Oxazolidine, 3-butyl-2-(1-ethylpentyl)-

Endpoint summary

Description of key information

Skin irritation

Based on the skin irritation study on New Zealand white rabbits the test substance Incozol 2 is regarded to be non irritant to the skin.

Eye irritation

Based on the findings in the eye irritation study on New Zealand white rabbits, Incozol 2 is not irritating to the eye.

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:

1995-11-14 to 1995-11-25

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:

July 17th 1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

July 31st 1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd, Manston
- Age at study initiation: 13-18 weeks old
- Weight at study initiation: 2.36-3.65 kg
- Housing: individually in single floor pens throughout the study
- Diet (e.g. ad libitum): SQC TRB Rabbit Diet 9603 (pelleted), ad libitum
- Water (e.g. ad libitum): mains water, ad libitum
- Acclimation period: three to six weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 10/14

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL undiluted

Duration of treatment / exposure:

4 hours

Observation period:

8 days (all irritation reactions resolved within 7 days)

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: clipped dorsum (30 x 20 mm area)
- Type of wrap if used: open weave, elasticated adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with moist cotton wool
- Time after start of exposure: 4 hours

SCORING SYSTEM:

Erythema and eschar

No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness)
or eschar preventing reading of erythema 4

Oedema

No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (edges raised approximately 1 mm) 3
Severe oedema (raised > 1 mm and
extending beyond area of exposure) 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

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:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

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

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Well defined erythema and very slight edema affected the dermal test site of one rabbit immediately after completion of a four hour exposure period. This dermal test site showed very slight erythema and very slight oedema one hour after treatment and very slight erythema alone 24, 48 and 72 hours after treatment. The other dermal test sites subjected to a four hour exposure to Incozol 2 showed no irritation reactions or other dermal changes.

Other effects:

No

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the skin irritation study on New Zealand white rabbits the test substance Incozol 2 is regarded to be non irritant to the skin.

Executive summary:

This study was conducted to determine the irritation/corrosion potential caused to the intact skin of rabbits following a single (4 hour) semi-occluded topical application of Incozol 2. The method followed was in compliance with that described EU Method B4 and OECD TG 404. A single rabbit was subject to a single topical application of 0.5 mL undiluted Incozol 2 at each of three closely clipped dermal test sites measuring 30 x 20 mm. The applied doses were covered by semi-occlusive dressings that remained in place for three minutes, one hour or four hours. Subsequently, two further rabbits were subject to a single semi-occluded topical application of the test substance at one dermal test site for four hours. The dermal test sites exposed to Incozol 2 for three minutes or one hour showed a very slight erythematous response that resolved within 24 hours of treatment. Well defined erythema and very slight edema affected the dermal test site of one rabbit immediately after completion of a four hour exposure period. This dermal test site showed very slight erythema and very slight edema one hour after treatment and very slight erythema alone 24, 48 and 72 hours after treatment. The other dermal test sites subjected to a four hour exposure to Incozol 2 showed no irritation reactions or other dermal changes. Therefore Incozol 2 does not classify as a skin irritant (Corning Hazleton, 1995).

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:

1997-04-15 to 1997-04-25

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:

February 24th 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

July 31st 1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd, Margate
- Age at study initiation: 11-14 weeks
- Weight at study initiation: 2.44-2.60 kg
- Housing: individually in floor-pens (floor area 0.6 m2)
- Diet: SQC TRB Rabbit Diet 9603 (pelleted), ad libitum
- Water: mains water, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22
- Humidity (%): 40-80
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

4 days (condition of the treated eye was confirmed normal on day 4)

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

SCORING SYSTEM:

Cornea - degree of opacity (area most dense assessed)

No ulceration or opacity 0
Scattered or diffuse areas of opacity other than
slight dulling of normal lustre, details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured 2
Nacreous area, no details of iris visible but size of pupil barely discernible 3
Opaque cornea, iris not discernible through opacity 4

Cornea - area of corneal opacity

Total area of opacity amounts to <25% of corneal area 1
Area of opacity amounts to 25-<50% of corneal area 2
Area of opacity amounts to 50- < 75 % of corneal area 3
Area of opacity amounts to 75 % or more of corneal area 4

Iris Grade

No reaction 0
Markedly deepened rugae, congestion, swelling, moderate
circumcorneal hyperaemia or injection, any of these or any
combination thereof; iris still reacting to light 1
No iridial reflex to light, haemorrhage or gross destruction
(any or all of these) 2

Conjunctivae - redness

Blood vessels normal 0
Some blood vessels definitely hyperaemic (injected) 1
Diffuse, crimson colour, individual vessels not easily discernible 2
Diffuse beefy red appearance 3

Conjunctivae - Chemosis

No swelling 0
Any swelling above normal 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half-closed 3
Swelling with lids more than half-closed 4

Conjunctivae - discharge

No discharge 0
Any discharge greater than normal, not including the small
amount normally present in the inner canthus 1
Discharge with moistening of eyelids and hairs just
adjacent to the eye 2
Discharge with moistening of eyelids and hair for a
considerable area around the eye 3

TOOL USED TO ASSESS SCORE: The treated eyes were examined visually and, where appropriate, with the aid of a device to illuminate or magnify the eye.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Instillation of Incozol 2 elicited a slight initial sting response from the sentinel rabbit but practically no reaction from the other two animals. Injection of the conjunctival vasculature was apparent in all three rabbits during the initial four hour observation period following instillation with a slight ocular discharge also produced in this period. The eyes of all rabbits were overtly normal by the 24 hour examination.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the findings in this eye irritation study on New Zealand white rabbits, Incozol 2 is not irritating to the eye.

Executive summary:

This study was conducted to determine the irritation caused to the rabbit eye following a single instillation of Incozol 2 into the conjunctival sac. The method followed was in compliance with that described in EU Method B5 and OECD TG 405. The undiluted test article (0.1 mL) was instilled into one conjunctival sac of each of three New Zealand White rabbits. Ocular reactions were assessed for three days after treatment. Instillation of Incozol 2 elicited a slight initial sting response from the sentinel rabbit but practically no reaction from the other two animals. Injection of the conjunctival vasculature was apparent in all three rabbits during the initial four hour observation period following instillation with a slight ocular discharge also produced in this period. The cornea and iris were overtly unaffected by treatment. The eyes of all rabbits were overtly normal by the 24 hour examination. Therefore the tested substance was regarded as non irritating to the eye (Covance, 1997).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion

A study was conducted to determine the irritation/corrosion potential caused to the intact skin of rabbits following a single (4 hour) semi-occluded topical application of Incozol 2. The method followed was in compliance with that described in EU Method B4 and OECD TG 404. A single rabbit was subject to a single topical application of 0.5 mL undiluted Incozol 2 at each of three closely clipped dermal test sites measuring 30 x 20 mm. The applied doses were covered by semi-occlusive dressings that remained in place for three minutes, one hour or four hours. Subsequently, two further rabbits were subject to a single semi-occluded topical application of the test item at one dermal test site for four hours. The dermal test sites exposed to Incozol 2 for three minutes or one hour showed a very slight erythematous response that resolved within 24 hours of treatment. Well defined erythema and very slight edema affected the dermal test site of one rabbit immediately after completion of a four hour exposure period. This dermal test site showed very slight erythema and very slight edema one hour after treatment and very slight erythema alone 24, 48 and 72 hours after treatment. The other dermal test sites subjected to a four hour exposure to Incozol 2 showed no irritation reactions or other dermal changes. Therefore Incozol 2 does not classify as a skin irritant (Corning Hazleton, 1995).

Eye irritation / corrosion

A study was conducted to determine the irritation potential caused to the rabbit eye following a single instillation of Incozol 2 into the conjunctival sac. The method followed was in compliance with that described in EU Method B5 and OECD TG 405. The undiluted test substance (0.1 mL) was instilled into one conjunctival sac of each of three New Zealand White rabbits. Ocular reactions were assessed for three days after treatment. Instillation of Incozol 2 elicited a slight initial sting response from the sentinel rabbit but practically no reaction from the other two animals. Injection of the conjunctival vasculature was apparent in all three rabbits during the initial four hour observation period following instillation with a slight ocular discharge also produced in this period. The cornea and iris were overtly unaffected by treatment. The eyes of all rabbits were overtly normal by the 24 hour examination. Therefore the tested substance was regarded as non irritating to the eye (Covance, 1997).

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for eye or skin irritation under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.