TTC concept: Non-oral routes and influence of local effects

The Threshold of Toxicological Concern (TTC) concept developed generic human threshold values by grouping compounds into three structural groups (Cramer et al., 1978). The present thresh-olds for non-genotoxic compounds were derived based on the 5thpercentile NOEL (no observed effect level) of a broad database containing in vivo studies with oral exposure (Munro et al., 1996).Route to route extrapolation is a difficult topic in human health risk assessment. Especially the evaluation of local effects, which frequently occur after inhalation but rarely after oral exposure is a difficult topic. It is therefore of interest to determine the conditions under which the TTC concept can be applied to assess toxicity for non-oral exposure i.e. inhalation or dermal. In this lecture recent results on TTC values for inhalation exposure will be introduced and strength and limitations discussed (Carthew et al., 2009; Escher et al., 2010, CEFIC LRI-B8). Further an overview on recent TTC approaches for dermal exposure will be given (www.cosmostox.eu).