Methyl ricinoleate

Endpoint summary

Description of key information

OECD 406, GLP: not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 Mar -19 Apr 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The LLNA guideline study was not validated at the time the guinea pig maximisation test was performed (1999).

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS- Source: Charles River France, 76410 Saint-Aubin-lès-Elbeuf, France- Females nulliparous and non-pregnant: yes- Age at study initiation: approximately 3 months - Weight at study initiation: 382 ± 14 g (males); 357 ± 10 g (females)- Housing: The animals were housed individually in polycarbonate cages (48 cm x 27 cm x 20 cm) equipped with a polypropylene bottle. Dust-free sawdust was provided as litter (SICSA, 92142 Alfortville, France).- Diet: 106 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 Ieast 5 days ENVIRONMENTAL CONDITIONS- Temperature (°C): 21 ± 2- Humidity (%): 30 - 70- Air changes (per hr): approximately 12 - Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal

Vehicle:

corn oil

Concentration / amount:

25%

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.5 mL

Day(s)/duration:

24 h

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.5 mL

Day(s)/duration:

24 h

No. of animals per dose:

5 males and 5 females (controls), 10 males and 10 females (treated)

Details on study design:

MAIN STUDY A. INDUCTION EXPOSURE - No. of exposures: 2 (intradermal and epicutaneous, respectively) - Exposure period: single injection (intradermal) and 48 h (epicutaneous) - Test groups: On day 1, intradermal injections of Freund's complete adjuvant mixed with the test substance at a concentration of 10% (w/w) in corn oil (treated group) or the vehicle (control group) were performed in the interscapular region.On day 7, the same region received a topical application of sodium lauryl sulfate in vaseline (10%, w/w) in order to induce local irritation.On day 8, the undiluted test substance (treated group) or the vehicle (control group) was applied to the same test site which was then covered by an occlusive dressing for 48 hours. B. CHALLENGE EXPOSUREOn day 22, after a rest period of 12 days, all animals of the treated and control groups were challenged by a cutaneous application of the undiluted test substance to the right flank. The left flank served as control and received the vehicle only. Test substance and vehicle were maintained under an occlusive dressing for 24 hours.Skin reactions were evaluated approximately 24 and 48 hours after removal of the dressing. At the end of the study, animals were killed without examination of internal organs. No skin samples were taken from the challenge application sites.The sensitivity of the guinea pigs in CIT experimental conditions was checked with a positive sensitizer, 2,4-Dinitro Chlorobenzene (DNCB). During the induction period, the reference substance DNCB was applied at the concentrations of 0.1% (w/w) (day 1) and 1% (w/w) (day 8) in corn oil. For the challenge application, the reference substance DNCB was applied at the concentration of 1% (w/w) in corn oil.

Challenge controls:

Challenge (all groups)topical application: RICINOLEATE DE METHYLE undiluted.

Positive control substance(s):

yes

Remarks:

2,4-Dinitro chlorobenzene (DNCB)

Positive control results:

The species and strain which were used showed a satisfactory sensitization response in 90% animals treated with DNCB.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

Induction: 25 and 100%; challenge: 100%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

very slight erythema observed in 1/10 controls and 5/20 treated animals

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

Induction: 25 and 100%; challenge: 100%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

Induction: 0%; challenge: 100%

No. with + reactions:

0

Total no. in group:

5

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

Induction: 0%; challenge: 100%

No. with + reactions:

0

Total no. in group:

5

Table 1: Scores of the control group

	Animal number	24 h				48 h
		Erythema		Oedema		Erythema		Oedema
		Left flank	Right Flank	Left flank	Right Flank	Left flank	Right Flank	Left flank	Right Flank
Male	31	0	0	0	0	0 / S	0 / S	0	0
	32	0	0	0	0	0	0	0	0
	33	0	0	0	0	0	0	0	0
	34	0	0	0	0	0	0 / S	0	0
	35	0	0	0	0	0 / S	0 / S	0	0
Female	46	0	0	0	0	0	0 / S	0	0
	47	0	0	0	0	0	0	0	0
	48	0	0	0	0	0	0 / S	0	0
	49	0	0	0	0	0	0	0	0
	50	0	0	0	0	0	0 / S	0	0

S: Dryness of skin

Table 2: Scores of the treatment group

	Animal number	24 h				48 h
		Erythema		Oedema		Erythema		Oedema
		Left flank	Right Flank	Left flank	Right Flank	Left flank	Right Flank	Left flank	Right Flank
Male	36	0	1	0	0	0	0 / S	0	0
	37	0	0	0	0	0	0 / S	0	0
	38	0	0	0	0	0	0 / S	0	0
	39	0	0	0	0	0	0	0	0
	40	0	0	0	0	0	0	0	0
	41	0	0	0	0	0	0 / S	0	0
	42	0	1	0	0	0	0 / S	0	0
	43	0	0	0	0	0	0	0	0
	44	0	0	0	0	0 / S	0 / S	0	0
	45	0	0	0	0	0	0	0	0
Female	51	0	0	0	0	0	0 / S	0	0
	52	0	1	0	0	0	0 / S	0	0
	53	0	0	0	0	0	0	0	0
	54	0	0	0	0	0	0	0	0
	55	0	0	0	0	0	0	0	0
	56	0	0	0	0	0	0	0	0
	57	0	0	0	0	0 / S	0	0	0
	58	0	0	0	0	0	0	0	0
	59	0	1	0	0	0 / S	0 / S	0	0
	60	0	0	0	0	0	0 / S	0	0

S: Dryness of skin

Interpretation of results:

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

Conclusions:

CLP: not classified

Executive summary:

The sensitization potential of the test substance was evaluated in the guinea pig according to the maximization procedure by Magnusson and Kligman. 20 Dunkin-Hartley guinea pigs (10 males and 10 females) were treated in the test group. The test substance was applied by intradermal injection at a concentration of 25% in corn oil, after 7 days, the animals were induced (and irritation by sodium lauryl sulfate in vaseline) epicutanously by the undiluted test item. On day 22, after a period of 12 days, treated animals and controls were challenged by a cutaneous application of the test substance to the right flank. The left flank served as control and received the vehicle only. Test substance and vehicle were maintained under an occlusive dressing for 24 h.

Skin reactions were evaluated approximately 24 and 48 h after removal of the dressing.

 

No symptoms, mortality or cutaneous reactions due to any sensitization process by treatment with the test substance were observed in guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

There are data available regarding skin sensitisation for methyl ricinoleate (CAS 141-24-2). In addition, read-across data from the appropriate substance methyl palmitate (CAS 112-39-0), fatty acids, C16-18 and C18-unsatd., Me esters (CAS 67762-38-3), ethyl ricinoleate (CAS 55066-53-0) and castor oil (CAS 8001-79-4) is 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).

CAS 141-24-2

A Guinea pig maximisation test was performed with the test substance according to OECD guideline 406 and under GLP conditions (Arkema, 1999). 20 Dunkin-Hartley guinea pigs (10 males and 10 females) were treated in the test group. The test substance was applied by intradermal injection at a concentration of 25% in corn oil, after 7 days, the animals were induced epicutanously by the undiluted test substance (in addition irritation by sodium lauryl sulfate in Vaseline was induced on Day 7). On day 22, after a period of 12 days, treated animals and controls were challenged by a cutaneous application of the test substance to the right flank. The left flank served as control and received the vehicle only. Test substance and vehicle were maintained under an occlusive dressing for 24 h. Skin reactions were evaluated approximately 24 and 48 h after removal of the dressing. No symptoms, mortality or cutaneous reactions due to any sensitization process by treatment with the test substance were observed in guinea pigs.

Read across (CAS 67762-38-3)

The potential skin sensitizing properties of rape-oil fatty acid methyl ester (CAS 67762-38-3) were assessed in the guinea pig maximization test using 20 test and 20 control animals according to OECD guideline 406 (BASF, 1993). Following induction exposure to the test article or the vehicle, the animals were subjected two weeks later to a challenge exposure with the test article. The induction concentration was 5% and the challenge concentration was 100%. The treated skin areas were evaluated 24 and 48 h after the end of the exposure period. Since no animal showed an allergic response, the test article rape-oil fatty acid methyl ester is considered to be a "non-sensitizer".

Human data

Read across (CAS 55066-53-0)

The skin sensitization potential of 20% ethyl ricinoleate in petrolatum was evaluated using 32 healthy male volunteers in the maximization test (RIFM 2000). The test substance was applied (under occlusion) to the same site on the forearms of each subject for five alternate-day 48-h periods. Each test site was pretreated with 5% aqueous sodium lauryl sulfate (under occlusion) for 24 h. At the end of a 10- to 14-day non-treatment period, challenge patches were applied (under occlusion) to new test sites for 48 h. Challenge applications were preceded by 30-min applications of 2% aqueous sodium lauryl sulfate (under occlusion) on the left side. On the right side, the challenge application was not preceeded by treatment with sodium lauryl sulfate. A fifth site (challenge with petrolatum) served as the control. Reactions classified as either significantly irritating or allergic were not observed.

Read across (CAS 8001-79-4)

Fujimoto et al. (1997) conducted a study involving 332 patients (25 males, 307 females; at the age between 20 and 70) suspected of having cosmetic contact dermatitis. The subjects were patch-tested with numerous cosmetic products and cosmetic ingredients. Patch tests (Finn chambers) were applied to the back for 48 h, and the test sites were examined at 30 minutes after patch removal, 1 day later, and 4 to 5 days after patch removal. None of the 49 patients patch-tested with castor oil had a positive reaction.

In a study by Hino et al. (2000), 346 patients (31 males, 315 females; at the age between 20 and 70) suspected of having cosmetic dermatitis were patch tested with various cosmetic products and cosmetic ingredients. Patch tests (Finn chambers) were applied to the back for 48 h. Test sites were examined according to the schedule in the preceding study. Of the 76 patients patch-tested with castor oil, one had a positive reaction. This reaction was observed only during the second reading (i.e., the day after the 30-min reading).

Read across (CAS 112-39-0)

In a 24 h Patch Test according to COLIPA skin sensitising effects were determined with 20 subjects (BASF, 1998). The test substance was applied on the skin side by side undiluted and was observed after 6, 24, 48 and 72 h. No skin sensitisation was observed.

 

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) is not considered to be a skin sensitiser.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

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