Year of Publication
2023
College
Public Health
Date Available
4-27-2025
Degree Name
Master of Public Health (M.P.H.)
Committee Chair
Erin Haynes, DPH
Committee Member
Anna Hoover, PhD
Committee Member
Florence Fulk, PhD
Abstract
Introduction
A broad category of synthetic organic compounds, per- and polyfluorinated alkyl substances (PFAS), forms the impetus for this project. Known compounds in this category are numerous and diverse, with over 4700 identified molecular entities (Panieri, Baralic, Djukic-Cosic, Buha Djordjevic, & Saso, 2022). Their only commonality is the presence of at least one carbon atom that is saturated with fluoride groups. These chemical bonds are exceptionally difficult to break (Tansel, 2022), which incepts both the utility of PFAS compounds and the concerns they raise for human health (Cousins et al., 2020). While PFAS are best known for their use in fire-retardant clothing and non-stick coating for cooking equipment, over 200 different use categories and subcategories have been identified, including PFAS in ammunition, artificial turf, and guitar strings (Glüge et al., 2020). Because there are many PFAS compounds that overlap in terms of structure and effects, it has been argued that it is more appropriate to consider PFAS as a category for scientific and regulatory purposes rather than focusing on individual molecular entities (Kwiatkowski et al., 2020).
PFAS Exposure
PFAS compounds degrade slowly, if at all, and are thus described as “forever chemicals” (National Academies of Sciences et al., 2022). They tend to bioaccumulate in aquatic environments (Lewis et al., 2022). PFAS have also been noted in air (Faust, 2022; Zhou et al., 2021) and soil (Brusseau, Anderson, & Guo, 2020) in areas without obvious sources of contamination. While people who work in industrial settings have a high risk of PFAS exposure (Lucas, Gaines, Paris-Davila, & Nylander-French, 2022), extensive literature has documented PFAS in human organs and tissues in the general population (Jian et al., 2018). While there are multiple routes of exposure, dietary intake, particularly drinking water (Domingo & Nadal, 2019), is believed to be the primary mode of PFAS bioaccumulation, but inhalation and dermal absorption may also be relevant contributors (De Silva et al., 2021). Because PFAS do not degrade naturally, chemical and mechanical processes have been developed to destroy PFAS compounds in water, but these are expensive and can lead to toxic breakdown products (Meegoda, Bezerra de Souza, Casarini, & Kewalramani, 2022). At present, PFAS compounds are part of human life.
PFAS and Human Health
The bioactivity of PFAS substances is an area of emerging research. The best documented ligand-receptor interactions are with nuclear receptors (Bjork, Butenhoff, & Wallace, 2011). However, the lipophilic properties of most PFAS substances may cause them to exert nonspecific effects through the disruption of lipid cell membranes (Fenton et al., 2021).
In humans, PFAS exposure shows evidence of immunosuppression, producing a lasting deficit in antibody response to vaccination (Grandjean et al., 2017) and high exposure has been associated awith an increased rate of infections in children (Goudarzi et al., 2017). Some evidence suggests PFAS exposure may positively or negatively affect risk for asthma and atopic conditions, though this appears to vary among common PFAS compounds and some variation by the sex of the child has also been noted (Kvalem et al., 2020).
Thyroid disease is largely autoimmune in nature, and multiple PFAS compounds have been associated with hypothyroidism (Lee & Choi, 2017). Biomarkers of liver cell damage have been noted to be positively associated with various PFAS compounds (Bassler et al., 2019; C. Y. Lin et al., 2010). The effects of PFAS on clinical liver disease are less well established, though one study did find an association between PFAS exposure and progression of nonalcoholic fatty liver disease in children (Jin et al., 2020).
Substantial literature documents an association between PFAS compounds and blood lipid levels (P. D. Lin et al., 2019; Liu et al., 2020), and clinical dyslipidemia has been reported as the best-established metabolic effect of PFAS compounds (Sunderland et al., 2019). PFAS have been reported as nephrotoxicants (Zhao, Hinton, Chen, & Jiang, 2020), but poor kidney function may also result in reduced clearance (Dhingra, Winquist, Darrow, Klein, & Steenland, 2017), suggesting a bidirectional relationship. PFAS have also been associated with increased risk of kidney cancer (Stanifer et al., 2018) and testicular cancer (Steenland & Winquist, 2021). PFAS can affect the placenta and have been associated with a variety of perinatal health outcomes (Blake & Fenton, 2020). Given that existing studies typically focus on individual compounds, new data analysis techniques are needed to elucidate effects of the thousands of compounds in this family (Rosato et al., 2022).
Health Communication
The diversity and ubiquity of PFAS compounds, their myriad effects on human health, and the uncertainty of still-evolving research in this area pose significant communication challenges. Health communications directed towards the public have been criticized for failing to convey the level of evidence surrounding different health claims and failing to suggest actions that could be taken by affected people (Ducatman, LaPier, Fuoco, & DeWitt, 2022). In addition, the uncertain legal status surrounding PFAS under environmental health law creates confusion (Langenbach & Wilson, 2021).
For clinicians, the Agency for Toxic Substances and Disease Registry (ATSDR) operating under the Centers for Disease Control and Prevention (CDC) has released guidance on PFAS (ATSDR, 2019). In a report released by the National Academies of Sciences, Engineering, and Medicine (NASEM) (National Academies of Sciences et al., 2022), this guidance has been criticized for imprecise use of terminology, failing to tailor information towards end-users, and lacking a protocol for update given the rapidly emerging evidence.
This manuscript offers a revised and updated clinical guidance document based on updated scientific literature and health communication principles. A revision based on clinical review is presented, and implications for the field of environmental health are discussed.
Recommended Citation
Bingham, John, "PFAS Clinical Guidance" (2023). Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.). 384.
https://uknowledge.uky.edu/cph_etds/384
