Oomen A G, Tolls J, Kruidenier M, Bosgra S S, Sips A J, Groten J P
Research Institute of Toxicology (RITOX), Environmental Toxicology and Chemistry, Utrecht University, Utrecht, The Netherlands.
Environ Health Perspect. 2001 Jul;109(7):731-7. doi: 10.1289/ehp.01109731.
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.
儿童可能会通过手口接触摄入受污染的土壤。为评估这一暴露途径,我们需要了解污染物的口服生物利用度。土壤传播污染物生物利用度的两个决定性步骤是在消化过程中从土壤中释放出来,随后是肠道吸收。第一步已在先前的研究中进行了调查,结果表明在人工消化过程中,相当一部分多氯联苯和林丹会从土壤中释放出来。此外,几乎所有污染物都吸附在人工人小肠液(即食糜)的成分上,而只有一小部分是自由溶解的。在本研究中,我们使用肠上皮Caco-2细胞来研究第二步。通过在相似或增加的总污染物浓度下添加人工食糜、胆汁或油酸来改变顶端暴露介质的组成。摄取曲线用速率常数来描述。摄取通量似乎是剂量依赖性的。此外,总污染物浓度相似的不同暴露介质导致了不同的摄取速率。这可归因于不同的自由溶解浓度和载体效应。此外,细胞中大量的污染物表明,吸附在胆汁、油酸和消化蛋白上的多氯联苯和林丹促成了向细胞的摄取通量。这些结果可以定性地外推到体内情况。由于应将吸附的污染物视为可吸收的,因此从土壤中释放的第一步是目前所研究的土壤传播污染物口服生物利用度的最重要步骤。