PBPK modeling for PFOS and PFOA: Validation with human experimental data

Fàbrega, Francesc; Kumar, Vikas; Schuhmacher, Marta; Domingo, José L.; Nadal, Martí

doi:10.1016/j.toxlet.2014.01.007

Cited by 79 publications

(51 citation statements)

References 52 publications

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“…When we adjusted the PFUnDA-BMI coefficient for GFR, it decreased slightly (from 63% to 59%), which is consistent with a small portion of the association being mediated by GFR. PFASs are not lipophilic, and PFASs distribute primarily to the liver, kidneys, and blood (Fabrega et al, 2014). Since PFASs are primarily in compartments other than the adipose tissue, a positive association with BMI or change in BMI is not expected.…”

Section: Discussionmentioning

confidence: 99%

Reliability of perfluoroalkyl substances in plasma of 100 women in two consecutive pregnancies

Papadopoulou

Haug

Sabaredzovic

et al. 2015

Environmental Research

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The potential toxicity of background exposure to perfluoroalkyl substances (PFASs) is currently under active investigation. Such investigations typically rely on a single measure of PFAS concentration, yet the longer-term reliability of a single measure has not been well characterized, especially among reproductive-aged women. Our aim was to investigate the association between PFAS plasma concentrations of 100 women in two consecutive pregnancies and explore changes in plasma concentration related to reproductive factors. The women in our study were enrolled in the Norwegian Mother and Child Cohort Study (MoBa) from 2003 to 2009. About half of them breastfed exclusively for 6 months and the rest of the participants did not breastfeed between the two consecutive pregnancies (median time between pregnancies: 18 months). Maternal blood was collected at mid-pregnancy and plasma was analyzed for 10 PFASs. Statistical analyses were restricted to 6 PFASs that were quantifiable in more than 80% of the samples. We estimated the correlation between repeated PFAS measurements, the percentage change between pregnancies and the effect of several reproductive factors in multivariate linear regression models of PFAS concentration in the second pregnancy. The Pearson correlation coefficient between repeated PFAS measurements was, for perfluorooctane sulfonate (PFOS), 0.80; perfluorooctanoate (PFOA), 0.50; perfluorohexane sulfonate (PFHxS), 0.74; perfluorononanoate (PFNA), 0.39; perfluoroundecanoate (PFUnDA), 0.71; and perfluorodecanoate (PFDA), 0.60. Adjustment for maternal age, delivery year, and time and breastfeeding between pregnancies did not substantially affect the observed correlations. We found 44-47% median reductions in the concentrations of PFOS, PFOA and PFHxS between pregnancies, while the change in concentrations between pregnancies was smaller and more variable for PFNA, PFUnDA and PFDA. The variation in plasma concentrations in the second pregnancy was mainly accounted for by the concentration in the first pregnancy; for PFOS, PFOA, and PFNA, breastfeeding also accounted for a substantial proportion. In conclusion, we found the reliability of PFAS measurements in maternal plasma to be moderate to high, and in these data, several factors, especially breastfeeding, were related to plasma concentrations.

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Section: Discussionmentioning

confidence: 99%

Reliability of perfluoroalkyl substances in plasma of 100 women in two consecutive pregnancies

Papadopoulou

Haug

Sabaredzovic

et al. 2015

Environmental Research

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“…Previous efforts to model PFOA exposure in humans include PBPK models that describe resorption kinetics by non-specific renal transporters in a filtrate compartment (Loccisano et al, 2011; Fabrega et al, 2014). The work presented here improves upon these models through the incorporation of in vitro to in vivo informed extrapolation of experimentally measured kinetic descriptors of specific OATs that play a role in the renal excretion and reabsorption of PFOA.…”

Section: Introductionmentioning

confidence: 99%

Physiologically based pharmacokinetic modeling of human exposure to perfluorooctanoic acid suggests historical non drinking-water exposures are important for predicting current serum concentrations

Worley

Yang

Fisher

2017

Toxicology and Applied Pharmacology

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Manufacturing of perfluorooctanoic acid (PFOA), a synthetic chemical with a long half-life in humans, peaked between 1970 and 2002, and has since diminished. In the United States, PFOA is detected in the blood of >99% of people tested, but serum concentrations have decreased since 1999. Much is known about exposure to PFOA in drinking water; however, the impact of non-drinking water PFOA exposure on serum PFOA concentrations is not well characterized. The objective of this research is to apply physiologically based pharmacokinetic (PBPK) modeling and Monte Carlo analysis to evaluate the impact of historic non-drinking water PFOA exposure on serum PFOA concentrations. In vitro to in vivo extrapolation was utilized to inform descriptions of PFOA transport in the kidney. Monte Carlo simulations were incorporated to evaluate factors that account for the large inter-individual variability of serum PFOA concentrations measured in individuals from North Alabama in 2010 and 2016, and the Mid-Ohio River Valley between 2005 and 2008. Predicted serum PFOA concentrations were within two-fold of experimental data. With incorporation of Monte Carlo simulations, the model successfully tracked the large variability of serum PFOA concentrations measured in populations from the Mid-Ohio River Valley. Simulation of exposure in a population of 45 adults from North Alabama successfully predicted 98% of individual serum PFOA concentrations measured in 2010 and 2016, respectively, when non-drinking water ingestion of PFOA exposure was included. Variation in serum PFOA concentrations may be due to inter-individual variability in the disposition of PFOA and potentially elevated historical non-drinking water exposures.

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“…PFOS is characterized by fluorocarbon hydrophobe that is thermally stable, repellent of water and oil, and resistant to hydrolysis, photolysis, biodegradation and metabolism [4]. Because of these chemical features, PFOS has been widely used in a lot of industrial and consumer products, including non-stick cookware, food packaging, stain protectors, lubricants, and fire-fighting foams [5,6].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of single and joint toxicity of perfluorooctane sulfonate and zinc to Limnodrilus hoffmeisteri : Acute toxicity, bioaccumulation and oxidative stress

Liu

Yan

et al. 2016

Journal of Hazardous Materials

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PBPK modeling for PFOS and PFOA: Validation with human experimental data

Cited by 79 publications

References 52 publications

Reliability of perfluoroalkyl substances in plasma of 100 women in two consecutive pregnancies

Reliability of perfluoroalkyl substances in plasma of 100 women in two consecutive pregnancies

Physiologically based pharmacokinetic modeling of human exposure to perfluorooctanoic acid suggests historical non drinking-water exposures are important for predicting current serum concentrations

Evaluation of single and joint toxicity of perfluorooctane sulfonate and zinc to Limnodrilus hoffmeisteri : Acute toxicity, bioaccumulation and oxidative stress

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