PRINCIPLES OF TOXICOLOGY

from non-Hodgkin’s lymphoma and from melanoma are also increasing. These data were confirmed
in the 1999 joint release from the CDC, NCI, and ACS.
As awareness of environmental contamination and the ubiquity of synthetic chemicals arose in the
1960s, specifically after the release of Rachel Carson’s Silent Spring in 1962, speculation persisted
that we were awash in a “sea of carcinogens” and that after an appropriate latency interval, a cancer
epidemic would hit. As has been shown in Figure 13.1, the hypothesized epidemic of cancer has never
arrived, and considering the data indicating decreasing cancers through 1995, it would seem that
perhaps our current reductions in smoking, food consumption, and alcohol might be starting to impact
the incidence of new cancers in the United States. Considering that the stability of the cancer incidence
(aside from lung cancer due primarily to smoking) occurred during a period of great industrialization
in the United States, the impact of occupation and environmental pollution on cancer incidence is
probably less than what was postulated 30 years ago. That is not to say, however, that exposure
reductions are not still warranted in these areas, but merely to point out that the current data indicate
that our future, with its concomitant exposure to new synthetic chemicals, is not a dire one.
13.11 SUMMARY
13.11 SUMMARY 321
Chemical-induced carcinogenesis represents a unique and complex area within toxicology. The
difficulty in assessing the carcinogenic hazards and human risks of chemicals stems from the following
characteristics of chemical carcinogenesis:
• It is a multistage process involving at least two distinct stages: initiation, which converts the
genetic expression of the cell from a normal to aberrant cell line; and promotion, in which
the aberrant cell is stimulated in some fashion to grow, thereby expressing its altered state.
• Since chemicals may increase cancer incidence at various stages and by different mechanisms,
the term carcinogen by itself is somewhat limiting and a number of descriptive labels
are applied to the chemical carcinogens that define or describe these differences, such as
cocarcinogens, initiators, promoters, and epigenetic.
• Chemicals may produce or affect only a single stage or a single aspect of carcinogenesis that
leads to a number of important differences and considerations about the potential health
impacts of chemical carcinogens. Perhaps the most important considerations are the concept
of thresholds and that qualitative differences do exist among carcinogens.
• Carcinogenicity testing raises many questions about interpretations of results. Considerations
such as mechanism (genotoxic vs. epigenetic), dose, and relevant test species,
are important in determining probable human risk; thus, many additional toxicity test
data are needed to improve the extrapolation of cancer bioassay data from test species
to humans.
• A number of lifestyle-related factors influence carcinogenesis, altering the risks posed by
carcinogenic chemicals and acting to confound epidemiological evidence.
Considering the complexities involved in (1) determining the mechanism of cancer causation, (2) using
animal and human data to identify carcinogenic substances, and (3) using these data to extrapolate
risks with the aim of reducing or eliminating environmental risk factors, it should be clear to the reader
that the best approach to occupational carcinogenesis is an interdisciplinary one. As depicted in Figure
13.13, identifying and reducing occupational cancer requires the interfacing of several scientific
disciplines and several kinds of health professionals:
• The toxicologist is responsible for testing and identifying chemical carcinogens;
through animal testing the toxicologist attempts to provide information about carcino-