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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation, other
Remarks:
In vivo study
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Studies were conducted according to generally valid and/or internationally accepted testing guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Principles of method if other than guideline:
The study was conducted according to the procedure originally suggested by Draize (Draize, H.J. "Appraisal of the Safety of Chemical in Foods, Drugs and Cosmetics", Assoc. of Food and Drug Officials of the U.S., Austin, Texas, 1959).
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The test article was supplied by the Sponsor as a clear liquid in an amber bottle labeled IFF #80-004-05 on 1/24/80. The composition was not stated on the label. It was assigned C.S.E. number 4450-139 upon its receipt. It was used as received.

After communication with the Sponsor, the identity of the sample 80-004-05 was confirmed to be dihydromyrcenol (100%), CAS. No. 18479-58-8.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: not stated
- Weight at study initiation: 2.0 to 3.5 kg at the preliminary eye examination
- Housing: singly under standard laboratory conditions; suspended pans beneath cages were littered with prepared bedding (Easi Litter)
- Diet: daily 100 g of Purina Rabbit Chow supplemented by whole oats
- Water (ad libitum): not stated
- Acclimation period: yes, but the period not stated
- Assurance of animal health: animals were examined by a veterinarian during quarantine and all animals assigned to the study were in good health prior to the start of the study and were selected to be free of apparent ocular defects


ENVIRONMENTAL CONDITIONS
The criteria used for housing and maintenance were those specified in the "Guide for the Care and Use of Laboratory Animals", DHEW Publication No. (NIH) 78-23, Revised 1978.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of each rabbit served as control
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
single application
Observation period (in vivo):
10 days
Number of animals or in vitro replicates:
6
Details on study design:
METHOD

Twenty-four hours prior to dosing, both rabbit eyes were examined using a hand held ophthalmoscope and then by fluorescein staining. One drop of Fluorescein Sodium Ophthalmic Solution USP was dropped onto the cornea which was then irrigated with Sodium Chloride Solution USP. Eyes were examined for corneal ulceration using an ultraviolet light.

On the day of dosing, the lower lid was everted from the eyeball of the right eye of each animal to form a cup into which the test article was instilled. The eyelids were then gently held shut for one second. The eye was not washed after instillation. Any untoward reaction to instillation of the test substance was recorded and the animal returned to its cage.

Both eyes of each rabbit were scored according to the method of Draize (Table 1) at 24, 48 and 72 hours and at 4 and 7 days after dosing. In addition, at 24 hours and 7 days, both eyes were examined with fluorescein stain under an ultra violet light.

Any persistent changes observed on Day 7 were re-evaluated on Day 10 using a hand-held ophthalmoscope and the fluorescein method described previously.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 hours
Score:
39.83
Max. score:
110
Reversibility:
fully reversible within: 10 days
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 48 hours
Score:
31
Max. score:
110
Reversibility:
fully reversible within: 10 days
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 hours
Score:
19.17
Max. score:
110
Reversibility:
fully reversible within: 10 days
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 4 days
Score:
14.83
Max. score:
110
Reversibility:
fully reversible within: 10 days
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 7 days
Score:
2.5
Max. score:
110
Reversibility:
fully reversible within: 10 days
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 10 days
Score:
0
Max. score:
110
Reversibility:
fully reversible within: 10 days
Irritant / corrosive response data:
All of the six animals developed corneal opacity within 24 hours of being dosed. Opacity had cleared in one of the six animals at 72 hours, and in four of the six animals by Day 7. The eyes of the last two animals had cleared by Day 10.

See the table below for individual animal irritation results.

Any other information on results incl. tables

The primary eye irritation data for individual animals and observation times is summarized in the following table.

Rabbit Cornea Iris Conjunctivae Total
Number Hr/Day A (Opacity) B (Area) (A x B x 5) A A X 5 A (Redness) B (Chemosis) C (Discharge) (A + B + C) x 2 Score
A-1126 24 hours 2 4 40 0 0 2 1 2 10 50
48 hours 2 4 40 0 0 1 0 0 2 42
72 hours 2 3 30 0 0 0 0 0 0 30
day 4 1 3 15 0 0 0 0 0 0 15
day 7 1 2 10 0 0 0 0 0 0 10
day 10 0 0 0 0 0 0 0 0 0 0
Mean= 1.33 2.67 0.00 0.50 0.17 0.33
Mean (24,48 and 72 hr) 2.00 3.67 0.00 1.00 0.33 0.67
A-1127 24 hours 2 3 30 1 5 3 2 3 16 51
48 hours 2 3 30 0 0 1 0 0 2 32
72 hours 2 1 10 0 0 1 0 0 2 12
day 4 2 1 10 0 0 0 0 0 0 10
day 7 0 0 0 0 0 0 0 0 0 0
day 10 0 0 0 0 0 0 0 0 0 0
Mean= 1.33 1.33 0.17 0.83 0.33 0.50
Mean (24,48 and 72 hr) 2.00 2.33 0.33 1.67 0.67 1.00
A-1128 24 hours 2 4 40 0 0 2 1 2 10 50
48 hours 2 4 40 0 0 2 0 0 4 44
72 hours 2 4 40 0 0 1 0 0 2 42
day 4 2 4 40 0 0 1 0 0 2 42
day 7 0 0 0 0 0 0 0 0 0 0
day 10 0 0 0 0 0 0 0 0 0 0
Mean= 1.33 2.67 0.00 1.00 0.17 0.33
Mean (24,48 and 72 hr) 2.00 4.00 0.00 1.67 0.33 0.67
A-1129 24 hours 2 3 30 0 0 3 2 2 14 44
48 hours 2 3 30 0 0 2 0 0 4 34
72 hours 1 1 5 0 0 2 0 0 4 9
day 4 1 1 5 0 0 1 0 0 2 7
day 7 0 0 0 0 0 0 0 0 0 0
day 10
Mean= 1.2 1.6 0 1.6 0.4 0.4
Mean (24,48 and 72 hr) 1.67 2.33 0.00 2.33 0.67 0.67
A-1139 24 hours 1 2 10 0 0 2 2 1 10 20
48 hours 1 2 10 0 0 1 0 0 2 12
72 hours 0 0 0 0 0 0 0 0 0 0
day 4 0 0 0 0 0 0 0 0 0 0
day 7 0 0 0 0 0 0 0 0 0 0
day 10 0 0 0 0 0 0 0 0 0 0
Mean= 0.33 0.67 0.00 0.50 0.33 0.17
Mean (24,48 and 72 hr) 0.67 1.33 0.00 1.00 0.67 0.33
A-1140 24 hours 1 4 20 0 0 1 1 0 4 24
48 hours 1 4 20 0 0 1 0 0 2 22
72 hours 1 4 20 0 0 1 0 0 2 22
day 4 1 3 15 0 0 0 0 0 0 15
day 7 1 1 5 0 0 0 0 0 0 5
day 10 0 0 0 0 0 0 0 0 0 0
Mean= 0.83 2.67 0.00 0.50 0.17 0.00
Mean (24,48 and 72 hr) 1.00 4.00 0.00 1.00 0.33 0.00
Mean by sample time =
24 hours 1.67 3.33 0.17 2.17 1.50 1.67 39.83
48 hours 1.67 3.33 0.00 1.33 0.00 0.00 31.00
72 hours 1.33 2.17 0.00 0.83 0.00 0.00 19.17
day 4 1.17 2.00 0.00 0.33 0.00 0.00 14.83
day 7 0.33 0.50 0.00 0.00 0.00 0.00 2.50
day 10 0.00 0.00 0.00 0.00 0.00 0.00 0.00

Applicant's summary and conclusion

Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: Draize scoring system
Conclusions:
The primary ocular irritation scores were 39.83 at 24 hours, 31.00 at 48 hours, 19.17 at 72 hours, 14.83 at 4 days, 2.5 at 7 days and 0 at 10 days. Under the conditions of this study, the test article was classified as moderately irritating to the eye of the albino rabbit.