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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:
1992-09-21 to 1992-10-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Deviations from the OECD 405 (2012): 4 animals instead of three animals were used. Animal with effect in the eye was not observed up to 21 days, but was terminated on day 14. Topical anaesthetics and systemic analgesics were not used. Systemic effects were not examined.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987-02-24
Deviations:
yes
Remarks:
Animal with effect in the eye was not observed up to 21 days, but was terminated on day 14.
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
1984
Deviations:
yes
Remarks:
Animal with effect in the eye was not observed up to 21 days, but was terminated on day 14.
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 1992-06-11

Test material

Constituent 1
Chemical structure
Reference substance name:
2-[({[(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl]oxy}carbonyl)oxy]ethan-1-ol
EC Number:
701-039-2
Cas Number:
156324-78-6
Molecular formula:
C13H24O4
IUPAC Name:
2-[({[(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl]oxy}carbonyl)oxy]ethan-1-ol
Specific details on test material used for the study:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: test material was ground to a fine powder using a mortar and pestle prior to use

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: approx. twelve to sixteen weeks old
- Weight at study initiation: 2.30 - 3.06 kg
- Housing: individually housed in suspended metal cages
- Diet (ad libitum): Spillers Rabbit Diet
- Water (ad libitum): mains drinking water
- Acclimation period: minimum of five days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 - 22 °C
- Relative humidity: 52 - 73%
- Air changes: approxi. 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of the test material (weighing approx. 62 mg)
Duration of treatment / exposure:
not applicable
Observation period (in vivo):
approx. 1 hour and 24, 48, and 72 hours as well as 7 and 14 days following treatment
Number of animals or in vitro replicates:
4 rabbits (3 males / 1 female)
Details on study design:
SCORING SYSTEM: Draize scale
Any other adverse ocular effects were also noted.
Immediately after administration of the test material, an assessment of the initial pain reaction was made.

TOOL USED TO ASSESS SCORE: standard ophthalmoscope

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: days 7
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #4
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #4
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Residual test material was noted around the treated eye of all animals one hour after treatment.
A dulling of the normal lustre of the corneal surface was noted in all treated eyes one hour after treatment. Areas of diffuse corneal opacity were noted in all treated eyes at the 24 and 48-hour observations with areas of diffuse to translucent corneal opacity at the 72-hour observation. Areas of diffuse corneal opacity persisted in one treated eye at the 7-day observation. Vascularisation of the cornea was also noted in this treated eye at the 7 and 14-day observations. At the beginning of the observation period the area of opacity was greater than three quarter, up to whole area for all treated eye and than became less severe until the opacity disappeared.
Iridial inflammation was noted in all treated eyes at the one, 24 and 48-hour observations, in three treated eyes at the 72-hour observation and in one treated eye at the 7-day observation. No other adverse iridial effects were noted.
Moderate conjunctival irritation was noted in all treated eyes one and 24 hours after treatment with minimal to moderate conjunctival irritation at the 48 and 72-hour observations. Minimal conjunctival irritation was noted in one treated eye at the 7-day observation. Petechial haemorrhage of the nictitating membrane was noted in one treated eye one hour after treatment.
Furthermore, moderate to severe discharge was observed 1 hour after treatment. Slight to moderate discharge was observed 24 hours after treatment.In two treated eyes the discharge was not observed anymore on day 7. In one treated eye discharge was not observed anymore at 48 hours after treatment. Lastly, in one treated eye the discharge disappeared at the 48 hour observation, but reappeared on day 7 and cleared on day 14.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
The substance is irritating to the eyes.
According to the EC Regulation No. 1272/2008 and subsequent adaptations, the substance is classified as an eye irritant (Category 2; H319).
Executive summary:

The eye irritation potential of substance was investigated according to the OECD guideline 405 (1987). A single dose (0.1 mL; approx. 62 mg) of the substance was placed into the conjunctival sac of one eye of four New Zealand White rabbits.The other eye remained untreated and served as control. Ocular damage and irritation were assessed according to the Draize scale approximately 1 hour and 24, 48, and 72 hours as well as 7 and 14 days following treatment with the substance. Any other adverse ocular effects were also noted.

The following results were recorded for the four rabbits:

Animal #1

Cornea score: 1.33

Iris score: 1

Conjunctivae score: 2

Chemosis score: 2

Animal #2

Cornea score: 1

Iris score: 0.67

Conjunctivae score: 1.67

Chemosis score: 1.33

Animal #3

Cornea score: 1

Iris score: 1

Conjunctivae score: 2

Chemosis score: 2

Animal #4

Cornea score: 1

Iris score: 1

Conjunctivae score: 1.67

Chemosis score: 1.33

Residual test material was noted around the treated eye of all animals one hour after treatment. Dulling of the normal lustre of the corneal surface was observed in all rabbits 1 hour after treatment as well as slight iridial effects. At the beginning of the observation period the area of opacity was greater than three quarter, up to whole area for all treated eye and than became less severe until the opacity disappeared. Moderate conjunctival redness and chemosis was observed in all animals 1 hour after treatment. Furthermore, moderate to severe discharge was observed 1 hour after treatment. Slight to moderate discharge was observed 24 hours after treatment.In two treated eyes the discharge was not observed anymore on day 7. In one treated eye discharge was not observed anymore at 48 hours after treatment. Lastly, in one treated eye the discharge disappeared at the 48 hour observation, but reappeared on day 7 and cleared on day 14. Petechial haemorrhage of the nictitating membrane was noted in one treated eye one hour after treatment.

Overall, all effects were fully reversible within 7 days, except for one rabbit. In this rabbit the effects were fully reversible within 14 days, except for vascularisation of the cornea which was still observed on day 14. The vascularisation of the cornea was already observed on day 7.

According to the EC Regulation No. 1272/2008 and subsequent regulations, the test substance is classified as an eye irritant (Category 2; H319).