days were summed up and the sum divided by 5. This procedure was carried out separately for unrinsed and rinsed eyes.

Index:
0 = none
0.1 - 10.9 = minimal
11.0 - 25.9 = slight
26.0 - 55.9 = moderate
56.0 - 84.0 = marked
above 84.0 = extreme




Irritation parameter:
cornea opacity score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
24 h
Score:
5
Max. score:
80
Reversibility:
fully reversible within: 2 days
Irritation parameter:
cornea opacity score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
80
Reversibility:
not specified
Irritation parameter:
cornea opacity score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
80
Reversibility:
not specified
Irritation parameter:
cornea opacity score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
80
Reversibility:
not specified
Irritation parameter:
iris score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
not specified
Irritation parameter:
iris score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
other: 4 days
Score:
0
Max. score:
10
Reversibility:
not specified
Irritation parameter:
iris score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
10
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
24 h
Score:
7.3
Max. score:
20
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
48 h
Score:
4.7
Max. score:
20
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
72 h
Score:
0.7
Max. score:
20
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
other: 4 days
Score:
0.7
Max. score:
20
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
7 d
Score:
0.7
Max. score:
20
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Remarks:
rinsed eyes
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
80
Reversibility:
not specified
Irritation parameter:
cornea opacity score
Remarks:
rinsed eyes
Basis:
mean
Time point:
other: 4 days
Score:
0
Max. score:
80
Reversibility:
not specified
Irritation parameter:
cornea opacity score
Remarks:
rinsed eyes
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
80
Reversibility:
not specified
Irritation parameter:
iris score
Remarks:
rinsed eyes
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
not specified
Irritation parameter:
iris score
Remarks:
rinsed eyes
Basis:
mean
Time point:
other: 4 days
Score:
0
Max. score:
10
Reversibility:
not specified
Irritation parameter:
iris score
Remarks:
rinsed eyes
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
10
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Remarks:
rinsed eyes
Basis:
mean
Time point:
24 h
Score:
2
Max. score:
20
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Remarks:
rinsed eyes
Basis:
mean
Time point:
48 h
Score:
2
Max. score:
20
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Remarks:
rinsed eyes
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
20
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Remarks:
rinsed eyes
Basis:
mean
Time point:
other: 4 days
Score:
0
Max. score:
20
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Remarks:
rinsed eyes
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
20
Reversibility:
not specified
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
80
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The test item was found to cause minimal irritation at cornea and conjunctiva (redness, chemosis, discharge) when applied to the rabbit eye mucosa (primary irritation index 3.8). When the application site was rinsed, irritation was minimized (primary irritation index 0.8) with effects at conjunctiva (redness, chemosis). Findings in cornea were observed in one animal and healed by the second day. Redness of the conjunctiva occurred in all animals with unrinsed eyes and a score 1 effect was still observed in one animal at the last observation time point.

Table 1. Calculation of the primary eye irritation index

Time after exposure (days)

Mean Reaction Score

Unrinsed eyes

Rinsed eyes

Cornea

Iris

Conjunctiva

Cornea

Iris

Conjunctiva

1

5

0

7.3

0

0

2

2

0

0

4.7

0

0

2

3

0

0

0.7

0

0

 0

4

0

0

0.7

0

0

 0

7

0

0

0.7

0

0

 0

Subtotal

5

0

14.1

0

0

4

Total

19.1

4

Primary irritation index in unrinsed eyes

19.1 / 5 = 3.8

Primary irritation index in rinsed eyes

4 / 5 = 0.8

Interpretation of results:
GHS criteria not met
Conclusions:
The test item was found to be not irritant to the eyes when rinsed 30 seconds after application.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Procedure and observation

Two studies were performed to evaluate irritating potential of the test material to skin or eyes. In the first study, six rabbits (3/sex/dose) were each administered a single dermal dose of 0.5 g given as 50% suspension of the test substance. Occlusive application of the test material to intact rabbit skin for 24 hours caused minimal, transient irritation. All effects recovered within 72h.

In a second study, six rabbits were each administered a single ocular dose of 100 mg of the test substance and observed for seven days after instillation. A single instillation of the test material into the eye of the rabbit elicited slight, transient chemosis and moderate redness of conjunctiva which was not fully reversible within post observation period.

Discussion

Application of the test substance onto skin did not cause corrosion or irritation. Application into the conjunctival sac of the eye caused slight to minimal conjuctival irritation. Conjunctival irritation was not reversible within 7 days post observation period but showed tendency to normalize and the score of irritation was below the threshold of regulation.

Justification for classification or non-classification

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

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