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Description of key information

Two rabbit studies (Klimisch 2) are available investigating the dermal irritation/corrosion potential of the test substance. A weight-of-evidence approach is applied to cover the endpoint: the substance is considered corrosive to skin. 
A rabbit study (Klimisch 2) is available investigating the eye irritation potential of the test substance: the substance is considered corrosive to the eye.

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:
weight of evidence
Study period:
1979-03-21 to 1979-03-23
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented and scientifically accepted study.
Qualifier:
according to
Guideline:
other: 49 CFR 172.240
Deviations:
not specified
GLP compliance:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): none used
- Sample label: 4236-21-35
- Substance type: Clear liquid
- Physical state: Liquid
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Perfection Breeders, Box 75, Douglasville, Pa.
- Weight at study initiation: 2 - 3 kg
- Housing: The animals were housed 2/cage (30" x 18" x 18") in a room reserved exclusively for rabbits on acute tests. The cages were identified by test material, starting date, animal number and sex. In addition, odd numbered animals in each cage were identified with an indelible ear mark.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21°C

Type of coverage:
occlusive
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/test site
Duration of treatment / exposure:
4 hours
Observation period:
Dermal reactions were scored at 4 and 48 hours. Signs of systemic effects were recorded at dermal observation time.
Number of animals:
6 (4 males and 2 females)
Details on study design:
TEST SITE
0.5 mL of the test material as received was applied once dermally to one site per animal under 2.5 cm square gauze patches. The trunk of the rabbits was wrapped with impervious material.

REMOVAL OF TEST SUBSTANCE
The test material was kept in contact with the skin for 4 hours, at which time the wrappings were removed

SCORING SYSTEM:
Corrosivity, defined as destruction or irreversible alteration of the tissue, 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:
erythema score
Basis:
mean
Time point:
other: 4h - 48h
Score:
1 - 3
Max. score:
4
Reversibility:
no data
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 4h - 48h
Score:
0 - 2
Max. score:
4
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: other time points used (4h-48h)
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: other time points used (4h-48h)
Irritant / corrosive response data:
Slight to moderate erythema and no or slight edema was noted in all animals at 4 hours or 48 hours.
Interpretation of results:
study cannot be used for classification
Conclusions:
The substance was observed to be non-corrosive.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1979-03-13 to 1979-03-15
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Well documented non-GLP study performed according to a method similar to OECD Guideline 404. The test substance was applied to intact skin but also to abraded skin. Exposure period was 24h instead of 4h. An occlusive dressing was used instead of a semi-occlusive dressing. Scoring of skin reactions occurred only at 24h and 72h after patch removal.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
The test substance was applied to intact skin but also to abraded skin. Exposure period was 24h instead of 4h. An occlusive dressing was used instead of a semi-occlusive dressing. Scoring of skin reactions occurred only at 24h and 72h after patch removal.
GLP compliance:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): non used
- Substance type: Clear liquid
- Sample number: 4236-21-35
- Physical state: Liquid
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: local supplier
- Age at study initiation: at least 8 weeks of age
- Housing: The rabbits were housed in elevated wire cages in a temperature controlled room reserved exclusively for rabbits on acute tests
- Diet (e.g. ad libitum): fresh Purina Rabbit Chow
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: no data

Type of coverage:
occlusive
Preparation of test site:
other: abraded and intact skin
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:
No data
Observation period:
24 and 72 hours
Number of animals:
6 animals
Details on study design:
TEST SITE
The material was placed on each site and covered with 2 ply gauze, 2.5 cm square. The patches were secured with advhesive tape and the entire trunk of the rabbit was wrapped with impervious material, 2 mil thick plastic.

SCORING SYSTEM: Draize scale
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24h
Score:
7.33
Max. score:
8
Reversibility:
no data
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72h
Score:
6.17
Max. score:
8
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: not measured - Primary dermal irritation index (PDII) used instead
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: not measured - Primary dermal irritation index (PDII) used instead
Irritant / corrosive response data:
The scores exceeded the maximum scores on the Draize scale. Consequently, the primary irritation index could not be calculated. However, the material is considered to be very hazardous to rabbit skin.
Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Conclusions:
The scores exceeded the maximum scores on the Draize scale. Consequently, the primary irritation index of DPA could not be calculated. However, the material is considered to be very hazardous to rabbit skin. The test substance is considered classified as cat 1 corrosive to skin according to CLP Regulation
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:
1979-03-12 to 1979-03-26
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented non-GLP study performed similar to OECD Guideline 405.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): none used
- Sample number: 4236-21-35
- Substance type: Clear liquid
- Physical state: Liquid
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: local supplier
- Housing: The rabbits were housed two per cage in suspended wire mesh cages in temperature controlled room reserved exclusively for rabbits on acute tests.
- Diet (e.g. ad libitum): Fresh Purina Rabbit Chow was freely available
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 1 week
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye of each rabbit served as a control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
No data; no washing after 24h
Observation period (in vivo):
The ocular reactions were graded at 1, 24, 48 and 72 hours and again at 7 days. If any corneal score was present on day 7, the eyes were scored again at 14 days.
Number of animals or in vitro replicates:
6 rabbits
Details on study design:
SCORING SYSTEM: Draize scoring

Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 24 hours
Score:
45.8
Max. score:
110
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 48 hours
Score:
48.6
Max. score:
110
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 72 hours
Score:
67.8
Max. score:
110
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 14 days
Score:
42.4
Max. score:
110
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Remarks:
maximum mean total score (MMTS) measured instead
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Remarks:
maximum mean total score (MMTS) measured instead
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Remarks:
maximum mean total score (MMTS) measured instead
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Remarks:
maximum mean total score (MMTS) measured instead
Irritant / corrosive response data:
Irritant response defined as 4 to 6 rabbits with positive scores.
Interpretation of results:
Category 1 (irreversible effects on the eye)
Conclusions:
The substance is defined as irritant to the eyes as 4 to 6 rabbits were observed to have positive scores. Based on these results and the fact that the substance is corrosive to the skin, the substance is classified as causing serious eye damage to eyes (category 1) according to CLP Regulation.
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 primary dermal irritation study by MB Research Laboratories (1979), 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. Necrotic areas are observed at both sites in all animals after 24h and 72h. As the test lasted only 72h, no judgement on reversibility can be done. According to the authors, the scores exceeded the maximum scores on the Draize scale.

In a DOT corrosivity study by MB Research Laboratories (1979), 6 rabbits were exposed to 0.5 ml of undiluted test substance on intact skin. Exposure time was 4h under an occlusive dressing. The skin was observed after 4h and 48h. At both points in time, no necrosis was observed, but slight to moderate erythema and no or slight edema.

A safety data sheet mentions a pH of 11.7. A pH of 11.5 or higher is normally sufficient to assume a chemical to be corrosive.

It is not ethical to perform another animal study to confirm the potential corrosive properties. It has been precautionary decided to classify the substance as corrosive, based on the results of the available studies and the high pH.

Eye irritation

In the non-GLP study by MB Research Laboratories (1979), 6 rabbits were instilled with 0.1 ml of undiluted test substance in one eye, while the other eye served as control. The eyes were scored according to Draize, after 1h, 24h, 48h, 72h and after 7 and 14 days. Also the results of this study result in the classification as a severe eye irritant according to the CLP criteria.


Justification for classification or non-classification

The substance will be classified as skin corrosive based on a weight-of-evidence approach, taking into account the results of the available studies and the high pH.

According to CLP, the substance will be classified as skin corrosive substance category 1C, H314 (causes severe skin burns and eye damage).

The substance will be classified as a severe eye irritant based on the results of the available key study.

According to CLP, the substance will be classified with H318 (causes serious eye damage).