title: Availability of polychlorinated biphenyls (PCBs) and lindane for uptake by intestinal Caco-2 cells.
abstract: 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.
authors.affiliation: Research Institute of Toxicology (RITOX), Environmental Toxicology and Chemistry, Utrecht University, Utrecht, The Netherlands. agnes.oomen@rivm.nl
authors.forename: A G
authors.initials: AG
authors.lastname: Oomen
authors.forename: J
authors.initials: J
authors.lastname: Tolls
authors.forename: M
authors.initials: M
authors.lastname: Kruidenier
authors.forename: S S
authors.initials: SS
authors.lastname: Bosgra
authors.forename: A J
authors.initials: AJ
authors.lastname: Sips
authors.forename: J P
authors.initials: JP
authors.lastname: Groten
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D018938:Caco-2 Cells / Q000187:drug effects / Q000502:physiology; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000493:pharmacokinetics*; D005227:Fatty Acids / Q000378:metabolism; D001556:Hexachlorocyclohexane / Q000493:pharmacokinetics*; D006801:Humans; D007306:Insecticides / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D007700:Kinetics; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics*; D012989:Soil Pollutants / Q000493:pharmacokinetics*; D012995:Solubility
chemical_list: D004785:Environmental Pollutants; D005227:Fatty Acids; D007306:Insecticides; D012989:Soil Pollutants; D001556:Hexachlorocyclohexane; D011078:Polychlorinated Biphenyls