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Description of key information

e-Caprolactone was not irritating to the skin of rabbits, but was found to be an eye irritant and should be classified as such under CLP.

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:
16th to 19th September 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Proprietary study conducted according to guidelines and GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Three SPF-derived male New Zealand White rabbits (2.5-3.0kg) were obtained from Harlan Olac and acclimatised for 11 days. The rabbits were individually housed in stainless steel wire cages; sawdust, woodchip, or any other extraneous material that may cause skin irritation were excluded. The rabbits received 80g standard laboratory diet per day, and they had free access to the food and water. The animal room was maintained at a temperature of 19-20oC, relative humditiy 55-72%, artificial light from 7am till 7pm, radio-sound from 7am till 7pm, and approximately 16 air changes per hour.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5g of test material 2x3cm area of skin.
Duration of treatment / exposure:
The patches were secured in place for 4 hours.
Observation period:
Observations were made at 30-60 minutes, and 24, 48 and 72 hours after substance removal.
Number of animals:
Three male rabbits.
Details on study design:
Areas on the backs of 3 rabbits were shaved (2x3cm). 0.5g e-Caprolactone was applied directly to the shaved skin, and held in place by occlusive Blenderm tape and standard adhesive tape. Elizabethan collars were fitted to the rabbits to prevent them disturbing the treatment area. The substance was left in place for 4 hours. Following this the collars and tape were removed, and the skin wiped to remove any remaining residue. Observations were made at 30 minutes, and 24, 48 and 72 hours after substance removal.
Treatment sites were scored based on erythema and eschar formation, and oedema formation (according to the scoring system in OECD 404).
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: No effects noted
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: No effects noted
Irritant / corrosive response data:
No erythma or oedema was observed in the three rabbits after 4 hours skin exposure to e-Caprolactone.
Other effects:
No other effects reported.

No erythma or oedema was observed in the three rabbits after 4 hours skin exposure to e-Caprolactone, at any time point post-substance removal.

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The application of e-Caprolactone caused no irritation to the shaven intact skin of 3 rabbits, therefore the substance was classified as non-irritant according to EEC labelling regulations.
Executive summary:

The primary irritation of e-Caprolactone to rabbit skin was investigated. 0.5 g e-Caprolactone was applied directly to an area of shaved skin on the backs of the rabbits (2x3cm), and held in place for 4 hours using occlusive tape. After removal of the tape the skin was wiped to remove any remaining residue, and observations were made at 0.5, 24, 48 and 72 hours after removal. No erythema or oedema was observed in the rabbits at any time point. Classification as a skin irritant is not required on the basis of this study.

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:
4th November to 2nd December 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Proprietary study conducted according to guidelines and GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
SPF-derived male New Zealad White rabbits (one animal weighed 1.8-2.2kg, three weighed 2.5-3.0kg), obtained from Harlan Olac. Animals underwent an 11 day acclimatisation period. Rabbits were housed individually in stainless steel wire cages without sawdust or woodchips (i.e. no extraneous material that might produce eye irritation). They received 80g food per day (standard laboratory diet), with free access to the food and water. Temperature of the animal room was maintained at 19-22oC, relative humidity 52-72%, artificial light from 7am till 7pm, radio-sound from 7am till 7pm, and approximately 16 air changes per hour.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1ml e-Caprolactone applied to conjunctival sac.
Duration of treatment / exposure:
Substance was applied to conjunctival sac, and eyelid held closed for approximately 1 second.
Observation period (in vivo):
Observations were made at 1, 24, 48, 72 hours and 7 days after treatment.
Number of animals or in vitro replicates:
Initially 4 animals were used, one of these animals was injured and euthanased 1 hour post-treatment. A replacement rabbit was obtained from the supplier.
Details on study design:
Four rabbits were used. 0.1ml test substance was dropped into the conjuctival sac of the left eye. Eye reactions were scored at 1, 24, 48, 72 hours and 7 days after treatment. The scoring system used was that according to Draize (1944), and the results were interpreted according to the Commission Directive 91/325/EEC. The right eye remained untreated to serve as a control.
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
mean
Time point:
24/48/72 h
Score:
1.78
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.89
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1.44
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.89
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
At 1 hour very slight opacity, iritis, redness and very slight chemosis were observed in three rabbits, and slight iritis, redness and chemosis was observed in the fourth. Severe discharge was observed in animal's 1-3 and moderate discharge in animal 4. The following observations are limited to 3 animals: at 24 hours slight opacity and iritis were observed, slight to moderate redness was observed. Very slight to sight chemosis was observed. At 48 hours opacity was very slight to slight. Redness was slight to moderate. Chemosis was very slight. At 72 hours very slight to slight opacity and slight iritis were observed. Slight to moderate redness were observed. All symptoms had disappeared by day 7.
Other effects:
No additional effects.

Scores for ocular effects

Observation

1h

24h

48h

72h

Mean (24-72h)

7d

Cornea

Opacity

1,1,0

2,2,2

2,2,1

2,2,1

1.78

0,0,0

Iris

Lesion

1,1,1

1,1,1

1,1,1

1,1,0

0.89

0,0,0

Conjunctivae

Erythema

1,1,1

2,2,1

1,2,1

1,2,1

1.44

0,0,0

Chemosis

1,1,2

2,1,1

1,1,1

0,1,0

0.89

0,0,0

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
According to labelling regulations e-Caprolactone is classified as irritating to the eye.
Executive summary:

The primary irritation of e-Caprolactone to the eye of male rabbits was determined in this guideline study. 0.1ml substance was introduced to the conjunctival sac of the left eye of three rabbits (the right eye remained untreated to serve as a control). The eyes of the rabbits were examined and the ocular reactions graded at intervals up to and including 7 days after treatment. Various signs of irritation were observed (corneal opacity, iris lesion, conjunctival erythema, chemosis and discharge), lthough all symptoms were reversible by Day 7. The substance requires classification as an eye irritant according to Regulation (EC) No 1272/2008 (CLP) and according to Directive 67/548/EEC. It is classified as an eye irritant and assigned the symbol Xi and the risk-phrase R36 "Irritating to eyes". It is an eye irritant category 2 and is assigned the pictogram GHS07 with the signal word "warning" and the hazard statement H319 "causes serious eye irritation".

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

The primary irritation of e-Caprolactone to rabbit skin was investigated in a GLP study according to OECD method 404 (Janssen, 1991). 0.5 g e-Caprolactone was applied directly to an area of shaved skin on the backs of the rabbits (2x3cm), and held in place for 4 hours using occlusive tape. After removal of the tape the skin was wiped to remove any remaining residue, and observations were made at 0.5, 24, 48 and 72 hours after removal. No erythema or oedema was observed in the rabbits at any time point. Classification as a skin irritant is not required on the basis of this study.

Eye irritation

The primary irritation of e-Caprolactone to the eye of male rabbits was determined in a GLP study according to OECD method 405 (Janssen, 1991). 0.1ml substance was introduced to the conjunctival sac of the left eye of three rabbits (the right eye remained untreated to serve as a control). The eyes of the rabbits were examined and the ocular reactions graded at intervals up to and including 7 days after treatment. Various signs of irritation were observed (corneal opacity, iris lesion, conjunctival erythema, chemosis and discharge), although all symptoms were reversible by Day 7. The substance requires classification as an eye irritant according to CLP.


Effects on eye irritation: irritating

Justification for classification or non-classification

No evidence of skin irritation was seen in a guideline study in the rabbit. Evidence of eye irritation sufficient to trigger classification was seen in a guideline study in the rabbit.

The available data indicate that the substance requires classification as an eye irritant according to Regulation (EC) No 1272/2008 (the CLP Regulation). It is an eye irritant category 2 and is assigned the pictogram GHS07 with the signal word "warning" and the hazard statement H319 "causes serious eye irritation".

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