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Mechanistic Use of Cell Models

For the evaluation of a possible relationship between the molecular structure of a potential candidate and its transport abilities to cross the epithelial membrane of the gut, the mechanism or route of transport must be known [1,4]. This is due to the structural requirements for the transcellular route being different from the paracellular route. During the lead optimization phase - when many mechanistically based studies are performed - the cell culture-based models can also be used with great confidence. [Pg.111]


Advances in the understanding of the immunobiology of skin sensitization have led to the establishment of predictive in vivo tests which not only identify sensitizing hazards but also characterize their potency. Recently, appreciation of the underlying biology has also resulted in the development of mechanistically based in vitro alternatives which offer the prospect of the replacement of current in vivo methods. Assays under active validation include the Direct Peptide Reactivity Assay (DPRA), the human Cell Line Activation Test (h-CLAT), and KeratinoSens. None of the methods have a sufficient level of accuracy or freedom from applicability domain limitations to allow them to act as a standalone replacement. Consequently, it will be necessary to consider how to deploy these assays, perhaps in combination and/or in a structured assessment of skin sensitization hazard, to ensure at least the same level of predictive accuracy as the in vivo methods. However, a challenge remains the capacity of these methods to provide potency information on skin-sensitizing chemicals has yet to be assessed. This is an essential requirement for future risk assessment without use of animal models if we are to retain the same level of human health protection that is currently delivered. [Pg.225]

In vitro cell culture models of human nasal epithelium based on primary culture technologies have proven to be extremely useful for mechanistic studies of nasal epithelial permeability and drug absorption [13]. However, efforts... [Pg.217]

There are three main sources of evidence for pro-tumorigenic activity of bile acids in the lower gastro-intestinal tract (activity in rodent CRC models, human observational data and mechanistic studies using CRC cells in vitro), which together create a strong case for a role for colorectal mucosal bile acid exposure during human colorectal carcinogenesis. [Pg.86]

The use of in vitro cell culture models for mechanistic studies and as permeability screens for the blood-brain barrier in the pharmaceutical Industry-Background and current status in the drug discovery process. Vascular Pharmacology, 38, 355-364. [Pg.138]

The conventional dye cell uses I /I2 as the redox couple, and no other known redox couple works nearly as well [49]. The use of most other redox couples, and most substrates besides Sn02, is expected to accelerate the recombination reactions relative to the conventional dye cell and thus diminish Voc, independent of the mechanistic model (see Section VI). Because this would obscure what we were looking for, the relationship between and Voc, we used only the reduced half of the redox couple in order to minimize recombination rates and maximize Voc. Versus vacuum, the work functions of the clean electrodes are = 4.3 eV [88], 8 02 = 4.8 eV [88], = 5.1 eV [89], and 1 =... [Pg.76]


See other pages where Mechanistic Use of Cell Models is mentioned: [Pg.111]    [Pg.111]    [Pg.113]    [Pg.115]    [Pg.117]    [Pg.119]    [Pg.111]    [Pg.111]    [Pg.113]    [Pg.115]    [Pg.117]    [Pg.119]    [Pg.184]    [Pg.120]    [Pg.295]    [Pg.375]    [Pg.143]    [Pg.125]    [Pg.59]    [Pg.235]    [Pg.36]    [Pg.132]    [Pg.142]    [Pg.97]    [Pg.422]    [Pg.393]    [Pg.307]    [Pg.343]    [Pg.371]    [Pg.203]    [Pg.229]    [Pg.258]    [Pg.315]    [Pg.175]    [Pg.177]    [Pg.188]    [Pg.174]    [Pg.337]    [Pg.369]    [Pg.33]    [Pg.123]    [Pg.216]    [Pg.105]    [Pg.110]    [Pg.405]    [Pg.137]    [Pg.118]    [Pg.444]    [Pg.826]    [Pg.32]    [Pg.687]   


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Cell models

Mechanistic modeling

Mechanistic models

Modeling, use

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