Influence of the uncertainty in the validation of PBPK models: A case-study for PFOS and PFOA

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

doi:10.1016/j.yrtph.2016.03.009

Cited by 23 publications

(18 citation statements)

References 43 publications

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“…Physiologically based toxicokinetic (PBTK) models incorporating absorption, distribution, metabolism, and excretion metrics have been developed to assess the toxicokinetic of PFOS and PFOA in various animal models, including fish and mammals (Andersen et al 2006;Tan et al 2008;Consoer et al 2014Consoer et al , 2016Fabrega et al 2014Fabrega et al , 2016Cheng and Ng 2017;Khazaee and Ng 2018). Such models are particularly useful for assessing the influence of membrane transporters and revealing important challenges in equilibrium modeling of PFAS bioaccumulation.…”

Section: Pfas Bioaccumulation Modelingmentioning

confidence: 99%

PFAS Exposure Pathways for Humans and Wildlife: A Synthesis of Current Knowledge and Key Gaps in Understanding

Silva

Armitage

Bruton

et al. 2021

Enviro Toxic and Chemistry

403

225

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We synthesize current understanding of the magnitudes and methods for assessing human and wildlife exposures to poly‐ and perfluoroalkyl substances (PFAS). Most human exposure assessments have focused on 2 to 5 legacy PFAS, and wildlife assessments are typically limited to targeted PFAS (up to ~30 substances). However, shifts in chemical production are occurring rapidly, and targeted methods for detecting PFAS have not kept pace with these changes. Total fluorine measurements complemented by suspect screening using high‐resolution mass spectrometry are thus emerging as essential tools for PFAS exposure assessment. Such methods enable researchers to better understand contributions from precursor compounds that degrade into terminal perfluoroalkyl acids. Available data suggest that diet is the major human exposure pathway for some PFAS, but there is large variability across populations and PFAS compounds. Additional data on total fluorine in exposure media and the fraction of unidentified organofluorine are needed. Drinking water has been established as the major exposure source in contaminated communities. As water supplies are remediated, for the general population, exposures from dust, personal care products, indoor environments, and other sources may be more important. A major challenge for exposure assessments is the lack of statistically representative population surveys. For wildlife, bioaccumulation processes differ substantially between PFAS and neutral lipophilic organic compounds, prompting a reevaluation of traditional bioaccumulation metrics. There is evidence that both phospholipids and proteins are important for the tissue partitioning and accumulation of PFAS. New mechanistic models for PFAS bioaccumulation are being developed that will assist in wildlife risk evaluations. Environ Toxicol Chem 2021;40:631–657. © 2020 SETAC

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Section: Pfas Bioaccumulation Modelingmentioning

confidence: 99%

PFAS Exposure Pathways for Humans and Wildlife: A Synthesis of Current Knowledge and Key Gaps in Understanding

Silva

Armitage

Bruton

et al. 2021

Enviro Toxic and Chemistry

403

225

View full text Add to dashboard Cite

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“…However, in the case of the specific populations, such as developing fetuses, growing infants, and young children, whose chemical metabolizing systems (glucuronidation activity) are underdeveloped, even moderate exposure can lead to higher internal concentration of BPA [32,33]. In recent years, use of physiologically based pharmacokinetic (PBPK) modelling has been quite popular in human health risk assessment [34,35]. Most publications addressed PBPK modelling of BPA adult exposure [33,36].…”

Section: Occurrence Of Edcs In Milk and Toxicokineticsmentioning

confidence: 99%

The dark side of the breastfeeding: In the light of endocrine disruptors

Chemek

Nevoral

2019

Medical Journal of Cell Biology

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Breastfeeding plays an essential role in the healthy development of a newborn, but human milk is obviously compromised by pollutants from our environment. The main contaminants of human milk with endocrine-disrupting compound (EDCs) have raised concern for public and environmental health. Bisphenol A (BPA), which can leach from plastics, are among the most well-studied. Since EDs are known to cross the mammary gland barrier and BPA may accumulate in the neonate, “BPA-free” products have been introduced to the market. However, recent studies have shown that alternative bisphenols (e.g. BPS, BPF) can be detected in breast milk, have ED activities and may have developmental effects similar to BPA.

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“…4Where, Ci is the concentration in the tissue i (ng/L), Qi is the blood flow in the tissue i (L/h), Ca is the arterial concentration (ng/L), Ki:p is the partition coefficient of tissue i, and Vi is the volume of the tissue i (L). Detail description of PBPK model can be found in our other publications (Fabrega et al, 2014;Fàbrega et al, 2016).…”

Section: Pfos Pbpk (A Case Study)mentioning

confidence: 99%

“…Dose reconstruction approach has been used, so that the given equivalent oral dose will provide the AUC in the brain that matches the AUC for the 12 different in-vitro doses (6 for 24hr and 6 for 48hr), a similar approach has been used in the previous study (Thiel et al, 2017). The oral equivalent doses were estimated to be way higher, as the PFOS concentration reaching to the brain was found to be relatively very low (Fabrega et al, 2014;Fàbrega et al, 2016). The estimated oral equivalent doses for the corresponding in-vitro doses are provided in Table 1.…”

Section: Ivive For Dose Equivalencymentioning

confidence: 99%

Developing integrated PBPK/PD coupled mechanistic pathway model (miRNA-BDNF): An approach towards system toxicology

2017

Self Cite

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Integration of a dynamic signal transduction pathway into the tissue dosimetry model is a major advancement in the area of computational toxicology. This paper illustrates the ways to incorporate the use of existing system biological model in the field of toxicology via its coupling to the Physiological based Pharmacokinetics and Pharmacodynamics (PBPK/PD) model. This expansion framework of integrated PBPK/PD coupled mechanistic system pathway model can be called as system toxicology that describes the kinetics of both - the chemicals and - biomolecules, help us to understand the dynamic and steady-state behaviors of molecular pathways under perturbed condition. The objective of this article is to illustrate a system toxicology based approach by developing an integrated PBPK/PD coupled miRNA-BDNF pathway model and to demonstrate its application by taking a case study of the PFOS mediated neurotoxicity. System dynamic involves miRNA-mediated BDNF regulation, which plays an important role in the control of neuronal cell proliferation, differentiation, and survivability.

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Influence of the uncertainty in the validation of PBPK models: A case-study for PFOS and PFOA

Cited by 23 publications

References 43 publications

PFAS Exposure Pathways for Humans and Wildlife: A Synthesis of Current Knowledge and Key Gaps in Understanding

PFAS Exposure Pathways for Humans and Wildlife: A Synthesis of Current Knowledge and Key Gaps in Understanding

The dark side of the breastfeeding: In the light of endocrine disruptors

Developing integrated PBPK/PD coupled mechanistic pathway model (miRNA-BDNF): An approach towards system toxicology

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