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HYPERSUSCEPTIBILITY TO OCCUPATIONAL HAZARDS 80 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. criminatory hiring practices is the sickle-cell trait, the incidence of which is between 7 percent and 13 percent among blacks but generally rare in the rest of the population (Gardner, 1972). Under normal conditions, blood from individuals with this trait functions as it should. However, people with the sickle-cell trait have been barred from certain occupations because of the possibility that they are at greater risk from hazards that compromise the oxygen-carrying capacity of blood. Before any individual is denied work because of belonging to a so-called high-risk group, sound scientific evidence should clearly demonstrate that that person is hypersusceptible to hazards in the workplace and that there is no reasonable way to protect that person from these hazards. Understanding hypersusceptibility requires careful analysis of complex scientific, medical, legal, ethical, and economic problems. To facilitate discussion, this paper will focus on examples of hypersusceptible groups, screening and monitoring procedures, and fairness in making decisions regarding special groups. HYPERSUSCEPTIBLE GROUPS A hypersusceptible group is defined by a characteristic or set of characteristics that increase the probability that members of the group are more susceptible than others to particular hazards. These characteristics, called risk factors, fall into two basic categories, genetic and life history. Genetic factors are inherited traits that determine the fundamental biochemical machinery with which an individual can deal with environmental insults. Genetic factors include sex, capacity for enzymatic detoxification and elimination of harmful chemicals, and immunologic competence. In addition, certain developmental and metabolic abnormalities and predispositions to specific diseases can be inherited. Life-history factors are nongenetic forces that act through time to modify the body's ability to deal with environmental insults. These factors include age, illness, nutritional status, drug use, socioeconomic status, behavioral traits, and occupational and ambient exposures to noxious agents. In- depth analyses of genetic and life-history risk factors have been presented elsewhere (Calabrese, 1978, 1985a, 1985b). The following examples of some of the better-characterized genetic and life-history factors are presented to demonstrate determinants of hypersusceptibility. The most conspicuous genetic factor is sex. Despite considerable research, mostly in animals, there are few data that indicate significant sexual differences in susceptibility among humans (Calabrese, 1985a). In animal experiments, sexual differences in sensitivities to chemicals generally range from negligible to tenfold, although for a few chemicals this difference may be as high as a hundred times. An extremely important point
HYPERSUSCEPTIBILITY TO OCCUPATIONAL HAZARDS 81 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. to remember when trying to apply such data to humans is that the degree and direction of sexual difference in susceptibility depend on both the species of animal and the type of compound being tested. In addition, the data for all compounds indicate that neither sex has an overall advantage in susceptibility. A more selective and sensitive indicator than sex for possible hypersusceptibility comes from direct analysis of metabolic abnormalities that may render certain individuals more sensitive to environmental insult (Stanbury et al., 1972; Calabrese, 1978, 1985b). One such abnormality, glucose-6- phosphate dehydrogenase (G-6-P) deficiency, occurs in 11 percent of black American males but in other individuals and ethnic groups as well. The G-6-P enzyme plays a critical role in maintaining the structure of red blood cells. Therefore, persons deficient in the enzyme may be at greater risk from foreign agents such as carbon monoxide, lead, nitrate, nitrite, ozone, and radiation, which attack red blood cells. Another metabolic abnormality that increases the body's susceptibility to toxic chemicals is due to genetic variation in an enzyme called pseudocholinesterase. This and a closely related enzyme, cholinesterase, are required for proper functioning of the nervous system. Anticholinesterase insecticides, which block these enzymes, have been developed because for a number of reasons humans are generally far less susceptible to their effects than insects. However, in humans there are numerous genetic variants of pseudocholinesterase, some of which are much more sensitive to anticholinesterase agents. This results in significant individual differences in susceptibility to a class of compounds for which the potential for human exposure is very high. Individual differences can also occur in an important class of enzymes that detoxify and lead to the excretion of foreign compounds (Calabrese, 1978, 1985b). An example is catalase, which detoxifies highly reactive forms of oxygen that are produced in the body by exposures to ozone or radiation. An estimated 5 million Americans are deficient in catalase and therefore may be at greater risk to ozone and radiation toxicity. Differences in another detoxifying enzyme, glucuronyl transferase, leads to Gilbert's syndrome in about 6 percent of the normal adult population. In addition to a decreased ability to excrete normal metabolic wastes, people with Gilbert's syndrome are less able to clear foreign substances such as polychlorinated biphenyls (PCBs) from their bodies and are therefore more susceptible to the adverse effects of exposure to these chemicals. In contrast to deficiencies in detoxifying enzymes, there are examples of elevated levels of enzymes that increase the toxicity of foreign agents (Calabrese, 1978, 1985b). Approximately 45 percent of the American population may be at greater risk to the carcinogenic effects of polycyclic aromatic
HYPERSUSCEPTIBILITY TO OCCUPATIONAL HAZARDS 82 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. hydrocarbons (PAHs), a common class of pollutants found in combustion products and cigarette smoke, because their bodies produce larger quantities of an enzyme called aryl hydrocarbon hydroxylase (AHH). As one of a group of enzymes known as mixed-function oxidases, AHH metabolizes PAHs to highly reactive compounds that combine with, and thus alter the functions of, normal cellular constituents such as DNA. A large body of evidence suggests that these reactions initiate processes that eventually lead to cancer; therefore, persons with elevated levels of AHH are at greater risk from cancer caused by PAHs. Abnormalities in metabolic processes, other than those that deal directly with toxins, can also lead to hypersusceptibility (Stanbury et al., 1972; Calabrese, 1978). Cystinosis, cystinuria, and tyrosinemia are genetic disorders that affect kidney function. These disorders may act in concert with, and thus render the kidney hypersusceptible to, compounds such as heavy metals, which damage the kidney. Hypersusceptibility may result from interactions of compounds with other abnormal biological systems (Calabrese, 1978, 1985a, 1985b). Low levels of serum alpha antitrypsin (SAT), a blood component that regulates repair processes in the lung, render the lung more susceptible to respiratory irritants. SAT deficiencies occur in 4 percent to 9 percent of individuals of northern European descent. Defects in the immunologic system may also lead to hypersusceptibility. For example, decreased immunoglobulin A makes the lung more sensitive to respiratory irritants. More commonly, the immunologic system overreacts to foreign agents. An estimated 2 percent of the work force will develop a hypersensitive reaction when exposed to isocyanates. When one examines these genetic differences that may have the potential for causing varying toxic responses to chemicals, it is clear that many of these traits can be easily and accurately tested for. However, the relationships between these traits and the risk of occupational disease are far from clear. At present, it is not possible to determine specifically which, if any, individuals are at increased risk due to genetic differences. Attempts to "select out" susceptible individuals are very uncertain and have unknown effects on reducing occupational disease. Immunologic, metabolic, and other genetic factors that govern hypersusceptibility are not static but are modified throughout a person's life. The most inescapable life-history factor is age (Calabrese, 1978). From conception to birth, the developing fetus relies on the mother's detoxification system for protection from foreign agents. A few months after birth, an infant's metabolic detoxification system is fully developed, but the immunological system will continue to mature for 10 to 12 years and then begin a slow decline in function. Diminished immunologic competence in the very young
HYPERSUSCEPTIBILITY TO OCCUPATIONAL HAZARDS 83 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. and the very old makes these populations more susceptible to infectious disease, respiratory irritants, and carcinogens. These two populations may also be at greater risk from some ingested pollutants. For instance, the higher rates of intestinal absorption of metals such as lead among the young and the slower excretion rates for flouride among the old may increase the respective dangers of these agents for these two age groups. In the working population, long-term processes of aging may not affect susceptibility as much as daily and seasonal variations in biological processes (Calabrese, 1978). Although not well studied in man, these cycles have been shown to play important roles in the sensitivities of experimental animals to hazardous agents. An example of a relatively long-term cycle is pregnancy, which, because of its dramatic physiological effects on women, may be overly stressed as a risk factor. An objective view of the topic reveals much speculation but little evidence that pregnancy in normal, healthy women leads to increased sensitivity to occupational hazards (Wilson, 1977; Calabrese, 1985a). Many illnesses increase sensitivity to occupational hazards. In addition to the genetic disorders that have been mentioned, numerous infectious and noninfectious diseases damage organs and reduce their tolerance to foreign agents (Calabrese, 1978). For example, diseases can reduce the tolerance of the kidney to heavy metals and flouride, the liver to chlorinated hydrocarbons, the lung to respiratory irritants, and the heart to numerous chemicals. In developed countries, infectious disease is probably superseded by behavioral traits as a cause of hypersusceptibility to occupational hazards (Calabrese, 1978). The most widespread deleterious behavioral trait is tobacco smoking. This habit increases the body's susceptibility to legions of agents such as infectious pathogens, heavy metals, hydrocarbons, carcinogens, and respiratory irritants. The habitual use of alcohol and other drugs also lowers the body's tolerance to many compounds, including lead, pesticides, and PCBs. In underdeveloped nations, one would expect suboptimal nutrition to be a key determinant of hypersusceptibility. Unfortunately, this may also be true of sizable populations in developed countries, including the United States, where dietary deficiencies are found in children of the poor. However, insufficient intake of key nutrients such as vitamins C and E, magnesium, riboflavin, and protein is widespread in the working population. These forms of malnutrition may cause significant increases in susceptibility to a large number of industrial hazards (Calabrese, 1978). A final factor to consider when discussing hypersusceptibility to a particular agent is previous and ongoing exposures to other agents, both in the workplace and in the ambient environment. For cumulative toxins like lead, it may be safe to say that, regardless of the source of exposure, the degree of
