Assessing the toxic effects of complex mixtures is a challenging task in both experimental design and interpretation of results.Various standards are available to guide the study of contaminant co-exposure related to drinking water hazards in human cell models. Since exposure to more than one chemical substance occurs after ingestion of contaminated water, more data is needed to aid in safety assessment of complex mixtures related to human health effects. Copper and lead ions in drinking water are regulated by the U.S. EPA at 1.3 ppm and 15 ppb, respectively. Glyphosate, the key ingredient in many broad range pesticides, is detected at measurable levels in water and is ingested through drinking water and consumption of crops. We developed dose-response curves and utilized concentration addition models to build isobolograms to assess the synergistic effects of copper, lead, and glyphosate binary and tertiary mixtures in a newly developed human neuronal cell model that mimic adult neuronal phenotype <i>in vivo</i>. Data shows that depending on composition and concentration, health effects of simultaneous exposure to more than one species at a time can be tabulated as additive, antagonistic, or synergistic as compared to the health effects seen after exposure to individual chemical moieties. Our results show that copper plus lead and copper plus glyphosate induced an antagonistic effect in cells (as measured by cell viability over a wide dose range). Interestingly, exposures to lead plus glyphosate induced an additive effect as compared to individual chemical inoculations. Tertiary mixtures of copper, lead, and glyphosate were also studied and results indicate an induced synergistic effect, but is strongly dependent upon molar ratios of the three individual chemicals. The 2D isobologram was expanded to a third dimensional analysis. Interactions were compared to a plane of additivity to identify synergistic effects of the tertiary mixtures. Inductively coupled plasma mass spectrometry was used to quantify metal uptake and reactive oxygen species production was measured in both cell and cell-free conditions to postulate oxidative stress induced inflammatory response. Further studies will focus on gene and protein expressions related to single, binary, and tertiary chemical exposures. This data not only adds value to the water quality and safety literature, but also presents a systematic method to assess complex mixtures in a routine and high-throughput fashion.

Chemical transformations and toxicological effects of binary and tertiary mixtures of copper, lead, and glyphosate drinking water contaminants using a neuronal cell model

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.