PFAS mixtures more toxic than single compounds. First-of-its-kind research highlights need for change to regulation (Sep 2024) Neurotoxic Effects of Mixtures of Perfluoroalkyl Substances (PFAS) at Environmental and Human Blood Concentrations Study 

Michael Harrop

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https://www.theguardian.com/environment/2024/nov/01/pfas-mixtures-water-toxic
https://pubs.acs.org/doi/10.1021/acs.est.4c06017

Mixtures of different types of PFAS compounds are often more toxic than single chemicals, first-of-its-kind research finds, suggesting humans’ exposure to the chemicals is more dangerous than previously thought.

Humans are almost always exposed to more than one PFAS compound at a time, but regulatory agencies largely look at the chemicals in isolation from one another, meaning regulators are probably underestimating the health threat.

“Our point is that PFAS needs to be regulated as mixtures,” said Diana Aga, a study co-author with the University of Buffalo, which partnered with the Helmholtz Centre for Environmental Research in Germany.

PFAS are a class of about 15,000 compounds most frequently used to make products water-, stain- and grease-resistant. They have been linked to cancer, birth defects, decreased immunity, high cholesterol, kidney disease and a range of other serious health problems. They are dubbed “forever chemicals” because they do not naturally break down in the environment.

Abstract​

Per- and polyfluoroalkyl substances (PFAS) may cause various deleterious health effects. Epidemiological studies have demonstrated associations between PFAS exposure and adverse neurodevelopmental outcomes.

The cytotoxicity, neurotoxicity, and mitochondrial toxicity of up to 12 PFAS including perfluoroalkyl carboxylates, perfluoroalkyl sulfonates, 6:2 fluorotelomer sulfonic acid (6:2 FTSA), and hexafluoropropylene oxide-dimer acid (HPFO-DA) were tested at concentrations typically observed in the environment (e.g., wastewater, biosolids) and in human blood using high-throughput in vitro assays.

The cytotoxicity of all individual PFAS was classified as baseline toxicity, for which prediction models based on partition constants of PFAS between biomembrane lipids and water exist. No inhibition of the mitochondrial membrane potential and activation of oxidative stress response were observed below the cytotoxic concentrations of any PFAS tested. All mixture components and the designed mixtures inhibited the neurite outgrowth in differentiated neuronal cells derived from the SH-SY5Y cell line at concentrations around or below cytotoxicity. All designed mixtures acted according to concentration addition at low effect and concentration levels for cytotoxicity and neurotoxicity. The mixture effects were predictable from the experimental single compounds’ concentration–response curves. These findings have important implications for the mixture risk assessment of PFAS.
 
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