Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26.06.2006 to 23.10.2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was performed according to the OECD guideline 405 and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
OS Menthol Ester
IUPAC Name:
OS Menthol Ester
Constituent 2
Chemical structure
Reference substance name:
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5R)-5-hydroxy-1,3-oxathiolane-2-carboxylate
EC Number:
604-569-1
Cas Number:
147126-62-3
Molecular formula:
C14H24O4S
IUPAC Name:
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5R)-5-hydroxy-1,3-oxathiolane-2-carboxylate
Test material form:
other: White solid

Test animals / tissue source

Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: Approx. 4.5 months at test item administration
- Weight at study initiation: males 2.1 - 2.6 kg
- Housing: individually or X animals/cage
- Diet: ad libitum before and after the exposure period.
- Water: ad libitum before and after the exposure period.
- Acclimation period: 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 08.08.2006 To: 13.09.2006

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye, which remained untreated, served as a control.
Amount / concentration applied:
100 mg Menthyloxathiolane
Duration of treatment / exposure:
100 mg of the test item per eye were administered and tested in three animals. In 2 of the 3 animals a washout with 20 mL aqueous NaCl solution was carried out
24 hours after instillation.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: In 2 of the 3 animals a washout with 20 mL aqueous NaCl solution was carried out2.
- Time after start of exposure: 24 hours

TOOL USED TO ASSESS SCORE: The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48, 72 hours and 4 to 15 days after the administration. 24 hours, 7 and 14 days after administration the eyes were treated additionally with fluorescein3 and examined.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24h to 5d
Score:
1
Reversibility:
not specified
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24h to 5d an after 14d
Score:
1
Reversibility:
not specified
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24h to 5d
Score:
1
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24h and 4d
Score:
1
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24h and 48h
Score:
1
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24h
Score:
1
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 1h, 24h, 48h, 7d
Score:
1
Max. score:
2
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 1h, 24h, 4d, 5d, 10d
Score:
1
Max. score:
2
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 1h, 5d
Score:
1
Reversibility:
not specified
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 1h, 24h, 4d, 5d, 6d
Score:
1
Max. score:
2
Reversibility:
not specified
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 1h, 24h, 48h, 4d, 5d, 6d
Score:
1
Max. score:
3
Reversibility:
not specified
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 1h, 24h, 48h, 4d, 5d
Score:
1
Max. score:
3
Reversibility:
not specified
Irritant / corrosive response data:
An irritation index was not determined due to the corrosive effects observed.

Applicant's summary and conclusion

Interpretation of results:
Category II
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Corneal opacity (grade 1) was observed in all animals24 hours to 5 days after instillation, in animal no. 2 until 14 days after instillation.
Irritation of the iris (grade 1) was observed in all animals 24 hours after instillation, in animal no. 2 until 48 hours and in animal no. 1 until 4 days
after instillation.
Conjunctival redness was observed in all animals.
- animal no. 1: 24 hours (grade 2), 1 hour and 48 hours to 7 days (grade 1) after instillation;
- animal no. 2: 24 hours to 4 days (grade 2), 1 hour and 5 to 10 days (grade 1) after instillation;
- animal no. 3: 1 hour to 5 days (grade 1) after instillation.
Chemosis was observed in all animals:
- animal no. 1: 24 hours to 4 days (grade 2), 1 hour, 5 and 6 days (grade 1) after instillation;
- animal no. 2: 24 hours (grade 3), 48 hours to 4 days (grade 2), 1 hour, 5 and 6 days (grade 1) after instillation;
- animal no. 3: 24 hours (grade 3), 1 hour and 48 hours to 4 days (grade 2) and 5 days (grade 1) after instillation.
Executive summary:

Based on the above described findings the substance is considered to be irritating to the eyes under the conditions of this study.