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

Endpoint summary

Description of key information

Skin irritation: not irritating (OECD 404; GLP)

Eye irritation: irritating (OECD 405; GLP)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992-08-31 to 1992-09-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Deviations from the OECD 404 (2015): 4 animals were tested instead of 3 animals. Systemic effects were not investigated. 5 test item concentrations were tested simultaneously (undiluted, 1, 5, 10, & 20 %) with each rabbit. 30 min. observation was conducted instead of a 1 h observation.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981-05-12

Deviations:

yes

Remarks:

4 animals were tested instead of 3 animals. Systemic effects were not investigated. 5 test item concentrations were tested simultaneously (undiluted, 1, 5, 10, & 20 %) with each rabbit.

GLP compliance:

yes

Species:

rabbit

Strain:

other: Mol:Russian

Details on test animals or test system and environmental conditions:

TEST ANIMALS - SPF albino rabbits
- Weight at study initiation: 2.2 - 2.7 kg
- Housing: kept in single PPL cages, 45 x 55 cm, with perforated floor
- Diet (ad libitum): feed 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

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: Diethyl phthalate (DEP)

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the undiluted test substance moistened with the vehicle


VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL


VEHICLE CONTROL
- Amount(s) applied (volume or weight): 0.5 mL of the vehicle

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

4 female rabbits

Details on study design:

TEST SITE
- Area of exposure: area of 10 x 10 cm on the back

- Type of wrap if used: to a patch (2.5 x 2.5 cm) the test substance was applied and the patch were placed on the back. The gauze patch was secured with adhesive type and fixed with Scanpor tape loosely wound round the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing: treated skin was cleaned with soap and lukewarm water
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
30 minutes as well as 24, 48, and 72 hours after application

SCORING SYSTEM: according to the Draize scale
- Method of calculation: scores for erythema and oedema formation for the last 3 readings of each rabbit (24, 48 and 72 hours) for each test concentration were obtained separately and divided by 3. The results are the mean scores for erythema and oedema formation of the individual rabbit.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

At the 24 hour observation very slight erythema was observed at two test sites with a 100% test concentration.

TEST CONCENTRATION: 20 %

At the 24 hour observation very slight erythema (score 1) was observed at one test site treated with a 20% test concentration.

TEST CONCENTRATIONS: 10 %, 5 %, and 1 %

No skin reactions were observed after test item applications, except for very slight oedema (barely perceptible) (score 1) at one test site treated with the 1 % test concentration during the 30 minute observation.

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is not irritating to the skin based on an in vivo study (OECD 404).
According to Regulation (EC) No 1272/2008 and subsequent adaptations, the substance does not require classification as skin irritant.

Executive summary:

The skin irritation potential of the substance was investigated according to the OECD guideline 404. A single dose of 0.5 g of the substance moistened with the vehicle was applied to the skin of four female Mol: Russian rabbits and covered semi-occlusive for an exposure period of 4 hours. In addition the vehicle alone was also applied to the skin of the rabbits. The test sites were examined for skin reactions after test item treatment and scored according to the Draize scale after 30 minutes as well as 24, 48 and 72 hours after application.

The following results were recorded:

Animal #1

Erythema: 0

Oedema: 0

Animal #2

Erythema: 0.33

Oedema: 0

Animal #3

Erythema: 0

Oedema: 0

Animal #4

Erythema: 0.33

Oedema: 0.33

At the 24 hour observation very slight erythema (score 1) was observed at two test sites. No further skin reactions were observed.

According to Regulation (EC) No 1272/2008 and subsequent adaptations, the substance does not require classification as skin irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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.

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

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

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:

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

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.

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).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin irritation

The substance does not possess a skin irritation potential based on an in vivo OECD 404 test and does not require classification as skin irritant according to Regulation (EC) No 1272/2008 and its subsequent adaptations.

Eye irritation

The substance does possess an eye irritation potential based on an in vivo OECD 405 test and does require classification as eye irritant according to Regulation (EC) No 1272/2008 and its subsequent adaptations (Category 2; H319).

.