Animal models exposure

Guilmette RA, Eidson AF. 1992. Using animal dosimetry models to interpret human bioassay data for actinide exposures. J Radioanal Nucl Chem 156(2) 425-449. 

At this time, the above equation is for animal exposures of 30 minutes and includes deaths that occur within the following 24 hours. Post-exposure deaths that occur after that are not predicted by the model. Some data exists to expand this equation to other exposure times (11,13). 

Animal experimental models of nickel-induced skin sensitivity are few and have been conducted only under very specialized conditions (USEPA 1986). Studies examining the mechanism of nickel contact sensitization and its extent in wildlife are needed (USPHS 1993). The importance of the surface properties and crystalline structure of nickel compounds in relation to their reactivity and protein-binding activities is well documented. It is therefore necessary to identify clearly the nickel compounds to which exposure occurs (Sunderman etal. 1984). Acute and chronic dermal and... 

Exposure models are a key tool in deriving SQSs for human health and environmental quality. These models should include all relevant soil processes and descriptions of human and animal behavior. Exposure models can be used to assess the likely spatial extent and severity of standard exceedance and provide input to prioritization of substances for which soil standards may be developed. 

In the 1980s, investigators at NIST began examining the possibility of combining the analytical chemical method with the animal exposure approach to develop empirical mathematical models to predict the toxicity. These predictions were based... 

Simple in vivo assays of blood or tissue provide the first measurement ofthe ADME properties of the compound. In early discovery, studies of mixtures of compounds [23-25], which are co-administered to a single animal, can efficiently provide this exposure and tissue-penetration information. Early in vivo exposure studies help to establish dosing levels for animal models. Blood samples can also be obtained from the animal activity model following dosing to correlate in vivo pharmacology with plasma levels. Lower than expected in vivo activity can often be correlated with low plasma or tissue levels. 

When inadequate in vivo exposure or PK properties are observed, pharmaceutical profiles can be used to troubleshoot the cause of poor in vivo exposure or PK [26]. Assays for solubility, permeability, and stability (metabolic, plasma, acid) can help to track down the inadequate properties responsible for poor in vivo performance. Property optimization synthesis can then be initiated. Subsequent series analogs can be assayed to rank order compounds by properties for subsequent in vivo tests, in order to give the highest likelihood of success. Often animal studies are expensive and time-consuming, especially if they are performed using the animal activity model. Simple in vitro profiling assays can provide information for improved decisions and efficiency. 

Whole-animal test models are commonly used to determine the potential carcinogenicity of an agent (see Chapter 14). Animal models provide a platform to evaluate cancer outcomes after long-term exposure to the agent at various doses, as well as to identify possible modes of action. Although epidemiologic studies are favored... 

In this model, Pr(T)) is the lifetime probability of cancer death from lifetime exposure to dose D (often expressed in units of mg/kg-day, consistent with animals exposures). 

The GLP-1 receptor is expressed in the heart [56], In GLP-1 receptor knock-out mice structural and functional cardiac abnormalities are typical [217], In animals, exposure to GLP-1 reduces the size of myocardial necroses in the case of induced infarction [218]. In a pilot study with patients treated for acute myocardial infarction, a 48-h infusion of GLP-1 improved left-ventricular function and a waU-motility index [219]. In a dog model of dilated cardiomyopathy, GLP-1 increased glucose uptake and left-ventricular function [220]. These findings. 

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