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HYPERSUSCEPTIBILITY TO OCCUPATIONAL HAZARDS 84 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. toxicity and risk from future exposures is more or less related to body burden of the toxin. If a system exists for monitoring the amount of toxin in the body, as is the case for lead, then it is relatively easy to prevent the effects of excessive exposure. For exposure to multiple agents, particularly those that are difficult to analyze in the body, the risk from future exposures will be difficult to predict. This will be especially true where large differences occur in the structures and modes of action of the confounding agents. Another complicating aspect of multiple exposure is the control of exposures outside the workplace. The technical, ethical, and legal obstacles to reducing ambient exposures of workers may force companies to relocate in areas where either there are lower numbers of hypersusceptible workers or outside exposures are lower or both. Complex and often synergistic interactions of genetic and life-history factors determine the overall health of a worker and his susceptibility to occupational hazards. Hypersusceptibility may result from one major risk factor or the coexistence of numerous minor risk factors. Overall good health and compensatory mechanisms may overcome the effects of a major risk factor for hypersusceptibility. Conversely, the summation of minor risk factors or the presence of an undetected major risk factor may render an apparently normal individual hypersusceptible to an occupational hazard. Although much has been learned about risk factors, it is difficult to determine precisely which workers will exhibit hypersusceptibility. Caution must therefore be exercised when advising workers as to who is and who is not safe from occupational exposures. SCREENING AND MONITORING Given the underlying complexities, identification of hypersusceptible workers poses an important challenge to occupational health professionals. The traditional activities of occupational health are identifying and measuring exposures to occupational hazards, determining adverse health effects of these exposures, and devising means for controlling hazards and preventing adverse health effects. To cope with hypersusceptibility, these activities must be expanded to include identifying factors that predispose workers to increased risk, identifying populations of hypersusceptible workers, developing procedures for screening and monitoring for hypersusceptibility, and designing measures to protect hypersusceptible workers. In many cases, occupational hazards are identified by observations of increased morbidity or mortality among specific populations of workers. This often requires the careful and painstaking efforts of epidemiologists. Laboratory experiments are conducted to gain further understanding of the relationships between known hazards and occupational disease and to pre
HYPERSUSCEPTIBILITY TO OCCUPATIONAL HAZARDS 85 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. dict problems before they are detected in the workplace. It is often difficult to relate results from laboratory experiments to humans because the experiments use specific species, strains, and sexes of inbred animals that have been raised under carefully controlled conditions. This is done to reduce biological variability that might obscure relationships between disease and exposure to agents. However, biological variability, is the basis of hypersusceptibility. Other experiments are therefore conducted to compare differences in sex, strain, and species, and ''normal'' versus "abnormal" animals. Although often difficult to extrapolate to humans, data from this type of research provide scientists with valuable clues of what to look for when identifying hypersusceptibility in workers. This research is having a great impact on medical screening, monitoring, and early identification of adverse health effects. Medical screening is a procedure that usually takes place prior to employment (Levy and Wegman, 1983). One of the purposes of medical screening is to determine whether an individual is at increased risk of developing disease in the work environment. Thus, a medical screen should include determination of genetic and life-history factors relevant to hazards encountered in the workplace. Screens for genetic risk factors often use laboratory tests whose validity depends on three requirements: (1) the tests must be sensitive and specific for the traits being tested; (2) there must be a clear relationship between these traits and disease resulting from exposures to hazards encountered in the workplace; and (3) it should be economically feasible to apply the test to populations of workers exposed to a particular hazard. To date, a few tests for genetic risk factors meet these requirements only partially (Calabrese, 1978; Lappé, 1983). For instance, there are tests for low levels of serum antitrypsin activity, which predict chronic obstructive lung disease in coal miners; for glucose-6-phosphate dehydrogenase deficiency, which indicates susceptibility to red blood cell destruction caused by exposure to ozone or hemolytic chemicals; for sickle-cell anemia and sickle-cell trait, both of which decrease one's tolerance to oxygen deprivation; and for allergic reactions to organic chemicals such as isocyanates. Future advances in biomedical research will undoubtedly produce additional useful screening tests for genetic risk factors. Initial screening for life-history factors does not normally require extensive laboratory tests. Most of the needed information can be gathered by questionnaire and physical examination (Levy and Wegman, 1983). However, initial findings or the presence of particular hazards in the prospective employee's workplace may require further laboratory evaluation. For example, persons previously employed as lead workers should have their blood lead levels checked. At present, when conducting screens for hypersusceptibility, the high degree of relevance of life-history information and the ease
HYPERSUSCEPTIBILITY TO OCCUPATIONAL HAZARDS 86 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. with which it can be gathered make life-history factors more important than genetic factors. In addition to preliminary screening for hypersusceptibility, ongoing monitoring of workers and the workplace is often carried out. This is done to identify hazards, determine workers' exposure to hazards, and detect illness. Traditional monitoring for hazardous agents uses instruments placed in the workplace or worn by workers. Sampling and analysis of data collected by these instruments are used to determine workers' probable exposure to hazardous agents and allow companies to comply with laws regulating exposure levels. A newer approach to monitoring relies on analysis of biological samples, usually blood or urine (Baselt, 1980; Levy and Wegman, 1983; Alessio et al., 1984). Biological monitoring is used to measure the levels of toxins in the body and biological responses to these toxins. In many cases, biological monitoring may be more appropriate than traditional means of monitoring because it can more accurately determine the level of a toxin in the body. It allows not only for idiosyncracies of exposure in the workplace but also for biological variability among workers. Biological monitoring relates to the problem of hypersusceptibility in three ways: (1) it makes it possible to identify workers who are at increased risk due to abnormally high body burdens or who display greater biological responses to toxins; (2) exposures can be more carefully monitored for workers at greater risk because of accompanying genetic or life- history factors; and (3) measurements of preclinical biological responses to toxins may be the best means for predicting and avoiding frank illness. One form of biological surveillance that holds great promise is genetic monitoring. Unlike genetic screening, which looks for inherited familial traits that might contribute to hypersusceptibility, genetic monitoring uses cytogenetic techniques to examine chromosomes directly for damage resulting from environmental insults (Baselt, 1980; Levy and Wegman, 1983). Genetic damage can also be detected indirectly by looking for abnormal degradation products of chromosomal DNA in urine (Weinstein, 1983). Chemicals that cause cancer and birth defects often exert their effects by reacting with chromosomal DNA. This damaged DNA is removed by cellular repair processes and excreted in urine. Analysis of these excretion products yields valuable insight into types and levels of exposure and the degree of hypersusceptibility to agents that damage chromosomes. It is always with caution that comments regarding biological monitoring are presented because, by its very nature, certain types of biological monitoring are reflective of a "public health failure"; that is, the failure becomes apparent after exposure and perhaps after sentinels of injury are produced. The first line of defense remains environmental monitoring. Biological monitoring, however, can provide important and essential information in