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Description of key information

Skin irritation: Mallory VT (1984) determined in a K2, key study the skin corrosion potential of the test substance in New Zealand White rabbits according to a method similar to OECD Guideline 404. The test substance was observed to be corrosive to the skin.  

Eye irritation: Mallory VT (1983) determined in a K1 study the eye irritation potential of the test substance in New Zealand White rabbits according to a method similar to OECD Guideline 405. The test substance was observed to be corrosive to the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 27, 1984 - February 29, 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Well documented study performed according to a method similar to OECD Guideline 404 with a minor deviation: occlusive dressing used instead of semi-occlusive
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Occlusive dressing used instead of semi-occlusive
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material (as cited in study report): 5601-23-1
- Substance type: Clear liquid
- Physical state: liquid
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sgarlat's Rabbitry, Harvey's Lake, Pennsylvania
- Weight at study initiation: 2 - 3 kilograms
- Housing: 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.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/stie
Duration of treatment / exposure:
4 hours
Observation period:
Animals were observed at 4 and 48 hours after application of the test material.
Number of animals:
Iniatially, two rabbits will be administered the test article. The test will be considered positive if both animals exhibit a positive response and the study will be terminated. If only one animal or no animals exhibit a positive response, the test will be repeated with a different group of two rabbits. If one animal exhibits a positive response in the second group, the test article will be considered corrosive and the study will be terminated provided there was no positive response in group I. If no positive reactions are observed in group II, an additional group of two rabbits will be added and conclusions will be based on a total of six rabbits.
Details on study design:
SCORING SYSTEM:
Corrosion will be considered to have resulted if the substance in contact with the rabbit skin has caused destruction or irreversible alteration of the tissue on at least two out of each six rabbits tested. Tissue destruction is considered to have occurred if, at any of the readings, there is ulceration or necrosis. Tissue destruction does not include merely sloughing of the epidermis or erythema, edema or fissuring.
Irritation parameter:
other: Skin necrosis
Basis:
animal #1
Time point:
other: 4h
Reversibility:
not reversible
Remarks on result:
other: skin necrosis was visible at 4h in two animals
Irritation parameter:
other: Skin necrosis
Basis:
animal #2
Time point:
other: 4h
Reversibility:
not reversible
Remarks on result:
other: skin necrosis ws visible at 4h in two animals
Irritation parameter:
other: Skin necrosis
Basis:
animal #1
Time point:
48 h
Reversibility:
not reversible
Remarks on result:
other: Skin necrosis was visible in two animals
Irritation parameter:
other: Skin necrosis
Basis:
animal #2
Time point:
48 h
Reversibility:
not reversible
Remarks on result:
other: Skin necrosis was visible in two animals
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Remarks:
Skin corrosion (tissue destruction) was considered to have occurred if ulceration or necrosis was observed in any of the readings
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Remarks:
Skin corrosion (tissue destruction) was considered to have occurred if ulceration or necrosis was observed in any of the readings
Irritant / corrosive response data:
Skin necrosis was visible in both rabbits at 4 and 48 hours after application of the test article.

Skin necrosis was visible in both rabbits at 4 and 48 hours after application of the test article.

Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Conclusions:
Based upon the results of the DOT Corrosivity Study in Rabbits, the test substance was considered to be corrosive.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
October 18, 1983 - November 1, 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Well documented GLP study performed according to a method similar to OECD Guideline 404. The test substance is applied to intact skin, but also to abraded skin. An occlusive dressing is used, instead of a semi-occlusive dressing.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
The test substance is applied to intact skin, but also to abraded skin. An occlusive dressing is used, instead of a semi-occlusive dressing.
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
- Name of test material (as cited in study report): 5601-23-1
- Substance type: light yellow liquid
- Physical state: liquid
- Stability under test conditions: There was no apparent change in the physical state of the test article during administration.
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Perfection Breeders, Douglassville, Pennsylvania
- Weight at study initiation: 2 - 3 kilograms
- Housing: 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.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark
Type of coverage:
occlusive
Preparation of test site:
other: one abraded and one intact skin site
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/site

Duration of treatment / exposure:
24 hours
Observation period:
Animals were observed and signs of erythema and edema were scored according to the Draize scale at 24 and 72 hours and on days 4 through 14 after application of the test material.
Number of animals:
6 animals (3 males and 3 females)
Details on study design:
TEST SITE
- Type of wrap if used: Following the application of the test material, one-inch square gauze patches were applied to each of the two sites. The trunk of the animal was wrapped with a rubber dam and an Ace bandage to retard evaporation. The test substance was kept in contact with the skin site for twenty-four hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the twenty-four hour exposure period, the wrappings were removed and the remaining material was removed in a suitable manner.

SCORING SYSTEM:
The irritation was scored according to the technique of Draize JH (1959), The Appraisal of Chemicals in Foods, Drugs, and Cosmetics, pp 36-45. Association of Food and Drug Officials of the United States. Austin, Texas.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Score:
5
Max. score:
8
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: time points include 24 and 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
0.7
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: abraded skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
1.2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: abraded skin
Irritant / corrosive response data:
Severe erythema was observed at 24 and 72 hours and on days 4 through 14. Very slight to slight edema was also observed at 24 and 72 hours and on days 4 through 14. Skin necrosis was also observed at the application sites throughout the study.The study was terminated on day 14.

The pH of the test article was 12.5.

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Severe erythema was observed at 24 and 72 hours and on days 4 through 14. Very slight to slight edema was also observed at 24 and 72 hours and on days 4 through 14. Skin necrosis was also observed at the application sites throughout the study. According to the criteria of the CLP Regulation, the substance should be classified as category 2 skin irritant.
Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 30, 1983 - October 13, 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Well documented GLP study performed according to a method similar to OECD Guideline 405.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
- Name of test material (as cited in study report): 5601-23-1
- Substance type: clear liquid
- Physical state: liquid
- Stability under test conditions: There was no apparent change in the physical state of the test article during administration
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Sgarlat's Rabbitry, Harvey's Lake, Pennsylvania and Perfection Breeders, Douglassville, Pennsylvania
- Weight at study initiation: 2 - 3 kilograms
- Housing: 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.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Vehicle:
unchanged (no vehicle)
Controls:
other: The contralateral eye remained untreated and served as a control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:
The upper and lower lids were gently held together for one second to prevent loss of material.
Observation period (in vivo):
The eyes were examined at 1, 24, 48 and 72 hours and 7, 10, and 13 days after treatment. The grades of ocular reaction were recorded at each examination.
Number of animals or in vitro replicates:
6
Details on study design:
SCORING SYSTEM:
Grading of irritation is according to the method of Draize, J.H., et al., J. Pharm, Exp. Ther. 82: 377 - 390 (1944).

An animal exhibited a positive reaction when the test substance produced one or more of the following signs:
ulceration of the cornea (other than a fine stippling), opacity of the cornea (other than a slight dulling of the normal luster), inflammation of the iris (other than a slight deepening of the rugae or a light hyperemia of the circumcorneal blood vessels), or an obvious swelling in the conjunctivae (excluding the cornea and iris) with partial eversion of the eyelids and a diffuse crimson color with individual vessels not easily discernible.

Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 48 hours
Score:
95.3
Max. score:
100
Reversibility:
not fully reversible within: 13 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Max. score:
2
Reversibility:
not fully reversible within: 13 days
Remarks on result:
other: Scoring after 1 hour: 2; No scoring possible after 24 hours due to high degree of opacity
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Max. score:
2
Reversibility:
not fully reversible within: 13 days
Remarks on result:
other: No scoring possible after 1 hour due to high degree of opacity
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Max. score:
2
Reversibility:
not fully reversible within: 13 days
Remarks on result:
other: Scoring after 1 and 24 hours: 2. No scoring possible after 48 hours due to high degree of opacity
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Max. score:
2
Reversibility:
not fully reversible within: 13 days
Remarks on result:
other: No scoring possible after 1 hour due to high degree of opacity
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Max. score:
2
Reversibility:
not fully reversible within: 13 days
Remarks on result:
other: Scoring after 1 and 24 hours: 2. No scoring possible after 48 hours due to high degree of opacity
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Max. score:
2
Reversibility:
not fully reversible within: 13 days
Remarks on result:
other: Scoring after 1 hour: 2. No scoring possible after 24 hours due to high degree of opacity
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 13 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 13 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 13 days
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 13 days
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 13 days
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 13 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 13 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 13 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 13 days
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 13 days
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 13 days
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 13 days
Irritant / corrosive response data:
Positive ocular responses were observed at 1, 24, 48 and 72 hours and on days 7, 10 and 13. Rupture of the globe, conjunctival necrosis and red discharge were observed during the course of the study.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Positive ocular responses were recorded at 1, 24, 48 and 72 hours and on days 7, 10 and 13. Rupture of the globe, conjunctival necrosis and red discharge were observed during the course of the study. Based on the results and the criteria of the CLP Regulation, the substance is classified as category 1 eye corrosive.
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 conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion:

In a key, K1 DOT corrosivity study by Mallory VT (1984), 2 New Zealand White rabbits were exposed to 0.5 ml of undiluted test substance on clipped skin (equivalent to OECD guideline 404, K2, GLP). Exposure time was 4h under an occlusive dressing. The skin was observed after 4h and 48h. Skin necrosis was visible in both rabbits at 4 hours and 48 hours after application of the test article. This study was selected as key study.

In a supporting primary dermal irritation study by Mallory VT (1983) (K2, equivalent to OECD guideline 404, GLP), 6 rabbits were exposed to 0.5 ml of undiluted test substance on both intact and abraded skin. Exposure time was 24h under an occlusive dressing. Scoring according to Draize occurred after 24h and 72h, and after days 4 through 14. Necrosis was observed at 24 and 72 hours after treatment and on Days 4 through 14. Severe erythema was observed at 24 and 72 hours and on days 4 through 14. Very slight to slight edema was also observed at 24 and 72 hours and on days 4 through 14. Skin necrosis was also observed at the application sites throughout the study. The study was terminated on day 14.

No in vitro skin irritation study needs to be conducted because adequate data from an in vivo skin irritation study are available.

Eye irritation:

In a key acute eye irritation test by Mallory VT (1983) (equivalent to OECD guideline 405, K1, GLP), 6 rabbits were instilled 0.1 ml of undiluted test substance in one eye, while the other eye served as control. The eyes were examined at 1, 24, 48 and 72 hours and 7, 10 and 13 days after treatment. Positive ocular responses were observed at 1, 24, 48 and 72 hours and on Days 7, 10 and 13. Rupture of the globe, conjunctival necrosis and red discharge were observed during the course of the study. The substance is considered to be corrosive to the eyes.

No in vitro eye irritation study needs to be conducted because adequate data from an in vivo eye irritation study are available.

Justification for classification or non-classification

Based on the available data and the criteria of the CLP Regulation, the test substance is classified as skin corrosive category 1C (H314).

Based on the available data and the criteria of the CLP Regulation, the test substance is classified as corrosive to eyes (serious eye damage Cat. 1 (H318). These classifications are however covered already within the classification for skin corrosion.