Background: Oral ingestion, inhalation, and skin contact are important exposure routes for humans to uptake per- and polyfluoroalkyl substances (PFAS). However, nasal and dermal exposure to PFAS remains unclear, and accurately predicting internal body burden of PFAS in humans via multiple exposure pathways is urgently required.
Objectives: We aimed to develop multiple physiologically based toxicokinetic (PBTK) models to unveil the route-specific pharmacokinetics and bioavailability of PFAS via respective oral, nasal, and dermal exposure pathways using a mouse model and sought to predict the internal concentrations in various tissues through multiple exposure routes and extrapolate it to humans.
Methods: Mice were administered the mixed solution of perfluorohexane sulfonate, perfluorooctane sulfonate, and perfluorooctanoic acid through oral, nasal, and dermal exposure separately or jointly. The time-dependent concentrations of PFAS in plasma and tissues were determined to calibrate and validate the individual and combined PBTK models, which were applied in single- and repeated-dose scenarios.
Results: The developed route-specific PBTK models successfully simulated the tissue concentrations of PFAS in mice following single or joint exposure routes as well as long-term repeated dose scenarios. The time to peak concentration of PFAS in plasma via dermal exposure was much longer (34.1-83.0 h) than that via nasal exposure (0.960 h). The bioavailability of PFAS via oral exposure was the highest (73.2%-98.0%), followed by nasal (33.9%-66.8%) and dermal exposure (4.59%-7.80%). This model was extrapolated to predict internal levels in human under real environment.
Discussion: Based on these data, we predict the following: PFAS were absorbed quickly via nasal exposure, whereas a distinct hysteresis effect was observed for dermal exposure. Almost all the PFAS to which mice were exposed via gastrointestinal route were absorbed into plasma, which exhibited the highest bioavailability. Exhalation clearance greatly depressed the bioavailability of PFAS via nasal exposure, whereas the lowest bioavailability in dermal exposure was because of the interception of PFAS within the skin layers. https://doi.org/10.1289/EHP11969.
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http://dx.doi.org/10.1289/EHP11969 | DOI Listing |
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Marine College, Shandong University, Weihai, Shandong 264209, China. Electronic address:
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School of Biosciences, The University of Sheffield, Alfred Denny Building, Western Bank, Sheffield S10 2TN, United Kingdom.
This study analyzed surface water from the River Swat, Pakistan, using inductively coupled plasma mass spectrometry, multivariate statistical techniques, and US-EPA risk assessment models to evaluate the concentrations, distribution, pathways, and potential risks of arsenic (As) and heavy metals, including chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), cadmium (Cd), mercury (Hg), and lead (Pb). The results revealed significant correlations (p ≤ 0.01) among metals that indicated common pollution sources, likely influenced by anthropogenic point and non-point activities.
View Article and Find Full Text PDFRegul Toxicol Pharmacol
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Gradient, One Beacon St., 17th Floor, Boston, MA, 02108, USA. Electronic address:
To date, only four studies directly measured dermal absorption kinetics of perfluorooctanoic acid (PFOA) in human skin. Reported kinetic parameters spanned two to five orders of magnitude, demonstrating the need to determine the causes of variability and identify the most appropriate dermal absorption factors for use in exposure assessments. We evaluated the reliability and physiological relevance of studies that measured PFOA fractional absorption, steady-state flux (J), and dermal permeability coefficient (K).
View Article and Find Full Text PDFEnviron Geochem Health
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Department of Microbiology, Institute of Quality Sciences and Product Management, Krakow University of Economics, Sienkiewicza 4, 30-033, Krakow, Poland.
Total concentrations, toxicity, and health risks of 16 polycyclic aromatic hydrocarbons (PAH) in street dust from Warsaw (Poland) in 6 granulometric fractions were investigated. Street dust was collected from 149 sampling points distributed among Area 1 (central districts, left bank of the Vistula River, mostly traffic-related pollution) and Area 2&3 (suburb area, mostly residential, right bank of the river). Street dust was investigated before ("all") and after separating into 5 size-dependent samples: (1-0.
View Article and Find Full Text PDFAging Cell
December 2024
Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", Athens, Greece.
Ultraviolet B (UVB) radiation is a major contributor to skin photoaging. Although mainly absorbed by the epidermis, UVB photons managing to penetrate the upper dermis affect human dermal fibroblasts (HDFs), leading, among others, to the accumulation of senescent cells. In vitro studies have shown that repeated exposures to subcytotoxic UVB radiation doses provoke HDFs' premature senescence shortly after the end of the treatment period.
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