Registration Dossier

Administrative data

Endpoint:
eye irritation, other
Remarks:
in vivo study available
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well-documented GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
GLP compliance:
yes (incl. certificate)
Remarks:
testing lab.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of the test substance used in the study report: C-01650 (4-HAP)
Purity: 99.97%

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Weight: 2.0 - 4.0 kg at time of dosing
Each animal was assigned a unique and individual number. This number was permanently indicated on each animal with an ear tag.
Animals were housed separately from any other species. They were individually housed in stainless steel, wire mesh bottom cages.
Room temperature: 63 - 73°F; relative humidity: 30 - 70%; day/night rhythm: 12 h dark/12 h light.
Fresh certified rabbit feed and fresh potable water were provided ad libitum.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animal
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
24 h
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
4
Details on study design:
The eyes were examined 1, 24, 48 and 72 h following test article administration and also on days 4, 7, 14 and 21 of the study where appropriate. Scoring was done according to the method of Draize.
Responses of cornea, iris and conjunctivae were examined using a hand held ophthalmoscope.
In addition, the eyes were examined at 24, 48 and 72 h as well as on day 4 and day 7 where appropriate with fluorescein
stain.
One animal was dosed initially to determine the potential for the test article to produce ocular irritation prior to treating multiple animals. For this animal the treated eye remained unrinsed. Dependent upon the response noted in this animal, additional testing was performed, i.e. in this case, additional testing was done in 3 rabbits, where anesthetic was used prior to dosing as well as for the control eye. The eyes were rinsed 30 seconds after test material administration for approx. 30 seconds using a volume of approx. 120 ml 0.9% saline at room temperature.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 48 h
Score:
0
Max. score:
0
Remarks on result:
other: rinsed eye
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 48 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: rinsed eye
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 48 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: rinsed eye
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 48 h
Score:
0
Max. score:
1
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: rinsed eye
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 48 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: unrinsed eye
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 48 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: unrinsed eye
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 48 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 21 d
Remarks on result:
other: unrinsed eye
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 48 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 14 d
Remarks on result:
other: unrinsed eye

Any other information on results incl. tables

Results for the initially treated animal that remained unrinsed:

-At the 1 h reading corneal opacity 2 was noted with the area involved ranging from 50 to 75%: Conjunctival redness 2, chemosis 3 and discharge 2 were also noted.

-At the 24 h reading corneal opacity 2 was noted with the area involved ranging from 75 to 100%.

Iridial irritation 1 was noted.

Conjunctival redness 2, chemosis 3 and discharge 3 were also noted.

Fluorescein staining of the corneal epithelium was evident with the area involved ranging from 75-100%.

Hair loss below the lower eyelid was also seen which remained the same until day 14 when new hair started growing in the

area.

-At the 72 h reading corneal opacity 2 was noted with the area involved ranging from 50-75%.

Iridial irritation 1, conjunctival redness 2, chemosis 2 and discharge 3 were still noted.

Fluorescein staining was evident with the corneal area involved ranging from 25-50%.

On day 21 of the study, the unrinsed animal was free of ocular irritation.

The maximum Draize score was recorded 48 h after treatment and was 63/110.

Results for the animals of the rinsed group:

The rinsed eyes showed somewhat milder conjunctival effects which were completely resolved by observation day 7. Slight corneal opacity was reported in 2/3 animals but only at the 24-h reading.

On day 7 of the study, all of the rinsed animals were free of ocular irritation.

According to the authors, the classification of the test material is considered to be a severe irritant based upon the maximum total score of 63 calculated for the initially treated rabbit, that remained unrinsed.

The irritation appeared to be essentially fully reversible within 21 days of treatment. The rinsing procedure for the additional 3 treated animals appeared to have reduced the severity and duration of irritation. Based upon the mean total score of 22 calculated for the three rabbits in the rinsed group, the classification considered to be as a moderate irritant.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information