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Biomedical subjects

A G Oomen

Publications and source records attributed to A G Oomen.

6 recordsLinked to original sources

Effect of bile type on the bioaccessibility of soil contaminants in an in vitro digestion model.

Soil ingestion is an important pathway of exposure for many nonvolatile contaminants for man and in particular for children. A fraction of the ingested contaminant may not dissociate from the soil particles during digestion in the gastrointestinal tract, and is thus not available for transport across the intestinal epithelium. In order to estimate the contaminant fraction that is mobilized from soil, i.e., the bioaccessible fraction, several in vitro digestion models have been developed. The currently existing digestion models display many differences. One aspect that may affect bioaccessibility and may induce differences between digestion models is the bile that is used. Often freeze-dried bile of animal origin is preferred to purified bile salts. However, also the animal origin of bile may give rise to differences in bioaccessibility because bile composition appears to be species dependent. In the present study, we compared the bioaccessibility of benzo[a]pyrene, arsenic, cadmium, and lead of four different soils after digestion with ox bile from two different suppliers, pig bile, and chicken bile. Bioaccessibility appeared to vary amongst the different soils and contaminants. Only chicken bile increased the bioaccessibility of lead and cadmium significantly and relevantly for one of four soils. For chicken bile, the bioaccessibility of lead was 3-5.5 times greater than for the other bile types and the bioaccessibility of cadmium was 1.5 times greater. In all other cases, the bioaccessibility differences were less than 10%, which is considered irrelevant for risk assessment purposes.

Animals↗

Lead speciation in artificial human digestive fluid.

For children, soil ingestion via hand-to-mouth behavior can be a main route of exposure to contaminants such as lead. The ingested lead can be mobilized from the soil and form new species during the digestion process. Speciation is known to affect the availability of metals for transport across biological membranes. In the present study, in vitro digestions were performed with (artificially contaminated) standard soil. Lead speciation was investigated in the artificial human intestinal fluid, i.e., chyme, to gain insight into the lead species and lead fractions that may be available for transport across the intestinal epithelium. To that end, both a lead ion selective electrode (Pb-ISE) and a voltammetric technique (differential pulse anodic stripping voltammetry, DPASV) were used. The results indicate that in chyme only a negligible lead fraction is present as free Pb(2+), whereas lead phosphate and lead bile complexes are important fractions. The lead phosphate complexes appear to be voltammetrically labile, i.e., in dynamic equilibrium with Pb(2+). Labile complexes can dissociate and the produced metal ions can subsequently be transported across the intestinal epithelium. Lead bile complexes may behave in a similar manner, or this organometal complex may be able to traverse the intestinal membrane. Therefore, substantially more than only the free metal ion should be considered available for transport across the intestinal epithelium.

Administration, Oral↗

In vitro intestinal lead uptake and transport in relation to speciation.

Children might be exposed substantially to contaminants such as lead via soil ingestion. In risk assessment of soil contaminants there is a need for information on oral bioavailability of soilborne lead. Oral bioavailability can be seen as the result of four steps: (1) soil ingestion; (2) mobilization from soil during digestion, i.e., bioaccessibility; (3) transport across the intestinal epithelium; and (4) first-pass effect. Lead bioaccessibility and speciation in artificial human small intestinal fluid, i.e., chyme, have been investigated in previous studies. In the present study, transport of bioaccessible lead across the intestinal epithelium was investigated using the Caco-2 cell line. Cell monolayers were exposed to (diluted) artificial chyme. In 24 h, approximately 27% of the lead were associated to the cells and 3% were transported across the cell monolayer, without signs of approaching equilibrium. Lead associated to the cells showed a linear relationship with the total amount of lead in the system. Bile levels did not affect the fraction of lead associated to Caco-2 cells. Extrapolation of the lead flux across the Caco-2 monolayer to the in vivo situation indicates that only a fraction of the bioaccessible lead is transported across the intestinal epithelium. Furthermore, the results indicate that as the free Pb(2+) concentration in chyme was negligible, lead species other than the free metal ion must have contributed to the lead flux toward the cells. On the basis of lead speciation in chyme, this can be attributed to dissociation of labile lead species, such as lead phosphate and lead bile complexes, and subsequent transport of the released free metal ions toward the intestinal membrane.

Administration, Oral↗

Development of an in vitro digestion model for estimating the bioaccessibility of soil contaminants.

Soil ingestion can be a major route of human exposure to many immobile soil contaminants. The present risk assessment is based on toxicity studies in which contaminants are typically ingested in liquid or food matrices. The difference in bioavailability of contaminants ingested in a soil matrix is not taken into account. To become bioavailable, contaminants first need to become bioaccessible, i.e., they must be mobilized from the soil during digestion. Soil contaminants may be less bioaccessible than contaminants from liquid or food, so that the risks can be overestimated. This article describes the development of an in vitro human digestion model that is physiologically based. It can be used as a tool to assess bioaccessibility. We explain the rationale behind the experimental design of the model. We address the aspects of the simulated compartments of the gastrointestinal tract, temperature, soil-to-fluid ratio, ratio of digestive juices, transit times, centrifugation, pH values, mixing, constituents and their concentrations, and bile. The optimized in vitro digestion model was applied in a case study. The bioaccessibility of lead in pottery flakes with glazing was determined and compared to the bioaccessibility of lead in the soil from which the pottery flakes were removed. The data indicate that pottery flake lead is considerably less bioaccessible (0.3 +/- 0.2%) than lead in soil without pottery flakes (42-66% at the same site, and 28-73% at other sites in the same town). Furthermore, bioaccessibility values of lead in soil appear to be less than calculated bioaccessibility values for dietary lead (which are based on the criterion used by the Dutch risk assessment and on literature absorption data). This indicates that accounting for the matrix of ingestion can affect the exposure assessment for lead. The in vitro digestion model is a promising tool for studying the effect of the ingestion matrix on bioaccessibility.

Biological Availability↗

Availability of polychlorinated biphenyls (PCBs) and lindane for uptake by intestinal Caco-2 cells.

Children may ingest contaminated soil from hand to mouth. To assess this exposure route, we need to know the oral bioavailability of the contaminants. Two determining steps in bioavailability of soil-borne contaminants are mobilization from soil during digestion, which is followed by intestinal absorption. The first step has been investigated in previous studies that showed that a substantial fraction of PCBs and lindane is mobilized from soil during artificial digestion. Furthermore, almost all contaminants are sorbed to constituents of artificial human small intestinal fluid (i.e., chyme), whereas only a small fraction is freely dissolved. In this study, we examine the second step using intestinal epithelial Caco-2 cells. The composition of the apical exposure medium was varied by addition of artificial chyme, bile, or oleic acid at similar or increasing total contaminant concentrations. The uptake curves were described by rate constants. The uptake flux seemed to be dose-dependent. Furthermore, different exposure media with similar total contaminant concentrations resulted in various uptake rates. This can be attributed to different freely dissolved concentrations and carrier effects. In addition, the large fractions of contaminants in the cells indicate that PCBs and lindane sorbed to bile, oleic acid, and digestive proteins contributed to the uptake flux toward the cells. These results can be extrapolated qualitatively to in vivo conditions. Because the sorbed contaminants should be considered available for absorption, the first step of mobilization from soil is the most important step for oral bioavailability of the presently investigated soil-borne contaminants.

Administration, Oral↗

Nonequilibrium solid-phase microextraction for determination of the freely dissolved concentration of hydrophobic organic compounds: matrix effects and limitations.

Solid-phase microextraction (SPME) has recently been applied to measure the freely dissolved concentration, as opposed to the total concentration, of hydrophobic substances in aqueous solutions. This requires that only the freely dissolved analytes contribute to the concentration in the SPME fiber coating. However, for nonequilibrium SPME the sorbed analytes that diffuse into the unstirred water layer (UWL) adjacent to the SPME fiber can desorb from the matrix and contribute to the flux into the fiber. These processes were described as a model. Experimentally, an equilibrated and disconnected headspace was used as a reference for the freely dissolved concentration. The expected contribution of desorbed analytes to the uptake flux was measured for PCB no. 52 in a protein-rich solution, while it was not measured in a matrix containing artificial soil. The latter was possibly due to slow desorption of the analyte from the artificial soil. On the basis of the present study, a contribution of desorbed analytes to the uptake flux is expected only if(1) the rate-limiting step of the uptake process is diffusion through the UWL, (2) the concentration of the sorbed analyte is high, and (3) desorption from the matrix is fast.

Chemical Phenomena↗