Toxicokinetic-toxicodynamic (TKTD) models quantify the time-course of internal concentration, which is defined by uptake, elimination and biotransformation (TK), and the processes which lead to the toxic effects (TD). TKTD models show potential in predicting pesticide effects in fluctuating concentrations, but the data requirements and validity of underlying model assumptions are not known. We calibrated TKTD models to predict survival of Gammarus pulex in propiconazole exposure and investigated the data requirements. In order to assess the need of TK in survival models, we included or excluded simulated internal concentrations based on pre-calibrated TK. Adding TK did not improve goodness of fits. Moreover, different types of calibration data could be used to model survival, which might affect model parameterization. We used two types of data for calibration: acute toxicity (standard LC50, 4 d) or pulsed toxicity data (total length 10 d). The calibration data set influenced how well the survival in the other exposure scenario was predicted (acute to pulsed scenario or vice versa). We also tested two contrasting assumptions in ecotoxicology: stochastic death and individual tolerance distribution. Neither assumption fitted to data better than the other. We observed in 10-d toxicity experiments that pulsed treatments killed more organisms than treatments with constant concentration. All treatments received the same dose, i.e. the time-weighted average concentration was equal. We studied mode of toxic action of propiconazole and it likely acts as a baseline toxicant in G. pulex during 10-days of exposure for the endpoint survival.Electronic supplementary materialThe online version of this article (doi:10.1007/s10646-012-0917-0) contains supplementary material, which is available to authorized users.

In 2013 the Organisation for Economic Co-operation and Development (OECD) test guideline (236) for fish embryo acute toxicity (FET) was adopted. It determines the acute toxicity of chemicals to embryonic fish. Previous studies show a good correlation of FET with the standard acute fish toxicity (AFT) test; however, the potential of the FET test to predict AFT, which is required by the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH) regulation (EC 1907(EC /2006) and the Classification, Labelling and Packaging (CLP) Regulation (EC 1272/2008), has not yet been fully clarified. In 2015 the European Chemicals Agency (ECHA) requested that a consultant perform a scientific analysis of the applicability of FET to predict AFT. The purpose was to compare the toxicity of substances to fish embryos and to adult fish, and to investigate whether certain factors (e.g., physicochemical properties, modes of action, or chemical structures) could be used to define the applicability boundaries of the FET test. Given the limited data availability, the analysis focused on organic substances. The present critical review summarizes the main findings and discusses regulatory application of the FET test under REACH. Given some limitations (e.g., neurotoxic mode of action) and/or remaining uncertainties (e.g., deviation of some narcotic substances), it has been found that the FET test alone is currently not sufficient to meet the essential information on AFT as required by the REACH regulation. However, the test may be used within weight-of-evidence approaches together with other independent, relevant, and reliable sources of information. The present review also discusses further research needs that may overcome the remaining uncertainties and help to increase acceptance of FET as a replacement for AFT in the future. For example, an increase in the availability of data generated according to OECD test guideline 236 may provide evidence of a higher predictive power of the test. Environ Toxicol Chem 2018;37:657-670. C 2017 SETAC

If an organism does not feed, it dies of starvation. Even though some insecticides which are used to control pests in agriculture can interfere with feeding behavior of insects and other invertebrates, the link from chemical exposure via affected feeding activity to impaired life history traits, such as survival, has not received much attention in ecotoxicology. One of these insecticides is the neonicotinoid imidacloprid, a neurotoxic substance acting specifically on the insect nervous system. We show that imidacloprid has the potential to indirectly cause lethality in aquatic invertebrate populations at low, sublethal concentrations by impairing movements and thus feeding. We investigated feeding activity, lipid content, immobility, and survival of the aquatic arthropod Gammarus pulex under exposure to imidacloprid. We performed experiments with 14 and 21 days duration, both including two treatments with two high, one day pulses of imidacloprid and one treatment with a low, constant concentration. Feeding of G. pulex as well as lipid content were significantly reduced under exposure to the low, constant imidacloprid concentration (15 µg/L). Organisms were not able to move and feed – and this caused high mortality after 14 days of constant exposure. In contrast, feeding and lipid content were not affected by repeated imidacloprid pulses. In these treatments, animals were mostly immobilized during the chemical pulses but did recover relatively fast after transfer to clean water. We also performed a starvation experiment without exposure to imidacloprid which showed that starvation alone does not explain the mortality in the constant imidacloprid exposure. Using a multiple stressor toxicokinetic-toxicodynamic modeling approach, we showed that both starvation and other toxic effects of imidacloprid play a role for determining mortality in constant exposure to the insecticide.