Target tissue, definition

By definition, the determinative procedure must be able to quantify the concentration of the marker residue. For compounds with a tolerance, it is critical that the analysis be able to determine accurately if the concentration of the marker residue is above or below the tolerance in the target tissue. The CVM guidelines for determinative procedures call for an average recovery >80% with a coefficient of variation (CV) of <10% for marker residue tolerances of lOOpgkg or greater and an average recovery of >60% with a CV of <20% for marker residues with a tolerance below 100 ppb. 

The PBPK model development for a chemical is preceded by the definition of the problem, which in toxicology may often be related to the apparent complex nature of toxicity. Examples of such apparent complex toxic responses include nonlinearity in dose-response, sex and species differences in tissue response, differential response of tissues to chemical exposure, qualitatively and/or quantitatively difference responses for the same cumulative dose administered by different routes and scenarios, and so on. In these instances, PBPK modeling studies can be utilized to evaluate the pharmacokinetic basis of the apparent complex nature of toxicity induced by the chemical. One of the values of PBPK modeling, in fact, is that accurate description of target tissue dose often resolves behavior that appears complex at the administered dose level. 

Remaining Problems. The most profound advance in asthma therapy would be a means for definitively altering the inherited molecular abnormality which predisposes one to become an asthmatic. Lacking this, other advances could clearly make asthma a more bearable problem. More efficient mechanisms for blocking the effects of specific allergens on the target tissues could... 

In plants it is difficult to define precise target organs, tissues, or cells for the various hormones. This is particularly apparent if one looks at the effects of each individual hormone as shown in Figs. 6.2 through 6.6. Similar difficulties are encountered with some animal hormones, for example adrenalin. In fact there is no theoretical reason nor does it follow from the definition of a hormone why each hormone must have only one target tissue or cell. This point is described in detail in Chapter 1, this Volume. 

In vivo systems have been employed first and foremost for the gross and microscopic description of the changes induced in target tissues by the administration of estrogenic hormones. These changes are utilized for the development of assay procedures upon which rest the definition and quantitative estimates of estrogenic activity. 

Marion Cottier and collaborators summarized in their chapter a set of observations that lead to the definition of NO as radiosensitizer molecule in bacteria and mammalian tumor cells. The effect of NO in the sensitization of tumor cell to radiotherapy has been demonstrated in preclinical and clinical studies. These effects can be either direct, by the cellular induction or generation of NO by the target tissue (NOS-mediated induction or activation) as revealed by Peter Siesjo in his chapter, or indirect by the use of NO-releasing compounds such as NO donors extensively discussed in these chapters. 

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