Castor oil, ester with glycerol

Endpoint summary

Description of key information

Skin irritation/corrosion (no guideline followed): not irritating

Eye irritation (OECD 405): not irritating

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

no information on test substance purity

Qualifier:

no guideline followed

Principles of method if other than guideline:

The test was performed as laid down in the F.D.A. Handbook, Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, F.D.A. (1959), p. 47.
- Principle of test: A 0.5 mL sample of the test material was applied to clipped areas of both intact and abraded skin of four New Zealand White rabbits under occlusive conditions for 24 h.
- Parameters analysed / observed: Skin reaction according to Draize scale was measured immediately and 48 h after patch removal.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

clipped

Remarks:

One side of each back was additionally abraded with a suitable abrading tool, the other back side was left intact.

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

24 h

Observation period:

48 h after patch removal
Reading time points: 0 and 48 h after patch removal

Number of animals:

4

Details on study design:

TEST SITE
- Area of exposure: animals back
- Type of wrap if used: One inch gauze pads were secured with adhesive tape and further occluded with a stockinette sleeve covering the entire trunk of the animal.

SCORING SYSTEM:
- Method of calculation: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal: #1 and #3

Remarks:

intact skin side

Time point:

other: 0 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

intact skin side

Time point:

other: 0 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #4

Remarks:

intact skin side

Time point:

other: 0 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of all 4 animals; intact skin sides

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

mean

Remarks:

of all 4 animals; intact skin sides

Time point:

other: 0 and 48 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

On intact skin, slight to well defined erythema (grade 1-2) was apparent in three rabbits immediately after patch removal. This irritation was reversible within 48 h after patch removal. No edema was observed in any animal at any reading time point.

Table 1. Results of skin irritation test on intact and abraided skin.

Observation time	Intact skin
	Rabbit no.
	1		2		3		4
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
0 h	1	0	0	0	1	0	2	0
48 h	0	0	0	0	0	0	0	0
	Abraded skin
0 h	1	0	0	0	1	0	2	0
48 h	1	0	0	0	0	0	2	1

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Under the conditions of this skin irritation study in rabbits the undiluted test substance was not irritating to the skin.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

02 - 05 Dec 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

The basic method followed that described in the Federal Register 1973, Volume 38, No. 187, 1500. 41, with minor modifications.
- Principle of test: The undiluted test substance was applied on abraded and intact clipped skin sides of 6 rabbits for 24 h under occlusive conditions. Erythema and edema was scored according to Draize scoring system immediately and 48 h after patch removal.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Nr. Loughborough, Leicestershire, England
- Weight at study initiation: 2.5 - 3.5 kg
- Housing: individually in suspended metal cages
- Diet: Rabbit Diet (John Waring (Feeds) limited, Shardlow, Derbyshire, England), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 ± 3
- Air changes (per hr): at least 20
- Photoperiod (hrs dark / hrs light): 10/14

Type of coverage:

occlusive

Preparation of test site:

clipped

Remarks:

The right side of each rabbit was abraded using an abrading tool and the left side was left intact.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

24 h

Observation period:

48 h
Reading time points: 0 and 48 h after patch removal

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 30 mm circle on the dorsal/flank area: right side: clipped and abraded; left side: clipped and intact
- Type of wrap if used: composite patch consisted of a 30 mm circle of absorbent lint S.P.C. backed by a 50 mm circle of polythene with a final backing of a 50 mm diameter of lint. The patch was held securely over the test sites by two lengths of sleek adhesive strapping in the form of a cross. A "rabbit corset" and "toby collar" were then applied to prevent the animals from interferrinq with the dressings.

SCORING SYSTEM:
- Method of calculation: Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of all 6 animals (intact skin side)

Time point:

other: 0/48 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

mean

Remarks:

of all 6 animals (intact skin side)

Time point:

other: 0/48 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

The test substance produced no evidence of erythema or edema in any of the test animals.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Under the conditions of the Primary Skin Irritation Test in rabbits the test substance does not possess any skin irritating potential.

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

no information on purity of test substance given; limited documentation; scoring of conjunctivae as redness, chemosis and discharge in combined score only

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

02 Oct 2012

Deviations:

yes

Remarks:

limited documentation; scoring of conjunctivae as redness, chemosis and discharge in combined score only

Qualifier:

according to guideline

Guideline:

other: F.D.A. Handbook, Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, F.D.A. (1959), p. 47.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:

single application without washing, 2 and 4 sec

Observation period (in vivo):

7 days
Reading time points: 1, 2, 3, 4 and 7 days

Number of animals or in vitro replicates:

3 per group (no washing, 2 and 4 sec exposure)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Treated eyes where washed with 20 mL lukewarm water.
- Time after start of exposure: 2 or 4 sec

SCORING SYSTEM: Draize scoring system; scoring of conjunctivae as redness, chemosis and discharge was given in combined score only (Scores of Redness + Chemosis + Discharge) x 2 = 20 (Maximum score)

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: treated eye not washed

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: treated eye not washed

Irritation parameter:

conjunctivae score

Remarks:

scoring of conjunctivae as redness, chemosis and discharge in combined score only

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

20

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: treated eye not washed

Irritation parameter:

conjunctivae score

Remarks:

scoring of conjunctivae as redness, chemosis and discharge in combined score only

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

20

Reversibility:

fully reversible within: 48h

Remarks on result:

other: treated eye not washed

Irritation parameter:

conjunctivae score

Remarks:

scoring of conjunctivae as redness, chemosis and discharge in combined score only

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

20

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: treated eye not washed

Irritation parameter:

chemosis score

Remarks on result:

not measured/tested

Irritant / corrosive response data:

The test substance produced mild conjunctival irritation (total conjunctivae score 4 and 6) 24 h after instillation without washing in all 3 rabbits. This conjunctival irritation was reversible within 48 h.
In rabbits in which the treated eyes were washed after 2 or 4 sec no irritation was observed at any observation time point.

Table 1: Results of Draize test in unwashed eye

Alteration	Animal No.	Time (h)
		24	48	72	mean 24/48/72 h	reversible within
Cornea	1	0	0	0	0	0
	2	0	0	0	0	0
	3	0	0	0	0	0
Iris	1	0	0	0	0	0
	2	0	0	0	0	0
	3	0	0	0	0	0
Conjunctivae Redness + Chemosis + Discharge *	1	4	0	0	0	0
	2	4	0	0	0	0
	3	6	0	0	0	0

 * Combined scores only; (Scores of redness + chemosis + discharge) x 2 = 20 (maximum score)

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Under the conditions of this eye irritation study in rabbits the test substance was not irritating to the eye.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

01 - 04 Dec 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

no information on purity of test substance given

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

02 Oct 2012

Deviations:

yes

Remarks:

scoring of conjunctivae as redness, chemosis and discharge in combined score only

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leics., England
- Weight at study initiation: approx. 2.5 kg
- Housing: individually in suspended metal cages
- Diet: Rabbit Diet, J. Waring (Feeds) Limited, Shardlow, Derbyshire, England; ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 ± 3
- Air changes (per hr):at least 20
- Photoperiod (hrs dark / hrs light): 10/14

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

6

Details on study design:

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

of all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Remarks on result:

not measured/tested

Irritant / corrosive response data:

No evidence of ocular irritation was seen in any of the test animals throughout the observation period.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Under the conditions of this eye irritation study in rabbits the test substance was not irritating to the eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The skin irritation potential of the test substance was determined by an in vivo skin irritation test (WoE, 1972) in albino rabbits. 0.5 mL of the test substance was applied to the clipped skin (abraded and non-abraded skin sites) of four rabbits under occlusive conditions for 24 hours. After the exposure period the patch was removed and scores were taken immediately and 48 hours after patch removal using the Draize scoring system. On intact skin, slight to well defined erythema (grade 1-2) was apparent in three rabbits directly after patch removal, and they were reversible within 48 h. No edema was observed in any animal at any reading time point. Based on the results, the undiluted test substance was not irritating to the skin under the conditions of the test.

 

The skin irritation potential of the test substance was determined by an in vivo skin irritation test (WoE, 1980) in albino rabbits. 0.5 mL of the test substance was applied to the clipped skin (abraded and non-abraded skin sites) of four rabbits under occlusive conditions for 24 hours. After the exposure period the patch was removed and scores were taken immediately and 48 hours after patch removal using the Draize scoring system. All skin areas, treated with the undiluted or with one of the three solutions of the test substances, did not show any alterations at any observation time point. Based on the results, the undiluted test substance was not irritating to the skin under the conditions of the test.

Conclusion:

Based on all available information on skin irritation toxicity from a weight-of-evidence approach, the target substance Castor oil, ester with glycerol (CAS 68459-67-6) was not irritating to the skin.

 

Eye irritation

The eye irritation potential of the test substance was investigated in six albino rabbits according to a protocol similar to OECD Guideline 405 (WoE, 1980). 0.1 mL of the test material was placed in the right eye of each animal. The left eye remained untreated and served as control. The eyes were examined and scored according to Draize 24, 48 and 72 hours after application. Cornea, conjunctivae and iris were not affected by the test substance. The overall mean scores after 24, 48 and 72 hours out of six rabbits were all 0.0 for cornea opacity, iris, conjunctivae and chemosis score, respectively. Based on the results of this study, the test substance was not irritating to the eyes under the conditions of the test.

 

A second insufficiently documented eye irritation study was performed in 9 albino rabbits according to a protocol similar to OECD 405 (WoE, 1972). 0.1 mL of the undiluted substance was applied to one eye of each rabbit. The contralateral eye was left untreated and served as control. The test substance was washed with lukewarm water in 3 rabbits 2 seconds and in other three rabbits 4 seconds after instillation. The eyes of three rabbits remained unwashed. The test substance produced mild conjunctival irritation 24 h after instillation without washing, reversible within 48 h. No changes on iris and cornea were observed. In rabbits in which the treated eyes were washed after 2 or 4 seconds no irritation was observed at any observation time point. Based on the results of this study, the test substance was not irritating to the eyes under the conditions of the test.

Conclusion:

Based on all available information on eye irritation toxicity from a weight-of-evidence approach, the target substance Castor oil, ester with glycerol (CAS 68459-67-6) was not irritating to the eyes.

 

Justification for classification or non-classification

The available data on skin and eye irritation of the test substance do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.