Registration Dossier

Administrative data

Description of key information

Skin Irritation

Under the conditions of this study, the test material had a severe corrosive effect on rabbit skin exposed for 4 hours in an occlusive manner.

Eye irritation

Under the conditions of this study, the test material was corrosive to eyes.

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:
15 February to 12 April 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Primary Dermal Irritation Protocols (FIFRA, TSCA)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: at least 8 weeks
- Housing: Animals individually housed in suspended stainless steel cages
- Diet: ad libitum
- Water: municipal water ad libitum
- Acclimation period: 56 days
- No known contaminants that were reasonably expected in food or water that would interfere with the study.
- Animals considered unsuitable were excluded from selection for the study

ENVIRONMENTAL CONDITIONS
- Temperature: 60-70 °F
- Relative humidity: 30-70 %
- Photoperiod: 12-h light/dark
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
The test material was administered as received (undiluted).
Duration of treatment / exposure:
4 hours
Observation period:
1 day (terminated in advance as a result of corrosive effect)
Number of animals:
3 animals per sex
Details on study design:
- Prior to exposure (~24 hours), the back of each rabbit was clipped, exposing the scapular-lumbar region.  
- Each animal was exposed to 0.5 mL of the test material via a treated 1 x 1 " gauze patch applied to the clipped area. 
- Patches were held in place with adhesive tape and gauze wrap for the 4-hour exposure period.  
- At the end of the exposure period, the gauze patches were removed and the skin reaction was observed every 30 minutes, for 24 hours.  
- Skin reactions were scored according to the Draize method.
- The most severely affected area was scored. Adjacent areas of untreated skin were used for comparison.
- Special notation was made of necrosis, eschar, or other evidence of irreversible alteration of tissue structure.
- Any abnormal pharmacologic or toxic signs were also noted.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
6 rabbits
Time point:
other: 30 minutes
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
due to accompanying necrosis in all 6 animals
Remarks on result:
other: One animal had eschar formation at the treatment site. All 6 animals sacrificed after the first observation time at 0.5 h after removal of treatment gauze.
Irritation parameter:
edema score
Basis:
mean
Remarks:
6 rabbits
Time point:
other: 30 minutes
Score:
1.17
Max. score:
4
Reversibility:
other: no data, animals were sacrificed
Remarks on result:
other: 2 rabbits with a score of 2, 3 rabbits with a score of 3, and 1 rabbit with a score of 0.
Irritant / corrosive response data:
At the first observation (i.e., 0.5 hours), all test animals exhibited severe erythema and either slight, very slight, or no oedema. Additionally, severe tissue destruction (i.e., necrosis, eschar, and lesions) was noted. Animals were sacrificed immediately for humane reasons. Under the conditions of the test, the test material was determined to be severely corrosive.
Interpretation of results:
other: EU: Category 1
Conclusions:
Under the conditions of this study, the test material had a severe corrosive effect on rabbit skin exposed for 4 hours in an occlusive manner.
Executive summary:

Primary skin irritation tests were conducted in New Zealand White albino rabbits with the test material.

After exposure of the shaved skin to the undiluted test material for 4 hours under occlusive conditions, severe corrosive effects were observed at the first observation time point at 0.5 h after the treatment gauze was removed. All 6 animals had severe erythema accompanied by necrosis. One animal had eschar formation at the treatment site. The extent of oedema in the animals varied between no oedema (1 animal), very slight oedema (3 animals), and slight oedema (2 animals). All animals were sacrificed after the first observation due to humane reasons.

Under the conditions of this study, the test material had a severe corrosive effect on rabbit skin exposed for 4 hours in an occlusive manner.

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:
February to April 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
A single dose was administered followed by a 1 day observation period. Due to severe ocular irritation and tissue damage, the animals were sacrificed on day 1 for humane reasons.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: at least 8 weeks
- Housing: Animals individually housed in suspended stainless steel cages
- Diet: ad libitum
- Water: municipal water ad libitum
- Acclimation period: 56 days
- No known contaminants that were reasonably expected in food or water that would interfere with the study.
- Animals considered unsuitable were excluded from selection for the study

ENVIRONMENTAL CONDITIONS
- Temperature: 60-70 °F
- Relative humidity of 30-70 %
- Photoperiod: 12-h light/dark
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Dose : 0.1 mL
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
1 day
Number of animals or in vitro replicates:
6 rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: according to the Draize scale

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
6 rabbits
Time point:
other: 1h
Score:
0.5
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: 1 rabbit with a score of 1, and one rabbit with a score of 2
Irritation parameter:
conjunctivae score
Remarks:
(chemosis)
Basis:
mean
Remarks:
6 rabbits
Time point:
other: 1h
Score:
2.5
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 4 rabbits with a score of 2 and 2 rabbits with a score of 1
Irritation parameter:
conjunctivae score
Remarks:
(discharge)
Basis:
mean
Remarks:
6 rabbits
Time point:
other: 1h
Score:
2.17
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: 5 rabbits with a score of 2, one rabbit with a score of 3
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
mean
Remarks:
6 rabbits
Time point:
other: 1h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: All rabbits have a score of 4
Irritation parameter:
cornea opacity score
Remarks:
(area)
Basis:
mean
Remarks:
6 rabbits
Time point:
other: 1h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: All rabbits have a score of 4
Irritant / corrosive response data:
The test material was corrosive to the eye. All six animals exhibited severe conjunctival and corneal tissue destruction. Due to the severe ocular response, all animals were sacrificed after the 1-hour observation for humane reasons.
Score of iritis cannot be calculated because of necrosis.
Interpretation of results:
other: EU Category 1
Conclusions:
Under the conditions of this study, the test material was corrosive to eyes.
Executive summary:

The potential of the test material to cause irritation to the eye was investigated.

A single dose of the test material was administered into the eye of a rabbit, followed by a one day observation period.

The test material was corrosive to the eye. All six animals exhibited severe conjunctival and corneal tissue destruction. Due to the severe ocular response, all animals were sacrificed after the 1-hour observation for humane reasons.

Under the conditions of this study, the test material was corrosive to eyes.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin Irritation

Primary skin irritation tests were conducted in New Zealand White albino rabbits with the test material.

After exposure of the shaved skin to the undiluted test material for 4 hours under occlusive conditions, severe corrosive effects were observed at the first observation time point at 0.5 h after the treatment gauze was removed. All 6 animals had severe erythema accompanied by necrosis. One animal had eschar formation at the treatment site. The extent of oedema in the animals varied between no oedema (1 animal), very slight oedema (3 animals), and slight oedema (2 animals). All animals were sacrificed after the first observation due to humane reasons.

Under the conditions of this study, the test material had a severe corrosive effect on rabbit skin exposed for 4 hours in an occlusive manner.

Eye Irritation

The potential of the test material to cause irritation to the eye was investigated.

A single dose of the test material was administered into the eye of a rabbit, followed by a one day observation period.

The test material was corrosive to the eye. All six animals exhibited severe conjunctival and corneal tissue destruction. Due to the severe ocular response, all animals were sacrificed after the 1-hour observation for humane reasons.

Under the conditions of this study, the test material was corrosive to eyes.

Justification for classification or non-classification

Skin irritation :

According to Regulation EC no.1272/2008 (CLP), the test material is classified in the Category 1 "Causes severe skin burns and eye damage" (H314).

Justification : All animals have a erythema score equal to 4 out of 4 at 30 minutes after administration.

Eye irritation:

The test material is classified as Category 1 "Causes serious eye damage" (H318) according to Regulation EC no.1272/2008 (CLP).

Justification: All animals tested demonstrated severe effects such as tissue distruction or ulceration upon administration and the test were terminated on humane grounds.

Respiratory irritation:

Based on the results of the repeated study (inhalation route), the test material is classified as irritant to the tract respiratory, STOT SE 3 (H335:May cause respiratory irritation) according to Regulation EC no.1272/2008 (CLP). In addition, the supplemental hazard information EUH071 "Corrosive to the respiratory tract" according to Annex II of Regulation EC no. 1272/2008 (CLP) is considered appropriate for inclusion on the label.