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Your search keyword '"Fabian, Eric"' showing total 219 results
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219 results on '"Fabian, Eric"'

1. Minimum information for reporting on the TEER (trans-epithelial/endothelial electrical resistance) assay (MIRTA)

Author

Sharma, Monita, Huber, Erin, Arnesdotter, Emma, Behrsing, Holger P., Bettmann, Adam, Brandwein, David, Constant, Samuel, Date, Rahul, Deshpande, Abhay, Fabian, Eric, Gupta, Amit, Gutierrez, Robert, Gutleb, Arno C., Hargrove, Marie M., Hollings, Michael, Hutter, Victoria, Jarabek, Annie M., Kaluzhny, Yulia, Landsiedel, Robert, Milchak, Lawrence, Moyer, Robert A., Murray, Jessica R., Page, Kathryn, Patel, Manish, Pearson, Stephanie N., Petersen, Elijah J., Reinke, Emily, Roldan, Nuria, Roper, Clive, Scaglione, Jamie B., Settivari, Raja S., Stucki, Andreas O., Verstraelen, Sandra, Wallace, Joanne L., McCullough, Shaun, and Clippinger, Amy J.

Published
2025
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10. Next-generation risk assessment read-across case study: application of a 10-step framework to derive a safe concentration of daidzein in a body lotion.

Author

Najjar, Abdulkarim, Kühnl, Jochen, Lange, Daniela, Géniès, Camille, Jacques, Carine, Fabian, Eric, Zifle, Anne, Hewitt, Nicola J., and Schepky, Andreas

Subjects
PHYTOESTROGENS, OINTMENTS, FACIAL creams (Cosmetics), DAIDZEIN, RISK assessment, SAFETY factor in engineering
Abstract

Introduction: We performed an exposure-based Next Generation Risk Assessment case read-across study using New Approach Methodologies (NAMs) to determine the highest safe concentration of daidzein in a body lotion, based on its similarities with its structural analogue, genistein. Two assumptions were: (1) daidzein is a new chemical and its dietary intake omitted; (2) only in vitro data were used for daidzein, while in vitro and legacy in vivo data for genistein were considered. Methods: The 10-step tiered approach evaluating systemic toxicity included toxicokinetics NAMs: PBPK models and in vitro biokinetics measurements in cells used for toxicogenomics and toxicodynamic NAMs: pharmacology profiling (i.e., interaction with molecular targets), toxicogenomics and EATS assays (endocrine disruption endpoints). Whole body rat and human PBPK models were used to convert external doses of genistein to plasma concentrations and in vitro Points of Departure (PoD) to external doses. The PBPK human dermal module was refined using in vitro human skin metabolism and penetration data. Results: The most relevant endpoint for daidzein was from the ERa assay (Lowest Observed Effective Concentration was 100 ± 0.0 nM), which was converted to an in vitro PoD of 33 nM. After application of a safety factor of 3.3 for intra-individual variability, the safe concentration of daidzein was estimated to be 10 nM. This was extrapolated to an external dose of 0.5 µg/cm2 for a body lotion and face cream, equating to a concentration of 0.1%. Discussion: When in vitro PoD of 33 nM for daidzein was converted to an external oral dose in rats, the value correlated with the in vivo NOAEL. This increased confidence that the rat oral PBPK model provided accurate estimates of internal and external exposure and that the in vitro PoD was relevant in the safety assessment of both chemicals. When plasma concentrations estimated from applications of 0.1% and 0.02% daidzein were used to calculate bioactivity exposure ratios, values were >1, indicating a good margin between exposure and concentrations causing adverse effects. In conclusion, this case study highlights the use of NAMs in a 10-step tiered workflow to conclude that the highest safe concentration of daidzein in a body lotion is 0.1%. [ABSTRACT FROM AUTHOR]

Published
2024
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25. Predictive Performance of Next Generation Physiologically Based Kinetic (PBK) Model Predictions in Rats Based on In Vitro and In Silico Input Data

Author

Punt, Ans, Louisse, Jochem, Pinckaers, Nicole, Fabian, Eric, van Ravenzwaay, Bennard, Punt, Ans, Louisse, Jochem, Pinckaers, Nicole, Fabian, Eric, and van Ravenzwaay, Bennard

Abstract

The goal of the present study was to assess the predictive performance of a minimal generic rat physiologically based kinetic (PBK) model based on in vitro and in silico input data to predict peak plasma concentrations (Cmax) upon single oral dosing. To this purpose, a dataset was generated of 3960 Cmax predictions for 44 compounds, applying different combinations of in vitro and in silico approaches for chemical parameterization, and comparison of the predictions to reported in vivo data. Best performance was obtained when (1) the hepatic clearance was parameterized based on in vitro measured intrinsic clearance values, (2) the method of Rodgers and Rowland for calculating partition coefficients, and (3) in silico calculated fraction unbound plasma and Papp values (the latter especially for very lipophilic compounds). Based on these input data, the median Cmax of 32 compounds could be predicted within 10-fold of the observed Cmax, with 22 out of these 32 compounds being predicted within 5-fold, and 8 compounds within 2-fold. Overestimations of more than 10-fold were observed for 12 compounds, whereas no underestimations of more than 10-fold occurred. Median Cmax predictions were frequently found to be within 10-fold of the observed Cmax when the scaled unbound hepatic intrinsic clearance (Clint,u) was either higher than 20 l/h or lower than 1 l/h. Similar findings were obtained with a test set of 5 in-house BASF compounds. Overall, this study provides relevant insights in the predictive performance of a minimal PBK model based on in vitro and in silico input data.

Published
2022

26. Predictive performance of next generation human physiologically based kinetic (PBK) models based on in vitro and in silico input data

Author

Punt, Ans, Louisse, Jochem, Beekmann, Karsten, Pinckaers, Nicole, Fabian, Eric, Van Ravenzwaay, Bennard, Carmichael, Paul L., Sorrell, Ian, Moxon, Thomas E., Punt, Ans, Louisse, Jochem, Beekmann, Karsten, Pinckaers, Nicole, Fabian, Eric, Van Ravenzwaay, Bennard, Carmichael, Paul L., Sorrell, Ian, and Moxon, Thomas E.

Abstract

The goal of the present study was to assess the predictive performance of a generic human physiologically based kinetic (PBK) model based on in vitro and in silico input data and the effect of using different input approaches for chemical parameterization on those predictions. For this purpose, a dataset was created of 38,772 Cmax predictions for 44 compounds by applying different combinations of in vitro and in silico approaches for chemical parameterization, and these predicted Cmax values were compared to reported in vivo data. Best results were achieved when the hepatic clearance was parameterized based on in vitro (i.e., hepatocytes or liver S9) measured intrinsic clearance values, the method of Rodgers and Rowland for calculating tissue:plasma partition coefficients, and the method of Lobell and Sivarajah for calculating the fraction unbound in plasma. With these parameters, the median Cmax values of 34 out of the 44 compounds were predicted within 5-fold of the observed Cmax, and the Cmax values of 19 compounds were predicted within 2-fold. The median Cmax values of 10 compounds were more than 5-fold overestimated. Underestimations (> 5-fold) did not occur. A comparison of the current generic PBK model structure with chemical-specific PBK models available in literature was made to identify possible kinetic processes not included in the generic PBK model that might explain the overestimations. Overall, the results provide crucial insights into the predictive performance of PBK models based on in vitro and in silico input and the influence of different input approaches on the model predictions.

Published
2022

34. Xenobiotic metabolism capacities of human skin in comparison with a 3D epidermis model and keratinocyte-based cell culture as in vitro alternatives for chemical testing: activating enzymes (Phase I)

Author

Götz, Christine, Pfeiffer, Roland, Tigges, Julia, Blatz, Veronika, Jäckh, Christine, Freytag, Eva-Maria, Fabian, Eric, Landsiedel, Robert, Merk, Hans F, Krutmann, Jean, Edwards, Robert J, Pease, Camilla, Goebel, Carsten, Hewitt, Nicola, and Fritsche, Ellen

Published
2012
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38. Measurement of the penetration of 56 cosmetic relevant chemicals into and through human skin using a standardized protocol

Author

Hewitt, Nicola J., primary, Grégoire, Sébastien, additional, Cubberley, Richard, additional, Duplan, Hélène, additional, Eilstein, Joan, additional, Ellison, Corie, additional, Lester, Cathy, additional, Fabian, Eric, additional, Fernandez, Julien, additional, Géniès, Camille, additional, Jacques‐Jamin, Carine, additional, Klaric, Martina, additional, Rothe, Helga, additional, Sorrell, Ian, additional, Lange, Daniela, additional, and Schepky, Andreas, additional

Published
2019
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39. Measurement of the penetration of 56 cosmetic relevant chemicals into and through human skin using a standardized protocol.

Author

Hewitt, Nicola J., Grégoire, Sébastien, Cubberley, Richard, Duplan, Hélène, Eilstein, Joan, Ellison, Corie, Lester, Cathy, Fabian, Eric, Fernandez, Julien, Géniès, Camille, Jacques‐Jamin, Carine, Klaric, Martina, Rothe, Helga, Sorrell, Ian, Lange, Daniela, and Schepky, Andreas

Subjects
SKIN permeability, SKIN, CHEMICAL testing, PROTEIN binding, PRECIPITATION forecasting, DERMIS
Abstract

OECD test guideline 428 compliant protocol using human skin was used to test the penetration of 56 cosmetic‐relevant chemicals. The penetration of finite doses (10 μL/cm2) of chemicals was measured over 24 hours. The dermal delivery (DD) (amount in the epidermis, dermis and receptor fluid [RF]) ranged between 0.03 ± 0.02 and 72.61 ± 8.89 μg/cm2. The DD of seven chemicals was comparable with in vivo values. The DD was mainly accounted for by the amount in the RF, although there were some exceptions, particularly of low DD chemicals. While there was some variability due to cell outliers and donor variation, the overall reproducibility was very good. As six chemicals had to be applied in 100% ethanol due to low aqueous solubility, we compared the penetration of four chemicals with similar physicochemical properties applied in ethanol and phosphate‐buffered saline. Of these, the DD of hydrocortisone was the same in both solvents, while the DD of propylparaben, geraniol and benzophenone was lower in ethanol. Some chemicals displayed an infinite dose kinetic profile; whereas, the cumulative absorption of others into the RF reflected the finite dosing profile, possibly due to chemical volatility, total absorption, chemical precipitation through vehicle evaporation or protein binding (or a combination of these). These investigations provide a substantial and consistent set of skin penetration data that can help improve the understanding of skin penetration, as well as improve the prediction capacity of in silico skin penetration models. The penetration of 56 chemicals was tested in human skin using a standard protocol. Dermal delivery correlated with the amount in the receptor fluid (RF). The impact of solvent on penetration was evaluated. Despite finite doses being applied, different profiles of cumulative absorption kinetics into the RF were observed. These data may help understand skin penetration and improve the prediction capacity of in silico skin penetration models. [ABSTRACT FROM AUTHOR]

Published
2020
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46. Can rat plasma metabolomics help to define maternal toxicity in rat developmental toxicity studies?

Author

Mellert, Werner, primary, Schneider, Steffen, additional, Hofmann, Thomas, additional, Keller, Jana, additional, Sperber, Saskia, additional, Jiang, Xiaoqi, additional, Strauss, Volker, additional, Fabian, Eric, additional, Herold, Michael, additional, Walk, Tilmann, additional, van Ravenzwaay, Bennard, additional, and Kamp, Hennicke, additional

Published
2017
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48. t4 report : metabolomics in toxicology and preclinical research

Author

Ramirez, Tzutzuy, Kamp, Hennicke, Bois, Frederic Y., Clench, Malcolm R., Coen, Muireann, Donley, Beth, Fischer, Steven M., Ekman, Drew R., Fabian, Eric, Guillou, Claude, Heuer, Joachim, Hogberg, Helena T., Jungnickel, Harald, Keun, Hector C., Krennrich, Gerhard, Krupp, Eckart, Luch, Andreas, Noor, Fozia, Peter, Erik, Riefke, Bjoern, Seymour, Mark, Skinner, Nigel, Smirnova, Lena, Verheij, Elwin, Wagner, Silvia, van Ravenzwaay, Bennard, Daneshian, Mardas, Hartung, Thomas, and Leist, Marcel

Subjects
ddc:570
Abstract

Metabolomics, the comprehensive analysis of metabolites in a biological system, provides detailed information about the biochemical/physiological status of a biological system, and about the changes caused by chemicals. Metabolomics analysis is used in many fields, ranging from the analysis of the physiological status of genetically modified organisms in safety science to the evaluation of human health conditions. In toxicology, metabolomics is the -omics discipline that is most closely related to classical knowledge of disturbed biochemical pathways. It allows rapid identification of the potential targets of a hazardous compound. It can give information on target organs and often can help to improve our understanding regarding the mode-of-action of a given compound. Such insights aid the discovery of biomarkers that either indicate pathophysiological conditions or help the monitoring of the efficacy of drug therapies. The first toxicological applications of metabolomics were for mechanistic research, but different ways to use the technology in a regulatory context are being explored. Ideally, further progress in that direction will position the metabolomics approach to address the challenges of toxicology of the 21st century. To address these issues, scientists from academia, industry, and regulatory bodies came together in a workshop to discuss the current status of applied metabolomics and its potential in the safety assessment of compounds. We report here on the conclusions of three working groups addressing questions regarding 1) metabolomics for in vitro studies 2) the appropriate use of metabolomics in systems toxicology, and 3) use of metabolomics in a regulatory context.

Published
2013

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