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. 2020 Feb 24;19:23. doi: 10.1186/s12940-020-00578-x

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© The Author(s) 2020

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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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)