Biomarkers of exposure

In traditional epidemiological studies, exposure is usually assessed by questionnaires, job titles, job exposure matrixes (conducted by occupational hygienists based 

5 Body Burden after Enviromnental and Occupational Exposure. 92 

3 Analytical Methods for the Quantification of the Retinol Binding Protein. 94 

Abstract Analyses of cadmiutn concentratiOTis in biological material are performed using inductively coupled plasma mass spectrometry (ICP-MS) and atomic absorption spectrometiy (AAS), but also electrochemical methods, neutron activation 

Institute and Outpaticuit Oinic of Occupatitmal, Social and Environmental Medicine, Friedrich-AlexandM- University (FAU) of Erlangen-Nuremberg, Schillerstr. 25/29, D-91052 Erlangen, Gtnmany e-mail katrin.klotz ipasum.med.uni-erlangen.de 

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). 

When appropriately validated and understood, biomarkers present unique advantages as tools for exposure assessment (Gundert-Remy et al, 2003). Biomarkers provide indices of absorbed dose that account for all routes and integrate over a variety of sources of exposure (IPCS, 1993, 2001a). Certain biomarkers can be used to represent past exposure (e.g. lead in bone), recent exposure (e.g. arsenic in urine), and even future target tissue doses (e.g. pesticides in adipose tissue). Once absorbed dose is determined using biomarkers, the line has been crossed between external exposure and the dose metrics that reflect the pharmacokinetics and toxicokinetics of an agent (see section 5.3.3). 

Currently, there are only a few cases where biomarkers can be used for quantitative exposure assessment. Biomarkers can be used to indicate that a person has been exposed and that the chemical has been absorbed into the body. They can often be used to rank exposure among individuals. Biomarkers alone cannot provide information on the source, route, or duration of exposure. Even with these limitations, biomarkers, when appropriately validated, can effectively be used to evaluate trends in these exposures (CDC, 2005) and determine the effect of exposure mitigation strategies as well as predict target tissue dose. 

Deterministic models use a single value for input variables and provide a point estimate of exposure or dose. Probabilistic models take into account the fact that most input variables will have a distribution of values. These models use probability distributions to develop a range of plausible exposures for the population of concern. Understanding exposure distributions will allow understanding of the range of exposures as well as prediction of risk for the entire population. It will also allow prediction of risk for the most highly exposed individuals. Sophisticated models can be used to develop distributions for different pathways and populations. They can also be used to develop information on interindividual variability and uncertainty in the estimated distributions and to predict the variables that are most important for both exposure and dose. 

Exposure models use available information on concentrations of chemicals in exposure media along with information about when, where, and how individuals might contact the exposure media to estimate exposure. For population assessments, distributional data on exposure factors and environmental concentrations are used to estimate exposure distributions for a population. Examples of various exposure models are summarized in Table 6. 

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COMPARATIVE STUDY OF SPE AND LEE FOR PRECONCENTRATION OF URINARY 1-HYDROXYPYRENE AS A BIOMARKER OF EXPOSURE TO PAHS PRIOR TO HPLC... 

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. 

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

The most specific biomarker of exposure to methyl parathion is the presence of the compound in serum or tissue. This is an especially good biomarker for detection shortly after acute exposure. For example, methyl parathion levels were detected in the sera of five men who were exposed for 5 hours in a cotton field 12 hours after it was sprayed with methyl parathion. The route of exposure was dermal, through unprotected hands. Serum levels averaged 156 ppb after 3 hours of the 5-hour exposure, and averaged 101.4 and 2.4 ppb at 7 and 24 hours postexposure, respectively (Ware et al. 1975). 

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. 

Section 2.8 Biomarkers of Exposure and Effect Section 2.11 Methods for Reducing Toxic Effects... 

Exposure. Known biomarkers of exposure to endosulfan include the measurement of endosulfan or its metabolites in tissue and excreta (Deema et al. 1966 Dorough et al. 1978 Gorbach et al. 1968) these measurements can indicate whether absorption of endosulfan has occurred. The presence of the parent compound and its metabolites are specific biomarkers for endosulfan exposure. However, no studies are available that quantify the concentrations of endosulfan or its metabolites in relation to specific environmental exposure levels. Since endosulfan induces cytochrome P450-dependent monooxygenases... 

There are no biomarkers of exposure or effect that have been validated in children. There are no data on interactions of endosulfan with other chemicals in children, and the existing data in adults are inadequate to determine whether the same effects will be observed in children. There are no pediatric-specific... 

Methods for Determining Biomarkers of Exposure and Effect. GC/ECD, GC/MS, and GC/MC are analytical techniques used for measuring endosulfan in blood, urine, hand rinses, and various biological tissues and excreta at low- and sub-ppb levels (Coutselinis et al. 1976 Demeter and Heyndrickx 1978 Demeter et al. 1977 Griffith and Blanke 1974 Guardino et al. 1996 Kazen et al. 

The problem of potentiation was discussed earlier (Chapter 2, Section 2.5). Potentiation is often the consequence of interactions at the toxicokinetic level, especially inhibition of detoxication or increased activation. The consequences of such potentiation may be evident not only at the whole animal level but also in enhanced responses of biomarker assays that measure toxicity (Figure 13.3). By contrast, biomarkers of exposure alone are unlikely to give any indication of potentiation at the toxicokinetic level. 

Matter, J.M., McMurry, C.S., and Anthony, A.B. et al. (1998). Development and implementation of endocrine biomarkers of exposure and effects in American alligators (Alligator mississippiensis). Chemosphere 37, 1905-1914. 

S.J. Gee, A.D. Lucas, and B.D. Hammock, Using immunochemical methods to analyze for biomarkers of exposure, in Methods of Pesticide Exposure Assessment, ed. PB. Curry,... 

Exposure. Americium may be detected in samples of urine, blood, feces, or body tissues. Due to the relatively long biological half-time of americium, short-term exposures cannot be readily distinguished from longer-term ones. No new biomarkers of exposure are needed at this time. 

Methods for Determining Biomarkers of Exposure and Effect. Analytical methods with satisfactory sensitivity and precision are available to determine the levels of americium in human tissues and body fluids. However, improved methods are needed to assess the biological effects of americium in tissues. 

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