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Key value for chemical safety assessment

Skin irritation / corrosion

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Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
June 29th -July 12th 1982.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
The study was conducted in accordance with GLP and similar/equivalent OECD 404 guideline.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
The test material is a UVCB
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Rabbits were housed indiividually in cages sized in accordance with the "Guide for the Care and Use of Laboratory Animals" of the institue nof Laboratory resources, National Research Council. Waste material was removed daily. Cages and feeders were sanitized every two weeks. Light cycle was 12hours light and 12hours dark. Food and water was provided ad libitum and checked daily, added or replaced as required.
Type of coverage:
semiocclusive
Preparation of test site:
abraded
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.5ml of the neat test material
Duration of treatment / exposure:
24hours
Observation period:
14 days
Number of animals:
6
Details on study design:
The skin of each 6 adult abino rabbits were clipped free of fur, on four skin sites, 2 abraded and 2 intact sites. The skin was abraded, to penetrated the stratum corneum but not the derma, using a 21 gauge burred needle. Following the application of the test material, one -inch square quaze patches were applied to each site. The trunk of each animal was then wrapped with a rubber dam and an Ace bandage to retard evaporation. The test material was kept in contact with the skin for 24hours exposure period. At the end of the 24hrs exposure period, the wrapping were removed and skin wipped to remove remaining test material.

Animals were observed for signs of erythema and edema and scored according to draize scale at 24 hours, 48 hours, 72 hours after application of test material and daily for 13 days following application untill all irritation subsided.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24hrs and 72hrs
Score:
ca. 1.76
Reversibility:
fully reversible within: day 13
Remarks on result:
other: Skin scaling and cracking from Day 4 -12
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24hrs and 72hrs
Score:
ca. 1.75
Reversibility:
fully reversible within: day 13
Remarks on result:
other: Skin scaling and cracking from Day 4 -12
Irritant / corrosive response data:

Endpoint TIME (hrs) Rabbit Number/Response Mean Score
1 2 3 4 5 6

Erythema
Abraded 24hrs 2 2 1 2 2 2 1.83
72 hrs 2 2 1 1.5 2 2 1.75

Intact 24hrs 2 2 1 2 2 2 1.83
72hrs 2 2 1 1.5 2 2 1.75

Edema
Abraded 24hrs 2 1.5 1.5 2 2 1.5 1.75
72hrs 2 1.5 1.5 2 2 2 1.83

Intact 24hrs 2 1.5 1.5 2 2 1.5 1.83
72hrs 2 1.5 1.5 1.5 2 1.5 1.67
Interpretation of results:
other: Supporting Study.
Conclusions:
The results from the study considers the the test material to be skin corrosive. Therefore in accordance with the criteria set in the CLP guidiance document, the substance should be classified as Skin corrosive category 1, H314
Executive summary:

The test substance was assessed for dermal corrosive effects on rabbit skin. Substance was applied to one intact site. Slight to severe erthyema was observed at 24 and 72 hours and on day 4 through day 12. On Day 13, all sites returned to normal and the study was terminated. Based upon the criteria set in the CLP guidiance, the substance should be classified as a skin Corrosive, H314.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 14 1986 to May 28 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
The study was conducted in accordance with GLP and similar/equivalent OECD 404 guideline.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
The test material is a UVCB
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Rabbits were housed individually in cages sized in accordance with the "Guide for the Care and Use of Laboratory Animals" of the institute of Laboratory resources, National Research Council. Waste material was removed 3 times per week. Cages and feeders were sanitized every two weeks. Light cycle was 12hours light and 12hours dark. Food and water was provided ad libitum and checked daily, added or replaced as required.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.5ml of the neat test material.
Duration of treatment / exposure:
The test material was applied and kept in contact with the skin for 4hours. At the end of the 4hrs exposure period, the wrapping were removed and skin wiped to remove remaining test material.
Observation period:
Animals were observed up to 14 days.
Number of animals:
six animals which includes 3 females and 3 males.
Details on study design:
The skin of each 6 adult abino rabbits were clipped free of fur. Test material was administered at one intact skin site. Following the application of the test material, one -inch square guaze patches were applied to each site. The trunk of each animal was then wrapped with a rubber dam and an Ace bandage to retard evaporation. The test material was kept in contact with the skin for 4hours. At the end of the 4hrs exposure period, the wrapping were removed and skin wiped to remove remaining test material.

Animals were observed for signs of erythema and edema and scored according to draize scale at 30-60minutes, 24 hours, 48 hours, 72 hours after application of test material and daily for 14days following application.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 3.5
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Necrosis, fissuring, and sloughing observed.
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2
Reversibility:
fully reversible within: 11 days
Irritant / corrosive response data:
Individual animal scores are given below for 30mins , 24 and 72 hours observations:

Endpoint TIME (hrs) Rabbit Number/Response
1 2 3 4 5 6

Erythema 24hrs 3 4 3 3 3 3
48hrs 3 4 3 3 3 4
72hrs 4 4 4 4 4 4


Edema 24hrs 4 4 4 4 4 4
48hrs 1 1 1 1 1 1
72hrs 1 1 1 1 1 1
Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
The results from the study considers the test material to be skin corrosive. Therefore, in accordance with the criteria set in the CLP guidance document, the substance should be classified as Skin Corrosive, Category 1 C, H314.
Executive summary:

The test substance was assessed for dermal corrosive effects on rabbit skin. Substance was applied to one intact skin site. Slight to severe erythema was observed throughout the study. Slight severe edema was observed through day 10. Necrosis, fissuring and sloughing were also observed and the study was terminated on day 14. Therefore, based upon the observations made in the acute dermal corrosion test in rabbits, the test substance was determined to be corrosive to the skin under CLP classification criteria.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

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Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 20, 1982 to August 10, 1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
Study conducted according to GLP and was equivalent or similar to OECD 405 guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
The test material is a UVCB
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Rabbits were housed individually in cages sized in accordance with the 'Guide for the Care and Use of Laboratory Animals' of the Institute of Laboratory Resources. Waste material was removed daily. Cages and feeders were sanitized every two weeks. Food and water was provided ad libitum, checked daily and added or replaced as needed.

ENVIRONMENTAL CONDITIONS

Temperature: 20 ◦C ± 3 ◦C
Relative Humidity: 30-70%
Light cycle: 12 hours light, 12 hours dark
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.1 mL of neat test material
Duration of treatment / exposure:
Test substance was placed in the right eye of each animal by gently pulling the lower lid away from the eyeball to form a cup. The upper and lower lids were then held together for one seconf to prevent loss of material
Observation period (in vivo):
Up to 21 days post dosing
Number of animals or in vitro replicates:
six animals (3 males, 3 females)
Details on study design:
Twenty four hurs prior to the application of the test material, the eyes of the rabbits were examined using 2% sodium fluorescein stain. Animals showing preexisting corneal injury were eliminated from the study. The test susbtance was placed in the right eye of each animal by gently pulling the lower lid away from hte eyeball (conjunctival cul de sac) to form a cup. The upper and lower lids were then gently held together for one seconf to prevent loss of material. The contralateral eye remained untreated and served as a control. The eyes were examined at 1, 24, 48 and 72 hours and 7, 14 and 21 days after treatment. The grades of ocular reaction were recorded at each examination
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
2.973
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
1.86
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1.996
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
3.16
Max. score:
4
Reversibility:
not fully reversible within:
Remarks:
21 days
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Based on the results of this study, the test material is considered to cause irreversible damage to the eye. Therefore, under the criteria set forth in the CLP guidance document, this substance should be classified as Eye Damage, H318.
Executive summary:

The test article was instilled in the right eye of six rabbits. Positive ocular responses were observed at 1, 24, 48 and 72 hours, and on Days 7, 14 and 21 after treatment. Blistering and ulceration of the cornea, pannus and keratoconus were observed during the study. Based upon the observations made in the Acute Eye Irritation Test in Rabbits, the test substance was determined to be corrosive to the eye under CLP classification criteria.

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

Additional information

Both studies were considered when determining the skin corrosion/irritation endpoint of the test material. However, the Key study was used for Classifiaction purposes in accordance with the criteria set in the CLP guidiance document.

The study for eye damage was used for classification of the test material in accordance with the criteria set in the CLP document

Justification for classification or non-classification

Data from available for two in vivo skin corrosion studies were used for skin corrosion hazard assessment for the Test substance and the studies were conducted in accordance with a guideline comparable to OECD 404. Mallory, 1986, studies concluded that the test substance is corrosive based on the CLP criteria. Test substance was exposed to rabbits skin for 4hours. After exposure time substance was completely wiped off and animals were observed for 30 -60minutes, 24hrs, 48hrs , 72hrs and daily for 14days. Necrosis, fissuring and sloughing were observed on rabbits throughout the study. Edema mean score for 24, 48 and 72hrs was 2 and fully reversible effect was seen within 11days furthermore, erythema mean score for 24, 48 and 72hrs was 3.5 with no reversible effect was observed for 14 days observation period. In the second study, a supporting study, Mallory , 1982, study concluded that the test material was corrosive based on the CLP criteria. Rabbits skin abraded and intact were exposed to test material for 24hrs and observed at 24hrs, 72hrs and daily for 13days. Slight to well defined erythema was observed at 24hrs, 72hrs and on day 4 through day 12 similarly, slight to moderate edema was observed at 24hrs, 72hrs and on day 4 through day 12. Therefore, based on the conclusion drawn from Mallory, 1986 study, slight to severe erythema was observed at 30mins-60mins and throughout study with observation period of 14days, with evidence of necrosis fissuring and sloughing observed, the Test substance will therefore be classified as a Corrosive to the skin, H314 Cat. 1C.

In the eye damage study , the test article was instilled in the right eye of six rabbits. Positive ocular responses were observed at 1, 24, 48 and 72 hours, and on Days 7, 14 and 21 after treatment. Blistering and ulceration of the cornea, pannus and keratoconus were observed during the study. Based upon the observations made in the Acute Eye Irritation Test in rabbits, the test substance was determined to be corrosive to the eye under CLP classification criteria. Based on the results of this study, the test material is considered to cause irreversible damage to the eye.  Therefore, under the criteria set forth in the CLP guidance document, this substance should be classified as Eye Damage, H318.