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Description of key information

Key value for chemical safety assessment

Skin sensitisation

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

The key study for skin sensitisation (Morris et al, 1997, HTR report number: 96-1104-70A,B) was chosen as the study was conducted in humans which are the most relevant species. There is no recognised guideline for this type of test however a well documented study with good scientific principles was undertaken at a certified GLP laboratory which followed a protocol.

A reliability rating of 1 according to the criteria of Klimisch, 1997.

The following supporting animal studies are available to corroborate the results from the above key study:

- The Denton, 1994, supporting skin sensitisation study was not considered the key study as it was conducted less recently than the above key study and was tested on animals, where as the key study was a well documented human study. This study was conducted to the OECD Guideline 406 (Skin Sensitisation) and GLP. A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997.

In this study the test material produced evidence of skin sensitisation (delayed contact hypersensitivity) in five of the test animals.

According to the dangerous substances directive, 67/548/EEC, a response of at least 30% of the animals in the case of an adjuvant test method is considered positive. The guinea-pig maximisation is an adjuvant test method for skin sensitisation and so based on the results of this study the test material is considered to be non-sensitising according to the dangerous substances directive, 67/548/EEC.

- The Mercier, 1995b study (Report number: 63394) supporting skin sensitisation study was not considered the key study as it was conducted less recently than the above key study and was tested on animals, where as the key study was a well documented human study. This study was conducted to the OECD Guideline 406 (Skin Sensitisation) and GLP. A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997.

During induction, signs of irritation were noted in the treated group. No irritation was noted in the control group.

After challenge, the macroscopic and histopathological examinations did not show evidence of any pathological lesion of delayed hypersensitivity in the 20 guinea-pigs of the treated group. No noticeable cutaneous abnormality was noted in the 10 guinea-pigs of the control group.

From the results obtained under the experimental conditions employed, the test article did not provoke any reaction of cutaneous sensitization.

- The Thompson, 1985 study (Report number: SOCAL 2320) supporting skin sensitisation study was not considered the key study as it was conducted less recently than the above key study and was tested on animals, where as the key study was a well documented human study. There was no guideline specified in this study however it looks similar to the OECD Guideline 406 (Skin Sensitisation) with deviations. Less animals used in the study than specified in current guidelines. Skin irritation observed in naive control animals. A reliability rating of 2 was assigned according to the criteria of Klimisch, 1997.

The skin reactions observed in the thet test material and irritation control groups were very similar. Well-defined irritation was only observed at the 72-hour reading. No animals were found to be sensitized in this study.

- The Douds, 1996 study (Report number: 3356.2) supporting skin sensitisation study was not considered the key study as it was conducted less recently than the above key study and was tested on animals, where as the key study was a well documented human study. This study was conducted to the EPA OPP 81-6 (Skin Sensitisation) guideline and GLP. Skin irritation observed in naive control animals and so a reliability rating of 2 was assigned according to the criteria of Klimisch, 1997.

Based on the results of this study the test material does not meet the criteria to be considered a contact sensitizer. The presence of a higher incidence of grade 1 responses in the treated animals compared to the control animals is suggestive that a sensitization response might be induced.

- The Mercier, 1995a study (Report number: 63294) supporting skin sensitisation study was not considered the key study as it was conducted less recently than the above key study and was tested on animals, where as the key study was a well documented human study. This study was conducted to the OECD Guideline 406 (Skin Sensitisation) and GLP. A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997.

During induction, signs of irritation were noted in the treated group. No irritation was noted in the control group.

After challenge, the macroscopic and histopathological examinations did not show evidence of any pathological lesion of delayed hypersensitivity in the 20 guinea-pigs of the treated group. No noticeable cutaneous abnormality was noted in the 10 guinea-pigs of the control group.

From the results obtained under the experimental conditions employed, the test article did not provoke any reaction of cutaneous sensitization.

- The Morris, 1994 study (Report number: 94-8256 -21 (A)) supporting skin sensitisation study was not considered the key study as it was conducted less recently than the above key study and was tested on animals, where as the key study was a well documented human study. This study was conducted according to the OECD Guideline 406 (Skin Sensitisation) and GLP, however there was no skin sensitisation seen in the positive control data and so the study is considered to be invalid. On this basis a reliability rating of 3 was assigned according to the criteria of Klimisch, 1997.

Ambiguous results obtained.

- The Waid, 1993 study (Report number: CEHC 3206) supporting skin sensitisation study was not considered the key study as it was conducted less recently than the above key study and was tested on animals, where as the key study was a well documented human study. There was no guideline specified in this study however it looks similar to the OECD Guideline 406 (Skin Sensitisation). A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997.

Dermal irritation observed in animals induced with 10% of the test material and challenged twice with 5% of the test material were equivalent in severity and incidence compared to that observed in corresponding control animals. The test material is not considered to be a sensitizer under the conditions tested.


Migrated from Short description of key information:
A standard Repeated Insult Patch Test was preceded by a Pilot Phase to select a proper concentration of the test material. The test material was tested undiluted and diluted to 50% in Mineral Oil. The negative control was Mineral Oil. The testing was conducted under semi-occluded patch conditions.
A total of 24 subjects was tested; one half to undiluted test material and one half to 50% test material in mineral oil. Only minimal reactions were noted during the inductions and challenge so that undiluted test material was selected for testing in the Main Phase.

A total of 104 additional subjects completed the Main Phase. The test material was tested undiluted. The negative control was Mineral Oil. The testing was conducted under occluded patch conditions. Only mild to moderate responses were noted during the main phase of the study, and it is concluded that the test material is non-irritating and non-sensitizing under the condition of this test.

Justification for classification or non-classification

The key parameter chosen for skin sensitisation was greater than the criteria set out in Directive 67/548/EEC and also Regulation (EC) 1272/2008, therefore classification for skin sensitisation was not considered to be necessary.