Human Exposure Assessment for Airborne Pollutants Advances and Opportunities (1991) / Chapter Skim
Currently Skimming:
4 Use of Biological Markers in Assessing Human Exposure to Airborne Contaminants
4 Use of Biological Markers in Assessing Human Exposure to Airborne Contaminants
Pages 115-142
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 115... ...
However, as the emphasis on conducting accurate exposure assessments increases, biological markers of exposure will be used more frequently A dramatic indicator, particularly in occupational epidemiology studies, is death. Less drastic and more manipulable biological measures of health outcome do exist and continue to be developed.
|
From page 116... ...
The term dose can be subdivided into internal dose and biologically effective dose~oth are discussed in this chapter with regard to biological markers. ~Effect" is defined as an adverse health outcome or nuisance resulting from exposure.
|
From page 117... ...
Biological markers provide information on dose that can be related to exposure by using pharmacokinetic or pharmacodynamic models (e.g., blood lead or carboxyhemoglobin)
|
From page 118... ...
has stated that "markers of health effects are often less readily related to environmental exposures than are the markers of exposure.- Therefore, greater emphasis is given to markers of exposure. Biological markers of effect can be used for exposure analysis if and only if information concerning contaminant identity and route of exposure is incorporated into the exposure assessment.
|
From page 119... ...
The growing availability of sophisticated simulation packages that can solve large numbers of massbalance differential equations makes the construction and testing of models ncreasmgly easier. An example of use of pharmacokinetic techniques to relate various biological markers to each other and to an exposure is the study of halothane concentrations in the breathing zone and blood of operating-room personnel (Fiserova-Bergerova, 1987~.
|
From page 120... ...
Measures of biologically effective dose include DNA and hemoglobin adducts in peripheral blood and other cells and tissues c.g., lung macrophages, sputum, bronchial washes or bronchoalveolar ravage fluid, buccal mucosa, bone marrow, placental tissue, and lung tissue. Such measures can be used as markers of exposure only when the analyzed cells or tissues are the target of the exposure contaminant or its metabolites.
|
From page 121... ...
-DNA adducts involved lung tissue and peripheral white blood cells from lung-cancer patients and controls (Perera et al., 1982~. They have since been used to analyze white blood cells and other tissues from persons exposed to PAHs in cigarette smoke and in occupational settings (e.g., foundries and coke ovens)
|
From page 122... ...
hemoglobin adJucts in smokers (Bryant et al., 1987; Perera et al., 1987~. Sensitive GC-MS methods can measure protein adJucts in persons exposed to ethylene oxide from cigarette smoke and workplace sources (Osterman-Golkar et al., 1984; Farmer et al., 1986; Tornqvist et al., 1986~.
|
From page 123... ...
Many classes of carcinogens and mutagens are known to increase SCE frequency, and that could limit the usefulness of SCE frequency for exposure assessment. For example, increased SCE frequency has been found in workers exposed to ethylene once, styrene, benzene, arsenic, chloromethyl ether, chloroprene, organophosphates, or ionizing radiation (Evans, 1982~.
|
From page 124... ...
The application of the technique to exposure assessment holds the potential for being specific for a substance causing mutation and so would be useful in epidemiological studies, risk assessment, and risk management. In addition, it leads to a measure of a biological effect and thus could be more directly related to potential adverse health outcomes than biological markers of exposure.
|
From page 125... ...
Activation can occur through several mechanisms, including gene mutation and chromosomal breaks and rearrangements. Of particular interest in assessment of ambient environmental exposures is the ras oncogene, first identified in rat sarcoma, later in human bladder, colon, and lung cancers (Slamon et al., 1984; Spandidos and Kerr, 1984~.
|
From page 126... ...
Uptake, absorption, and distribution of a substance can vary with sex, age, health status, diet, hormonal status, and presence of other environmental exposures (Committee on Biological Markers of the National Research Council, 1987~. Biological markers help to compensate for many of those variables by integrating all routes of exposure and not only permit individual exposure assessments, but also support estimation of individual biologically effective doses.
|
From page 127... ...
Given the degree of alkylation of hemoglobin, it was possible to estimate ethylene oxide exposure during the preceding few months (Calleman, 1984~. Improvement of Risk Extrapolation Biological markers have the potential to improve risk extrapolation between species and between populations, and to allow better predictions of human risk.
|
From page 128... ...
Improved Epidemiological Study Design and Inference Accurate exposure assessments can reduce misclassification error and enhance the power of an epidemiological study. Early biological events are generally more common than disease end points, so markers of effect also expand a stubs statistical power (Gann et al., 1985~.
|
From page 129... ...
Disadvantages and Limitations Lack of Validation A major limitation of using biological markers for exposure assessments stems from the fact that most are in a developmental stage and not fully validated or field-tested. Methodological problems are similar to those faced in the development of any new technology and include limited availability of standardized protocols and reporting criteria; interlaboratory differences, including variability in quantitation methods and in sensitivity; and the costliness and labor intensiveness of most procedures.
|
From page 130... ...
In other instances, multiple compounds might produce the same metabolite, and that could hinder the proper interpretation of the biological marker. Examples of compounds sharing metabolites are styrene and ethyl benzene yielding mandelic acid and tetrachloroethylene and 1,1,1-trichloroethane yields fang trichloroacetic acid.
|
From page 131... ...
For workers exposed to propylene oxide, good agreement was seen between the degree of hemoglobin alkylation and estimated propylene oxide exposure (OstermanGolkar et al., 1984~. Better defined exposure-response relationships were shown by the significant correlation between PAM-DNA adducts measured by immunoassay in peripheral white blood cells from Finnish foundry workers and their occupational exposure to PAH (Perera et al., 1988~.
|
From page 132... ...
. With respect to tumorigenesis, most preclinical effect markers- such as fetal proteins, oncogene protein products, structural changes in oncogenes, and chromosomal deletions not reveal the identity of the environmental exposure responsible.
|
From page 133... ...
There is a need for research to identify biochemical correlates of structural changes, as well as to distinguish effects caused by a chemical from effects that are responses to cell injury (Smith et al., 1986~. It is therefore desirable to incorporate chemical-specific markers of exposure and early biological effect into a study design to complement the nonspecific biological markers.
|
From page 134... ...
. The current use of biological markers for exposure assessment is not without its pitfalls, and in some cases it cannot occur without adjustments and a stipulation of an independent determination of confounding variables.
|
From page 135... ...
Relating markers of early biological effect to an original causative agent and routes of exposure is much more difficult, requiring extensive validation studies with careful linkage of an exposure to a marker of effect. Understanding of Pharmacokinetics and Temporal Relevance The proper selection and use of biological markers depend on an understanding of the underlying pharmacokinetics and pharmacodynamics of suspected contaminants (WHO, 1986; Andersen, 1987; Smith, 1987; Yager, 1988)
|
From page 136... ...
. Thus, one should consider DNA adducts only in cells damaged while in circulation and not white-cell adducts in circulating white cells, which might result from damage to stem or precursor cells in the bone marrow.
|
From page 137... ...
or background in monitoring or epidemiological studies and should be characterized before large-scale application of a particular biological marker. Such data, however, can be generated only by large-scale surveys with repeated sampling and efforts to control for confounding variables.
|
From page 138... ...
Those inducers include cigarette smoke, char-broiled meat, alcohol, sedatives, and PCBs; the inhibitors include methylxanthines in foods, steroids, solvents, and spray paints. Thus, even pilot studies attempting to evaluate biological markers can become complex epidemiological exercises that involve careful interviewing.
|
From page 139... ...
When it is possible, different methods for assaying a given marker are useful for detecting artifacts In a method. An example of such a process is the cross-validation of various DNA-adduct marker techniques with immunoassays, 32P-postlabeling and GC-MS, such as that carried out on PAH adducts of Finnish foundry workers.
|
From page 140... ...
A battery of markers designed to assess the role of occupational exposure to aromatic amines in bladder cancer, for example, might include breathing-zone monitoring for the amines, immunoassays of specific aromatic amine-DNA adducts in white cells (lifetimes of days to years) , and cytogenetic effects in T cells (half-life, 3 years)
|
From page 141... ...
Relating a marker directly to an exposure becomes more uncertain as measurements are obtained within the progression toward an effect, because the variability associated with the human "receptor" increases along that progression. Properly measured, biological markers can reduce misclassification errors of degree of exposure and can increase the power of epidemiological studies
|
From page 142... ...
Analytical techniques with improved chemical specificity and sensitivity for biologically significant markers are needed to apply to exposure assessments, especially flexible assays that can analyze a number of markers simultaneously or be readily adapted to analyze numerous markers sequentially. For such techniques, validation studies are needed to link conclusively biological markers to putative causative agents.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.