Biomimetic insights into toxicokinetics and health risks of organic environmental pollutants

Insufficient monitoring of organic pollutants, including pharmaceuticals and pesticides, has led to their increasing presence in aquatic environments, raising concerns regarding long-term ecological and human health risks. Reliable tools for predicting the toxicokinetic behaviour and potential health outcomes of such contaminants are therefore needed. In this study, biomimetic human serum albumin (HSA) chromatography combined with in silico ADMET modeling was applied to evaluate the toxicokinetic and toxicological profiles of selected organic environmental pollutants. HSA chromatography was selected as a physiologically relevant model due to the key role of albumin in compound transport, distribution, and bioavailability in human plasma. Chromatographic experiments were performed under physiological conditions (pH 7.0) using an HSA column with varying acetonitrile contents (15–4.5%), enabling modulation of interaction strength between analytes and the protein. Obtained retention parameters were correlated with predicted ADMET and toxicity descriptors generated using the ADMETlab platform. A strong linear relationship (r > 0.95) between retention behaviour and mobile phase composition indicated that reversed-phase interactions dominate compound binding to HSA. At 6% acetonitrile, significant correlations (r > 0.80) were observed between HSA retention parameters and key toxicokinetic and toxicological endpoints, including lipophilicity, Caco-2 permeability, human intestinal absorption, volume of distribution, BBB and CNS permeability, clearance, LD₅₀, LOAEL, and aquatic toxicity. The investigated hydrophilic β-lactam antibiotics (penicillins and cephalosporins) exhibited high water solubility, low lipophilicity, high polarity, and poor membrane permeability, resulting in limited intestinal absorption, negligible BBB penetration, and restricted systemic exposure. In contrast, organophosphate pesticides showed high intestinal absorption, broader tissue distribution, and moderate to increased BBB permeability, indicating an elevated risk of systemic and neurotoxic effects, consistent with their acetylcholinesterase inhibition mechanism. The obtained results demonstrate that hydrophobicity-driven albumin interactions can effectively simulate biological behaviour, supporting biomimetic HSA chromatography as a robust screening tool for predicting toxicokinetic outcomes and human health risks associated with organic environmental pollutants.