2-hydroxypropyl [(1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl] carbonate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993-10-25 to 1993-11-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Deviations from the OECD 405 (2012): topical anaesthetics and systemic analgesics were not used. Non-ocular effects and systemic effects were not examined.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987-02-24

Deviations:

yes

Remarks:

non-ocular effects were not recorded.

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 1993-09-23

Test material

Test material information

Constituent 1

Reference substance name:

1-[({[(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl]oxy}carbonyl)oxy]propan-2-ol

EC Number:

607-858-0

Cas Number:

260781-16-6

Molecular formula:

C14H26O4

IUPAC Name:

1-[({[(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl]oxy}carbonyl)oxy]propan-2-ol

Test animals / tissue source

Species:

rabbit

Strain:

other: Mol:Russian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS - SPF albino rabbits
- Weight at study initiation: 2.2 - 2.6 kg
- Housing: kept in single PPL cages, 45 x 55 cm, with perforated floor
- Diet (ad libitum): food pellets "Altromin 2123"
- Water (ad libitum): drinking water acidified with hydrochloric acid to pH 2.5
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 3°C
- Relative humidity: 55 ± 15%
- Air changes: 10 times/hour
- Photoperiod (hrs dark / hrs light): 12/12

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 undiluted (100%) test item

Duration of treatment / exposure:

not applicable

Observation period (in vivo):

1, 24, 48, and 72 hours as well as 7 days after the treatment

Number of animals or in vitro replicates:

4 female rabbits

Details on study design:

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE:
Twenty-four hours after the treatment with the test item an examination was performed before and after instillation of oculoguttae fluoresceini. After instillation of oculoguttae fluoresceini the eyes were rinsed with 0.9% sodium chloride and examined using UV-light to detect possible corneal damage.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Results 5

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

Results 6

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 8

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

Results 9

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: 7 days

Results 10

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 11

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 12

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 13

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

Results 14

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 15

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #4

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 16

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #4

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

At the examination 1 hour after dosing cornea was slightly affected in one rabbit. Furthermore, at the 1 hour observation moderate conjunctival redness and slight chemosis were obesrved in three rabbits and slight conjunctival redness and moderate chemosis were observed in one rabbit.
24 hours after dosing cornea was slightly affected in all four rabbits. Moderate to severe chemosis as well as moderate to severe conjunctival redness were observed in all rabbits at the 24 hours observation. At the 48 hour observation slight to moderate chemosis as well as severe conjunctival redenss were observed in all rabbits. At the 72 hour observation slight chemosis was observed in three rabbits and severe conjunctival redness in all rabbits.
The area of opacitiy ranged from more than one quarter up to the whole area at the 24 hour observation and less in severity at the following observations. Discharge fully disappeared by day 7.
Iris was only slightly affected in one rabbit. Moderate discharge was observed at the 1 hour observation and moderate to severe discharge was observed at the 24 hour observation. Slight discharge was only observed in one rabbit at the 48 and 72 hour observations.
After 7 day all ocular effects had recovered.

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) of the neat substance was placed into the conjunctival sac of one eye of four Mol:Russian rabbits. The other eye remained untreated and served as control. Ocular reactions were assessed according to the Draize scale 1, 24, 48, and 72 hours as well as 7 days after treatment with the substance. Twenty-four hours after the treatment with the test item an examination was performed before and after instillation of oculoguttae fluoresceini.

The following results were recorded for the three rabbits:

Animal #1

Cornea score: 1.0

Iris score: 0

Conjunctivae score: 2.67

Chemosis score: 1.67

Animal #2

Cornea score: 1

Iris score: 0

Conjunctivae score: 3

Chemosis score: 1.33

Animal #3

Cornea score: 1

Iris score: 0

Conjunctivae score: 3

Chemosis score: 1.67

Animal #4

Cornea score: 1

Iris score: 0.33

Conjunctivae score: 3

Chemosis score: 2.33

At the examination 1 hour after dosing cornea was slightly affected in one rabbit. Furthermore, at the 1 hour observation moderate conjunctival redness and slight chemosis were obesrved in three rabbits and slight conjunctival redness and moderate chemosis were observed in one rabbit. 24 hours after dosing cornea was slightly affected in all four rabbits. Moderate to severe chemosis as well as moderate to severe conjunctival redness were observed in all rabbits at the 24 hours observation. At the 48 hour observation slight to moderate chemosis as well as severe conjunctival redenss were observed in all rabbits. At the 72 hour observation slight chemosis was observed in three rabbits and severe conjunctival redness in all rabbits. The area of opacitiy ranged from more than one quarter up to the whole area at the 24 hour observation and lessened in severity at the following observations. Discharge fully disappeared by day 7. Iris was only slightly affected in one rabbit. Moderate discharge was observed at the 1 hour observation and moderate to severe discharge was observed at the 24 hour observation. Slight discharge was only observed in one rabbit at the 48 and 72 hour observations. After 7 day all ocular effects were recovered.

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