Methyl ricinoleate

Endpoint summary

Description of key information

Skin Irritation:

OECD 404, GLP: not irritating

Eye Irritation:

OECD 405, GLP: not irritating

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:

23 - 31 Mar 1999

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS - Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France - Weight at study initiation: 2.3 ± 0.1 kg - Housing: The animals were housed individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm). Each cage was equipped with a food container and a water bottle. - Diet: 112 C pelleted diet (UAR, 91360 Villemoisson­ sur-Orge, France), ad libitum - Water: filtered (FG Millipore membrane (0.22 micron)) drinking water, ad libitum - Acclimation period: at least 5 days before the beginning of the studyENVIRONMENTAL CONDITIONS - Temperature (°C): 18 ± 3 - Humidity (%): 30 to 70 - Air changes (per hr): approximately 12; filtered, non-recycled air - Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL - Amount(s) applied: 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

Reading time points: 1, 24, 48 and 72 h

Number of animals:

3 males

Details on study design:

TEST SITE - Type of wrap if used: The test substance and the dry gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semiocclusive dressing and a restraining bandage. OBSERVATION TIME POINTS1, 24, 48 and 72 h

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Basis:

animal: #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 6 days

Irritant / corrosive response data:

Animal #1 showed an erythema grade of 2 at the 24-h reading time point and an erythema score of 1 at the 48-h reading time point, which persisted up to Day 6. A well-defined edema was observed up to the 72-h reading time point, which was fully reversible on Day 5. Animal #2 showed very slight erythema at the 24-h and 48-h reading time point. Animal #3 showed well-defined erythema from the 24-h reading time point, which persisted up to the 72-h reading time point, and a slight erythema on Day 5, which was fully reversible on Day 6.In animal #2 and #3 no edema were noted at the 24-h, 48-h and 72-h reading time point. Dryness of the skin was recorded in animal # 1 on day 6 and in animal # 3 from Day 4 - 8.Mean scores over 24, 48 and 72 hours for each animal were 1.3, 0.7 and 2.0 for erythema and 2.0, 0.0 and 0.0 for edema.

Table: Results of skin irritation study

Observation time	Rabbit no.
	1		2		3
	Erythema	Edema	Erythema	Edema	Erythema	Edema
1 h	2	2	2	2	2	2
24 h	2	2	1	0	2	0
48 h	1	2	1	0	2	0
72 h	1	2	0	0	2	0
Mean value 24 + 48 + 72 h	1,33	2,00	0,67	0,00	2,00	0,00
Day 5	1	0	0	0	1	0
Day 6	1	0	0	0	0	0
Day 7	0	0	0	0	0	0

Interpretation of results:

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

Conclusions:

CLP: not classified

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:

30 Mar - 04 Apr 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France- Weight at study initiation: 2.5 ± 0.2 kg- Housing: The animals were housed individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm). Each cage was equipped with a food container and a water bottle.- Diet: 112 C pelleted diet (UAR, 91360 Villemoisson­ sur-Orge, France), ad libitum- Water: filtered drinking water (FG Millipore membrane (0.22 micron)), ad libitum- Acclimation period: at least 5 days ENVIRONMENTAL CONDITIONS- Temperature (°C): 18 ± 3- Humidity (%): 30 to 70- Air changes (per hr): approximately 12; filtered, non-recycled air- 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

Observation period (in vivo):

Reading time points: 1, 24, 48 and 72 h

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE - Washing: The eyes were not rinsed after administration of the test substance.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritant / corrosive response data:

Slight conjunctivae redness and chemosis (score 1) were observed in 1/3 animals at the 1-h reading time point, which cleared within 24 h. Moderate conjunctivae and chemosis (score 2) were observed in 1/3 animals at the 1-h reading time point, which disappeared within 24 h. No effects on the iris and cornea were noted in any rabbit at any time point.

Table 1: Individual scores

Rabbit #	Time [h]	conjunctivae		iris	cornea
		redness	swelling
1	1	0	0	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0,0	0,0	0,0	0,0
2	1	2	2	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0,0	0,0	0,0	0,0
3	1	1	1	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0,0	0,0	0,0	0,0

Interpretation of results:

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

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are data available regarding irritation/corrosion for methyl ricinoleate (CAS 141-24-2). In addition, read-across data from the appropriate substances methyl palmitate (CAS 112-39-0), fatty acids, rape-oil, me esters (CAS 85586-25-0), ethyl ricinoleate (CAS 55066-53-0), castor oil (CAS 8001-79-4) and fatty acids, C14-18 and C16-18-unsatd., me esters (CAS 67762-26-9) are taking into account as supporting information. Structural similarities and similarities in properties and/or activities of the source and target substances are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Skin Irritation

CAS 141-24-2

The skin irritation potential of the test substance was determined by an in vivo skin irritation test in rabbits performed according to OECD guideline 404 and in compliance with GLP (Arkema, 1999). A dose of 0.5 mL of the undiluted test substance was applied to the clipped skin of 3 male rabbits for 4 h, using a semiocclusive dressing. Skin reactions were assessed 1, 24, 48 and 72 h after exposure. Up to moderate erythema and edema were observed during the first 72 hours after exposure. The erythema scores (mean 24/48/72 h) were 1.33, 0.67 and 2.00 for each rabbit, respectively, and the erythema effects were reversible on Day 7, Day 4 and Day 6, respectively. The mean edema score (24/48/72 h) was 2.00 for one rabbit which was fully reversible on Day 6. For the other two rabbits no edema were observed. All edema were fully reversible within 21 days. The test substance methyl ricinoleate was considered not to be a skin irritant based on the results and under the conditions of this study.

Read across (CAS 85586-25-0)

The substance fatty acids, rape-oil, Me esters (CAS 85586-25-0) was tested for skin irritation potential on the shaved back skin of three rabbits (Kleinrussen, Chbb:HM) similar to OECD guideline 404 and according to GLP (Cognis, 1990). The contact time under semiocclusive conditions amounts to 4 h. The erythema score was 0 for animal 1. Erythema occurred with a score of 0.33 in animal 2 and with a score of 0.66 in animal 3. The reactions disappeared within 48 hours. The edema score was 0 for all animals. The source substance fatty acids, rape-oil, Me esters has proved to be not irritating on the skin.

Read across (CAS 112-39-0)

The undiluted read across substance Methyl Palmitate (CAS 112-39-0) was tested for skin irritation potential on the dorsal shaved skin of three rabbits (Kleinrussen, Chbb:HM) in a dose of 0.5 g according to OECD guideline 404 and GLP (BASF, 1992). The contact time under semiocclusive conditions lasted four hours. Up to moderate erythema and edema were observed during the first 72 hours after exposure. The erythema score (mean 24/48/72 h) was 1.67 for animal one and 3 for animal two and three. Erythema effects were reversible within 21 days for animal one and three and not reversible for animal 2. The mean edema score was 1 for animal 1, 2.67 for animal 2 and 2.33 for animal 3. All edema effects were fully reversible within 21 days. The source substance Methyl Palmitate proved to be irritating to skin according to the conditions applied.

Human data

Read across (CAS 55066-53-0)

The skin irritation potential of 20% ethyl ricinoleate in petrolatum was evaluated using 32 healthy male volunteers (ages not stated) in a 48-h closed patch test. Skin irritation was not observed (RIFM 2000).

Read across (CAS 112-39-0)

A 24 h Patch Test was performed with methyl palmitate (CAS 112-39-0) and was conducted according to COLIPA standard, which is in accordance with generally accepted scientific standards. Slight erythema was seen in 4/20 volunteers, 5 of them showed slight desquamation (mean score for erythema: 0.21; mean score for erythema, edema, desquamation and fissure: 0.47). The slight reactions occurring under 24 h occlusive test conditions indicate that the undiluted test substance methyl palmitate is not irritating to human skin (BASF, 1998).

Conclusion

Based on the available data with the target substance methyl ricinoleate (CAS 141-24-4) and in consideration of the available supporting data with the source substances, methyl ricinoleate (CAS 141-24-4) revealed no skin irritation potential.

Eye Irritation

CAS 141-24-2

The eye irritation potential of the test substance was determined by an in vivo eye irritation test in rabbits according to OECD guideline 405 and GLP (Arkema, 1999). A dose of 0.1 mL of the undiluted test substance methyl ricinoleate (CAS 141-24-2) was instilled into one eye of each of three male rabbits (Kleinrussen, Chbb:HM). Observations were made at 1, 24, 48 and 72 h after instillation. Slight conjunctivae and chemosis (score 1) were observed in 1/3 animals at the 1-h reading time point, which cleared within 24 h. Moderate conjunctivae and chemosis (score 2) were observed in 1/3 animals at the 1-h reading time point; which disappeared within 24 h. No effects on the iris and cornea were noted in any rabbit at any time point.

Read across (CAS 112-39-0)

In vivo

The undiluted test substance methyl palmitate (CAS 112-39-0) was tested for eye irritation (24 h contact) in rabbits (Kleinrussen, Chbb:HM) according to OECD TG 405 and GLP (BASF, 1992, in vivo). The single instillation dose amounted to 0.1 mL per conjunctival sac. The conjunctivae score (24/48/72h) was determined to be 0.33 for animal one and three. The effect was fully reversible within 48 h. The conjunctivae score for animal 2 was 0.66 and was reversible within 72 h. Cornea and iris effects were not observed.

In vitro

The intention of the HETCAM assay is to assess the acute irritation potential of a test substance to mucous membranes in analogy to the Draize Eye Irritation Test. For this purpose, a definitive dose of the test substance is applied to the corioallantoix membrane (CAM) of three fertilized and incubated hen´s eggs (BASF, 1992, in vitro). Undiluted methyl palmitate (CAS 112-39-0) was not irritating under the conditions of this study. According to this result the substance is considered as not eye irritating.

Read across (CAS 67762-26-9)

The substance fatty acids, C14-18 and C16-18-unsatd., Me esters (CAS 67762-26-9) was tested for primary eye irritation on rabbits by a single application of 0.1 mL of the undiluted test substance according to OECD TG 405 and GLP (BASF, 1988). The cornea, iris conjunctival scores were 0 for all animals, thus the test substance does not show eye irritant properties.

Human data

Read across (CAS 8001-79-4)

In a study by Secchi et al. (1990), a double-masked clinical trial was performed using a group of nine patients (ages not stated) with vernal keratoconjunctivitis. One eye was treated with 2% cyclosporine in castor oil four times daily for 15 days. The other eye was treated with castor oil solution only according to the same procedure. Mild and transient discomfort and minor epithelial changes were observed in both eyes.

Conclusion

Based on the available data with the target substance methyl ricinoleate (CAS 141-24-4) and in consideration of the available supporting data with the source substances, methyl ricinoleate (CAS 141-24-4) revealed no eye irritation potential.

Justification for classification or non-classification

The available target and source substance data on skin irritation and eye irritation/corrsoion do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.