2-hydroxypropyl [(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:

1993-10-11 to 1993-10-15

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. Systemic effects were not investigated. 5 test item concentrations were tested (undiluted, 1, 5, 10, and 25 %). 30 min. observation was conducted instead of a 1 h observation. In one animal the skin effects were not reversible by 72 h, but still the study was terminated.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992-07-17

Deviations:

yes

Remarks:

4 animals were tested instead of 3. Toxic effects not investigated. 5 test item concentrations were tested. 30 min. observation was conducted instead of a 1 h observation. skin effects in 1 animal not reversible by 72 h, but the study was terminated.

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 1993-09-23

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: 2.3 - 2.9 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:

unchanged (no vehicle)

Controls:

yes, concurrent negative control

Amount / concentration applied:

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


NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 0.5 mL of diethyl phthalate

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 or vehicle 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

Remarks on result:

other: reading of 100% test concentration

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: reading of 100% test concentration

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: reading of 100% test concentration

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: reading of 100% test concentration

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

other: not specified, if skin reaction was reversible, since the observation period lasted only 72 hours and was not extended unitl reversal occurred or 14 days had elapsed.

Remarks on result:

other: reading of 100% test concentration

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: reading of 100% test concentration

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

other: observation was only made at the 48 hour observation

Remarks on result:

other: reading of 100% test concentration

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: reading of 100% test concentration

Irritant / corrosive response data:

At the one hour reading very slight erythema (grade 1) was observed in three rabbits. One of these rabbits still showed a very slight erythema (grade 1) at the 24 and 48 hour observations and another rabbit of these three rabbits showed the same reaction at the 24, 48, and 72 hours observations.
Lastly, one rabbit only showed very slight erythema (grade 1) at the 48 hour observation.
Apart from that no signs of skin reaction were recorded.

TEST CONCENTRATIONS:100%, 25 %, 10 %, 5 %, and 1 % (w/w) plus vehicle

No signs of skin irritation were recorded.

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 (1992). A single dose of 0.5 mL of the undiluted substance was applied to the skin of four female Mol: Russian rabbits and covered semi-occlusive for an exposure period of 4 hours. 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: 0.67

Oedema: 0

Animal #3

Erythema: 1

Oedema: 0

Animal #4

Erythema: 0.33

Oedema: 0

At the one hour reading very slight erythema (grade 1) was observed in three rabbits. One of these rabbits still showed a very slight erythema (grade 1) at the 24 and 48 hour observations and another rabbit of these three rabbits showed the same reaction at the 24, 48, and 72 hours observations. Lastly, one rabbit only showed very slight erythema (grade 1) at the 48 hour observation. Apart from that no signs of skin reaction were recorded.

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:

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.

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

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

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.

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

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

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

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

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

Max. score:

2

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

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: 7 days

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

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

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

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:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

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

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.

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).

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).