Registration Dossier

Administrative data

Description of key information

Skin sensitisation studies (LLNA) have been conducted on three substances in the TDI-I category. Local Lymph node assays have been conducted on Diurea 8 (Sanders 2012) and Tetraurea 2 (Sanders, 2011e), and on the reaction product of m-tolylidene diisocyanate, cyclohexamine, cyclohex-1,2 -ylenediamine and (Z)-octadec-9 -enylamine (Toussaint 2009). For Diurea 8 and Tetraurea 2, the substance are considered to be non-sensitisers under the conditions of the test with the highest stimulation index of 1.24 and 1.13 recorded at the 5 % concentration in 1 % pluronic L92 in distilled water for Diurea 8 and Tetraurea 2, respectively. At the highest concentrations tested a Stimulation Index of 1.15 and 1.02 was reported for Diurea 8 and Tetraurea 2, respectively.

In the LLNA study conducted on The reaction product of m-tolylidene diisocyanate, cyclohexamine, cyclohex-1,2 -ylenediamine and (Z)-octadec-9 -enylamine the highest Stimulation Index observed was 1.49 at the 50 % concentration in DMSO, the highest concentration tested. The study concluded that the substance was a senstiser due to using an amended Stimulation Index 1.4 as the classification of sensitisation. The study has been thorough reviewed in accordance with the ECHA guidance for non-guideline studies and has been deemed unreliable; therefore Keratino-Sens and U-Sens assay have been commissioned to review the applicability of the result. Therefore, all of the TDI-I category members are not classifed as skin senstisers.

Key value for chemical safety assessment

Skin sensitisation

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

The study Richeux (2009b) is a non-guideline study and in accordance with the draft ECHA guidelines for sensitisation testing (Chapter R7a – draft) indicate that data obtained from non-guideline compliant tests or from refinements of a standard assay need to be further assessed. Additionally, it was noted that non-guideline test data are not referred to in the CLP Regulation with specific classification criteria. Information from such studies should only be used as supporting evidence which would normally require expert judgement in a weight of evidence approach and will generally not be considered adequate for classification on their own.

After the review of the study, although the study design is an acceptable one for assessment purposes, the dose concentrations selected for the LLNA itself are too high based on irritancy potential. Additionally, the choice of 1.4 for the SI threshold is based on validation data performed by BASF. The results of the irritation pre-screen showed ear thickness measurements >25% of the controls at the selected test concentrations, which under the current LLNA protocol is considered too irritating for testing. Consequently, our interpretation of this study is that, whilst it is acceptable for consideration, it is not regulatory compliant in its design (in accordance with the obsolete OECD 429 dated 24/04/2002), it is also not compliant with the current OECD 429 regarding the selection of dose concentrations (see Sections 18, 21-23 of the updated OECD 429 guideline). Therefore, for these reason this study is not used for the purposes of classification and a Keratino-Sens and U-Sens assay have been commissioned for this susbstance.

The data of Sanders (2011e and 2012) is deemed appropriate for read-across to the other TDI-I category members. PU TDI-I substance all contain the same core structure, with predominantly linear alkyl chains (C8 - C18) attached. The same substance can contain structures with different alkyl chain lengths, and some substances may contain small amounts of structures with cyclic groups. PU TDI-I structures are therefore similar between all category members, and organisms will be exposed to very similar compounds. Organisms would be exposed to common structures, only differing by the length of the alkyl chain or whether cyclic groups are present.

Justification for classification or non-classification

No classification is required for the category members as in the studies conducted on Diurea 8 (Sanders 2012) and Tetraurea 2 (Sanders 2011e) the highest Stimulation Index, and the Stimulation Index at the highest tested concentration was < 3.