Short-chain PFAS - Alarming circadian disruptors?

Overview

Project Summary

SPARK project will answer to the question: “Are Per- and polyfluoroalkyl substances (PFAS) circadian disruptors?”. Currently, the research regarding emerging contaminants as circadian disruptors is very scarce. However, some works have given cues that the persistent PFAS can disrupt the circadian rhythm and cause sleep disturbances or other associated diseases such has metabolic diseases.
The circadian rhythm coordinates several processes in the body including temperature, sleepiness and metabolic activity. Several circadian clocks are present in the human body, the main clock in the hypothalamus and several peripheral clocks in other organs. These clocks can be influenced by several environmental cues, for example light. The disruption of the circadian rhythm will have a detrimental impact on the organisms and is associated with several disorders such as metabolic and neurological diseases. Recent reports show evidence that some environmental contaminants can disrupt the circadian rhythm and possible contribute to the development of associated diseases. The SPARK project will evaluate if short-chain PFAS belong to circadian disruptors group.
PFAS are a group of chemicals widely used, already detected in human blood and in Portuguese river waters. The so-called “Long-chain” PFAS, such as Perfluorooctanoicacid (PFOA) and Perfluoroctane sulfonic acid (PFOS) were included in the Persistent Organic Pollutants (POPs) list in the Stockholm Convention and their use is now restricted. However, this restriction prompted the industry to switch to non-regulated short-chain PFAS.
Although the information regarding the effects of these short-chain PFAS is scarce, their persistence and the concerns regarding their adverse effects in the human health granted their entry in the class “Substances of Very High Concern” of the European Chemical Agency. The uncertain toxicity levels of the short-chain PFAS set off a debate concerning the regulation of PFAS as a group or individually. While the debate takes place, these compounds continue to be used, to reach our ecosystems and even our plate and glass. Therefore, it is urgent to understand the extent PFAS impact in human health, including to understand the ability of these compounds to act through the disrupt of circadian rhythm.
SPARK project brought together a multidisciplinary team to evaluate the potential of short-chain PFAS detected in the Portuguese river waters to disrupt circadian rhythm in humans. Several members of SPARK team have a profound knowledge regarding circadian disruption in humans and the associated diseases, while other members are experts in emergent contaminants.
SPARK project will use synchronized hypothalamic neurons exposed to a range of short-chain PFAS at relevant concentrations to evaluate alteration in circadian rhythm characteristics, such as period length, phase, and amplitude. The possible degradation and the internalization of PFAS by the cells will also be measured. An omics approach will be used to have a broader picture of the effects of short-chain PFAS in hypothalamic neurons.

Main Goals

i. Identification of the circadian disruptor potential of short-chain PFAS;
ii. Data regarding internalization of PFAS by hypothalamic neurons for future toxicokinetic studies;
iii. Identification of the pathways affected by the selected short-chain PFAS;
iv. Increase public awareness regarding PFAS exposure routes and risks by organizing dissemination actions.

Project Details