1,6-hexanediyl-bis(2-(2-(1-ethylpentyl)-3-oxazolidinyl)ethyl)carbamate

Endpoint summary

Description of key information

The results indicate that the test substance does not have a significant irritation potential on skin and eye. Thus, the test substance can be regarded as non-irritating to the skin and eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 1990-08-28 to 1990-09-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 1981-05-12

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, England
- Weight at study initiation: The animals were weighted immediately before application of the test substance.
- Housing: The rabbits were individually housed in stainless steel cages with flat rod bases or plastic cages with perforated bases, under standardized conventional conditions.
- Nutrition: Standard diet "Ssniff K 4", approx. 100 - 120 g per animal/day, once per day in the morning.
- Water: tap water, ad libitum.
- Other: healthy animals. The health of the animals was routinely examined for the main specific pathogens by the breeder. No vaccinations or treatment with antibiotics were performed prior to receipt of the animals or during the acclimatization phase or study period. If females were used they were nulliparous and non-pregnant.
- State of health: After the acclimatization phase, the animals were examined one day prior to the start of the study to establish that they were biologically normal. Only animals not exhibiting any alterations to skin or eyes were used.
- Acclimatization: at least 14 days
- Animal housing conditions: All the animals in this study were kept in one room. For capacity reasons rabbits treated with other test substances were also housed in the same room. Adequate separation, clear cage and individual marks, as well as appropriate organization of working procedures ensured that the test animals were not mixed up.
- Randomization: Each rabbit was randomly assigned to the respective treatment groups. Randomization was performed by means of a random number generator with varying starting conditions, using an Apple 2e, Fachbereich Toxikologie.

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Relative Humidity: ca. 50 %
- Air changes: ca. 10 times per hour
- Photoperiod: 12 hours artificial illumination from 6 to 18 hrs CET

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: Contralateral skin area not treated with test substance served as control.

Amount / concentration applied:

500 µL

Duration of treatment / exposure:

4 hours

Observation period:

24, 48 and 72 hours after application

Number of animals:

three rabbits

Details on study design:

TEST SITE
- Area of exposure: 6 cm²
- Type of wrap: Test substance was applied to a hypoallergenic Hansamed-patch. A further patch was moistened with water.
- Site: The patches prepared were placed on the opposite dorso-lateral areas of the trunk of each animal and were loosely held in place with a semiocclusive dressing for the duration of the exposure period. Thus, access by the animal to the patch and resultant ingestion/inhalation of the test substance was prevented.

REMOVAL OF TEST SUBSTANCE
- Washing: The exposed skin areas were carefully washed with water without altering the existing response, or the integrity of the epidermis.
- Time after start of exposure: After an exposure period of four hours the dressing and patches were removed.

CLINICAL OBSERVATION AND SCORING SYSTEM:
Dermal irritation was scored and recorded after termination of exposure at the times 1h, 24 h, 48 h, 72, 7 d and 14 d. The degree of erythema/eschar formation and oedema formation was recorded as specified by Draize, and any serious lesions or toxic effects other than dermal irritation were also recorded.

EVALUATION OF RESULTS:
For each animal the Draize scores were recorded approx. 24, 48, and 72 hours after application were added. The total of these tree values was divided by three to give the irritation index. This index was separately calculated for erythema/eschar formation and for oedema formation. Where three animals were used, interpretation was based on the individual indices obtained from the two most sensitive animals. Where more than three animals were used, the mean irritation index was calculated averaging the total scores of all rabbits tested. If delayed reactions occurred, or where no irritation indices could be calculated (e.g. due to coloration by the test substance) other interpretation criteria were applied.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Interpretation of results:

GHS criteria not met

Conclusions:

The results indicate that the test substance does not have a significant irritation potential on skin. Thus, the test substance can be regarded as non irritating to the skin.

Executive summary:

The irritant/corrosive potential of the test substance was studied on the skin of the rabbit in accordance with OECD guideline 404. Whilst considering OECD Interpretation Guides results were interpreted in conjunction with the nature, intensity and reversibility of responses observed. The irritation was scored according to Draize after 1 h, 24 h, 48 h, 72 h and 7 d. All three animals showed irritation indices of 0 for both erythema and edema formation. The results indicate that the test substance does not have a significant irritation potential on skin. Thus, the test substance can be regarded as non-irritating to the skin.

 

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

No details on GLP and guideline conformity available. No details on study design and result assessment reported.

Principles of method if other than guideline:

The test item was applied once on rabbit's skin. After 24 hours, the test item was washed off and animals were observed for the following seven days for dermal signs.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 3 - 4 kg
- Housing: single housing
- Sex: male/female

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

Dose: 500 µL/animal

Duration of treatment / exposure:

- Exposure period: 24 h

Observation period:

7 days

Number of animals:

1 male and 1 female animal

Details on study design:

TEST SITE
The test substance was applied on a patch and was fixed onto skin of the inner area of the ear.

REMOVAL OF TEST SUBSTANCE
- Washing: After exposure the skin was cleaned with water and soap/vegetable oil in order to remove the test substance.

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The test substance was reported to be non irritating.

Interpretation of results:

study cannot be used for classification

Conclusions:

The test substance was reported to be non irritating.

Executive summary:

In this skin irritation study using rabbits the test substance was reported to be non irritating.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 1990-08-28 to 1990-09-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 24.2.1987

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, England
- Weight at study initiation: The animals were weighted immediately before application of the test substance.
- Housing: The rabbits were individually housed in stainless steel cages with flat rod bases or plastic cages with perforated bases, under standardized conventional conditions.
- Identification of animals: The rabbits were identified by individual ear marks (tattoos) and cage cards.
- Nutrition: Standard diet "Ssniff K 4", approx. 100 - 120 g per animal/day, once per day in the morning.
- Water: tap water, ad libitum.
- Other: healthy animals. The health of the animals was routinely examined for the main specific pathogens by the breeder. No vaccinations or treatment with antibiotics were performed prior to receipt of the animals or during the acclimatization phase or study period. If females were used they were nulliparous and non-pregnant.
- State of health: After the acclimatization phase, the animals were examined one day prior to the start of the study to establish that they were biologically normal. Only animals not exhibiting any alterations to skin or eyes were used.
- Acclimatization: at least 14 days
- Animal housing conditions: All the animals in this study were kept in one room. For capacity reasons rabbits treated with other test substances were also housed in the same room. Adequate separation, clear cage and individual marks, as well as appropriate organization of working procedures ensured that the test animals were not mixed up.
- Randomization: Each rabbit was randomly assigned to the respective treatment groups. Randomization was performed by means of a random number generator with varying starting conditions, using an Apple 2e, Fachbereich Toxikologie.

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Relative Humidity: ca. 50 %
- Air changes: ca. 10 times per hour
- Photoperiod: 12 hours artificial illumination from 6 to 18 hrs CET

Vehicle:

unchanged (no vehicle)

Controls:

other: The other untreated eye served as control.

Amount / concentration applied:

100 µL

Duration of treatment / exposure:

Single treatment for 24 h

Observation period (in vivo):

1 h, 24 h, 48 h, 72 h, 7 d

Number of animals or in vitro replicates:

three animals

Details on study design:

PROCEDURE:
After gently pulling the lower lid away from the eyeball, the test substance was instilled into the conjunctival sac of one eye of each of three rabbits. The lids were then gently held together for about 1 second in order to limit loss of the material.

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing with saline
- Time after start of exposure: 24 h after instillation

CLINICAL OBSERVATION AND SCORING SYSTEM:
Eye irritation was scored and recorded at the times after administration. The signs of cornea (opacity and area affected), iris (hyperaemia, reaction to light), conjunctivae - i.e. conjunctiva of bulbus, lids, and nictitating membrane - (erythema, chemosis), and discharge were recorded as described by Draize, and the aqueous humour (opacity) as described by McDonald and Shadduck. In addition any serious lesions or toxic effects other than ocular ones were recorded. The examinations of cornea, iris and aqueous humour were facilitated using optical instruments (e.g. hand slit-lamp). To define epithelial damage, one drop of a 1 % fluorescein solution was applied to the corneal surface 24 h after administration of the test substance; where positive effects were recorded this was repeated at the later observation times. The eye was then rinsed with saline to remove excess and non-absorbed fluorescein. Evaluation was performed by ultraviolet illumination (area) in a darkened room and diffuse white illumination (intensity).

EVALUATION OF RESULTS:
Only effects persisting for one than 24 hours were included on the evaluation. The irritation indices/mean irritation indices were calculated for cornea (degree of opacity), iris, erythema and swelling (chemosis) of the conjunctivae. Where three animals were used, interpretation was based on the individual indices obtained from the two most sensitive animals. Where there were delayed reactions, or where no irritation indices could be calculated (e.g. coloration by the test substance) other interpretation criteria were applied.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: regarding opacity and area

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: regarding opacity and area

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: regarding opacity and area

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

other: regarding redness and swelling

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

other: regarding redness and swelling

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

other: regarding redness and swelling

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Interpretation of results:

GHS criteria not met

Conclusions:

The results indicate that the test substance does not have a significant irritation potential on the eye. Thus, the test substance can be regarded as non irritating to the eyes.

Executive summary:

The irritant/corrosive potential of the test substance was studied on the eye of the rabbit in accordance with OECD guideline 405. Whilst considering OECD Interpretation Guides results were interpreted in conjunction with the nature, intensity and reversibility of responses observed. The irritation was scored according to Draize after 1 h, 24 h, 48 h, 72 h and 7 d. All three animals showed irritation indices of 0 for both cornea, iris conjunctivae and epithelial defects. Irritation indices for aqueous humour and discharge were 2 and 3, respectively after 1 hour. But these signs were fully reversible after 24 h. The results indicate that the test substance does not have a significant irritation potential on eye. Thus, the test substance can be regarded as non-irritating to the eye.

 

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

No details on GLP and guideline conformity available. No details on study design and result assessment reported.

Principles of method if other than guideline:

The test item was applied to rabbits eye. Animals were observed for the following 7 days for irritation signs.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 3 - 4 kg
- Housing: single housing
- Sex: male/female

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

100 µL/animal

Duration of treatment / exposure:

The test item was applied once.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

1 male and 1 female rabbit

Details on study design:

Application:
- Application in conjuctival sac

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

The test substance was reported to be slighty irritating.

Interpretation of results:

study cannot be used for classification

Conclusions:

The test substance was reported to be slighty irritating.

Executive summary:

In this eye irritation study using rabbits the test substance was reported to be slighty irritating.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Key study:

The irritant/corrosive potential of the test substance was studied on the skin and eye of the rabbit in accordance with OECD guideline 404 and 405. Whilst considering OECD Interpretation Guides results were interpreted in conjunction with the nature, intensity and reversibility of responses observed. The irritation was scored according to Draize after 1 h, 24 h, 48 h, 72 h and 7 d.

- Regarding skin irritation: All three animals showed irritation indices of 0 for both erythema/eschar formation and oedema formation.

- Regarding eye irritation: All three animals showed irritation indices of 0 for both cornea, iris conjunctivae and epithelial defects. Irritation indices for aqueous humour and discharge were 2 and 3, respectively after 1 hour. But these signs were fully reversible after 24 h.

The results indicate that the test substance does not have a significant irritation potential on skin and eye. Thus, the test substance can be regarded as non-irritating to the skin and eye.

 

Supporting study:

In this skin and eye irritation study using rabbits the test substance was reported to be non-irritating.

Justification for classification or non-classification

Based on the results the test substance does not have to be classified as irritating to skin and/or eye according to Regulation (EC) No 1272/2008, as amended for the 17th time in Regulation (EU) 2021/849.