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EC number: 701-029-8
CAS number: -
All substances of the MDI category contain the reactive NCO group on all constituents, and therefore a similar toxicokinetic response is indicated. In vitro GSH reactivity studies show similar qualitative and quantitative reaction profiles of the mMDI isomers when alone (i.e. in mono-constituent monomeric MDI) or as part of UVCB substances (pMDI, 4,4’-MDI homopolymer and 4,4’-MDI/DPG/HMWP). GSH adducts with non-monomeric MDI constituents were not identified and is attributed to precipitation of these constituents. These results and underlying mechanism clearly demonstrate that all substances of the MDI category are not expected to be mutagenic and is supported by Ames testing using several substances of the MDI category which all give negative responses. Taken together, the available data indicate that MDI substances lack genotoxic potential both at the site of contact and systemically and is consistent with the overall hypothesis that effects are driven by the toxicokinetic activities at the site of contact. Specifically for mutagenicity, this mechanism is reflected by a) the reactive NCO groups on the MDI substances is unavailable in the cell cytosol and MDI-adducts have not been found to be reactive with DNA either with cells at the site of contact (BALC) or systemically (bone marrow and blood cells), and b) absorption and metabolism of MDI substances occurs without detectable formation of the mutagenic diamine (MDA). As reactive NCO groups are a common feature of all substances of the MDI category, it is predicted that these have a similar reactivity profile with GSH and proteins and not available to react with DNA. Therefore, all category substance are not classified for genotoxicity according to EU GHS 1272/2008 CLP.
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