In vitro gastrointestinal method

Rodriguez, R. R., Basta, N. T., Casteel, S. W., and Pace, L. W. (1999). An in vitro gastrointestinal method to estimate bioavailable arsenic in contaminated soils and solid media. Environ. Sd. Technol. 33, 642-649. 

Gastrointestinal absorption of metal contaminants is a dynamic process involving dissolution and absorption (Fig. 1). In vitro gastrointestinal methods based solely... 

Rodriguez et al. (34) evaluated the ability of the two in vitro gastrointestinal methods to estimate bioavailable As in contaminated soil and media. One method incorporated an adsorbent in a permeable membrane to act as a sink for dissolved As to mimic gastrointestinal absorption (IVG-AB). The other method (IVG) did not use an adsorbent and simply relied on dissolution of As from soil. In vitro results were compared with in vivo relative bioavailable As determined from dosing trials using immature swine. Fifteen contaminated soils collected from mining/smelter sites ranging from 401 to 17,500 mg As kg were evaluated. 

The IVG and PBET in vitro gastrointestinal methods were correlated with bioavailable As in contaminated media. Recent studies have shown the IVG method of Rodriguez et al. (34) can be used to estimate Pb bioavailability in contaminated soil and media (38). 

SAS. SAS/STAT User s Guide, Release 6.03 ed. Cary, NC SAS Institute Inc., 1988. JL Schroder, NT Basta, DC Ward, RR Rodriguez, SW Casteel. Estimating hioavaU-able As, Ph, and Cd in contaminated soil hy an in vitro gastrointestinal method. Proc Agron Soc Am Soil Sci Soc of Am, Minneapolis, MN, 2000, p. 235. 

By combining Uquid chromatography and ICP-MS and LC-electrospray ionization (ESI)-MS-MS, the major compounds determined were SeMet and SeCys [56]. This method was further extended to the analyses of in vitro gastrointestinal digests of the Brazil nut. CE-ICP-MS was also used, but did not unravel any other species [46]. 

For some substances, a wealth of genotoxicity data may be available from studies conducted in vitro and/or in vivo. In addition to studies conducted according to test guidehne methods, there may be nonstandard studies available in which first site of contact tissues, i.e., skin, epithelium of the respiratory or gastrointestinal tract, have been examined. In addition, data from plant, fungal, or insect Drosophila) systems may be available. Occasionally, studies of genotoxic effects in humans may also be available. The vahdity and usefulness of each of the data sets to the overall assessment... 

Certain substances may need special consideration, such as highly electrophilic substances, which give positive results in vitro, particularly in the absence of metabolic activation. Although these substances may react with proteins and water in vivo and thus be rendered inactive toward many tissues, they may be able to express their mutagenic potential at the first site of contact with the body. Consequently, the use of test methods that can be applied to the respiratory tract, upper gastrointestinal tract, and skin may be appropriate. 

The permeability class boundary is based indirectly on the extent of absorption (fraction of dose absorbed, not systemic BA) of a drug substance in humans and directly on measurements of the rate of mass transfer across human intestinal membrane. Alternatively, nonhuman systems capable of predicting the extent of drug absorption in humans can be used (e.g., in vitro epithelial cell culture methods). In the absence of evidence suggesting instability in the gastrointestinal tract, a drug substance is considered to be highly permeable when the extent of absorption in humans is determined to be 90% or more of an administered dose based on a mass balance determination or in comparison to an intravenous reference dose. 

The following methods can be used to determine the permeability of a drug substance from the gastrointestinal tract (1) in vivo intestinal perfusion studies in humans (2) in vivo or in situ intestinal perfusion studies using suitable animal models (3) in vitro permeation studies using excised human or animal intestinal tissues or (4) in vitro permeation studies across a monolayer of cultured epithelial cells. 

In Vitro Methods. In recent years, there has been great interest in the development of laboratory test systems that can simulate the disintegration and dissolution of a drug product in the human gastrointestinal... 

A simple, rapid, and inexpensive in vitro method for estimating food iron availability is described. The method involves a simulated gastrointestinal digestion using commercially available enzymes. Soluble, low molecular weight iron is used as an indicator of iron availability. Similar results are obtained when the soluble iron is intrinsic food iron or added extrinsic radioiron. 

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