Non-stick Nemesis: molecular origins of PFAS toxicity
PFAS (Per- and polyfluroalkyl substances) are a large group of synthetic compounds with a common molecular component consisting of chains of carbon atoms bonded to fluorine[1]. The comparatively high strength of the carbon-fluorine bond renders PFAS extremely resistant to thermal or metabolic degradation, enabling them to persist in the environment long after disposal. Due to their ability to achieve high levels of water- and oil-repellence, they are routinely applied to “non-stick” cookware, “stain-repellent” fabrics, and have more recently been used to improve moisture resistance in “biodegradable” food packaging[2].
Ingestion and bioaccumulation of PFAS is linked to a host of health issues both in laboratory, environmental and human population studies, including cancers, thyroid disease, altered sex hormone levels, reduced kidney function and lower birth weight in babies[2]. These effects have prompted thousands of lawsuits and multi-billion dollar settlements in US courts[3].
Water testing in Australia, Europe, China and North America has shown these regions to be “hot-spots” for PFAS contamination[2]. The majority of sampling locations in Australia indicated a toxin concentration of greater than the EU safety limit of 100 nanograms per litre.
The wide variety of chemicals in the PFAS family and the broad range of associated health impacts complicate attempts to understand the direct molecular origins of toxicity[4].
Common PFAS precursors have a molecular structure consisting of a hydrophilic chain (containing the Carbon-Fluorine bonds) attached to a hydrophillic group.The combination of hydrophilic and hydrophobic properties is what makes many PFAS such effective cleaning agents.
The hydrophobic section of the molecule will be attracted to grease or oil whilst the hydrophilic section will stabilise the formation of oil droplets suspended in the surrounding water. This is the same mechanism by which soaps and other detergents work, though these are typically non-fluorinated and more susceptible to degradation over time.
Whilst the properties of PFAS are optimal in the laundry or industry, they are more than problematic in the biosphere.
Biological cells are bound by a phospholipid membrane, which also consists of molecules containing hydrophilic and hydrophobic sections.
This similarity between the molecular structure of PFAS and phospholipids means that PFAS will insert into the membrane, altering its physical properties to become more fluid and permeable[6]. This disruption of the cellular membrane is one potential basis for the observed relationship between PFAS ingestion and negative health impacts.
The other major route by which PFAS is thought to impact biological processes is due it is ability to disrupt regular protein function. Proteins are the workhorse for all aspects of cellular activity (e.g. signalling, metabolism, transport etc) and contain binding sites where smaller molecules can attach.
One molecular route that has been identified to explain how PFAS results in immune system disorders is via attachment to nuclear receptor proteins[7]. Nuclear receptors are bind hormones and other small molecules and subsequently activate the expression of particular genes.
Various PFAS compounds have been shown to bind to nuclear receptors, altering the rates at which different genes are expressed, which can lead to cellular malfunction and/or cellular death.
Disturbingly, many modern PFAS alternatives have demonstrated higher affinity to proteins [7] than the legacy products they were designed to replace. It has also been found that the presence of specific proteins in the placenta means that there is potential for higher PFAS concentrations on the fetal side compared to that of the mother[8].
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Extreme environmental persistence[9], combined with ongoing uncontrolled disposal of both legacy and novel PFAS compounds [10], means that adverse effects are likely to become more severe, complex and intractable.
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