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Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

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

In general there is no need for skin sensitisation testing in case of corrosive substances. This is due to reasons of animal protection and because testing for skin sensitisation proves to be challenging as well as interpretation of results is difficult. Nevertheless available data on the members of the amine heads category are presented. Skin sensitisation potential of the category members was assessed using mainly guinea pigs (some reliable and one not reliable test are available), but also one study in mice is available for DCH (not reliable LLNA). Observations on humans after occupational exposure are reported.

There are two skin sensitization tests (intracutaneous induction treatment) on guinea pigs with MPMD as test material.

In an intracutaneous test 5 male and 5 female guinea pigs per dose group (5% or 0.5% of test substance) were subject to a skin sensitisation assay. First Primary irritation was tested (1 drop open epikutan). Two days thereafter 4 intradermal injections with 0.1 ml of 1% (v/v) emulsion (1 injection per week) followed. After challenge (done open epicutaneous; two weeks after last induction injection) with MPMD the animals in the 5% group showed mild erythema in the 24 and 48 h reading (5/10 and 2/10 animals). In the 0.5 % test group no effects were observed. Positive control substance showed the expected positive result. According to the authors MPMD is no skin sensitiser.

In another intracutaneous guinea pig test (conducted as described above) 10 male guinea pigs were treated with two concentrations of MPMD each (10 % or 1 % of test substance). After challenge with the test substance animals in the 10 % group showed very slight erythema in the 24 and 48 h reading (i.e. 8/10 and 10/10 animals). In the corresponding control group (animals were only treated once with the test substance during challenge) 8/10 animals showed also slight erythema in the 24 and 48 h reading, revealing the irritant potential of the test substance at this concentration level. In the 1 % test group no effects were observed. According to the authors MPMD is no skin sensitiser.

Using DCH as test material another intracutaneous guinea pig test was performed. 5 male and 5 female guinea pigs were treated with two concentrations of test substance each (10 % or 1 % of DCH; Primary irritation phase: 1 drop open epikutan). Two days thereafter followed by induction phase (4 intradermal injections with 0.1 ml of 1% (v/v) emulsion, 1 injection per week). Additional animals were used as negative and positive control animals. After challenge (open epicutaneous, was done two weeks after last induction injection) with the test substance animals in the 10 % group showed very slight to moderate erythema in the 24 and 48 h reading (8/9 and 8/9 animals). In the corresponding negative control group 3/5 animals showed slight erythema in the 24 and 48 h reading, revealing the irritant potential of the test substance at this concentration level. In the 1 % test group no effects were observed. Due to this observed results rechallenge was performed in the same way as challenge procedure but one week thereafter. 48 hours after rechallenge with 10% DCH 6/9 animals showed slight or mild erythema, whereas none of the negative control animals showed skin response. In the 1 % test group and negative control group no effects were observed. Under the applied test conditions, results of this skin sensitisation assay with guinea pigs are ambiguous, as corrosiveness of the substance complicated interpretation of results. A rechallenge exposure therefore was needed. According to the study authors the test substance reveals weak skin sensitising effects taken the results from the rechallenge exposure.

In a publication (Gamer et al., 2008) groups of 6 female CBA mice per dose group were used to test skin sensitisation properties of the test material in three independent LLNA experiments. Experiment I was conducted using acetone as vehicle with concentration levels of 0.1%, 0.3% or 1%. Experiment II was performed using acetone as vehicle but concentration levels of 0.3%, 1% and 3%. Experiment III was performed using the same concentration levels but instead acetone/olive oil as vehicle. Experiment I resulted in an EC3 value of 0.4%. Experiment II resulted in an EC1.5 value of 0.89%. An EC3 value could not be determined as a Stimulation index of 3 was never achieved even though higher test material concentrations were used. In Experiment III even an EC1.5 value could not be calculated as the Stimulation index of 1.5 was never exceeded. It has to be mentioned that Experiment III should have been conducted using higher test material concentration based on expected results of the pre-testing or irritant properties in the respective test vehicle. Hence a somewhat different result could be expected for Experiment III (maybe even an EC3 value). Overall as the study authors stated that results obtained with the vehicle acetone would seem to overestimate the skin sensitising potential of the tested materials, the results with acetone/olive oil are negative and a potential positive outcome is only speculative the overall evaluation of this study is ambiguous.

The aim of a further study was to analyse the skin sensitisation potential of HMD at 2% and 1%. Experiment was realised with 10 Guinea Pigs. A 2% HMD aqueous solution was applied (Epicutaneous route) onto the clipped skin of Guinea Pigs. Three successive applications were performed the first day on the same area. Then, six successive subcutaneous injections of solution of 1% HMD were performed on the left side through 13 days followed by a 8-day rest period. Then a final patch application was performed with 1% and 2% HMD aqueous solution. Skin lesions were recorded after patch removal. Afterwards a seventh final test substance subcutaneous injection was administered to the animals. Finally guinea pigs were sacrificed with gas two days after final injection and a gross-autopsy was performed for some animals. Skin reactions were analysed and weight measured for approximately for one month through both treatment period. Under the test conditions, no skin sensitisation was observed in any animals after final patch application. Necrosis was observed 24 -hour after the last injections following the final patch application.

There are two publications which deal with sensitization to DCH in humans:

In the study of Kirkup et al (2001) 4 cases with eczema after occupational exposure to epoxy resin systems were reported. Patch testing with several constituents of the used epoxy resin systems were performed. Only in one case positive reactions were found for the submission susbtance (0.1% and 0.2). In the three other cases positive reactions were found for a derivate only.

In this study presented by Geier et al. (2004) patients with suspected contact allergy due to epoxy resin systems were patch tested with various constituents of epoxy resin systems. Patch tests with the submission substance at 0.25% in petroleum jelly were performed in 87 patients. 86 patients showed no skin reaction and only person revealed a questionable test result. The study authors mention that it cannot be excluded that the tested concentration was too low and further tests should be carried out with higher test concentrations. Because of this in a later stage of the study 81 patients were tested with 0.5% DCH in petroleum jelly. Two patients were found to have positive skin reactions. Nevertheless no details on clinical relevance of these findings are given.


Migrated from Short description of key information:
Skin sensitisation of the amine heads category was mostly assessed using guinea pigs, but also a test with mice is available. In various tests MPMD and HMD showed always clear negative results. For DCH some slightly positive or ambiguous results were reported for skin sensitisation properties.

Justification for selection of skin sensitisation endpoint:
No single study was selected as an overall evaluation of all available studies was performed.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

As seen in section on skin corrosion/irritation and eye irritation the substances within this category are very alkaline substances and therefore bear corrosive characteristics. Based on this substance characteristics testing for skin sensitisation proves to be somewhat challenging as well as interpretation of results is difficult as seen in the supporting studies presented. No clear conclusions can be drawn from studies with occupational exposure to DCH. Taken this fact together with the negative results from MPMD and HMD and the slight positive or ambiguous results from DCH overall no classification for skin sensitizing properties is proposed for the members of this category according to Regulation (EC) No. 1272/2008 as well as Council Directive 67/548/EEC.