PRINCIPLES OF TOXICOLOGY - Biology East Borneo

21.5 DISEASE AND HUMAN HEALTH EFFECTS ISSUES 515community environmental exposures, the possibility of both inhalation of airborne pollutants andingestion from the foodchain and water as routes of exposure must be considered.Particular to the food chain are issues of bioaccumulation and bioconcentration (as seen withmercury as well as with many lipophilic chemicals). This means that as a chemical goes up the foodchain, the concentrations of the chemical increases due to increased storage; therefore, humans, oftenat the top of the foodchain, will receive the highest doses. Furthermore, within human beings, theability of certain chemicals to concentrate in fat (i.e., lipophilic) means that increased doses of achemical can be delivered to the fetus and to the nursing child from the mother, as was shown withDDT and other organochlorine chemicals. In addition, repeated low-dose lifetime exposure can beprovided with slow but continual release from fat-stored lipophilic chemicals even when externalexposure has ceased.Traditionally, many disease–exposure connections in humans were established by the evaluationof workers and their occupational diseases. This is because, with rare exceptions (such as methylmercury exposure in Minamata, Japan), workers tend to have much higher exposures to chemicals inthe workplace than the general public. However, for issues such as community exposure to hazardouswaste incineration, occupational exposure information may not be entirely appropriate for extrapolationto community exposure and chronic health effects. The reasons are that community exposures areusually much lower and may occur over the entire lifetime of a person, not just during a 40-h workweek.To determine low-level exposures in communities in epidemiologic studies, large populations of peoplemust be followed for long periods of time to see any disease effects; these studies are exceedinglydifficult to perform and interpret.Another exposure issue relevant to community exposures and human health effects is the effect ofbrief and/or intermittent exposures. For example, much of the existing hazardous waste literatureconcerns brief “accidental” exposures such as seen in Seveso (Italy); however, the relevance of thehealth outcomes seen with these single exposures to the more likely scenario of chronic, low-levelexposures is unknown. Recently, interest in the scientific community has focused on the issue of indooras well as outdoor exposures, since most persons in the “developed” nations spend the majority oftheir time (over 90 percent) indoors; in some studies, indoor exposures to various chemicals exceededoutdoor exposures by 10–100-fold.Mixed low-level exposure with multiple different chemicals, as would be expected from communityexposures to industrial processes, are another difficult exposure issue. Mixed exposure incidents aredifficult to classify, to quantify, and even to measure. Furthermore, the particular mixture of exposureincidents in one community is probably not the same mixture found in another community. In addition,it is possible that mixed exposure incidents may cause more or less health effects than exposures tosingle chemicals since there is the possibility of synergism and/or antagonism of chemicals within theorganism.21.5 DISEASE AND HUMAN HEALTH EFFECTS ISSUESBesides the issues of exposure, disease or human health effects must be defined and measured. In thepast, completely developed end-stage diseases were considered as the most important human healtheffects to be studied. But because of issues of prevention, as well as the ability to detect subtlerphysiologic changes which are possibly reversible before the development of full-blown disease,human health effects can no longer be studied in this fashion. For example, in the past, lead toxicitywas defined as encephalopathy and even death; lead levels being set are now based on the preventionof subtle neurologic effects of lead on the cognition of fetuses and young children. As discussed withbiomonitoring, these subtle measures of health effect, or biomarkers of effect, have their own inherentproblems since their prognostic value have not been determined.In the past, epidemiology focused on acute infectious disease, which is relatively easy to both noticeand define. However, evaluation of subchronic and chronic diseases, often months to years after initialexposure, can be very difficult. For example, in asbestos-related cancer, the exposure can be 20–40