A kinetic model for the formation of acrylamide in a glucose-asparagine reaction system is proposed. Equimolar solutions (0.2 M) of glucose and asparagine were heated at different temperatures (120-200°C) at pH 6.8. Besides the reactants, acrylamide, fructose, and melanoidins were quantified after predetermined heating times (0-45 min). Multiresponse modeling by use of nonlinear regression with the determinant criterion was used to estimate model parameters. The proposed model resulted in a reasonable estimation for the formation of acrylamide in an aqueous model system, although the behavior of glucose, fructose, and asparagine was slightly underestimated. The formation of acrylamide reached its maximum when the concentration of sugars was reduced to about 0. This supported previous research, showing that a carbonyl source is needed for the formation of acrylamide from asparagine. Furthermore, it is observed that acrylamide is an intermediate of the Maillard reaction rather than an end product, which implies that it is also subject to a degradation reaction.
DOCUMENT
Development of novel testing strategies to detect adverse human health effects is of interest to replace in vivo-based drug and chemical safety testing. The aim of the present study was to investigate whether physiologically based kinetic (PBK) modeling-facilitated conversion of in vitro toxicity data is an adequate approach to predict in vivo cardiotoxicity in humans. To enable evaluation of predictions made, methadone was selected as the model compound, being a compound for which data on both kinetics and cardiotoxicity in humans are available. A PBK model for methadone in humans was developed and evaluated against available kinetic data presenting an adequate match. Use of the developed PBK model to convert concentration–response curves for the effect of methadone on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in the so-called multi electrode array (MEA) assay resulted in predictions for in vivo dose–response curves for methadone-induced cardiotoxicity that matched the available in vivo data. The results also revealed differences in protein plasma binding of methadone to be a potential factor underlying variation between individuals with respect to sensitivity towards the cardiotoxic effects of methadone. The present study provides a proof-of-principle of using PBK modeling-based reverse dosimetry of in vitro data for the prediction of cardiotoxicity in humans, providing a novel testing strategy in cardiac safety studies.
MULTIFILE
Three empirical models were used to fit the formation of acrylamide in crisps of three different cold-sweetened potato genotypes, fried under the same experimental conditions. Statistical methods were used to compare the performance of the models, with the "Logistic-Exponential" model performing the best. The obtained model parameters for the formation of acrylamide showed improvement in precision compared to an earlier study, the precision of the parameter estimates for the degradation of acrylamide was still problematic. Nevertheless, the predictive capacity of the "Logistic-Exponential" model was tested, as this model showed a strong correlation between parameter a and the reducing sugar content of the raw potato. The predictions from this model for the formation of acrylamide in potato crisps were close to earlier reported experimental values. Therefore, the use of the "Logistic-Exponential" model as a tool to predict acrylamide in potato crisps seems promising and should be developed further.
DOCUMENT
