Considerations for toxicity experiments and risk assessments with PFAS mixtures

Abstract

Per‐ and polyfluoroalkyl substances (PFAS) have been around for decades and have been the subject of laboratory and field research studies for nearly as long. Although attention to PFAS has grown in recent years, many unanswered questions remain. Accordingly, the number of research projects designed to improve our understanding of PFAS toxicity, bioaccumulation, and biomagnification, and to improve our ability to predict the interactions of PFAS mixtures, is also increasing. The growing number of ongoing and future research projects focusing on these chemicals will benefit from lessons learned in previous studies. This perspectives article discusses available approaches to mixture risk assessment with specific focus on application to PFAS mixtures. We discuss ongoing research as well as lessons learned from approaches to handling mixtures of other groups of chemicals. Many of these approaches require some detailed understanding of a manageable number of representative chemicals, yet only limited toxicological data are available for most PFAS. With the limited amount of published data currently available, the need for single‐chemical and binary‐mixture studies persists. Based on our previous work with single‐chemical exposures for understudied PFAS, we explored some of the challenges of trying to design and interpret an aquatic concentration–response experiment for a binary mixture of two commonly detected PFAS: perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonic acid (PFHxS). Based on our findings, we propose that addressing risk from PFAS mixtures will likely require combinations of approaches incorporating findings from traditional whole‐organism toxicity studies and novel methods relying on in vitro assays, read‐across, or quantitative structure activity relationships. Complicating a limited understanding of PFAS mixture toxicity is that relative concentrations of PFAS mixtures vary across sites and time, even at one site. Thus, reliance on empirical data, such as site‐specific toxicity sampling or community structure studies, may be needed to fully understand potential impacts of mixtures. Integr Environ Assess Manag 2021;17:697–704. © 2021 SETAC

Potential Properties of Natural Nutraceuticals and Antioxidants in Eye Protection

“…Second of all, the total antioxidant potential of the mixture should be calculated, which is not necessarily equal to the sum of that of the individual components [252][253][254]. Finally, specific toxicity experiments should be conducted in order to demonstrate that the mixture under consideration does not cause harm in any body district [255,256]. After carrying out these preliminary tests, in vitro and in vivo tests could be carried out and, subsequently, clinical trials.…”

PFAS Molecules: A Major Concern for the Human Health and the Environment

“…Similarly, relevant concentrations of PFAS have been detected in the air [33,34], groundwater [35,36], freshwater [17,37], marinewater [38,39], drinking water [40,41] and soil [42][43][44] potentially causing ecotoxic effects in the aquatic and terrestrial ecosystems at the trophic levels of primary producers, primary consumers and secondary consumers [45,46]. An additional layer of complexity is given by the coexistence of different mixtures of PFAS substances and other contaminants in the environmental media, for which quantitative risk assessment analysis and toxicologic/ecotoxicologic information is still scarce if not absent [47,48]. Therefore, it is of utmost importance to rapidly fill the gap of scientific knowledge and to develop not only the adequate analytical methods to detect PFAS contamination and the high-throughput approaches to predict PFAS toxicity but also effective strategies of legislative regulation, remediation and therapeutic interventions to mitigate potential effects on humans and biota.…”

Chronic Reproductive Toxicity Thresholds for Northern Bobwhite Quail (Colinus virginianus) Exposed to Perfluorohexanoic Acid (PFHxA) and a Mixture of Perfluorooctane Sulfonic Acid (PFOS) and PFHxA

“…Many factors currently exist that complicate the characterization of chronic oral PFAS toxicity to avian ecological receptors at environmentally relevant concentrations and mixture ratios. For example, chemicals like PFAS that are chronically ingested at low experimental doses are probable endocrine-disrupting and carcinogenic compounds and occur in mixtures that often produce nonmonotonic, biphasic, and/or hormetic dose-response relationships that confound traditional dose-response modeling and threshold derivation (Organisation for Economic Co-operation and Development 2006;Jensen and Leffers 2008;Calabrese 2009;Buck et al 2011;Anderson et al 2016;Dennis et al 2020;Goodrum et al 2020;Temkin et al 2020;East et al 2021;McCarthy et al 2021a). In addition, findings are inconsistent for the same health endpoint among and between avian field and laboratory PFAS toxicology studies (Newsted et al 2005;Custer et al 2012Custer et al , 2014Custer et al , 2019Tartu et al 2014;Groffen et al 2019;Dennis et al 2020Dennis et al , 2021, which complicates interpretation of study results and introduces uncertainty among responses.…”