Comparison of five in vitro digestion models to in vivo experimental results: Lead bioaccessibility in the human gastrointestinal tract

Abstract

1This paper presents a multi-laboratory comparison study of in vitro models assessing 2 bioaccessibility of soil-bound lead in the human gastrointestinal tract under simulated fasted 3 and fed conditions. Oral bioavailability data from a previous human in vivo study on the same 4 soil served as a reference point. In general, the bioaccessible lead fraction was significantly 5 (P<0.05) different between the in vitro methods and ranged for the fasted models from 2% to 6 33% and for the fed models from 7% to 29%. The in vivo bioavailability data from literature 7 were 26.2 ± 8.1% for fasted conditions, compared to 2.5 ± 1.7% for fed conditions. Under fed 8conditions, all models returned higher bioaccessibility values than the in vivo bioavailability, 9 whereas three models gave a lower bioaccessibility than bioavailability under fasted 10 conditions. These differences are often due to the method's digestion parameters that need 11 further optimization. An important outcome of this study was the determination that the 12 method for separating the bioaccessible lead from the non-bioaccessible fraction 13 (centrifugation, filtration, dialysis) is crucial for the interpretation of the results. 14 Bioaccessibility values from models that use more stringent separation methods better 15 approximate in vivo bioavailability results, yet at the expense of the level of conservancy. We 16 conclude from this study that more optimization of in vitro digestion models is needed for use 17 in risk assessment. Moreover, attention should be paid to the separation method since it 18 largely influences what fraction of the contaminant is considered bioaccessible. 19 20

Lead bioaccessibility in 12 contaminated soils from China: Correlation to lead relative bioavailability and lead in different fractions

“…Differences in other assay parameters (e.g., soil:solution ratio) and gastric fluid components (e.g., chyme composition)were probably responsible. By comparing five in vitro methods, Van de Wiele et al [15]reported that less Pb was dissolved under lower soil:solution ratio condition.…”

“…As a result, various in vitro assays to determine Pb bioaccessibility have been developed, whichmeasures the soluble Pb fraction from soil in simulatedhuman gastrointestinalfluids [10][11][15][16]. Commonmethods includeSolubility/Bioavailability Research Consortium method (SBRC), in vitro gastrointestinalmethod (IVG), physiologically based extraction test (PBET), DeutschesInstitutfürNormunge.V.…”

“…method (DIN), and unified BARGE method(UBM) [17][18][19][20][21]. However, due to variation in gastrointestinal fluid components and assay parameters (e.g., pH, soil/solution ratio, and extraction time), different assays often producedifferentbioaccessibility results [10,15,22]. Therefore, before these assays can be used to accurately predict Pb-RBAin contaminated soils, they need to be correlated toPb-RBA determined via animal models.…”

An inter-laboratory trial of the unified BARGE bioaccessibility method for arsenic, cadmium and lead in soil

“…BARGE has been involved in comparing and evaluating the physico-chemical processes within the many models and systems that have been developed over the years to measure bioaccessibility and contaminant exposure e.g. (Oomen et al, 2002;Basta et al, 2007;Cave et al, 2007;Chan et al, 2007;Gal et al, 2007;Gron et al, 2007;Ljung et al, 2007;Nathanail and Smith, 2007;Palumbo-Roe and Klinck, 2007;Subacz et al, 2007;Van de Wiele et al, 2007;Wragg and Klinck, 2007). A priority objective is to provide robust and defensible data on bioaccessibility that can be used in human health risk assessments and policy making.…”

“…The key contaminants included in this work are arsenic (As), lead (Pb) and cadmium (Cd) as they are potentially harmful to human health (ATSDR, 2007b;ATSDR, 2007a;ATSDR, 2008) and the most common elements undergoing bioaccessibility research Ruby et al, 1993;Ruby et al, 1996;Albores et al, 2000;Oomen et al, 2002;Marschner et al, 2006;Chan et al, 2007;Datta et al, 2007;Drexler and Brattin, 2007;Finzgar et al, 2007;Hansen et al, 2007;Juhasz et al, 2007aJuhasz et al, , 2007bLjung et al, 2007;Sarkar et al, 2007;Subacz et al, 2007;Turner and Ip, 2007;Van de Wiele et al, 2007;Beak et al, 2008;Moseley et al, 2008;Girouard and Zagury, 2009;Morman et al, 2009;Nagar et al, 2009;Poggio et al, 2009;Smith et al, 2009;Zhang et al, 2009;Demetriades et al, 2010;Juhasz et al2010). …”