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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
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Reason / purpose:
data waiving: supporting information
Reference

Skin irritation: The test material was found to be non-irritating to human skin at concentrations of 2, 6 and 12% in EtOH/DEP 1:1, single application patch test under occlusion, Küster & Goluchowski (1999)

Skin sensitisation: Not sensitising at concentrations of 8 and 15 % in EtOH/DEP 1:1 in a human repeat insult patch test under occlusive conditions, Middeke & Küster (2000)

Skin sensitisation: Not sensitising in a human maximisation test, Kligman (1975)

The skin irritation potential of the test material was assessed in 50 human volunteers using a single application patch test. Test material at concentrations of 2, 6 and 12% in EtOH/DEP 1:1 was applied to the back of each volunteer under occlusive cutaneous test plasters. After a test period of 48 hours the test plasters were removed and the test area was assessed. Further assessments were performed after 72 and 96 hours. With the exception of two slight reactions noted in the 2% product, the test material was found to be well tolerated by the skin under the conditions of the study.

The skin sensitisation potential of hexenyl-3-cis salicylate was assessed in 50 volunteers using repeated application closed patch epicutaneous testing under occlusion. Informed written consent was sought prior to study initiation. The test material was found to be very well tolerated by the skin under the conditions of the test at 8% and 15% concentrations in EtOH/DEP 1:1.

Supporting information on the skin sensitisation potential of the test material, in humans, is available in the form of a report by Kligman (1975). The report documents results of a patch test during which the test material was applied under occlusion to the forearms of 25 adult volunteers for five alternate day 48 hour periods. The patch sites was pre-treated for 24 hours with 5% aqueous sodium lauryl sulfate under occlusion. The challenge sites were read on removal of the patch and 24 hours thereafter. Under the conditions of the study, there were no instances of contact-sensitisation from the test material on the Maximisation Test. It is unlikely that this test material would present a danger of contact-sensitisation in normal, intended use.

All studies were presented in a sufficient level of detail to assess accuracy of the conclusions presented. All studies were performed in line with good scientific principles. The data were therefore all assigned a reliability score of 2 in accordance with the principles for assessing data quality described by Klimisch (1997).

Reason / purpose:
data waiving: supporting information
Reference

Test substance produced a 0% sensitisation rate and was determined to be non-sensitising; study conducted in accordance with OECD 406, EU B.6; Sanders (1999)

Test substance well tolerated by the skin; repeated application closed patch test in humans; Middeke & Küster (2000)

Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In a GLP compliant sensitisation study conducted in line with standardised guidelines, the sensitisation of (z)-3-hexenyl salicylate was determined using the maximisation test. Induction was performed intradermally (first exposure) at a concentration of 5%, the later topically using the undiluted test substance. Animals were challenged with a topical application of undiluted test substance and observed for reaction at 24 and 48 hours post exposure. No reactions were noted at either observation period post challenge. Hexenyl-3-cis salicylate was considered to be non-sensitising. The study was performed to GLP and standard guidelines and so was allocated a reliability score of 1 and considered to be a key study.

The skin sensitisation potential of the test substance was further assessed in 50 volunteers using repeated application closed patch epicutaneous testing under occlusion. Informed written consent was sought prior to study initiation. The test substance was found to be very well tolerated by the skin under the conditions of the test at 8% and 15% concentrations in EtOH/DEP 1:1. The study was performed in line with sound scientific principles and so was allocated a reliability score of 2. It is also considered a key study on the basis that it is a reliable study performed in humans and complements the animal study performed using the maximisation test.

In a GLP compliant LLNA study conducted in line with standardised guidelines, (z)-3-hexenyl salicylate was determined to be a sensitiser. However, the results of the study appear to be a false positive reaction, when compared with the results of a human repeat insult patch testing and a guinea pig maximisation test and taking into account the lack of significant reports of sensitisation occurring in the general population. Therefore, the use of the LLNA model is not considered to be appropriate for assessing this particular substance. The study was allocated a reliability score of 3 and has been disregarded.

Endpoint conclusion:
no study available

According to the EU Regulation EC 1272/2008, the substance does not meet the criteria for classification for skin sensitisation. There is no evidence to suggest that the substance should be classified for respiratory sensitisation.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion