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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:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Purity of the test material was not listed.

Data source

Reference
Reference Type:
publication
Title:
The comparative acute toxicity and primary irritancy of the monohexyl ethers of ethylene and diethylene glycol.
Author:
Ballantyne B.; Myers R. C.
Year:
1987
Bibliographic source:
Vet Human Tox 29:361-366

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Method: other
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): diethylene glycol monohexyl ether (DGHE)
- Physical state: Colorless liquid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
The animals were maintained on appropriate commercial diet and municipal water. Both were available ad libitum.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
undiluted, 0.1 and 0.005 mL
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
12
Details on study design:
Rabbits (2 to 3 kg) whose eyes did not stain after exposure to 2% fluorescein for 20 seconds were used in the study. Test material was instilled into the interior conjunctival sac of one eye of 6 rabbits (0.1 ml) or the surface of the cornea (0.005 ml) of 6 other rabbits. Eyes were inspected for signs of local inflammation at 1, 4 and 24 hours and 2, 3, 7, 14 and 21 days after instillation. Particular attention was paid to the development of injection  of the conjunctiva and nictitating membrane, chemosis, discharge, iritis, and corneal injury (both severity and area of involvement).  Corneal opacity and area involved were scored from 0 to 4,  injury to the iris was scored from 0 to 2, conjunctival redness and  discharge were scored from 0 to 3, and chemosis from 0 to 4.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
over all animals
Time point:
24/48/72 h
Score:
1.8
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: Dose volume: 0.1 mL
Irritation parameter:
iris score
Basis:
mean
Remarks:
over all animals
Time point:
24/48/72 h
Score:
0.8
Max. score:
1
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Dose volume: 0.1 mL
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
over all animals
Time point:
24/48/72 h
Score:
2.1
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: Dose volume: 0.1 mL
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
over all animals
Time point:
24/48/72 h
Score:
1.8
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: Dose volume: 0.1 mL
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
over all animals
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Dose volume: 0.005 mL
Irritation parameter:
iris score
Basis:
mean
Remarks:
over all animals
Time point:
24/48/72 h
Score:
0.6
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Dose volume: 0.005 mL
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
over all animals
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Dose volume: 0.005 mL
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
over all animals
Time point:
24/48/72 h
Score:
1.4
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Dose volume: 0.005 mL
Irritant / corrosive response data:
Within an hour of instillation of 0.1 ml of test material into the interior conjunctival sac, all animals developed a moderate to marked conjunctivitis, seen as hyperemia, chemosis and discharge (scores of 2 to 3). This started to resolve by Day 2, but 3 animals still had slight hyperemia and chemosis at Day 21. Mild iritis was present from 1 hour (all score of 1) until about 7 days. By 1 hour of instillation, mild-moderate corneal injury that affected up to 3/4 of the cornea was observed in 5 animals (average opacity and area scores of 1.3 and 2.2, respectively). By 24 hours, the 6th animal also showed evidence of mild corneal injury. All but one animal had no evidence of corneal injury after 7 days. Corneal injury was just detectable in this animal at 21 days.
Similar effects were seen in animals treated with 0.005 ml test material on the surface of the cornea, but they resolved quicker. Conjunctivitis was moderate to marked for the first 24 hours(scores of 2 to 3) but was resolved by 7 days in all but one animal. All had normal conjunctiva by Day 14. Minimal iritis was observed in all animals within 1 to 24 hours. This cleared after 2 to 7 days. Mild to moderate corneal injury that affected up to 3/4 of the cornea developed within 4 hours in all rabbits (average opacity and area scores of 1.5 and 3.0, respectively). No injury was observed in any of the animals after 7 days.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye)
Conclusions:
Instillation of 0.1 mL or 0.005 mL of test material into rabbit eyes produced moderate to severe ocular effects.
Executive summary:

Fluorescein (2%) staining was used to determine corneal injury before dosing and at readings after one day. Rabbits whose eyes did not stain after exposure to 2% fluorescein for 20 seconds were used in the study.  Test material was instilled into  the interior conjunctival sac of one eye of 6 rabbits (0.1 mL) or the surface of the cornea (0.005 mL) of 6 other rabbits.  Eyes were inspected for signs of local inflammation at 1, 4 and 24 hours and 2, 3, 7, 14 and 21 days after instillation.  Particular attention was paid to the development of injection  of the conjunctiva and nictitating membrane, chemosis, discharge, iritis, and corneal injury (both severity and area of involvement).  Corneal opacity and area involved were scored from 0 to 4,  injury to the iris was scored from 0 to 2, conjunctival redness and  discharge were scored from 0 to 3, and chemosis from 0 to 4.

Within an hour of instillation of 0.1 mL of test material into the interior conjunctival sac, all animals developed a moderate to marked conjunctivitis, seen as hyperemia, chemosis and discharge (scores of 2 to 3).  This started to resolve by Day 2, but 3 animals still had slight hyperemia and chemosis at Day 21.  Mild iritis was present from 1 hour (all score  of 1) until about 7 days.  By 1 hour of instillation, mild-moderate corneal injury that affected up to 3/4 of the cornea was observed in 5 animals (average opacity and area scores of 1.3 and 2.2, respectively).  By 24 hours, the 6th animal also showed evidence of mild corneal injury. All but one animal had no evidence of corneal injury after 7 days.  Corneal injury was just detectable in this animal at 21 days.

Similar effects were seen in animals treated with 0.005 ml test material on the surface of the cornea, but they resolved quicker. Conjunctivitis  was moderate to marked for the first 24 hours (scores of 2 to 3) but was  resolved by 7 days in all but one animal. All had normal conjunctiva by  Day 14. Minimal iritis was observed in all animals within 1 to 24 hours. This cleared after 2 to 7 days. Mild to moderate corneal injury that  affected up to 3/4 of the cornea developed within 4 hours in all rabbits (average opacity and area scores of 1.5 and 3.0, respectively).  No  injury was observed in any of the animals after 7 days.