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Commercially available pesticides were examined as Mus musculus and Homo sapiens acetylcholinesterase ( m AChE and h AChE) inhibitors by means of ligand-based (LB) and structure-based (SB) in silico approaches. Initially, the crystal structures of simazine, monocrotophos, dimethoate, and acetamiprid were reproduced using various force fields. Subsequently, LB alignment rules were assessed and applied to determine the inter synaptic conformations of atrazine, propazine, carbofuran, carbaryl, tebufenozide, imidacloprid, diuron, monuron, and linuron. Afterwards, molecular docking and dynamics SB studies were performed on either m AChE or h AChE, to predict the listed pesticides' binding modes. Calculated energies of global minima ( E glob_min ) and free energies of binding (∆ G binding ) were correlated with the pesticides' acute toxicities (i.e . , the LD 50 values) against mice, as well to generate the model that could predict the LD 50 s against humans. Although for most of the pesticides the low E glob_min correlates with the high acute toxicity, it is the ∆ G binding that conditions the LD 50 values for all the evaluated pesticides. Derived pLD 50 = f (∆ G binding ) m AChE model may predict the pLD 50 against h AChE, too. The h AChE inhibition by atrazine, propazine, and simazine (the most toxic pesticides) was elucidated by SB quantum mechanics (QM) DFT mechanistic and concentration-dependent kinetic studies, enriching the knowledge for design of less toxic pesticides.