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TTC: A new concept for inhalation exposure

: Tluczkiewicz, Inga; Batke, Monika; Kühne, Ralph; Schüürmann, Gerrit; Mangelsdorf, Inge; Escher, Sylvia

Naunyn-Schmiedebergs archives of pharmacology 387 (2014), Supplement 1, pp.S37, A144
ISSN: 0028-1298
ISSN: 1432-1912
Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie (Annual Meeting) <80, 2014, Hannover>
Journal Article, Conference Paper
Fraunhofer ITEM ()

The threshold of toxicological concern (TTC) concept allocates thresholds to structural groups of compounds below which a risk for human health is not assumed. The current TTC concept is based on in vivo data with oral exposure and may not be appropriate for toxicity after inhalation exposure e.g. because of route specific differences. We present an integrative approach to derive threshold values for inhalation exposure. They are based on a dataset of 296 chemicals with repeated-dose toxicity studies ( Systemic and local NOEC values were discriminated. Groups of compounds with specific structural features (SF) were identified by using atom centered fragments. Few SF were explicit for local or systemic activity indicating that this mode of action is not a determining factor. The structural and toxicological boundaries of the initial SFs were further evaluated considering differences in absorption, mechanism/metabolism and sensitive targets/effects observed in the in vivo studies. 28 SF groups resulted: 9 low (L) and 19 toxic (T) groups. About 20% of the compounds are, however, not yet grouped. Compared to the Cramer classes the T and L-groups better discriminate low toxic versus toxic compounds. Two clearly distinguished TTC values are proposed. This project has been funded by the Cefic LRI ( up date.pdf).