Registration Dossier

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:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: non GLP study, done according to U.S. federal register § 191.12 17 Sptember 1964

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: U.S. federal register § 191.12 17 September 1964 with additional evaluations of pain response at instillation
Principles of method if other than guideline:
No further details
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Approximately 225 g (gross) of Dinol (Dibromoneopentyl glycol), a brown crystalline material

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Rabbit, New Zealand White
Weight: 2.75-3.30 kg , 24 weeks old on arrival.
Each-room within the limited-access building was assigned to one species alone.
All rooms were kept at a slight positive pressure relative to the outside and each had its own independent filtered air supply which gave 17 complete
air changes per hour without recirculation. The temperatures and relative humidities were recorded at the begining of each working day.
Thermostatic controls were set to maintain temperatures of 15°C ± 2°C and relative humidities of 50% ± 10% R.H.
Lighting cycle of 14 hours artificial light; 10 hours dark per day was maintained by electric time switches.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
100mg
Duration of treatment / exposure:
The animal was gently restrained. The test material was placed in the right eye of each rabbit by gently pulling the lower lid away from eyeball to form a cup into which the test material was dropped. The eyelids were gently held together for one second and then released.
Observation period (in vivo):
The behavoiur of the rabbit was observed for several minutes immediately following instillation of the test material to allow assessment of the initial pain response. The animals were returned to their cages and checked at intervals throughout the day to ensure that no reaction to treatment passed
unobserved. ocular reaction treatment was assessed at 24, 48 and 72 hours and seven days after installation.
Number of animals or in vitro replicates:
6

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of mild irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of mild irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of mild irritation
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
48 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of mild irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
48 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of mild irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
48 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of mild irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within:
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #4
Time point:
48 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #5
Time point:
48 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #6
Time point:
48 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of mild irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
48 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
48 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
48 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of mild irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #4
Time point:
72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #5
Time point:
72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #6
Time point:
72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
see attached data
Other effects:
Diffuse corneal opacity affecting less than a quarter of the corneal surface was exhibited by four of the test animals at the 24, 48 and 72 -hour post installation reading. One animal displayed diffuse crimson redness of the conjunctivae in addition to the corneal lesions. All animals exhibited slight conjunctivitis at the 24, 48 and 72-hour readings. This persisted to day 8 in 2 animals. Immediate pain responses upon instillation of the test material ranged from practically no initial pain to moderate initial pain.

Any other information on results incl. tables

see attached data

Applicant's summary and conclusion

Interpretation of results:
other: mild irritant
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
A single installation of 100 mg of test substance into the conjunctival sac of six New Zealand White rabbits provoked corneal and conjunctival lesions in four animals regarded as positive reactions under this method. Therefore the test substance was considered to elicit a positive result as an eye irritant. The positive reactions had resolved by Day 8 and may therefore be considered as reversible. According to current clasification criteria this substance can be considered mild irritant.