PRINCIPLES OF TOXICOLOGY - Biology East Borneo

512 EPIDEMIOLOGIC ISSUES IN OCCUPATIONAL AND ENVIRONMENTAL HEALTHTABLE 21.1 Cholera Deaths in London (1984) by Water SupplyWater Company Population (1851) Cholera Deaths Rate per 1000 PopulationSouthwark 167,654 844 5.0Lambeth 19,133 18 0.9Sources: Snow (1855); Beaglehole et al. (1993).record sources commonly used by epidemiologists include employment records, trade union files,hospital records, motor vehicle registrations, and disease registries. All of these data sources have theirown individual advantages and limitations.Since Snow, epidemiology has expanded from a method for the investigation of acute infectiousdisease epidemics to a multi-faceted scientific discipline. Epidemiology now includes research intothe causes of chronic diseases such as cardiovascular disease and cancer. Epidemiologists oftenspecialize in particular areas of human health, such as nutrition, occupational and environmental health,and genetics. Nevertheless, the basic epidemiologic principles have changed little since the time ofSnow and his colleagues.Epidemiology has been used to investigate the possible associations between disease and exposuresin both the workplace and in the environment. Occupational epidemiologic studies established theassociations between asbestos and lung cancer, vinyl chloride and angiosarcoma of the liver, benzeneand leukemia, repetitive trauma, and carpal tunnel syndrome, as well as many other occupationalexposure–human health effects. Environmental epidemiologic studies have investigated the associationsbetween methyl mercury exposure and severe neurologic disease near Minamata Bay (Japan),the effects of radiation in atomic bomb survivors, and the possible carcinogenic effects of electromagneticfields. The advantages and limitations of research in these two overlapping areas of epidemiologyare discussed below.21.2 EPIDEMIOLOGIC CAUSATIONIn science, proof that a given exposure causes human health effects is established by a hierarchy ofevidence. This evidence could be the existence of a medical literature with multiple individual casereports, which associates human disease with a particular exposure. There could be toxicologicevidence in experimental animals in which the particular exposure causes diseases in animals similarto those seen in humans. Regardless, epidemiologic studies are considered to be the highest level ofscientific evidence for proving an association between a particular toxic exposure and human healtheffects.In epidemiology, proof of causality (or the association of a particular exposure with a particulardisease) is based on a variety of criteria. These criteria were first expounded by Hill in 1965, withsubsequent refinement and embellishment. These criteria include a temporal relation, plausibility,consistency, strength, a dose–response relationship, and reversibility and/or preventability. In addition,consideration must be given to the appropriateness of the design and to limitations, such as samplesize, in each individual epidemiologic study. Ultimately, evidence of causality is the body ofepidemiologic studies meeting all of these criteria.When considering the possibility of an association between an exposure and a disease, the exposuremust precede the onset of disease. Evidence of a dose–response relationship is necessary; with anincreased dose of a chemical, the risk of disease is increased. The association between the exposureand the disease must make scientific sense (e.g., have biological plausibility).Statistical significance does not in itself signify a true association; the association must bebiologically plausible as well as statistically significant. If possible, the association should bereproducible in toxicologic studies with laboratory animals and other systems such as in vitro systems.