PARENT SESSION

4A - Integrated ecological and human health RA
Hall 18
10:45 AM - 12:30 PM, Monday, 28 April 2003
Chair: Van den Brink, P.J.¹, ¹
Co-chair: Webb, S.², ²

(MO18/10) Human physiologically based in vitro digestion models simulating fasting and fed conditions.

Versantvoort, C.¹, Oomen, A.¹, Sips, A.¹, ¹ RIVM, Lab. Exposure Assessment, Bilthoven, Netherlands

ABSTRACT- It is known that the fasted or fed status can have a large impact on the bioavailability of compounds. The presence of food markedly alters the conditions in the gastrointestinal tract. The effect of food on the bioavailability of compounds is often due to the bioaccessibility (dissolution) of compounds from in the chyme and their transport across the intestinal epithelium. We present in vitro digestion models reflecting the conditions of the gastrointestinal tract for the fasted and fed state of man in order to study the bioaccessibility of compounds form their matrix. The method involves a three-step procedure simulating human digestion for the fasted cq fed state in subsequently mouth, stomach and small intestinal compartment. Infant formula feedings were used as food and physiological based conditions i.e. composition of media, pH and residence time periods typical for each compartment were applied. The effects of fasted vs fed conditions were studied on the bioaccessibility of different types of compounds from soil: metals (lead, cadmium, arsenic (metalloid)) and a lipophilic compound (benzo[a]pyrene). The bioaccessibility of lead, cadmium, arsenic and benzo[a]pyrene from soil was on average 22%, 30%, 44% and 6%, respectively, for fasting conditions. The fed state had no (arsenic and cadmium) or little (lead < factor 2) effect on the bioaccessibility of the metals. In contrast, the bioaccessibility of benzo[a]pyrene was 3 to 8 fold increased under fed conditions compared to the fasted conditions. Prolongation of the residence time in the stomach from 2h to 16h had no effect on the bioaccessibility of either compound. Doubling the bile concentration increased the bioaccessibility of only benzo[a]pyrene by a factor of 1.5 to 2. Thus, the bioaccessibility from soil was compound specific, whereas fed conditions had a major effect on the bioaccessibility of the lipophilic compound benzo[a]pyrene. The in vitro digestion models, which closely simulate fasted and fed conditions, can be used to model events occurring during digestion and solubilisation of compounds in the gastrointestinal tract. Furthermore, the digestion models in combination with the Caco-2 transport model (data will be presented at the meeting) can assist in more accurate predictions of absorption of compounds.

Key words: digestion models, human exposure