(1), (2), (3), (4) and (5) is shown. The average IC50 obtained with CA and IA are: 0.21 and 0.18 μM for 20MUS–80VER; 0.076 and 0.071 μM for 50M–50V; and 0.049 and 0.045 μM 80MUS–20VER, respectively. With the exception of 20MUS–80VER, the predicted results are lower than what was calculated from the experimental fit. In this case CA and IA produce nearly identical results. Fluoxetine acts on the serotonergic system by inhibiting the serotonin (5-HT) reuptake thus enhancing BMS354825 its effect on the central

nervous system. Using the fitted curves from FLU and MUS we have compared the predicted CA and IA mixture toxicity with the experimental values. The bottom of Fig. 9 shows the results obtained for the three curves using

fitted Morgan-Mercier Flodin curves for the pure compounds, whereas on the top, the fitting of the experimental MLN0128 mouse data using Eqs. (1), (2), (3), (4) and (5) is shown. The average IC50 values obtained with CA and IA are: 0.18 and 0.16 μM for 20MUS–80FLU; 0.076 and 0.071 μM for 50MUS–50FLU; and 0.049 and 0.045 μM 80MUS–20FLU, respectively. With the exception of 20MUS–80FLU, the predicted results are lower than the fitted experimental data, implying that the real toxicity is lower than the calculated one applying additivity. In this case CA and IA produce nearly identical results. Kainic acid is a specific agonist Chlormezanone for the ionotropic glutamate receptor and mimics the effect of glutamate, the major excitatory neurotransmitter of the central nervous system (Moloney, 2002). Therefore, together with Muscimol, it provides a good set of compounds to study binary mixtures where the two compounds have opposite effects (excitatory for kainic acid and inhibitory for Muscimol) and a different mode of action. Using the fitted curves from the pure compounds we have compared the predicted CA and IA mixture toxicity with the experimental values. The bottom of Fig. 10 shows the results obtained for the three mixtures using fitted Box–Cox transformed Weibull curves for the pure compounds, whereas on the

top, the fitting of the experimental data using Eqs. (1), (2), (3), (4) and (5) is shown. The IC50 obtained with CA and IA are: 0.19 and 0.17 μM for 20MUS–80KAI; 0.075 and 0.071 μM for 50MUS–50KAI; and 0.048 and 0.045 μM 80MUS–20KAI, respectively. With the exception of 20MUS–80KAI where the results are within the range of experimental variability, the predicted results are lower that the fitted experimental data, implying that the real toxicity is lower than the calculated using additivity. Also in this case, CA and IA produce nearly identical results. Neurotoxicity assessment represents a major challenge within the mixtures context, because regulatory testing guidelines rely exclusively upon in vivo observations (see U.S.