Registration Dossier

Administrative data

Description of key information

The test item was tested for skin and eye irritation in rabbits and was found to be non-irritant. Upon occlusive application to skin for 24, no indication of erythema and edema was observed during the observation period of 3 days. Upon instillation of 100 mg into eyes, for non-rinsed eyes, conjunctivae redness was observed at the 1h and 4h reading, but not at later time points. Experimental data on respiratory irritation is not available.

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:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP, but well reported. Testing procedure more stringent than OECD testing guideline 404.
Qualifier:
no guideline followed
Principles of method if other than guideline:
The Draize test was used to assess primary skin irritation. Six rabbits were used. The back of each rabbit was clipped free of hair 24 h before application of the mixture. Four sites, two intact and two abraded, were established. The material was applied at each location. The test sites were covered with a gauze pad and the entire back was overlaid with an adhesive plastic surgical drape. Each rabbit was then placed in a rabbit jacket. The jackets and wraps were removed 24 h later, and each test site was scored visually for erythema and edema. Readings were recorded at 24, 48, and 72 h. A final irritation score was calculated for the 24- and 72-h readings.
GLP compliance:
no
Specific details on test material used for the study:
- Storage condition of test material: 25 °C in a glass container sealed inside a polyethylene bag
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Keen Ridge Rabbit Ranch, Edgewood, New Mexico
- Weight at study initiation: 2.0 - 3.0 kg
Type of coverage:
semiocclusive
Preparation of test site:
other: shaved and abraded
Vehicle:
other: corn oil
Controls:
no
Amount / concentration applied:
500 mg substance in 0.5 mL of corn oil
Duration of treatment / exposure:
24 h
Observation period:
72 h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: Back
- Type of wrap if used: The test sites were covered with a gauze pad, and the entire back was overlaid with an adhesive plastic surgical
drape.

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72h
Score:
0
Max. score:
4
Irritant / corrosive response data:
None
Interpretation of results:
GHS criteria not met
Conclusions:
None of the 6 rabbits exhibited edema or erythema in 24 h; therefore, all animals were judged normal. The total primary irritation score was 0.00.
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:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, no separate chemosis scores given.
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:
- Storage condition of test material: 25 °C in a glass container sealed inside a polyethylene bag
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Keen Ridge Rabbit Ranch, Edgewood, New Mexico
- Weight at study initiation: 2.7 - 2.9 kg
Vehicle:
unchanged (no vehicle)
Controls:
other: right eye
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 100 mg
Duration of treatment / exposure:
Single application
Observation period (in vivo):
72 h (1h, 4h, 24h, 48h and 72 h)
Number of animals or in vitro replicates:
6 (2 per wash condition)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): 4 animals out of 6
- Time after start of exposure: 30 s and 5 min

SCORING SYSTEM: Draize
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1h, 4h, 24h,48h and 72h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1h, 4h, 24h,48h and 72h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1h and 4h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 24h
Remarks on result:
other: Values for animals with the unwashed eyes. Animals with washed eyes had lower scores.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Irritation was observed only in conjunctival tissue. Conjunctival responses were observed at all treatment levels at 1 h and generally consisted of mild redness. All treatment groups were judged normal at 48 h. The eye irritation caused by the test article was mild and transitory.

Table 1. Eye irritation response in rabbits treated with test materiala

Tissue graded Average Irritationb
hours days
1 4 1 2 3
Wash at 30 s




Cornea 0 0 0 0 0
Iris 0 0 0 0 0
Conjunctive 1 2 0 0 0
Wash at 5 m




Cornea 0 0 0 0 0
Iris 0 0 0 0 0
Conjunctive 1 1 1 0 0
No wash




Cornea 0 0 0 0 0
Iris 0 0 0 0 0
Conjunctive 3 3 0 0 0

a) Two rabbits per wash condition.

b) Maximum cornea response = 80; maximum iris response = 10; maximum conjunctivae response = 20.

Interpretation of results:
GHS criteria not met
Conclusions:
Irritation was observed only in conjunctival tissue during the first day after application.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key studies for skin and eye irritation were performed prior to the introduction of GLP but are reported in adequate detail and followed a procedure that allowed for classification and labelling. The test design of the eye irritation study is comparable to that of OECD testing guideline 405 whereas that of the skin irritation is more stringent than that of OECD testing guideline 404. The tests were performed with a commercial product. The results are consistent with the findings of an older study that was also performed with a commercial sample.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008.