Registration Dossier

Administrative data

Description of key information

Studies of skin and eye irritation in the rabbit are available for the submission substance 2 -oxepanone, polymer with 1,4-butanediol.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16th September 1991 - 11th December 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
CAPA 203 (2-oxepanone, polymer with 1,4-butanediol)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac, Zeist, The Netherlands.
- Age at study initiation: No information provided.
- Weight at study initiation: 2.5 - 3 kg
- Housing: Housed individually in stainless steel wire cages KK 102. Sawdust, woodchips or other extraneous material that might produce skin irritation were excluded.
- Diet: 80 g food, consisting of a standard laboratory diet LKK-20 per day during the acclimatisation period, with food available ad libitum during the testing period.
- Water: Available ad libitum.
- Acclimation period: 11 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 20°C
- Humidity: 55 - 72%
- Air changes: Approximately 16 air changes per hour
- Photoperiod: 12 hours light/12 hours dark
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g


Duration of treatment / exposure:
4 hours
Observation period:
72 hours after patch removal.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6cm2 patch on the back of each rabbit.
- Type of wrap if used: Occlusive wrap.

REMOVAL OF TEST SUBSTANCE
- Washing: The skin was wiped after removal of the patch to remove any remaining test substance.
- Time after start of exposure: 4 hours.

SCORING SYSTEM: Graded according to responses observed.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable.
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
A single dermal exposure to CAPA 203 for 4 hours did not cause erythema or oedema in the 3 rabbits on 30 minutes, 24, 48 and 72 hours after removal of the patch.

Individual scores for erythema and oedema

Animal

0.5 hours

24 hours

48 hours

72 hours

Total

Mean

 Erythema

1

0

0

0

0

0

0

 

2

0

0

0

0

0

0

 

3

0

0

0

0

0

0

 

Animal

0.5 hours

24 hours

48 hours

72 hours

Total

Mean

Oedema

1

0

0

0

0

0

0

 

2

0

0

0

0

0

0

 

3

0

0

0

0

0

0

 
Interpretation of results:
GHS criteria not met
Conclusions:
CAPA 203 was not found to be irritating to the skin of rabbits under the conditions of this study and does not require classification for skin irritation.
Executive summary:

To assess the primary skin irritation of CAPA 203 (2 -oxepanone, polymer with 1,4 -butanediol) in rabbits, a study was conducted in accordance with OECD Test Guideline 404 and GLP. A sample of 0.5 g CAPA 203 was applied to the shorn intact skin of three male rabbits and occluded under patches for four hours. Readings of the reactions for erythema and oedema were made at 30 minutes and at 24, 48 and 72 hours after patch removal. CAPA 203 did not cause any signs of skin irritation at any observation time. CAPA 203 was found to be non-irritating under the conditions of this study.

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
A study of skin irritation / corrosion in the rabbit is available; in vitro testing is not required
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15th November 1991 to 10th January 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not relevant.
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
CAPA 203 (2-oxepanone, polymer with 1,4-butanediol)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac, Zeist, The Netherlands.
- Age at study initiation: No information provided.
- Weight at study initiation: 2.5 - 3.0 kg
- Housing: The rabbits were housed individually in stainless steel wire cages KK 102. Sawdust, woodchips or other extraneous material that might produce eye irritation were excluded.
- Diet: 80 g food consisting of a standard laboratory LKK-20 ad libitum.
- Water: Water available ad libitum
- Acclimation period: 11 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 22°C
- Humidity 52 - 70%
- Air changes: Approximately 16 air changes per hour.
- Photoperiod: 12 hours light/12 hours dark.
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of each rabbit acted as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml

Duration of treatment / exposure:
Single exposure
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
After the acclimatisation period, both eyes of each rabbit were examined with the aid of a slit-lamp. Only those rabbits without eye defects or signs of irritation were used. A quantity of 0.1 mL CAPA 203 was placed in the conjunctival sac of the left eye by gently pulling the lower lid away from the eyeball to form a cup into which the test substance was placed. The lids were then gently held together for a short period and the rabbit was released. The other eye remained untreated and served as a control. Readings of reactions were made in all three rabbits at 1, 24, 48 and 72 hours after treatment. Scoring of the irritation was performed according to the grades given in the Draize method.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No signs of irritation were observed in any of the three rabbits after instillation of 0.1 mL CAPA 203.

Individual irritation scores

Animal #

Finding

Pretest

Hours (h) after treatment

Mean (24 -72h)

1h

24h

48h

72h

1

Cornea

Opacity

Area involved

0

0

0

0

0

0

0

0

0

0

0

Iris

 

0

0

0

0

0

0

Conjunctiva

Redness

Chemosis

Discharge

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2

Cornea

Opacity

Area involved

0

0

0

0

0

0

0

0

0

0

0

Iris

 

0

0

0

0

0

0

Conjunctiva

Redness

Chemosis

Discharge

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3

Cornea

Opacity

Area involved

0

0

0

0

0

0

0

0

0

0

0

Iris

 

0

0

0

0

0

0

Conjunctiva

Redness

Chemosis

Discharge

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
There were no signs of irritation in any rabbit at any timepoint in this study. CAPA 203 was not shown to be an eye irritant and does not therefore require classification for eye irritation according to the CLP Regulation.
Executive summary:

A study to assess the primary eye irritation of CAPA 203 (2 -oxepanone, polymer with 1,4 -hexanediol) in rabbits was conducted in accordance with OECD Guideline 405 and GLP. 0.1 mL CAPA 203 was instilled into the conjunctival sac of one eye of each of three male rabbits. The eyes of the rabbits were examined and ocular reactions were graded at intervals up to and including 72 hours after treatment. Following the observation period, there were no signs of irritation observed in the three rabbits.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
A study of eye irritation in the rabbit is available. In vitro testing is not required.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion

The skin irritation potential of 2-Oxepanone, polymer with 1,4-butanediol was investigated in rabbits in a GLP study conducted according to OECD Test Guideline 404 (Janssen, 1991). In the study, a sample of 0.5 g of the test material, CAPA 203, was applied to the shaven intact skin of three male rabbits and occluded under patches for four hours. Readings of the reactions for erythema and oedema were made at 30 minutes and at 24, 48 and 72 hours after patch removal. The test material did not cause skin irritation in the rabbits. Under the conditions of the study, 2-Oxepanone, polymer with 1,4-butanediol was not found to be irritating to skin.

Eye irritation

The eye irritation potential of 2-Oxepanone, polymer with 1,4-butanediol was investigated in rabbits in a GLP study conducted according to OECD Test Guideline 405 (Janssen, 1991). In the study, a sample of 0.1 ml of test material, CAPA 203 was placed into the conjuctival sac of one eye of each of three male rabbits. The eyes of the rabbits were examined and the ocular reactions were graded at intervals up to and including 72 hours after treatment. Following the observation period, there were no signs of irritation observed in the three rabbits. The test material did not cause eye irritation in rabbits. Under the conditions of the study, 2-Oxepanone, polymer with 1,4-butanediol was not found to be irritating to the eyes.

Justification for classification or non-classification

The submission substance (2 -oxepanone, polymer with 1,4 -butanediol) did not cause skin irritation in an acute dermal irritation/corrosion study. The substance does not meet the criteria for classification for skin corrosion or skin irritation according to the CLP Regulation.

The submission substance (2 -oxepanone, polymer with 1,4 -butanediol) did not cause irritation in an eye irritation study. The substance does not meet the criteria for classification for serious eye damage or serious eye irritation according to the CLP Regulation.