Sex-specific risk assessment of PFHxS using a physiologically based pharmacokinetic model

Abstract

Perfluorohexanesulfonate (PFHxS), which belongs to the group of perfluoroalkyl and polyfluoroalkyl substances (PFASs), has been extensively used in industry and subsequently detected in the environment. Its use may be problematic, as PFHxS is known to induce neuronal cell death, and has been associated with early onset menopause in women and with attention deficit/hyperactivity disorder. Due to these impending issues, the aim of this study is to develop and evaluate a physiologically based pharmacokinetic (PBPK) model for PFHxS in male and female rats, and apply this to a human health risk assessment. We conducted this study in vivo after the oral or intravenous administration of PFHxS in male (dose of 10 mg/kg) and female rats (dose of 0.5-10 mg/kg). The biological samples consisted of plasma, nine tissues, urine, and feces. We analyzed the sample using ultra-liquid chromatography coupled tandem mass spectrometry (UPLC-MS/MS). Our findings showed the tissue-plasma partition coefficients for PFHxS were highest in the liver. The predicted rat plasma and tissue concentrations using a simulation fitted well with the observed values. We extrapolated the PBPK model in male and female rats to a human PBPK model of PFHxS based on human physiological parameters. The reference doses of 0.711 µg/kg/day (male) and 0.159 µg/kg/day (female) and external doses of 0.007 µg/kg/day (male) and 0.006 µg/kg/day (female) for human risk assessment were estimated using Korean biomonitoring values. This study provides valuable insight into human health risk assessment regarding PFHxS exposure.

Risk to human health related to the presence of perfluoroalkyl substances in food

“…Kim et al. () developed a model for simulating the kinetics of PFHxS in male and female rats. The model includes compartments representing plasma (including a bound and free fraction), kidney and renal glomerular filtrate, gastrointestinal tract as absorption site, liver (taking into consideration enterohepatic circulation), brain, heart, lung and the rest of the body.…”

“…The rat PBPK model was extrapolated to humans, considering the interspecies physiological parameters, on the basis of the same allometric equation described by Kim et al. (), as reported above.…”

Endocrine Disruptor Potential of Short- and Long-Chain Perfluoroalkyl Substances (PFASs)—A Synthesis of Current Knowledge with Proposal of Molecular Mechanism

“…It was demonstrated that the elimination ratio of individual compounds belonging to the group of PFASs depended on the type of absorbed compound, species of the exposed individual as well as its age and sex. A general tendency has indicated a more rapid elimination of PFASs by females [23,100,101], which may be explained by differences in renal activity, including differences in activity of proteins transporting organic anions [102]. Furthermore, rapid elimination of PFASs by women may be partially explained by PFASs offloading into menstrual blood, as well as in childbirth [103].…”

Occurrence, partition and environmental risk assessment of per- and polyfluoroalkyl substances in water and sediment from the Baiyangdian Lake, China

“…Since current toxicity data of PFHxS and PFBS indicate that they are less toxic than PFOS and PFOA, it was expected that they should have higher PNEC than PFOS [48][49][50][51][52] . The measured concentration of PFHxS and PFBuS in water and sediment were even lower than the PNEC of PFOS.…”