Fig. 9

Bench mark responses (BMR) for synaptogenesis. The absolute BMR of single chemicals, calculated considering the concentrations used in the mixtures ('3-Sim' in a-c, '3-Diss' in d-f, and 'All' in g-i), are plotted and compared with the absolute percentage of response experimentally observed in the mixtures for each synaptogenesis feature (normalised to control), respectively: total SYP levels (a, d, g), total PSD95 levels (b, e, h), and number of synapses (c, f, i). The orange line represents the threshold of 5%, corresponding to a Toxic Unit (TU) = 1. According to this approach, when the TU calculated on the basis of single chemical contribution is ≤1, and the percentage of response experimentally observed in the mixtures is > 1, a synergistic effect can be predicted (highlighted by solid arrows). This was observed for the following conditions: total SYP, upon treatment with 3-Sim mixture at LOAEC/2-syn (a) and 3-Diss mixture at LOAEC-syn (d); total PSD95, upon treatment with 3-Sim mixture at LOAEC-syn (b), 3-Diss mixture at LOAEC/2-syn (e), and All mixture at LOAEC-syn (h); synapses, upon treatment with 3-Diss mixture at LOAEC/2-syn (f) and with All mixture at LOAEC/2-syn (i)