Registration Dossier

Skin irritation

Data available for the structurally similar read across chemicals has been reviewed to determine the skin irritation potential of the test chemical Castor oil, ester with sorbitol (CAS No: 97488-70-5). The studies are as mentioned below:

The Schwartz Prophetic Patch was conducted by peer reviewed journal on 50 human subjects to assess the skin irritation potential of read across chemical under occlusive condition.The material was applied under occlusion for 72 hours. The occlusion was then removed and the skin site evaluated. Seven days later, the material was reapplied under occlusion for 72 hours. The patch was removed, and the site was evaluated.Neither the first nor the second application produced irritation in the treated subjects hence the chemical was considered as not sensitizing to the human skin.

The above result was further supported by the another dermal irritation study conducted by peer reviewed journal for another read across substanceusing six miniature swine of the Pitman-Moore strain to evaluate its skin irritation potential.The undiluted test substance (0.05 g) was introduced under a 15-mm-diameter patch that was secured with adhesive tape. The entire trunk was wrapped with rubberized cloth during the 48-h exposure period. Reactions were scored after patch removal.The skinreactions were scored according to the following scale: − (no reddening) to+++(severe reddening, beet redness).Since none of the treated animals had positive skin reaction, the test chemical was considered as not irritating to the skin ofsix miniature swine

Based on the above summarized studies for target chemical Castor oil, ester with sorbitol (CAS No: 97488-70-5) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.

Eye irritation

Data available for the structurally similar read across chemicals has been reviewed to determine the ocular irritation potential of the test chemical Castor oil, ester with sorbitol (CAS No: 97488-70-5). The studies are as mentioned below:

An ocular irritation test was conducted by peer reviewed journal on 9 albino rabbits to assess the eye irritation potential of read across chemical. About 0.1ml of undiluted test chemical was installed into one eye of each of 9 albino rabbits. Six eyes were non-irrigated and three were irrigated with 20 ml of water after 2 seconds of exposure. Each eye was evaluated after 1,2, 3,48, 72, and 96 hours and 7 days. Scoring was based on the Draize scale of 0 (no irritation) to 110 (maximum irritation). All scores were recorded as zeroand thus the test chemical was considered as not irritating to the eyes of albino rabbits.

The above result was further supported by another ocular irritation study conducted by peer reviewed journal for another read across substance.The ocular irritation potential of test chemical was determined in a study in which the test chemical served as one of the control vehicle to investigate the effect of topical cyclosporine A on the abraded and intact rabbit cornea.Two castor oil vehicle control groups of outbred male rabbits were used. In both groups (10 eyes/group), 10 drops of castor oil were instilled daily for 3 weeks, and all eyes were examined using a slit-lamp. At the end of the 3-week period, the animals were killed and their corneas were excised and prepared for scanning and transmission electron microscopy. For eyes (no corneal abrasion) treated with Castor oil and examined by scanning electron microscopy, there were increased numbers of medium dark and dark epithelial cells (compared to the normal epithelium). The cell borders were intact and the number of holes was reduced. By transmission electron microscopy, corneal endothelial cells were intact. By scanning electron microscopy, an intact cell pattern, with more cell microstructures than normal, for the corneal endothelium was reported. Ultrathin sections appeared normal. The test chemical did not damage the rabbit corneal epithelium or endothelium. Hence the test chemical was considered as not irritating to the eyes of albino rabbits.

Based on the above summarized studies for target chemical Castor oil, ester with sorbitol (CAS No: 97488-70-5) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

experimental data of read across substances

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar read across chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Skin irritation study of test chemical was conducted on humans and miniature swine to assess its skin irritating effects.

GLP compliance:

not specified

Species:

other: 1.Human 2.miniature swine

Strain:

other: 1. Not applicable 2.Pitman-Moore

Details on test animals or test system and environmental conditions:

1. Not specified
2.- Age at study initiation: 1 month old

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

1.100%
2.Amount :500 mg (0.5 g)
concentration applied: 100%

Duration of treatment / exposure:

1.72 hours
2.48 hours

Observation period:

1.72 hours
2.48 hours

Number of animals:

1.50 subjects
2.6 swine

Details on study design:

1.The material was applied under occlusion for 72 hours. The occlusion was then removed and the skin site evaluated. Seven days later, the material was reapplied under occlusion for 72 hours. The patch was removed, and the site was evaluated.

2.TEST SITE
- Area of exposure: 15-mm-diameter patch
- Type of wrap if used: the patch was secured with adhesive tape. The entire trunk was wrapped with rubberized cloth during the 48-h exposure period.

- Time after start of exposure: after patch removal.
SCORING SYSTEM: skin reactions were scored according to the following scale:
− (no reddening) to+++(severe reddening, beet redness).

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

48 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

1.Neither the first nor the second application produced irritation in the treated subjects.
2.None of the treated animals had positive skin reaction.

Interpretation of results:

other: Not irritating

Conclusions:

The test material Castor oil, ester with sorbitol (CAS No: 97488-70-5) was considered to be irritating to the skin.

Executive summary:

Data available for the structurally similar read across chemicals has been reviewed to determine the skin irritation potential of the test chemical Castor oil, ester with sorbitol (CAS No: 97488-70-5). The studies are as mentioned below:

The Schwartz Prophetic Patch was conducted by peer reviewed journal on 50 human subjects to assess the skin irritation potential of read across chemical under occlusive condition.The material was applied under occlusion for 72 hours. The occlusion was then removed and the skin site evaluated. Seven days later, the material was reapplied under occlusion for 72 hours. The patch was removed, and the site was evaluated.Neither the first nor the second application produced irritation in the treated subjects hence the chemical was considered as not sensitizing to the human skin.

The above result was further supported by the another dermal irritation study conducted by peer reviewed journal for another read across substanceusing six miniature swine of the Pitman-Moore strain to evaluate its skin irritation potential.The undiluted test substance (0.05 g) was introduced under a 15-mm-diameter patch that was secured with adhesive tape. The entire trunk was wrapped with rubberized cloth during the 48-h exposure period. Reactions were scored after patch removal.The skinreactions were scored according to the following scale: − (no reddening) to+++(severe reddening, beet redness).Since none of the treated animals had positive skin reaction, the test chemical was considered as not irritating to the skin ofsix miniature swine

Based on the above summarized studies for target chemical Castor oil, ester with sorbitol (CAS No: 97488-70-5) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar read across chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

WoE report is based on 2 eye irritation studies as- WoE-2 and WoE-3.
An eye irritation study of test chemical was conducted on rabbits to assess its eye irritating effects.

GLP compliance:

not specified

Species:

rabbit

Strain:

other: albino

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

other: 1. unchanged 2. not sepcified

Controls:

not specified

Amount / concentration applied:

1.100% (0.1ml)
2.10 drops

Duration of treatment / exposure:

1.7 days
2.10 drops of castor oil were instilled daily for 3 weeks

Observation period (in vivo):

1.1,2, 3,48, 72, and 96 hours and 7 days.
2.3 weeks

Number of animals or in vitro replicates:

1. 9 rabbits
2.2 groups of outbred male rabbits (10 eyes/group)

Details on study design:

1.TEST SITE
- Area of exposure: one eye of each rabbit

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Six eyes were non irrigated and three were irrigated with 20 ml of water after 2 seconds of exposure.

SCORING SYSTEM: Draize method

2.SCORING SYSTEM: all eyes were examined using a slit-lamp.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

7 d

Score:

0

Max. score:

110

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 3 weeks

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

1.All scores were recorded as zero, and the compound was not an eye irritant.
2.The chemical did not damage the rabbit corneal epithelium or endothelium.

Other effects:

1. Not specified
2.For eyes (no corneal abrasion) treated with Castor oil and examined by scanning electron microscopy, there were increased numbers of medium dark and dark epithelial cells (compared to the normal epithelium). The cell borders were intact and the number of holes was reduced. By transmission electron microscopy, corneal endothelial cells were intact. By scanning electron microscopy, an intact cell pattern, with more cell microstructures than normal, for the corneal endothelium was reported. Ultrathin sections appeared normal.

Interpretation of results:

other: Not irritating

Conclusions:

The test chemical Castor oil, ester with sorbitol (CAS No: 97488 -70 -5) was considered to be not irritating to the eyes.

Executive summary:

Data available for the structurally similar read across chemicals has been reviewed to determine the ocular irritation potential of the test chemical Castor oil, ester with sorbitol (CAS No: 97488-70-5). The studies are as mentioned below:

An ocular irritation test was conducted by peer reviewed journal on 9 albino rabbits to assess the eye irritation potential of read across chemical. About 0.1ml of undiluted test chemical was installed into one eye of each of 9 albino rabbits. Six eyes were non-irrigated and three were irrigated with 20 ml of water after 2 seconds of exposure. Each eye was evaluated after 1,2, 3,48, 72, and 96 hours and 7 days. Scoring was based on the Draize scale of 0 (no irritation) to 110 (maximum irritation). All scores were recorded as zeroand thus the test chemical was considered as not irritating to the eyes of albino rabbits.

The above result was further supported by another ocular irritation study conducted by peer reviewed journal for another read across substance.The ocular irritation potential of test chemical was determined in a study in which the test chemical served as one of the control vehicle to investigate the effect of topical cyclosporine A on the abraded and intact rabbit cornea.Two castor oil vehicle control groups of outbred male rabbits were used. In both groups (10 eyes/group), 10 drops of castor oil were instilled daily for 3 weeks, and all eyes were examined using a slit-lamp. At the end of the 3-week period, the animals were killed and their corneas were excised and prepared for scanning and transmission electron microscopy. For eyes (no corneal abrasion) treated with Castor oil and examined by scanning electron microscopy, there were increased numbers of medium dark and dark epithelial cells (compared to the normal epithelium). The cell borders were intact and the number of holes was reduced. By transmission electron microscopy, corneal endothelial cells were intact. By scanning electron microscopy, an intact cell pattern, with more cell microstructures than normal, for the corneal endothelium was reported. Ultrathin sections appeared normal. The test chemical did not damage the rabbit corneal epithelium or endothelium. Hence the test chemical was considered as not irritating to the eyes of albino rabbits.

Based on the above summarized studies for target chemical Castor oil, ester with sorbitol (CAS No: 97488-70-5) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Skin irritation

Data available for the structurally similar read across chemicals has been reviewed to determine the skin irritation potential of the test chemical Castor oil, ester with sorbitol (CAS No: 97488-70-5). The studies are as mentioned below:

The Schwartz Prophetic Patch was conducted by peer reviewed journal on 50 human subjects to assess the skin irritation potential of read across chemical under occlusive condition.The material was applied under occlusion for 72 hours. The occlusion was then removed and the skin site evaluated. Seven days later, the material was reapplied under occlusion for 72 hours. The patch was removed, and the site was evaluated.Neither the first nor the second application produced irritation in the treated subjects hence the chemical was considered as not sensitizing to the human skin.

The above result was further supported by the another dermal irritation study conducted by peer reviewed journal for another read across substanceusing six miniature swine of the Pitman-Moore strain to evaluate its skin irritation potential.The undiluted test substance (0.05 g) was introduced under a 15-mm-diameter patch that was secured with adhesive tape. The entire trunk was wrapped with rubberized cloth during the 48-h exposure period. Reactions were scored after patch removal.The skinreactions were scored according to the following scale: − (no reddening) to+++(severe reddening, beet redness).Since none of the treated animals had positive skin reaction, the test chemical was considered as not irritating to the skin ofsix miniature swine

Based on the above summarized studies for target chemical Castor oil, ester with sorbitol (CAS No: 97488-70-5) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause skin irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.

Eye irritation

Data available for the structurally similar read across chemicals has been reviewed to determine the ocular irritation potential of the test chemical Castor oil, ester with sorbitol (CAS No: 97488-70-5). The studies are as mentioned below:

An ocular irritation test was conducted by peer reviewed journal on 9 albino rabbits to assess the eye irritation potential of read across chemical. About 0.1ml of undiluted test chemical was installed into one eye of each of 9 albino rabbits. Six eyes were non-irrigated and three were irrigated with 20 ml of water after 2 seconds of exposure. Each eye was evaluated after 1,2, 3,48, 72, and 96 hours and 7 days. Scoring was based on the Draize scale of 0 (no irritation) to 110 (maximum irritation). All scores were recorded as zeroand thus the test chemical was considered as not irritating to the eyes of albino rabbits.

The above result was further supported by another ocular irritation study conducted by peer reviewed journal for another read across substance.The ocular irritation potential of test chemical was determined in a study in which the test chemical served as one of the control vehicle to investigate the effect of topical cyclosporine A on the abraded and intact rabbit cornea.Two castor oil vehicle control groups of outbred male rabbits were used. In both groups (10 eyes/group), 10 drops of castor oil were instilled daily for 3 weeks, and all eyes were examined using a slit-lamp. At the end of the 3-week period, the animals were killed and their corneas were excised and prepared for scanning and transmission electron microscopy. For eyes (no corneal abrasion) treated with Castor oil and examined by scanning electron microscopy, there were increased numbers of medium dark and dark epithelial cells (compared to the normal epithelium). The cell borders were intact and the number of holes was reduced. By transmission electron microscopy, corneal endothelial cells were intact. By scanning electron microscopy, an intact cell pattern, with more cell microstructures than normal, for the corneal endothelium was reported. Ultrathin sections appeared normal. The test chemical did not damage the rabbit corneal epithelium or endothelium. Hence the test chemical was considered as not irritating to the eyes of albino rabbits.

Based on the above summarized studies for target chemical Castor oil, ester with sorbitol (CAS No: 97488-70-5) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified.

The skin and eye irritation potential of test chemical Castor oil, ester with sorbitol (CAS No: 97488-70-5) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical is unlikely to cause skin and eye irritation. Hence Castor oil, ester with sorbitol (CAS No: 97488-70-5) can be classified under the category “Not Classified” for skin and eye as per CLP.