Degree of Uptake and Accumulation of Perfluorinated Alkyl Acids Drives Their Toxicity
Long-chain perfluorinated alkyl acids (PFAA) are currently substituted by short-chain variants based on the view that these are less toxic. This study shows that the toxic potency of short-chain and long-chain PFAA may be similar and that the key factor is the uptake and accumulation in the body, independent of the chain length.
Perfluorinated alkyl acid carboxylates and sulfonates (PFAA) are a group of persistent organofluorine chemicals that have been broadly used in commercial and industrial products (e.g., surfactants, fluorinated polymers, coatings, fire-resistant foams). Several studies show that PFAA may cause multiple adverse health effects, such as toxicity to the liver, immune system, developing foetus, nervous system, reproductive system etc. Many different PFAA have been detected in serum samples in humans worldwide and relative levels of PFAA found in autopsy tissues (i.e., liver, kidney, lung, brain, bone) indicate that the distribution of these chemicals in the human body varies depending on their chemical properties such as chain lengths and functional groups. Short-chain PFAA are believed to be less toxic compared to long-chain PFAA which has led to replacement of the long-chain PFAA to ones with shorter chain. Still, how their fate in the human body, so called toxicokinetic processes (absorption, biotransformation, distribution and excretion of a chemical), differ depending on chemical properties are poorly understood. These toxicokinetic processes are important to study as they increase our understanding of how chemicals affect human health.
The aim of the study was to describe and compare the toxicokinetic profiles for four PFAA (PFOS, PFHxS, PFOA, PFBA) with different chain lengths (4, 6, 8) and functional groups (sulfonic and carboxyl acid) in zebrafish embryo. To this end, the time courses of the external (ambient water) and internal concentrations were determined over time at three exposure concentrations. Three of the four PFAA showed a slow chemical uptake before hatching, suggesting that the chorion, which surrounds the embryo, functions as uptake barrier until they hatch.
Further investigation was carried out regarding the impact of the toxicokinetic differences on the toxicity of the PFAA. When comparing the toxicity to internal dose of respective PFAA instead of comparing the toxicity to ambient dose, the difference in toxic potency between the PFAA was reduced from 3000-fold to 3-fold. Altogether, the results show that most of the differences in toxicity between the four PFAA can be explained by their variability of the toxicokinetics and that the toxic potency of short-chain and long-chain PFAA may be similar when accounting for the differences in uptake and accumulation.
Carolina Vogs, Gunnar Johanson, Markus Näslund, Sascha Wulff, Marcus Sjödin, Magnus Hellstrandh, Johan Lindberg, and Emma Wincent.
Toxicokinetics of Perfluorinated Alkyl Acids Influences Their Toxic Potency in the Zebrafish Embryo (Danio rerio).
Environ. Sci. Technol., 2019, 53 (7), pp 3898–3907.