1160 TOXICOLOGY
which is probably due to few chemicals, at least in mixtures,
using exactly the same metabolic pathways. Other meth-
ods exist for evaluating mixtures (e.g., the mixture-toxicity
index; Lange et al., 1997). Determination of interactions for
more than one chemical can in many ways be identified as
an art (Marking, 1985). However, as science develops, better
methods are being developed to evaluate combinations.CARCINOGENICITYThe existence of cancer-causing chemicals has been known
for thousands of years. However, it was not until recently
that a direct relationship between environment or occupa-
tion and cancer was established. One of the early examples
of an occupational relationship was provided by the English
physician Percival Pott around 1775. Pott observed a high
number of cases of scrotum cancer in chimney sweeps. He
concluded that this cancer was a result of soot exposure
in this occupational group. Later Japanese investigators
(Yamagawa and Ichikawa, 1915) determined that coal tar
(a common component of which is polyaromatic hydrocar-
bons), a component in soot, exhibited carcinogenic effects
on animals, providing a basic animal model to support the
occupational observations of Pott.
Cancer in its simplest term is the unregulated or uncon-
trolled growth of cells in an organism. Cancer, or neoplasm,
can be either benign or malignant. Those that are benign
generally occupy a given space and do not spread to other
parts of the body. If the cancer is said to be malignant, it is
then metastatic and can spread and form secondary sites at
various other locations within the body.
Probably the best-known cancer-causing agent is ciga-
rette smoke. Studies have shown that direct and indirect use
of this product can result in cancer. Doll and Hill (1954)
demonstrated that cigarette smoking was a major cause of
lung cancer. Although this was an epidemiological study,
these types of investigations opened up a new era of investi-
gation into cancer-causing agents.
A cancer-causing agent generally has two processes in
the causation of a tumor: initiation and promotion. This has
resulted in chemicals being identified as either initiators or
promoters, although there are some, known as “complete
carcinogens,” that exhibit both properties. This concept was
developed by painting chemicals on the skin of mice at dif-
ferent time periods and observing whether tumor formation
occurred. It was discovered that for some chemical combi-
nations, the initiator had to be applied before the promoter.
When the promoter was applied first, a time period waited,
and then the initiator applied, no tumor formation occurred.
Cancer can also be caused by other nonchemical factors such
as heredity and viruses.
There has been considerable debate as to the amount of
cancer caused by environmental pollutants and exposures in
the occupational environment. However, it is known that there
are a large number of agents capable of causing cancer in both
the environmental and occupational settings. A list of a few
occupationally associated carcinogens is shown in Table 7.This list is not complete but demonstrates the large variety
and locations of cancers. Most environmental engineers look
at the agents capable of or identified as causing cancer when
evaluating a situation; however, this is usually done for sim-
plicity, in that cancer is an endpoint of clarity—it exists or
it does not exist. It must be kept in mind that there are other
endpoints of interest as well that are noncarcinogenic (e.g.,
kidney toxicity).
To classify carcinogens, several agencies list chemi-
cals or substances according to their degree of carcino-
genicity. One of the most frequently cited agencies is the
International Agency for Research on Cancer (IARC). The
IARC is located in Lyon, France, and is part of the World
Health Organization. As part of this agency’s charter, it pub-
lishes monographs for various substances and is considered
by many an excellent reference on information on carcino-
gens. This agency classifies cancer-causing agents into five
different groups (Table 8). These grouping are based on data
from epidemiological and animal studies. Many consider the
IARC to be the best source of information and classification
for carcinogens.
Group 1 indicates that there is sufficient epidemiological
data that the substance is a human carcinogen. This is the
highest level of classification, and as noted in Table 8, an
example is arsenic. Group 2 has two classifications, A and B.
Group 2A represents limited epidemiological evidence but
sufficient animal evidence that the substance is a carcino-
gen, while with group 2B there is sufficient animal evidence,
but epidemiological data are lacking or of poor quality. With
Group 3 there is inadequate evidence for classifying a chem-
ical or substance as a carcinogen. Group 4 evidence supports
that it is not a carcinogen.
The IARC is not the only agency that classifies carcinogens.
The National Toxicity Program (NTP) provides a classification
scheme. Here carcinogens are listed as known human carcino-
gens or as reasonably anticipated to be a human carcinogen.TABLE 7
Some carcinogenic chemicals (substances) and the cancers
they causeSubstance Cancer CausedAniline Bladder
Arsenic Skin, lung
Benzene Leukemia
Cadmium oxide Prostate, lung
Carbon tetrachloride Liver
Cement dust (Portland cement) Lung, stomach
Coke oven gases Lung, kidney
Ethylene oxide Leukemia
Lead arsenate Lung, skin
Mustard gas Larynx, lung
Nickel Lung, nasal
Styrene oxide Stomach
Toxaphene LiverC020_003_r03.indd 1160C020_003_r03.indd 1160 11/18/2005 11:09:30 AM11/18/2005 11:09:30 AM