Biomarker measurement

Buckley TJ, Liddle J, Ashley BE, et al. 1997. Environmental and biomarker measurements in nine homes in the lower Rio Grande Valley Multimedia results for pesticides, metals, PAHs, and VOCs. Environ Int 23 705-732. 

The average values of the biomarker measurements in flounder are also shown in Table 3. For several of the biomarkers, there was a distinct and significant difference between the average values at the saltwater and freshwater reference sites. This was the case for CYPIA, protein content in the liver, GST measured by lab 1 (GST at the saltwater reference site was not measured by lab 2), SOD analysed by lab 3, microsomal 2-Keto-4-methiolbutyric acid (KMBAmic), RNA/ DNA ratio (differences with p<0.01), AChE and VTG in male fish (all with p<0.05). 

Center for Environmental Health Flemish biomonitoring program for surveillance of environmental health Program will include development of an early warning system based on biomarker measurements in people living in Flanders. Study population includes 1,600 people (European Commission 2004). 

In the most straightforward risk-based approach, epidemiologic studies have developed exposure-response relationships based on biomarker measurements in hair, blood, urine, or other matrices (e.g., mercury, lead) (see Figure 5-2a). The relationships can be applied directly to new biomonitoring data to determine where on the exposure-response curve any person is. That may facilitate an understanding of risk, but it does not analyze sources of exposure, so other techniques (such as environmental sampling and behavioral surveys) may be needed to assess where the exposure came from. 

Rigas, M.L., M.S. Okino, and J.J. Quackenboss. 2001. Use of a pharmacokinetic model to assess chlorpyrifos exposure and dose in children, based on urinary biomarker measurements. Toxicol. Sci. 61(2) 374-381. 

Biomarkers do not measure exposure directly, but are an indicator of absorbed dose. A biomarker of exposure is defined as a xenobiotic substance or its metabolite(s) or the product of an interaction between a xenobiotic agent and some target molecules(s) or cell(s) that is measured within a compartment of an organism and can be related to exposure. Urine, blood, nail, saliva, hair, and faeces are common media collected for biomarker measurements. Maternal biomarkers of exposure can also be measured in amniotic fluid and breast milk. These matrices can also provide a measure of exposure for children, both prenatally and postnatally. Biomarkers in first teeth have also been used to assess early childhood exposure, whereas biomarkers in meconium and cord blood have been used to assess in utero exposures. Biomarkers of genetic damage (e.g. DNA adducts) have been extensively used to assess exposure to genotoxic agents (Neri et al., 2006). 

Perinatal stage - 29th week of pregnancy to 7 days after birth Neonate - birth to 28 days Infant - 28 days to 1 year Birth to 3 months Child s exposure measured or modelled biomarker measurements may be affected by differential uptake and metabolism depending upon age and... 

Empirical PD models describe the relationship between drug concentrations in body fluids and the observed drug effect (efficacy, safety, biomarker measurements). Similar to empirical PK models, PD models are relatively simple and a variety of drug effects can be described with a few P D models. Empirical PD mod-... 

An especially useful form of validation is where the results of an assessment can be compared with independent data or information (e.g. comparing predicted exposure with biomarker measurements or epidemiological studies). When making such comparisons, it is important to remember that both sides of the comparison are subject to uncertainty. The methods described in this document should be applied to the independent data, as well as to the exposure assessment, to provide a fair comparison between the two. 

Known, not novel, dose-responsive biomarkers measured in monkey Unknown, observed in mice only Single escalating dose in healthy subjects No NOAEL identified in mice, no AEs observed at any dose level in monkeys NOEL identified in monkey 0.015 mg/kg Not determined... 

Martfn-Dfaz ML, Villena-Lincoln A, Bamber S, Blasco J, DelValls TA. 2005b. An integrated approach using bioaccumulation and biomarker measurements in female shore crab, Carcinus maenas. Chemosphere 58 615-626. 

Does the biomarker measure exposure accurately or does it cross-react with other potential risk factors ... 

Major problems with CSF biomarkers such as A(h 42, total tau, and phosphorylated tau are large variations in biomarker measurements among and within laboratories. The overall variability remains too high to allow assignment of universal biomarker cutoff values for a specific intended use [127]. 

This class of biomarkers measures actual toxic effects at the molecular, cellular and physiological levels. It is more closely related to pathological conditions (morbidity) that could lead to death. The oxidative status of cells has been proposed as a universal mechanism leading to cell dysfunction. The normal metabolism (e.g. (3-oxidation, pentose shunt pathway, immune function) produces oxidizing precursors such as hydrogen peroxide (H2O2), nitric oxide (NO) and peroxynitrite (ONOO) that are rapidly eliminated by non-enzymatic and enzymatic antioxidants to prevent tissue damage. 

Akcha, F., Izuel, C., Venier, P., Budzinski, H., Burgeot, T. and Narbonne, J. (2000) Enzymatic biomarker measurement and study of DNA adduct formation un benzo(a)pyrene treated... 

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