Biomarkers assessment practices

Our new appreciation of the role of inflammation in atherosclerosis shows the way for translation of these novel biological insights to clinical practice, for example by aiding the identification of individuals at risk of adverse cardiovascular events [5]. In this context, inflammatory biomarkers such as CRP merit rigorous consideration for inclusion in risk assessment strategies. In addition, these scientific advances provide a framework... 

At the practical level, an ideal mechanistic biomarker should be simple to use, sensitive, relatively specific, stable, and usable on material that can be obtained by nondestructive sampling (e.g., blood or skin). A tall order, no doubt, and no biomarker yet developed has all of these attributes. However, the judicious use of combinations of biomarkers can overcome the shortcomings of individual assays. The main point to emphasize is that the resources so far invested in the development of biomarker technology for environmental risk assessment has been very small (cf the investment in biomarkers for use in medicine). Knowledge of toxic mechanisms of organic pollutants is already substantial (especially of pesticides), and it grows apace. The scientific basis is already there for technological advance it all comes down to a question of investment. 

The approaches described previously can be used to relate biomonitoring results to a reference population or to workplace exposures, but they do not evaluate the risk associated with the amount of a chemical found in the body. To do that, one needs to develop a relationship between biomarker concentration and toxic response, a relationship that is not commonly derived in standard toxicologic practice. The following sections outline methods for deriving such a relationship. The approaches include the ideal case of existing risk assessments based on biomarker-response relationships established in epidemiologic research. Lead and mercury are used as examples of cases in which exposure was quantified according to hair or blood biomarkers and dose-response associations were developed on this basis. 

See also Ames Test Analytical Toxicology Animal Models Biomarkers, Human Health Epidemiology Good Laboratory Practices (GLP) In Vitro Test In Vivo Test Risk Assessment, Human Health Risk Characterization Toxicity, Acute Toxicity, Chronic Toxicity, Subchronic. 

Introduction of cardiac troponin (cTn) in the early nineties for assessment of myocardial infarct in humans demonstrated that cardiac injury could be monitored with high sensitivity, high specificity, and high practicality—in contrast to all previous biomarkers (Babuin and Jaffe 2005). It is now the preferred biomarker for myocardial infarctions in humans (Alpert et al. 2000) because it stratifies risk, increasing with severity of disease and with life expectancy. In human myocardial infarct, cTn concentration peaks at 18-24 hours and correlates highly with scintigraphic measurements of infarct size made at 72 hours following injury. The increase in blood cTn may persist for a couple of weeks. 

Ideally, a biomarker of cardiac hypertrophy would be predictive, that is, its concentration in serum or plasma would be altered in advance of eventual increases in heart weight, and specific for the heart in both humans and animals commonly used in safety assessment. This would allow early detection of cardiac risk in short-duration toxicology studies (e.g., l days), serial monitoring in longer-duration toxicology studies, or pharmacology studies in order to enable the prediction of cardiac hypertrophy liabilities in humans. In practice, biomarkers are not always specific for a certain organ or... 

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