Physiological Model for Absorption

Non-animal approaches for toxicokinetics in risk evaluations of food chemicals

“…Evaluation of the use of in vivo kinetic data within the investigated risk evaluations of food chemicals and pesticides (EFSA) and medicines (EMA) shows distinct differences between food (Peters, 2012). Though not often accounted for, the fraction that escapes luminal degradation, by, e.g., digestive enzymes or conversion by the intestinal microbiota, also affects the oral bioavailability.…”

“…In general, digestion models have been developed to predict i) the release of chemicals from a formulation (dissolution of medicines) (Cascone et al, 2016;Klein, 2010), ii) the release of chemicals from a complex matrix (i.e., bioaccessibility) (Oomen et al, 2003;Versantvoort et al, 2005) or iii) predicting digestion of macronutrients (e.g., Kopf-Bolanz et al, 2012). However, digestion methods are also increasingly used to study the stability of chemicals in the presence of digestive enzymes and the gastro-intestinal pH (e.g., Islam et al, 2014;Peters et al, 2012;Walczak et al, 2015aWalczak et al, , 2012 and in some cases the breakdown by microbiota (Verwei et al, 2016). New types of dynamic models that are gaining increasing attention are microfluidic gut-on-a-chip models, which provide the potential to develop protocols where in vitro cellular models for absorption harbour intestinal microbiota.…”

“…Nonspecific binding of highly lipophilic compounds to the plastic surfaces may result in a poor predictive value of highly lipophilic compounds (Hubatsch et al, 2007;Krishna et al, 2001;Neuhoff et al, 2006). Finally, variability between laboratories occurs as a result of often minor differences in cell culture conditions (e.g., seeding density, composition of the media) and test conditions (Peters, 2012). This means that despite the gold standard use of Caco-2 cells, their use also has its boundaries.…”