Aquatic toxicity integrated testing and assessment strategies (ITS) for difficult substances: case study with thiochemicals

Abstract

Background: An Integrated Testing and Assessment Strategy (ITS) for aquatic toxicity of 16 thiochemicals to be registered under REACH revealed 12 data gaps, which had to be filled by experimental data. These test results are now available and offer the unique opportunity to subject previous estimates obtained by read-across (analogue and category approaches) to an external validation. The case study thiochemicals are so-called difficult substances due to instability and poor water solubility, challenging established ITS. Results: The new experimental data confirm the previous predictions of acute aquatic toxicity with the new test results indicating a 2–5 times lower toxicity than previously predicted. The previous predictions thus are conservative and close to the new experimental results. The good agreement can be attributed to the fact that we had limited the extrapolations to narrow chemical groups with similar SH-group reactivities. The new experimental data further strengthen and externally validate the existing trends based on similarity in chemical structures, mode of action (MoA), water solubility and stability of source and target compounds in aquatic media. Based on the new experimental data, reliable revised PNECs could be derived and the REACH requirements for these thiochemicals are largely fulfilled. Appropriately adapted ITS are therefore able to reduce in vivo tests with fish even for difficult substances and replace them with alternative information. Conclusions: Both experimental and alternative information for difficult substances such as thiochemicals that are rapidly transformed in water are subject to considerable uncertainty. For example, the use of either nominal, initial or time-weighted average concentrations contributes to the variability of aquatic toxicity data. In the case of these thiochemicals, a weight-of-evidence (WoE) approach to determining aquatic toxicity based on nominal and time-weighted average concentrations may be the most appropriate choice to reflect environmental conditions. Overall, uncertainties in historical test results and alternative information, here from read-across, have to be considered in relation to how much uncertainty is acceptable for environmental protection on the one hand and how much certainty is technically feasible on the other.