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Description of key information

Skin exposures of up to 4-hours did not cause corrosion but were irritating.  Exposure of 20-hours or longer were irritating (non-occluded) and corrosive (occluded).
Three different study designs all demonstrated irreversible eye damage when the material was not washed from the eye.  Washing after a 6 minute exposure  produced severe irritation that was reversible within 22 days.

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:
weight of evidence
Study period:
1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: test done before establishment of GLP
Qualifier:
no guideline followed
Principles of method if other than guideline:
A group of 6 male Albino rabbits 2.48 - 2.76 kg was used to test the effects of the drug on intact and abraded skin. 0.5 cc was applied to each side of the shaved belly. The areas were covered with layers of gauze sponge and the animals wrapped in sections of elastic bandage for 4 hours. The skin was evaluated for erythema and/or edema daily for 72 hours and weekly for 3 weeks.
GLP compliance:
not specified
Remarks:
test done before establishment of GLP
Species:
rabbit
Strain:
other: albino rabbits
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Duration of treatment / exposure:
4 hours
Observation period:
3 weeks
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: belly
- Type of wrap if used: layers of gauze sponge and wrapped in sections of elastic bandage

Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: all
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: No irritation was observed at the intact skin sites
Irritant / corrosive response data:
Not irritating to intact skin following a 4-hour exposure.
Reversible irritation was observed for the abraded skin site. A mild edema was present at 4 hours. A mild erythema was present for 2 weeks. The skin appeared normal at 3 weeks. No tissue destruction was observed.
Interpretation of results:
slightly irritating
Remarks:
Migrated information abraded skin Criteria used for interpretation of results: expert judgment
Conclusions:
Following a 4-hour exposure the material was not corrosive or irritating to intact skin. Reversible irritation was seen with abraded skin.
Executive summary:

After a 4-hour exposure the material was not irritating to intact skin. Reversible irritation was seen with abraded skin. A mild edema was present at 4 hours. A mild erythema was present for 2 weeks. The skin appeared "normal" at 3 weeks.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test was performed before GLP was established
Qualifier:
no guideline followed
Principles of method if other than guideline:
Group I (5 animals):
0.1 cc of the drug was placed in the conjunctival sacs. 6 minutes later, the eyes were washed with 300 cc of water over a 2 minute period. The eyes were examined 1 hour after the wash, daily for 3 days, and weekly for 3 weeks. The contralateral eye of each animal served as control.

Group II (3 animals):
0.1 cc was placed in the conjunctival sacs as above. The eyes were checked 1 hour after application, just after the wash procedure (as above) at 24 hours, daily for 3 days, and weekly for 3 weeks.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
other: contralateral untreated eye was used as control
Duration of treatment / exposure:
6 minutes - group I (5 animals)
permanent no washing - group II (3 animals)
Observation period (in vivo):
30 days
Number of animals or in vitro replicates:
5 animals group I
3 animals group II
Irritation parameter:
cornea opacity score
Remarks:
slight opacity
Basis:
other: all animals
Reversibility:
not fully reversible within: 30 days
Remarks on result:
other: Numerical scores were not provided. Severe irritation which included slight corneal opacities which were not fully reversible within 30 days
Irritant / corrosive response data:
Slight corneal opacity, reversible within 22 days (washed eyes), not reversible within 30 days (unwashed eyes).
No iritis was observed
Severe conjunctivitis, reversible within 18 days (consisted of severe redness and moderate to severe chemosis, and discharge) was seen for both the washed and unwashed groups.
Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
When not washed out of the eye, the compound caused irreversible destruction of the cornea and must be rated as corrosive. Washing after a six minute exposure di not minimize the initial irritation but the effects were reversible within 22 days.
Executive summary:

When not washed out of the eye, the compound caused irreversible destruction of the cornea and must be rated as corrosive. Washing after a six minute exposure did not minimize the initial irritation but the effects were reversible within 22 days.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Prolonged or repeated administration of the substance is corrosive. Skin exposures of up to 4-hours did not cause corrosion but were irritating. Exposure of 20-hours or longer were irritating (non-occluded) and corrosive (occluded).

Three different study designs all demonstrated irreversible eye damage when the material was not washed from the eye. Washing after a 6 minute exposure produced severe irritation that was reversible within 22 days.


Justification for selection of skin irritation / corrosion endpoint:
Only 4-hour exposure study available

Justification for selection of eye irritation endpoint:
Dose volume and observation period matched current guideline

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

According to the CLP rules, this material is conservatively classified as a Cat 2 for skin irritation. The material causes irreversible eye effects and is classified as a Cat 1 for eye damage/irritation.