216 Exposure Based Adaptation As an Application of Inhalation TTC Values

Abstract The European regulation on Registration, Evaluation and Authorization of Chemicals (REACH) requires generation of information on the intrinsic properties (including hazard) of registered substances depending on their tonnage. In situations where human or environmental exposure is absent or not significant, exposure-based adaptation (EBA) may be considered. EBA comprises all types of modifications of the standard information requirements, of which the exposure based waiving (EBW) is an option that allows to waive higher tier mammalian toxicity studies. In order to justify for a defined endpoint the omission of the standard information requirement, a high level of confidence is needed to demonstrate no or no significant exposure. Thresholds for toxicological concern (TTC) are used to decide on acceptable oral intakes. This concept has recently been expanded to inhalation route of exposure. These values can easily be converted in inhalation exposure levels or vapour pressures below which no concern exist. These cut off criteria provide the basis for robust science-based EBA justifications and can be used to identify the most relevant exposure route(s) for new testing proposals. Even though, this approach is more challenging for dermal uptake iTTC values can be used together with PBK modelling and dermal uptake to calculate maximal external exposure concentrations below which human exposure is considered safe, and which can be applied for exposure-based waiving.