Evaluating the toxicokinetics of some metabolites of a C6 polyfluorinated compound, 6:2 fluorotelomer alcohol in pregnant and nonpregnant rats after oral exposure to the parent compound.

The 6:2 fluorotelomer alcohol (6:2 FTOH) is a common impurity in per- and polyfluoroalkyl substances (PFASs) used in many applications. Our previous toxicokinetic (TK) evaluation of 6:2 FTOH calculated times to steady state (tss) of one of its metabolites, 5:3 fluorotelomer carboxylic acid (5:3A), in the plasma and tissues of up to a year after oral exposure to rats. Our current work further elucidated the TK of 5:3A and other metabolites of 6:2 FTOH in pregnant and nonpregnant rats after repeated oral exposure and examined the role of renal transporters in the biopersistence of 5:3A. The tss values for 5:3A in serum and tissues of adult nonpregnant animals ranged from 150 days to over a year. 4:3 fluorotelomer carboxylic acid (4:3A) was an additional potentially-biopersistent metabolite. 5:3A was the major metabolite of 6:2 FTOH in serum of pregnant dams and fetuses at each time interval. 5:3A was not a substrate for renal transporters in a human kidney cell line in vitro, indicating that renal reuptake of 5:3A is unlikely contribute to its biopersistence. Further research is needed to identify the underlying processes and evaluate the impact of these 6:2 FTOH metabolites on human health.

Comparative analysis of the physicochemical, toxicokinetic, and toxicological properties of ether-PFAS.

Perfluoropolyethers, also known as ether-PFAS, are linear or branched alkyl ether polymers, where the substituent hydrogens on the carbon atoms in the chain have been fully replaced by fluorine atoms. Some of these molecules may have a carboxylate functional group attached to one of the terminal carbon atoms to form an ether-PFAS carboxylate. Perfluoropolyethers are used as processing aids in the manufacture of various types of perfluorinated polymeric materials which are used in a variety of consumer applications. Although the physicochemical and toxicological properties of certain perfluoropolyether compounds have been extensively studied, data are relatively sparse for some members of this class of compounds. Moreover, the physicochemical, toxicokinetic, and toxicological properties of ether-PFAS as a class have not been elucidated in previous comprehensive review articles. This article reviews the nomenclature and uses of ether-PFAS and compares the physicochemical properties, toxicokinetic characteristics, apical effects in toxicological studies, and dose-response profiles across four specific ether-PFAS compounds. This comparison, including a description of identified data gaps should help to inform the design of studies to further elucidate the characteristics of ether-PFAS and to propose potential read-across assessment strategies for members of this class.

Comparative analysis of the toxicological databases for 6:2 fluorotelomer alcohol (6:2 FTOH) and perfluorohexanoic acid (PFHxA).

6:2 Fluorotelomer alcohol (6:2 FTOH) is a short-chain polyfluoroalkyl substance (PFAS) in polymeric PFAS used in fast food packaging and stain- and water-resistant textiles and may be degradation products of some components of aqueous film-forming foams (AFFF). The general population is exposed to 6:2 FTOH by inhalation of evaporates from treated surfaces or ambient concentrations in air, ingestion of indoor dust, or ingestion of food packaged in materials containing PFAS. Although exposure to 6:2 FTOH is pervasive, little is known concerning human health effects of this compound. Some published risk assessments have assumed that perfluorohexanoic acid (PFHxA), a metabolite of 6:2 FTOH, adequately models the human health effects of 6:2 FTOH. Recently identified studies conducted with 6:2 FTOH and its metabolite, 5:3 acid, have provided information that enables comparison of the toxicological profiles of PFHxA and 6:2 FTOH. This article summarizes a comparative analysis of the toxicological effects of PFHxA and 6:2 FTOH in rodents to determine whether data for PFHxA adequately models potential hazards of 6:2 FTOH exposure. Our analysis demonstrates that 6:2 FTOH is significantly more toxic than PFHxA. Use of toxicological studies conducted with PFHxA to assess 6:2 FTOH exposure may significantly underestimate human health risk.

C6-Perfluorinated Compounds: The New Greaseproofing Agents in Food Packaging.

Due to their oleophobic and hydrophobic properties and stability, perfluorinated compounds (PFCs) are used in many applications, particularly as greaseproofing agents for food contact. However, PFCs 8-carbons in length or greater (C8-PFCs) have raised concerns regarding environmental biopersistence, bioaccumulation in humans, and potent toxicity that have resulted in their gradual phase-out for food contact use. Industry has replaced C8-PFCs with shorter-chained C6-based greaseproofing agents, which are intended to have the same favorable physicochemical properties without the problematic toxicological effects in humans and wildlife. Compared with the large body of data available for C8 compounds, however, the available database on toxicity and exposure to the C6 compounds is fairly limited. This article summarizes the information in this database, focusing on aspects of human exposure and potential health risks associated with two types of C6 PFCs found in food packaging: perfluorohexanoic acid (PFHxA) and 6-2 fluorotelomer alcohol (C6-FTOH).