The threshold of toxicological concern has been suggested as a decision rule on whether a mixture risk assessment is required. According to the recent opinion on mixture toxicity, published by the EU scientific committees, mixture effects are not to be expected, if the mixture components do not share the same mode or mechanism of action and are present at or below their individual TTCs. This, however, ignores the statistical error propagation that is encountered when handling multi-component chemical mixtures, which results in a huge probability that one or more mixture components are de facto more toxic than estimated by the corresponding TTC. It is hence argued that the TTC is a valuable tool to bridge data gaps in case experimental toxicity data are missing, but it is unsuited without further refinement as a decision criterion on whether a mixture assessment is needed in a given exposure scenario.
The Threshold of Toxicological Concern Concept in Risk Assessment