Registration Dossier

Administrative data

Description of key information

Skin: not irritating
Eye: corrosive

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: 40 CFR, Part 798, Subpart E Section 798.4470, Toxic Substances Control Act, 1994
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: test substance was slightly moistened with USP 0.9% sodium chloride for injection
Controls:
other: Adjacent areas of untreated skin served as control sites
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g, slightly moistened with USP 0.9% sodium chloride for injection
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: Approximately 6 cm²

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test sited were wiped clean.
- Time after start of exposure: 4 hours.

SCORING SYSTEM:
Performed according to the Draize method
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of all 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: reversibility not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
of all 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritant / corrosive response data:
None of the test animals exhibited signs of erythema or edema during the 72 hour observation period. All the scores were 0 at all reading time points.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

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:
1995
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: 40 CFR, Part 798, Subpart E Section 798.4500, Toxic Substances Control Act, 1985
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
other: the right, untreated eye served as a control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
Test substance was not washed from the eye after administration
Observation period (in vivo):
96 hours
Number of animals or in vitro replicates:
6
Details on study design:
SCORING SYSTEM:
The eyes were examined at 1, 24, 48, 72 and 96 hours after administration and scored according to the Draize method for scoring ocular lesions

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Remarks:
The substance was considered to be corrosive.
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Remarks:
The substance was considered to be corrosive.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Remarks:
The substance was considered to be corrosive.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Remarks:
The substance was considered to be corrosive.
Irritation parameter:
other: pannus (corneal vascularisation)
Basis:
other: 4/6 animals
Time point:
other: 96 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: The study was terminated when pannus was observed. The substance was considered to be corrosive.
Irritant / corrosive response data:
All six test animals exhibited positive scores for irritation. Fluorescein staining was observed in 5/6 animals. In addition 4/6 animals developed pannus (corneal vascularization) by the 96-hour observation point. The study was terminated when pannus was observed. The control eye of all animals was normal (grade 0) throughout the observation period.
Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: Cat. 1, H318
DSD: Xi, R41
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A skin irritation study (Lister, 1995c) was performed according to 40 CFR, Part 798, Subpart E Section 798.4470, Toxic Substances Control Act, 1994). The test substance was applied to the shaved skin of 6 rabbits and covered with a semi-occlusive dressing for 4 hours. None of the 6 test animals exhibited any signs of erythema or edema during the 72-hour observation period.

These findings were confirmed in the acute dermal toxicity study performed by Lister (1995). In this study APD was administered to rats as a single dose of 2000 mg/kg bw under occlusive conditions for 24 hours.

Therefore, APD is considered not to cause skin irritation under the conditions of these studies.

An eye irritation study was performed using the test substance on rabbits, according to 40 CFR, Part 798, Subpart E Section 798.4500, Toxic Substances Control Act, 1985 (Lister, 1995d). APD was instilled into the eye of the animals and left without washing the eye at any time point. All 6 animals exhibited irritation of the exposed eye and 4/6 developed pannus (corneal vascularisation) within 96 hours. As this is an irreversible effect, the study was terminated after 96 hours. In conclusion, the substance was corrosive to the eye under the conditions of this study.


Effects on eye irritation: corrosive

Justification for classification or non-classification

The available data on skin irritation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification. The available data on eye irritation of the test substance meet the criteria for classification as Category 1 (H318) according to Regulation (EC) 1272/2008 and as Xi R41 according to Directive 67/548/EEC.