The applicability of DFT -based descriptors for the development of toxicological structure - activity relationships is assessed. Emphasis in the present study is on the quality of DFT -based descrip- tors for the development of toxicological QSARs and, more specifically, on the potential of the electrophili - city concept in predicting toxicity of benzidine derivatives and the series of polyaromatic hydrocarbons (PAH) expressed in terms of their biological activity data ( pIC50). First, two benzidine deriv atives, which act as electron -donating agents in their interactions with biomolecules are considered. Overall toxicity in general and the most probable site of reactivity in particular are effectively described by the global and local electrophilicity parameters re spectively. Interaction of two benzidine derivatives with nucleic acid (NA) bases/selected base pairs is determined using Parr's charge transfer formula. The experimental bi o- logical activity data ( pIC50) for the family of PAH, namely polychlorinated dibenz ofurans (PCDF), poly- halogenated dibenzo-p-dioxins (PHDD) and polychlorinated biphenyls (PCB) are taken as dependent variables and the HF energy (E), along with DFT-based global and local descriptors, viz., electrophilicity index (ω) and local electrophilic power (ω + ) respectively are taken as independent var iables. Fairly good correlation is obtained showing the significance of the selected descriptors in the QSAR on toxins that act as electron acceptors in the presence of biomolecules. Effects of populatio n analysis schemes in the cal- culation of Fukui functions as well as that of solvation are probed. Similarly, some electron -donor ali- phatic amines are studied in the present work. We see that global and local ele ctrophilicities along with the HF energy are adequate in explaining the toxicity of several substances, both electron donors or a c- ceptors when they interact with biosystems, in gas as well as solution phases.