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Administrative data

Description of key information

The test substance was found to be corrosive to the skin (Ciba-Geigy, 1983) and corrosive to the eyes (Ciba-Geigy, 1983).

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:
October 13, 1983 - October 20, 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP study following OECD guideline 404 performed under GLP-like QAU surveillance.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(1981)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: 211 - 2440 g
- Housing: Animals were housed individually in metal cages.
- Diet: Rabbit food, NAFAG, No. 814 Tox, NAFAG AG,Gossau, SG (Switzerland), ad libitum
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
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 ml
Duration of treatment / exposure:
4 h
Observation period:
Skin reaction was evaluated after 1, 24, 48, 72 hours.
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: 6 sq. cm
- Type of wrap if used: A gauze patch bearing 0.5 ml of the test substance was applied to the skin and loosely held in place by adhesive but non irritating tape

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4h

SCORING SYSTEM:
Erythema and Eschar Formation
No erythema = 0
Very slight erythema = 1
Well defined erythema = 2
Moderate to severe erythema = 3
Severe erythema (beet redness) to slight eschar formation = 4
Corrosion = +

Oedema Formation
No oedema = 0
Very slight oedema = 1
Slight oedema (edges of area well defined by definite raising) = 2
Moderate oedema (appr. 1 mm) = 3
Severe oedema (raised more than 1 mm, extended beyond appl. site) = 4
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1, 24, 48, 72 h
Score:
5.92
Max. score:
8
Remarks on result:
other: considered as severly irritant
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
3.6
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
3
Max. score:
4
Irritant / corrosive response data:
The test article caused severe irritant and corrosive reactions when applied to the rabbit skin; there was no tendency of recovery towards the end of the observation period. Due to extreme irritation in the skin the animals were killed after the 72 h scoring out of animal protection reasons.
Other effects:
The animals showed a normal body weight development.

Table 1 - Evaluation of the dermal reactions

Animal No. /Sex 1h 24h 48h 72h
Erythema and eschar formation
78/F 2 3 4+ 4+
79/F 2 3 4+ 4+
80/F 2 2 4+ 4+
Total

6 + 8 +  12 +  12 =  38  

         
Oedema formation
78/F 2 3 3 3
79/F 2 3 3 3
80/F 2 3 3 3
Total

6 + 9 +  9 +  9 =  33  

+ = corrosion

INDEX of skin irritation : 38 + 33 = 71 : 12 = 5.92 (= severly irritant)

Interpretation of results:
corrosive
Remarks:
Migrated information
Conclusions:
Under the conditions of the present experiment the test substance was found to be severely irritant and corrosive when applied to the rabbit skin.
Executive summary:

In a skin irritation study following OECD guideline 404 (1981) and performed under GLP-like QAU surveillance, 0.5 ml of the test article was applied to the rabbit skin under semiocclusive conditions for 4 hours. After removal of the dressings the skin reaction was assessed after 1, 24, 48 and 72 hours according to the Draize scoring scheme presented in the OECD guideline. The test substance was found to be severely irritant and corrosive when applied to the rabbit skin; there was no tendency of recovery towards the end of the observation period. Due to extreme irritation in the skin the animals were killed after the 72 h scoring out of animal protection reasons. Based on these results, the test substance was considered to be corrosive to the skin and requires classification.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

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:
October 13, 1983 - October 20, 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study following OECD guideline 405
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(1981)
GLP compliance:
yes
Remarks:
CIBA-GEIGT LTD/ GU2 TOXICOLOGY
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12 - 14 weeks
- Weight at study initiation: 2050-2210 g
- Housing: individually in metal cages
- Diet: Rabbit food, NAFAG, No. 814 Tox, NAFAG AG, Gossau, SG (Switzerland) provided ad libitum
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light/day
Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated and served as the control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
The test article was placed into the conjunctival sac of the right eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test material.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 males
Details on study design:
SCORING SYSTEM:
Evaluation score for ocular lesions

CORNEA
Opacity: degree of density (area most dense taken for reading).
No ulceration or opacity = 0
Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible = 1*
Easily discernible translucent area, details of iris slightly obscured = 2*
Nacrous area, no details of iris visible, size of pupil barely discernible = 3*
Opaque cornea, iris not discernible through the opacity = 4*

IRIS
Normal = 0
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) = 1*
No reaction to light, haemorrhage, gross destruction (any or all of these) = 2*

CONJUCTIVAE
Redness: (refers to palpebral and bulbar conjuctivae, cornea and iris)
Blood vessels normal = 0
Some blood vessels definitely hyperaemic (injected) = 1
Diffuse, crimson colour, individual vessels not easily discernible = 2*
Diffuse beefy red = 3*

CHEMOSIS
Lids and/or nictating membranes
No swelling = 0
Any swelling above normal (includes nictating membranes) = 1
Obvious swelling with partial eversion of lids = 2*
Swelling with lids about half closed = 3*
Swelling with lids more than half closed = 4*

* Starred figures indicate positive effect
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
2.3
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
2.7
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
2.7
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
1.7
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
1.7
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
2.7
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
3
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
3
Max. score:
3
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
3.3
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
4
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
4
Max. score:
4
Irritant / corrosive response data:
The test article is severely irritant and corrosive when applied to the rabbit eye mucosa. The eyes reacted with spontaneous swellings and hyperemias upon instillation of the test substance. 24 to 48 hours after administration these symptoms had deteriorated to severe irritations in the corneas and corrosions in the conjunctivas of all 3 animals. Due to this extreme irritation the animals were killed after the 72 h scoring out of animal protection reasons.
Other effects:
There was no tendency of recovery towards the end of the observation period of 3 days. The animals showed a normal body weight development.

Table 1 - Evaluation of the eye reactions

Animal No./Sex 75 / M 76 / M 77 / M  
After 1 h 2 2 2 Cornea
After 24 h 2 2 2
After 48 h 2 3 3
After 72 h 2 3 3
After 1 h 1 1 1 Iris
After 24 h 1 1 1
After 48 h 1 2 2
After 72 h 1 2 2
After 1 h 2 2 2 Conjunctivae
After 24 h 2 3 3
After 48 h 3+ 3+ 3+
After 72 h 3+ 3+ 3+
After 1 h 2 3 3 Chemosis
After 24 h 3 4 4
After 48 h 3 4 4
After 72 h 4 4 4

+ = corrosion

Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the present experiment the test substance was found to be severely irritant and corrosive when applied to the rabbit eye mucosa.
Executive summary:

In a GLP-compliant study following the OECD guideline 405, the test article's potential for irritation to the rabbit eye was investigated in three New Zealand White rabbits. 0.1 ml of the test substance was placed into the conjunctival sac of the right eye of each animal while the left eyes were kept untreated and served as a control. The ocular reactions were examined 1, 24, 48, and 72 hours after substance instillation and again during the following observation period. Under the conditions of the present experiment, the test substance was found to be severely irritant and corrosive when applied to the rabbit eye mucosa. There was no tendency of recovery towards the end of the observation period of 3 days.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In a skin irritation study following OECD guideline 404 (1981) and performed under GLP-like QAU surveillance, 0.5 ml of the test article was applied to the skin of three male New Zealand White rabbits under semiocclusive conditions for 4 hours. After removal of the dressings the skin reaction was assessed after 1, 24, 48 and 72 hours according to the Draize scoring scheme presented in the OECD guideline. Under the conditions of this experiment, the test substance was found to be severely irritant and corrosive when applied to the rabbit skin; there was no tendency of recovery towards the end of the observation period. Due to extreme irritation in the skin the animals were killed after the 72 h scoring out of animal protection reasons. Based on these results, the test substance is considered to be corrosive to the skin and requires classification.

Eye irritation

In a GLP-compliant study following the OECD guideline 405, the test article's potential for irritation to the rabbit eye was investigated in three New Zealand White rabbits. 0.1 ml of the test substance was placed into the conjunctival sac of the right eye of each animal while the left eyes were kept untreated and served as a control. The ocular reactions were examined 1, 24, 48, and 72 hours after substance instillation. Under the conditions of the present experiment, the test substance was found to be severely irritant and corrosive when applied to the rabbit eye mucosa. The eyes reacted with spontaneous swellings and hyperemias upon instillation of the test substance. 24 to 48 hours after administration of the test substance these symptoms had deteriorated to severe irritations in the corneas and corrosions in the conjunctivas of all 3 animals. Due to this extreme irritation the animals were killed after the 72 h scoring out of animal protection reasons. There was no tendency of recovery towards the end of the observation period of 3 days. Based on these results, the test article is considered to be corrosive to the eye and requires classification.


Justification for selection of skin irritation / corrosion endpoint:
OECD guideline study

Justification for selection of eye irritation endpoint:
OECD guideline study

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available data are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance requires classification with R34 under Directive 67/548/EEC.

 

Classification, Labeling, 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 requires classification for skin irritation Cat. 1B under Regulation (EC) No. 1272/2008.