Substances that accumulate to hazardous levels in living organisms pose environmental and human-health risks, which governments seek to reduce or eliminate. Regulatory authorities identify bioaccumulative substances as hydrophobic, fat-soluble chemicals having high octanol-water partition coefficients (K(OW))(>/=100,000). Here we show that poorly metabolizable, moderately hydrophobic substances with a K(OW) between 100 and 100,000, which do not biomagnify (that is, increase in chemical concentration in organisms with increasing trophic level) in aquatic food webs, can biomagnify to a high degree in food webs containing air-breathing animals (including humans) because of their high octanol-air partition coefficient (K(OA)) and corresponding low rate of respiratory elimination to air. These low K(OW)-high K(OA) chemicals, representing a third of organic chemicals in commercial use, constitute an unidentified class of potentially bioaccumulative substances that require regulatory assessment to prevent possible ecosystem and human-health consequences.

To better understand the bioaccumulation behavior of perfluoroalkyl contaminants (PFCs), we conducted a comparative analysis of PFCs and lipophilic organohalogens in a Canadian Arctic marine food web. Concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctansulfoamide (PFOSA), and C7-C14 perfluorocarboxylic acids (PFCAs) ranged between 0.01 and 0.1 ng x g(-1) dry wt in sediments and 0.1 and 40 ng x g(-1) wet wt in biota, which was equivalent to or higher than levels of PCBs, PBDEs, and organochlorine pesticides. In beluga whales, PFOS and PFCA concentrations were higher (P < 0.05) in protein-rich compartments (liver and blood), compared to other tissues/fluids (milk, blubber, muscle, and fetus). In the marine mammalian food web, concentrations of PFOSA and lipophilic organochlorines (ng x g(-1) lipid equivalent) and proteinophilic substances (i.e., PFOS and C8-C14 PFCAs, ng x g(-1) protein) increased significantly (P < 0.05) with trophic level. Trophic magnification factors (TMFs) of organochlorines ranged between 5 and 14 and exhibited significant curvilinear relationships (P < 0.05) with octanol-water and octanol-air partition coefficients (KOW, KOA). TMFs of perfluorinated acids (PFAs) ranged between 2 and 11 and exhibited similar correlation (P < 0.05) with protein-water and protein-air partition coefficients (KPW, KPA). PFAs did not biomagnify in the aquatic piscivorous food web (TMF range: 0.3-2). This food web specific biomagnification behavior was attributed to the high aqueous solubility and low volatility of PFAs. Specifically, the anticipated phase-partitioning of these proteinophilic substances, represented by their protein-water (KPW) and protein-air (KPA) partition coefficients, likely results in efficient respiratory elimination in water-respiring organisms but very slow elimination and biomagnification in air-breathing animals. Lastly, the results indicate that PFOS exposure in nursing Hudson Bay beluga whale calves (CI95 range = 2.7 x 10(-5) to 1.8 x 10(-4) mg x kg bw(-1) x d(-1)), exceedsthe oral reference dose for PFOS (7.5 x 10(-5) mg x kg bw(-1) x d(-1)), which raises concern for potential biological effects in these and other sensitive Arctic marine wildlife species.

We synthesize current understanding of the magnitudes and methods for assessing human and wildlife exposures to poly‐ and perfluoroalkyl substances (PFAS). Most human exposure assessments have focused on 2 to 5 legacy PFAS, and wildlife assessments are typically limited to targeted PFAS (up to ~30 substances). However, shifts in chemical production are occurring rapidly, and targeted methods for detecting PFAS have not kept pace with these changes. Total fluorine measurements complemented by suspect screening using high‐resolution mass spectrometry are thus emerging as essential tools for PFAS exposure assessment. Such methods enable researchers to better understand contributions from precursor compounds that degrade into terminal perfluoroalkyl acids. Available data suggest that diet is the major human exposure pathway for some PFAS, but there is large variability across populations and PFAS compounds. Additional data on total fluorine in exposure media and the fraction of unidentified organofluorine are needed. Drinking water has been established as the major exposure source in contaminated communities. As water supplies are remediated, for the general population, exposures from dust, personal care products, indoor environments, and other sources may be more important. A major challenge for exposure assessments is the lack of statistically representative population surveys. For wildlife, bioaccumulation processes differ substantially between PFAS and neutral lipophilic organic compounds, prompting a reevaluation of traditional bioaccumulation metrics. There is evidence that both phospholipids and proteins are important for the tissue partitioning and accumulation of PFAS. New mechanistic models for PFAS bioaccumulation are being developed that will assist in wildlife risk evaluations. Environ Toxicol Chem 2021;40:631–657. © 2020 SETAC

Methods for the regulatory assessment of the bioaccumulation potential of organic chemicals are founded on empirical measurements and mechanistic models of dietary absorption and biomagnification. This study includes a review of the current state of knowledge regarding mechanisms and models of intestinal absorption and biomagnification of organic chemicals in organisms of aquatic and terrestrial food chains and also includes a discussion of the implications of these models for assessing the bioaccumulation potential of organic chemicals. Four mechanistic models, including biomass conversion, digestion or gastrointestinal magnification, micelle-mediated diffusion, and fat-flush diffusion, are evaluated. The models contain many similarities and represent an evolution in understanding of chemical bioaccumulation processes. An important difference between the biomagnification models is whether intestinal absorption of an ingested contaminant occurs solely via passive molecular diffusion through serial resistances or via facilitated diffusion that incorporates an additional advective transport mechanism in parallel (i.e., molecular ferrying within gastrointestinal micelles). This difference has an effect on the selection of physicochemical properties that best anticipate the bioaccumulative potential of commercial chemicals in aquatic and terrestrial food chains. Current regulatory initiatives utilizing Kow threshold criteria to assess chemical bioaccumulation potential are shown to be unable to identify certain bioaccumulative substances in air-breathing animals. We urge further research on dietary absorption and biomagnification of organic chemicals to develop better models for assessing the bioaccumulative nature of organic chemicals.