Effect biomarkers

Which of the myriad uncertainties in biomonitoring are of most concern or most difficult to understand For example, are laypeople more interested in reduction of uncertainties about biomarker-effects relations or exposure-biomarker relations ... 

Case Example of Biomonitoring-Results Interpretation Based on Biomarker-Effect Relationship Developed in Epidemiologic Studies ... 

Since microarray can be viewed as high-dimensional dataset with fewer replicates. Traditional variable selection procedures like stepwise selection cannot identify the biomarkers effectively modifications or new procedures are developed to accommodate this. 

Animal studies have shown that teas are effective in blocking or slowing carcinogenesis (121,131,133). Administration of teas or tea polyphenols to mice or rats have also been shown to decrease oxidative biomarkers, suggesting that tea polyphenols act as antioxidants (125,134). 

Mechanistic studies to identify how endocrine disrupting chemicals interact with hormone systems are required. Although population effects coupled with biomarkers of exposure are strongly suggestive of endocrine disruption, the effect could be secondary to metabolic toxicity. Establishing mechanisms may avoid the need to make decisions on a weight of evidence approach alone. 

Extensive research is currently underway to use biological markers (biomarkers) in exposure and risk assessment. Biomarkers include the reaction products of chemicals or their metabolic products with biological macromolecules, especially with DNA. They also involve indicators of effect, such as chromosomal damage, and indicators of individual genetic susceptibility. 

Biomarkers for internal close of the intoxicant—dose monitoring. Bioniarkers for early biological changes following exposure— effect... 

Section 3.8 Biomarkers of E osure and Effect Section 3.11 Methods for Reducing Toxic Effects... 

Animal-to-Human Extrapolations ENDOCRINE DISRUPTION CHILDREN S SUSCEPTIBILITY BIOMARKERS OF EXPOSURE AND EFFECT... 

Biomarkers Used to Characterize Effects Caused by Methyl Parathion INTERACTIONS WITH OTHER CHEMICALS... 

Reductions in erythrocyte and plasma cholinesterase levels are considered biomarkers of neurological effects and not hematological effects as discussed in Sections 3.2.2.4 and 3.5.2. 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC 1989). 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism s ability to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are discussed in Section 3.10 Populations That Are Unusually Susceptible. 

Following exposure of humans to organophosphates, but not specifically methyl parathion, restoration of plasma cholinesterase occurs more rapidly than does restoration of erythrocyte cholinesterase (Grob et al. 1950 Midtling et al. 1985). These findings are supported by studies of methyl parathion in animals. Erythrocyte cholinesterase levels are representative of acetylcholinesterase levels in the nervous system, and, therefore, may be a more accurate biomarker of the neurological effects of chronic low level exposure of humans to methyl parathion (Midtling et al. 1985 NIOSH 1976). 

The purpose of this chapter is to describe the analytical methods that are available for detecting, measuring, and/or monitoring methyl parathion, its metabolites, and other biomarkers of exposure and effect to methyl parathion. The intent is not to provide an exhaustive list of analytical methods. Rather, the intention is to identify well-established methods that are used as the standard methods of analysis. Many of the analytical methods used for environmental samples are the methods approved by federal agencies and organizations such as EPA and the National Institute for Occupational Safety and Health (NIOSH). Other methods presented in this chapter are those that are approved by groups such as the Association of Official Analytical Chemists (AOAC) and the American Public Health Association (APHA). Additionally, analytical methods are included that modify previously used methods to obtain lower detection limits and/or to improve accuracy and precision. 

Gupta RC, Goad JT, Milatovic D, et al. 2000. Cholinergic and noncholinergic brain biomarkers of insecticide exposure and effects. Hum Exp Toxicol 19 297-308. 

For more information on biomarkers for renal and hepatic effects of chemicals, see ATSDR/CDC Subcommittee Report on Biomarkers of Organ Damage and Dysfunction (1990) and for information on biomarkers for neurological effects, see OTA (1990). 

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