Pentadecan-15-olide

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Table 7.4.1: Summary of skin sensitisation studies:

Test type	Reference	Test item	Purity	Classification
LLNA	Zurney, 2012	ST 11 C 12	98,30%	Sensitizer
	Zurney, 2012	ST 12 C 12	100%	NC at non-irritants levels
	Zurney, 2012	ST 18 C 18	100%	NC at non-irritants levels
	Bradshaw, 2009	Sym 09/689858	>99,8%	NC
	Bradshaw, 2009	Sym 09/660539	>98,5%	Sensitizer
	Hassler, 2011	Sym10/660539 S	99%	Sensitizer
	Hassler, 2010	Sym10/660539 F	98,30%	Sensitizer
GPMT	Bollen, 1997	HR 97/660539	99,60%	NC
	Driscoll, 1995	HR 94/660539	99,70%	NC
HRIPT	Eisenberg, 2006	Sym06/660539 Batch 225	98,90%	NC
	Thomsen, 1997	HR 97/660539	99,60%	NC
	Schrader, 1998	HR 97/660539	99,00%	NC (1/50 individuals showed response)

Two Guinea-pig maximisation tests have been performed on the substance (Bollen, 1997; Driscoll, 1995), both showed an absence of sensitizing potential:

- In a Magnusson & Kligman maximisation study (GPMT) performed by Bollen (1997) according to OECD Guideline 406 and in compliance with GLP, 20 female Dunkin-Hartley guinea pigs were induced with three pairs of intradermal injections (0.1 mL each) of Freund's complete adjuvant (FCA) emulsified 1:1 in sterile water, 10 % (w/w) test item, the test substance in sesame oil and 10 % (w/w) test article formulated in a 1:1 mixture (w/w) of FCA and sesame oil. On Day 8, the same area was topically induced with 50 % test article in Ethanol/diethyl phthalate 1:1 via occluded filter paper patch for 48 h for the treated group. On Day 21, challenge filter paper patch of 25 % (w/w) test article in Ethanol/diethyl phthalate 1:1 or vehicle (Ethanol/diethyl phthalate 1:1) was applied on the left anterior flank and left posterior flank, respectively. Challenge control group was applied with 25 % (w/w) test article in Ethanol/diethyl phthalate 1:1 on the left posterior flank. On Day 29, a rechallenge filter paper patch of 12.5 % (w/w) test article in Ethanol/diethyl phthalate 1:1 or vehicle (Ethanol/diethyl phthalate 1:1) was applied on the right anterior flank and right posterior flank, respectively. Rechallenge control group was applied with 12.5 % (w/w) test article in Ethanol/diethyl phthalate 1:1 on the right posterior flank. The test concentrations for the main study were determined from a sighting study using two animals per exposure. Slight or discrete erythema was observed at the rechallenge sites of test group animals at 24 and 48 h observations. The test substance produced a 0 % (0/19) sensitisation rate and was considered to be a non-sensitiser to guinea pig skin. Under these test conditions, the test item is not classified as skin sensitiser according to the Annex VI of the Directive 67/548/EEC and of the Regulation (EC) N° 1272-2008 (CLP).

- In a Magnusson & Kligman maximisation study (GPMT) performed by Driscoll (1995) according to OECD Guideline 406 and in compliance with GLP, 20 male Dunkin-Hartley guinea pigs were induced with three pairs of intradermal injections (0.1 mL each) of Freund's Complete Adjuvant plus distilled water in the ratio 1:1, 5 % w/v dilution of test material in arachis oil B.P, 5 % w/v dilution of test material in a 1:1 preparation of Freund's Complete Adjuvant plus distilled water, on Day 0 on three different sites on each side of the mid-line on shoulder region. After one week the same area was topically induced with undiluted test material via occluded filter paper patch for 48 h for the treated group. After 2 weeks, a challenge filter paper patch of 50 and 75 % v/v in 1:1 ethanol/diethylphthalate test material formulation was applied to the left and right flank, respectively in all animals. No skin reactions were noted at the challenge sites of the test or control group animals at the 24 and 48h observations. The test substance produced a 0 % (0/19) sensitisation rate and was considered to be a non-sensitiser to guinea pig skin. Under these test conditions, the test item is not classified as skin sensitiser according to the Annex VI of the Directive 67/548/EEC and of the Regulation (EC) N° 1272-2008 (CLP).

A total of seven LLNA studies have been performed on a variety of samples of the test substance, each with a different identified purity. The test substance seems to generate somme irritation to the skin in the LLNA test and this property may interfere with the accuracy of the LLNA, such that an arbitrary limit of an increase in ear thickness of 25% has been set as the threshold above which sensitizing results should be discounted. In the seven studies results were obtained that indicated that any sensitizing potential that may be detected is seen at a concentration very close to the concentration that also induces irritation at the threshold level. Furthermore, it may be said that generally as the purity of the tested sample increases then the sensitizing potential observed in the LLNA decreases and samples where the purity is 99.8% or greater may be non-classifiable as sensitizers.

Two human repeat insult patch tests and one patch test have been performed on the substance (Eisenberg, 2006; Thomsen, 1997; Schrader, 1998) with a total of 205 patients. All three studies were concluded to be negative for sensitization although 1/50 patients in one of the studies showed a reaction to the challenge.

Migrated from Short description of key information:
The sensitization potential of Pentadecan-15-olide has been investigated in a number of different studies and study types. The substance has been shown to be both sensitizing and non-sensitizing in the LLNA, with the purity of the sample being critical to the outcome of the test. The data indicate that if the substance has a purity ≥ 99.8% then it is not classifiable as a sensitizer. The substance is not sensitizing in the GPMT and not sensitizing in 3 HRIPT studies, although one individual in one study exhibited a response on challenge.

Justification for selection of skin sensitisation endpoint:
No study was selected since a weight-of-evidence approach was followed to conclude on the skin sensitisation potential of Pentadecan-15-olide.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Migrated from Short description of key information:
This information is not available.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No 1272/2008 including ATP3.

Self-classification:

Purity <99.8%:

The substance should be classified as skin sensitiser if the purity is less than 99.8%:

-Skin Sens. sub-category 1B (H317: May cause an allergic skin reaction.) according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP),

- Xi; R43 (May cause sensitization by skin contact) according to the Annex VI of the Directive 67/548/EEC.

Purity ≥ 99.8%:

Based on the available information, if the purity of the test substance is equal to or greater than 99.8% then no additional self-classification is proposed according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the Directive 67/548/EEC.

No information is available regarding respiratory sensitisation.