The Sum of Toxicity

Following decades of widespread use in consumer and industrial products, PFAS, better known as forever chemicals, are currently found throughout the environment and inside our bodies, typically in combination with other PFAS. And yet, until now, how they act as mixtures has been poorly understood.

It turns out they pose a much greater risk that way.

PFAS, short for per- and polyfluoroalkyl substances, are virtually indestructible—hence the name “forever chemicals.” They’re estimated to be in at least 45% of the nation’s drinking water and are in the blood of practically every American, and they have been linked to cancer and neurodevelopmental disorders.

Earlier this year, the Environmental Protection Agency issued the first-ever drinking water standards for six kinds of PFAS. However, it’s estimated that there could be more than 15,000 varieties present in the environment.

“Unfortunately, we cannot regulate other forms of PFAS until their toxicities are known,” said Diana Aga, Henry M. Woodburn Chair in the Department of Chemistry at the University at Buffalo and principal investigator of the EPA STAR grant that funded the research. “To regulate contaminants, it is crucial to know their relative potencies when they occur as mixtures in the environment, along with their predicted environmental concentrations.”

To conduct the study, researchers created two PFAS mixtures, at concentrations typically observed in ground and surface water for one and in human blood for the other. They then tested each of the mixtures on two types of cells to measure mitochondrial toxicity and neurotoxicity.

In both mixtures, PFOA, which is found in nonstick cookware and firefighting foam, caused much of the toxicity despite being present in relatively low concentrations. Similarly, PFOS, which is found in many cosmetics and in fast-food packaging, caused much more neurotoxicity in the water mixture than its concentration would suggest.

The researchers then analyzed real-world biosolids from a wastewater treatment plant and found very high toxicity despite, again, low concentrations of PFOA and other PFAS.

“This means that there are many more PFAS and other chemicals in the biosolids, which have not been identified, that contribute to the toxicity of the extracts observed,” Aga said.

On the plus side, the study showed that PFAS don’t act synergistically, i.e., their combined effect isn’t greater than the sum effect of the individual chemicals.

This means that an established “concentration addition” mixture toxicity prediction model can be used to assess the combined effect of mixtures—an important step toward eventually regulating PFAS as mixtures, which researchers say is critical to our environment and our health.