Registration Dossier

Administrative data

Description of key information

Guideline- and GLP-compliant rabbit eye and dermal irritation studies.

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:
Aug 5, 1988 to Aug 8, 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Separate isolation by test system. Light cycle: 12 hr light, 12 hr dark. Temperature/humidity: maintained at 22°C ± 3°C and 30 to 70% humidity. Housed individually in cages sized in accordance with “Guide for the Care and Use of Laboratory Animals” of the Institute of Laboratory Resources, National Research Council. Waste material removed twice weekly. Cages and feeder sanitized every 2 weeks. Wayne Rabbit Ration, ad libitum, checked daily and added or replaced as needed. Fresh tap water ad libitum.
Type of coverage:
occlusive
Preparation of test site:
other: clipped free of hair
Vehicle:
physiological saline
Controls:
not required
Amount / concentration applied:
500 mg/site
Duration of treatment / exposure:
4 hr
Observation period:
30-60 minutes, 24, 48 and 72 hours
Number of animals:
3M/3F
Details on study design:
Scoring according to Draize 1959
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 30-60 minutes
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 30-60 minutes
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hr
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hr
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hr
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicabl
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicabl
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicabl
Irritant / corrosive response data:
No erythema or edema was detected at any time point in any animal.
Other effects:
None observed.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The material is not a skin irritant.
Executive summary:

The test article (500 mg/site) was applied to one intact skin site on each of six New Zealand White rabbits (3 males and 3 females). The test article was administered once and remained in contact with the skin for 4 hours. The skin was observed for erythema and edema and scored according to the Draize Score at 30 to 60 minutes, 24, 48 and 72 hours after application of the test article. No signs of erythema or edema were observed throughout the 72 hour observation period in any of the animals on test. The test article was not a dermal irritant.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed using commercial product according to international guidelines and GLPs.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Separate isolation by test system. Light cycle: 12 hr light, 12 hr dark. Temperature/humidity: maintained at 22°C ± 3°C and 30 to 70% humidity. Housed individually in cages sized in accordance with “Guide for the Care and Use of Laboratory Animals” of the Institute of Laboratory Resources, National Research Council. Waste material removed twice weekly. Cages and feeder sanitized every 2 weeks. Wayne Rabbit Ratiobn, ad libitum, checked daily and added or replaced as needed. Fresh tap water ad libitum.
Vehicle:
unchanged (no vehicle)
Controls:
other: Each animal served as its own control.
Amount / concentration applied:
100 mg/eye
Duration of treatment / exposure:
Instilled once in conjunctival sac of one eye of each animal
Observation period (in vivo):
1, 24, 48 and 72 hr after treatment
Number of animals or in vitro replicates:
3M/3F
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
0
Time point:
other: 1 hr
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
0
Time point:
other: 24 hr
Score:
0
Max. score:
0
Reversibility:
other: does not apply
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
0
Time point:
other: 48 hr
Score:
0
Max. score:
0
Reversibility:
other: does not apply
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
0
Time point:
other: 72 hr
Score:
0
Max. score:
0
Reversibility:
other: does not apply
Irritation parameter:
iris score
Basis:
mean
Remarks:
0
Time point:
other: 1 hr
Score:
0
Max. score:
0
Reversibility:
other: does not apply
Irritation parameter:
iris score
Basis:
mean
Remarks:
0
Time point:
other: 24 hr
Score:
0
Max. score:
0
Reversibility:
other: does not apply
Irritation parameter:
iris score
Basis:
mean
Remarks:
0
Time point:
other: 48 hr
Score:
0
Max. score:
0
Reversibility:
other: does not apply
Irritation parameter:
iris score
Basis:
mean
Remarks:
0
Time point:
other: 72 hr
Score:
0
Max. score:
0
Reversibility:
other: does not apply
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
1.16
Time point:
other: 1 hr
Score:
1 - 2
Max. score:
2
Reversibility:
fully reversible within: 24 to 48 hr
Remarks on result:
other: redness
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
0.16
Time point:
other: 24 hr
Score:
0 - 1
Max. score:
1
Reversibility:
fully reversible within: 24 hr to 48 hr
Remarks on result:
other: redness
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
0.16
Time point:
other: 48 hr
Score:
0 - 1
Max. score:
1
Reversibility:
fully reversible within: 24 hr
Remarks on result:
other: redness
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
0
Time point:
other: 72 hr
Score:
0
Max. score:
0
Reversibility:
other: does not apply
Remarks on result:
other: redness
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
0.33
Time point:
other: 1 hr
Score:
0 - 1
Max. score:
1
Reversibility:
fully reversible within: 24 hr
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
0
Time point:
other: 24 hr
Score:
0
Max. score:
0
Reversibility:
other: does not apply
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
0
Time point:
other: 48 hr
Score:
0
Max. score:
0
Reversibility:
other: does not applty
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
0
Time point:
other: 72 hjr
Score:
0
Max. score:
0
Reversibility:
other: does not apply
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test article was not an eye irritant.
Executive summary:

The test article (100 mg/eye) was instilled into the right eye of each of six New Zealand White rabbits (3 males and 3 females). Observations were recorded at 1, 24, 48 and 72 hours after treatment and scored according to the method of Draize. One positive ocular score (due to redness of the conjunctiva in one animal) was recorded at the 1 hour observation period. No other positive scores were recorded at the 1, 24, 48 or 72 hour observation periods. All scores were normal at the 72 hour observation period and the study was terminated. The test article was not an eye irritant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Results of rabbit (New Zealand White) skin and eye irritation studies demonstrate the substance is not an irritant.

Justification for classification or non-classification

Non-classification: Results of rabbit (New Zealand White) skin and eye irritation studies demonstrate the substance is not an irritant.