PRINCIPLES OF TOXICOLOGY

community environmental exposures, the possibility of both inhalation of airborne pollutants and
ingestion 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 with
mercury as well as with many lipophilic chemicals). This means that as a chemical goes up the food
chain, the concentrations of the chemical increases due to increased storage; therefore, humans, often
at the top of the foodchain, will receive the highest doses. Furthermore, within human beings, the
ability of certain chemicals to concentrate in fat (i.e., lipophilic) means that increased doses of a
chemical can be delivered to the fetus and to the nursing child from the mother, as was shown with
DDT and other organochlorine chemicals. In addition, repeated low-dose lifetime exposure can be
provided with slow but continual release from fat-stored lipophilic chemicals even when external
exposure has ceased.
Traditionally, many disease–exposure connections in humans were established by the evaluation
of workers and their occupational diseases. This is because, with rare exceptions (such as methyl
mercury exposure in Minamata, Japan), workers tend to have much higher exposures to chemicals in
the workplace than the general public. However, for issues such as community exposure to hazardous
waste incineration, occupational exposure information may not be entirely appropriate for extrapolation
to community exposure and chronic health effects. The reasons are that community exposures are
usually 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 people
must be followed for long periods of time to see any disease effects; these studies are exceedingly
difficult to perform and interpret.
Another exposure issue relevant to community exposures and human health effects is the effect of
brief and/or intermittent exposures. For example, much of the existing hazardous waste literature
concerns brief “accidental” exposures such as seen in Seveso (Italy); however, the relevance of the
health outcomes seen with these single exposures to the more likely scenario of chronic, low-level
exposures is unknown. Recently, interest in the scientific community has focused on the issue of indoor
as well as outdoor exposures, since most persons in the “developed” nations spend the majority of
their time (over 90 percent) indoors; in some studies, indoor exposures to various chemicals exceeded
outdoor exposures by 10–100-fold.
Mixed low-level exposure with multiple different chemicals, as would be expected from community
exposures to industrial processes, are another difficult exposure issue. Mixed exposure incidents are
difficult to classify, to quantify, and even to measure. Furthermore, the particular mixture of exposure
incidents 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 to
single chemicals since there is the possibility of synergism and/or antagonism of chemicals within the
organism.
21.5 DISEASE AND HUMAN HEALTH EFFECTS ISSUES
21.5 DISEASE AND HUMAN HEALTH EFFECTS ISSUES 515
Besides the issues of exposure, disease or human health effects must be defined and measured. In the
past, completely developed end-stage diseases were considered as the most important human health
effects to be studied. But because of issues of prevention, as well as the ability to detect subtler
physiologic 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 toxicity
was defined as encephalopathy and even death; lead levels being set are now based on the prevention
of subtle neurologic effects of lead on the cognition of fetuses and young children. As discussed with
biomonitoring, these subtle measures of health effect, or biomarkers of effect, have their own inherent
problems since their prognostic value have not been determined.
In the past, epidemiology focused on acute infectious disease, which is relatively easy to both notice
and define. However, evaluation of subchronic and chronic diseases, often months to years after initial
exposure, can be very difficult. For example, in asbestos-related cancer, the exposure can be 20–40