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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

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. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
2,6-dimethyloct-7-en-2-ol
EC Number:
242-362-4
EC Name:
2,6-dimethyloct-7-en-2-ol
Cas Number:
18479-58-8
Molecular formula:
C10H20O
IUPAC Name:
2,6-dimethyloct-7-en-2-ol

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
- 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

24 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:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 4 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.66
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 4 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 24 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
positive indication of irritation
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

Table 2: Primary eye irritation data for individual animals and observation times


 

















































































































































































































































































































































































































































































































































































































































































































































































































































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:
Category 2 (irritating to eyes) based on GHS criteria
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.
Executive summary:

In a study in rabbits, 0.1 mL of undiluted test item was applied to six rabbit eyes followed by examinations at 24-, 48 and 72-hours and at days 4 and 7 days following treatment. Eyes were examined with fluorescein stain under ultraviolet light at 24-hours and 7 days. Any persistent changes noted at day 7 were re-evaluated on day 10. All animals developed corneal opacity by 24 hours (scores of 1 to 2). Opacity had cleared in one animal at 72 hours and in 4 of 6 animals by day 7. The eyes of the last 2 animals cleared by day 10. Based on the Draize scoring system, the material would be rated as moderately irritating to eyes. Mean overall scores at 24-, 48- and 72-hours were as follows: opacity, 1.56; iris, 0.06; conjunctival redness, 1.44; conjunctival chemosis, 0.50; and conjunctival discharge, 0.56. In a supporting study in rabbits, undiluted dimyrcetol was rated an eye irritant based on the Draize scoring system. Mean overall scores at 24-, 48- and 72-hours were as follows: opacity, 0.33; iris, 0.17; conjunctival redness, 0.83; conjunctival chemosis, 0.56; and conjunctival discharge, 0.56. Under the conditions of this study, the test article was classified as moderately irritating to the eye of the albino rabbit.