Superfund Research Program

October 2023

Hot Publication

Exposure to lead mixtures with other chemicals can impair mitochondrial function, according to Duke University SRP Center researchers. Mitochondria, special compartments found in the cells of most organisms, play a large role in energy production and metabolism. While it is known that lead can disrupt mitochondrial function by replacing calcium in cellular processes, there has not been much research on co-exposures with other environmental contaminants.

Lead was historically used in paint, gasoline, and water distribution systems. While the use of lead in paint and gasoline is now banned, and lead service lines are being phased out, people can still be exposed from the paint of older homes, older water distribution lines, and some industrial processes. There is no safe exposure level for lead in children, as it is known to affect neurodevelopment and is associated with behavioral disorders.

To understand the mechanisms of lead toxicity on mitochondria, the scientists exposed human liver cells to lead alone and in mixtures with the compounds carbonyl cyanide-p-tri-fluoromethoxyphenylhydrazone (FCCP) and Ruthenium Red (RuRed) — which are representative of other environmental chemicals that can damage mitochondria. Then, they established dose response curves for lead, lead and FCCP, lead and RuRed, and a combination of the three chemicals together.

Results showed that exposure to a combination of FCCP and RuRed without lead was not toxic to cells. However, nontoxic levels of lead became more toxic when cells were exposed to combinations of lead and FCCP and lead, FCCP, and RuRed. This suggests that FCCP and RuRed, while not toxic on their own, increase lead toxicity.

According to the authors, these findings suggest that studying exposures to mixtures has increasing importance as contaminants continue to interact both in the environment and within the human body.

To learn more, please refer to the following sources:

  • Lalwani P, King DE, Morton KS, Rivera NA, Huayta J, Hsu-Kim H, Meyer JN. 2023. Increased cytotoxicity of Pb2+ with co-exposures to a mitochondrial uncoupler and mitochondrial calcium uniporter inhibitor. Environ Sci Process Impacts doi:10.1039/d3em00188a PMID:37503664