Physiologically-based pharmacokinetic analysis of benzoic acid in rats, guinea pigs and humans: Implications for dietary exposures and interspecies uncertainty

Hoffman, Timothy E.; Hanneman, William H.

doi:10.1016/j.comtox.2017.06.002

Cited by 9 publications

(4 citation statements)

References 29 publications

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“…Thus, 2-ethylhexyl benzoate may be considered as a source of this alcohol within this study. The second product benzoic acid can be further converted into hippuric acid [18].…”

Section: Volatiles Produced and Metabolized By Ags Snu-1 And Ges-1 Ce...mentioning

confidence: 99%

Volatilomic Signatures of AGS and SNU-1 Gastric Cancer Cell Lines

et al. 2022

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In vitro studies can help reveal the biochemical pathways underlying the origin of volatile indicators of numerous diseases. The key objective of this study is to identify the potential biomarkers of gastric cancer. For this purpose, the volatilomic signatures of two human gastric cancer cell lines, AGS (human gastric adenocarcinoma) and SNU-1 (human gastric carcinoma), and one normal gastric mucosa cell line (GES-1) were investigated. More specifically, gas chromatography mass spectrometry has been applied to pinpoint changes in cell metabolism triggered by cancer. In total, ten volatiles were found to be metabolized, and thirty-five were produced by cells under study. The volatiles consumed were mainly six aldehydes and two heterocyclics, whereas the volatiles released embraced twelve ketones, eight alcohols, six hydrocarbons, three esters, three ethers, and three aromatic compounds. The SNU-1 cell line was found to have significantly altered metabolism in comparison to normal GES-1 cells. This was manifested by the decreased production of alcohols and ketones and the upregulated emission of esters. The AGS cells exhibited the increased production of methyl ketones containing an odd number of carbons, namely 2-tridecanone, 2-pentadecanone, and 2-heptadecanone. This study provides evidence that the cancer state modifies the volatilome of human cells.

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“…Thus, 2-ethylhexyl benzoate may be considered as a source of this alcohol within this study. The second product benzoic acid can be further converted into hippuric acid [18].…”

Section: Volatiles Produced and Metabolized By Ags Snu-1 And Ges-1 Ce...mentioning

confidence: 99%

Volatilomic Signatures of AGS and SNU-1 Gastric Cancer Cell Lines

et al. 2022

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“…A chemical specific PBK model is built using knowledge of the physicochemical / ADME properties and Mode of Action (MoA) for the specific chemical under study. For instance, distribution to relevant target organs and specific metabolite formation should be measured and included ( Kawai et al, 1994 , Abbiati and Manca, 2017 , Hoffman and Hanneman, 2017 , Moss et al, 2017 ). On the other hand, a more generic PBK model has a defined compartmental structure for all chemicals tested.…”

Section: Introductionmentioning

confidence: 99%

Physiologically based kinetic (PBK) modelling and human biomonitoring data for mixture risk assessment

Pletz

Blakeman

Paini

et al. 2020

Environment International

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Highlights Human Biomonitoring (HBM) provides valuable insight into co-exposure to multiple chemicals. HBM data can be interpreted in comparison to biomonitoring equivalents of health based guidance values. Two generic physiologically based kinetic models were tested for deriving biomonitoring equivalents. Uncertainties and limitations were identified and discussed. The use of biomonitoring equivalents in assessing chemical mixtures was illustrated in a case study.

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“…The bottom-up PBK models can be chemical-specific or generic. The development of a chemical-specific bottom-up PBK model requires understanding of the physiochemical and ADME properties and target organ of interest (Hoffman and Hanneman 2017;Najjar et al 2021;Pletz et al 2020). Each of these relevant processes are simulated based on in vitro and in silico input data.…”

Section: Introductionmentioning

confidence: 99%

Towards best use and regulatory acceptance of generic physiologically based kinetic (PBK) models for in vitro-to-in vivo extrapolation (IVIVE) in chemical risk assessment

et al. 2022

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With an increasing need to incorporate new approach methodologies (NAMs) in chemical risk assessment and the concomitant need to phase out animal testing, the interpretation of in vitro assay readouts for quantitative hazard characterisation becomes more important. Physiologically based kinetic (PBK) models, which simulate the fate of chemicals in tissues of the body, play an essential role in extrapolating in vitro effect concentrations to in vivo bioequivalent exposures. As PBK-based testing approaches evolve, it will become essential to standardise PBK modelling approaches towards a consensus approach that can be used in quantitative in vitro-to-in vivo extrapolation (QIVIVE) studies for regulatory chemical risk assessment based on in vitro assays. Based on results of an ECETOC expert workshop, steps are recommended that can improve regulatory adoption: (1) define context and implementation, taking into consideration model complexity for building fit-for-purpose PBK models, (2) harmonise physiological input parameters and their distribution and define criteria for quality chemical-specific parameters, especially in the absence of in vivo data, (3) apply Good Modelling Practices (GMP) to achieve transparency and design a stepwise approach for PBK model development for risk assessors, (4) evaluate model predictions using alternatives to in vivo PK data including read-across approaches, (5) use case studies to facilitate discussions between modellers and regulators of chemical risk assessment. Proof-of-concepts of generic PBK modelling approaches are published in the scientific literature at an increasing rate. Working on the previously proposed steps is, therefore, needed to gain confidence in PBK modelling approaches for regulatory use.

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Physiologically-based pharmacokinetic analysis of benzoic acid in rats, guinea pigs and humans: Implications for dietary exposures and interspecies uncertainty

Cited by 9 publications

References 29 publications

Volatilomic Signatures of AGS and SNU-1 Gastric Cancer Cell Lines

Volatilomic Signatures of AGS and SNU-1 Gastric Cancer Cell Lines

Physiologically based kinetic (PBK) modelling and human biomonitoring data for mixture risk assessment

Towards best use and regulatory acceptance of generic physiologically based kinetic (PBK) models for in vitro-to-in vivo extrapolation (IVIVE) in chemical risk assessment

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