Toxicity of binary mixtures of copper, lead, and glyphosate on neuronal cells

Abstract

Regulations for contaminants are primarily based on isolated exposures to an individual toxicant. This practice does not account for interactions that may happen between toxicants. The assessment of chemical mixtures ought to be routinely studied to better understand the risks to human health, yet no standard protocol exists. This study provides a framework focusing on the complex interactions between individual chemical toxicants and how that can affect a potential regulatory shift. The work evaluates the binary exposures of environmental contaminants, lead(II) acetate, copper(II) nitrate, and glyphosate, against a neuronal brain cell model (SH-SY5Y) by comparing the concentration addition (CA) model to experimental cytotoxicity values. Binary mixture effects were identified and interpreted using the interaction index and isobologram. Isobolograms were developed to visualize the comparative data. Against the concentration addition model, the EC50 values of binary mixtures composed of copper-lead and EC50 values of binary mixtures of copper-glyphosate showed antagonistic responses with interaction indices greater than one. The EC50 values of binary mixtures composed of lead-glyphosate produced additive effects with an interaction index within the 95% confidence interval of one. These results, along with mechanism elucidations, illustrate the complexity of mixture toxicology and the need for further studies emphasizing comparisons between prediction modeling and experimental results.