indicating occupational exposure have been inferred by comparison with the normal background levels of the biomarker.
1. Biomonitoring action levels vary in their derivation, some being from correlations with exposure, others with health effects. These reference levels should be used only when one has full understanding of their derivation. Sources of biomonitoring action levels include:
a. Biological Exposure Indices (BEI) adopted by the American Conference of Governmental Industrial Hygienists (ACGIH) [34];
b. Biological Tolerance Values for Working Materials (BAT) published by the Deutsche Forschungsgemeinschaft's (DFG) Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area [35];
c. Lauwerys' and Hoet's "Summary of Recommendations" in Industrial Chemical Exposure. Guidelines for Biological Monitoring [11];
d. Occupational Safety and Health Administration (OSHA) standards [36, 37].
2. When biomarker data are available for exposed and nonexposed populations that are otherwise similar, the upper limit of the range for the nonexposed population may serve as a reference level. Levels of biomarker significantly above that limit suggest occupational exposure to the agent. For those biomarkers for which there is no measurable background level in nonexposed humans, this reference level is effectively the detection limit of the analytical method. In any case, levels of the biomarker above the reference level suggest there was occupational exposure, but give no information on the potential health effect.
Variability. Biological monitoring data are subject to a number of sources of variability [2], including:
1. Rates at which an agent is taken up by the body, metabolized, and excreted. These vary from person to person and are affected by the person's age, sex, and physical workload.
2. Route of exposure. For example, absorption through the lungs is much faster than adsorption through the skin. Thus, the appearance and elimination of a biomarker will be slower if the agent entered through the skin. If the biomarker is rapidly excreted, the optimum timing for collection of biological samples will be different for the two routes of entry.
3. Fluctuation in environmental exposure. Such fluctuations will be tracked by the levels of rapidly eliminated biomarkers, those reflecting exposure of the immediately previous several hours.
4. Personal protective equipment worn and a person's work practices.
5. Existence of a biomarker in both a free and a conjugated form, the relative proportions of which can vary substantially from person to person. For example, aniline is present in urine as both the free amine and as acetanilide, its acetyl derivative. Some persons are genetically predisposed to excrete primarily free aniline; while others, primarily, acetanilide.
6. Concurrent exposure to several agents that compete for the same biotransformation sites in the body. This may lead to altered metabolism and excretion, which would change the relationship between exposure or health effect and the level of the biomarker [8].
7. Concurrent exposure to several agents, which are metabolized to the same biomarker. This frustrates the interpretation of the biological monitoring data. For example, trichloroacetic acid is a biomarker for trichloroethylene, 1,1,1-trichloroethane, and perchloroethylene.
Manual of Analytical Methods
