Patterns in Serum Toxicokinetics in Peromyscus Exposed to Per‐ and Polyfluoroalkyl Substances

Abstract

Per-and polyfluoroalkyl substances (PFAS) are compounds manufactured for use in paints, cleaning agents, fire suppressants, nonstick cookware, food containers, and water-resistant products. Concerns about PFAS stem from their ubiquitous presence in the environment, persistence, and variable/uncertain bioaccumulation and toxicity. In the present study, 5 perfluoroalkyl acids and one polyfluoroalkyl substance were administered to white-footed mice (Peromyscus leucopus) to elucidate the kinetics of each chemical over 28 d of exposure. Perfluorooctanoate, perfluorohexane sulfonate (PFHxS), and perfluorobutane sulfonate were administered to male and female mice via drinking water. Perfluorooctane sulfonate, perfluorononanoate, 6:2 fluorotelomer sulfonate, and PFHxS were administered to male and female mice via oral gavage. Blood samples collected after 14 or 21 and 28 d of exposure were analyzed for individual PFAS concentrations via liquid chromatography-tandem mass spectrometry. In general, a plateau in serum concentration in this toxicity test-relevant timeline depended on interactions between 1) the type of PFAS (i.e., perfluoroalkyl sulfonic acids [PFSAs] vs perfluoroalkyl carboxylic acids [PFCAs] vs polyfluorinated), 2) continuous versus bolus dosing, and 3) to a lesser extent, sex. Specifically, PFCAs were detected at higher concentration in females than males, whereas PFSAs were generally detected at similar levels across sex. An exception occurred when PFHxS yielded higher serum levels in males than females through bolus, but not continuous, dosing. Type of PFAS had the largest impact on serum concentrations, whereas sex had the lowest. As such, future work on the toxicokinetics of PFAS in common ecological receptors would be valuable to further explore these patterns.

Urine Excretion, Organ Distribution, and Placental Transfer of 6PPD and 6PPD-Quinone in Mice and Potential Developmental Toxicity through Nuclear Receptor Pathways

“…Therefore, there is an urgent need for continued research into the developmental toxicity of 6PPD and 6PPDQ using both chronic exposure animal studies and epidemiological investigations. Notably, we observed sex-specific excretion of 6PPD and 6PPDQ in mice urine samples, adding to the increasing evidence that sex can have strong influences on the toxicokinetics, toxicodynamics, and outcomes of environmental pollutants. ,, In future toxicology and epidemiological studies of 6PPD and 6PPDQ, separate considerations for males and females are merited.…”

“…Notably, we observed sex-specific excretion of 6PPD and 6PPDQ in mice urine samples, adding to the increasing evidence that sex can have strong influences on the toxicokinetics, toxicodynamics, and outcomes of environmental pollutants. 55,79,80 In future toxicology and epidemiological studies of 6PPD and 6PPDQ, separate considerations for males and females are merited.…”

Application of High-Resolution Mass Spectrometry to Evaluate UV-Sulfite-Induced Transformations of Per- and Polyfluoroalkyl Substances (PFASs) in Aqueous Film-Forming Foam (AFFF)

“…Data were acquired and processed using SCIEX OS version 1.3 to identify PFASs for which no standards were available by screening against an XIC list and MS/MS library. Only PFASs with peak areas of >20 (peak area range of 233–1 767 627; average peak area of 65 531) and eluting at retention times of >5 min were considered; retention times of <5 min likely reflect analytical noise (PFBA eluted at 6.3 min) . PFASs were then screened using the following criteria: mass error (parts per million), isotope ratio difference, and spectral library match.…”

“…Only PFASs with peak areas of >20 (peak area range of 233−1 767 627; average peak area of 65 531) and eluting at retention times of >5 min were considered; retention times of <5 min likely reflect analytical noise (PFBA eluted at 6.3 min). 36 PFASs were then screened using the following criteria: mass error (parts per million), isotope ratio difference, and spectral library match. A custom R script (version 3.6.1) was used to further process exported data and eliminate compounds outside acceptable criteria.…”

Perfluoroalkyl Mixture Exposure in Relation to Fetal Growth: Potential Roles of Maternal Characteristics and Associations with Birth Outcomes

“…Perfluoroalkyl substances (PFASs) comprise a group of synthetic fluorinated chemicals that have been widely used in cleaning products, textiles, adhesive food packaging, and fire foam for decades [1][2][3][4]. Through water drinking, food consumption, and air inhalation, PFASs chemicals are able to enter the human body, binding to serum albumin and then distributed in the lungs, liver, and brain [5,6].…”