PRINCIPLES OF TOXICOLOGY

13.10 CANCER TRENDS AND THEIR IMPACT ON EVALUATION OF CANCER CAUSATION 319
TABLE 13.19 Pharmaceutical Agents a with Carcinogenic Effects b
Generic Name Therapeutic Use Daily Dosage (mg/day) Tumor Site; Species
Rifampin Antibiotic: tuberculosis 600 Liver; mice
Isoniazid Antibiotic: tuberculosis 300 Lung; mice
Clofibrate Lowers cholesterol 2000 Liver; mice
Disulfiram Discourages alcohol abuse 125–500 Liver; rats
Phenobarbital Antiepileptic 100–200 Liver; mice
Acetaminophen Pain relief (OTC) 2000–4000 Liver; mice
Metronidazole Antibiotic, antiparasitic 500 Lung; rats/mice
Sulfisoxazole Antibiotic, urinary tract 8000
Dapsone Antibacterial, AIDS, leprosy, etc. 300 Spleen, thyroid, and
peritoneum; rats
Methimazole Hypothyroidism 15 Thyroid and pituitary
tumors; rats
Oxazepam Antianxiety 70 Thyroid, testes,
prostate; rats/mice
liver; mice
Furosemide Water retention in disease states 75
a List adapted from Waddell (1996).
b Cancer effects as listed in the Physicians Desk Reference (PDR), 1996, or Ames and Gold (1991).
tic agents used to treat cancer. Many antineoplastic drugs are potent genotoxic chemicals, and their
damage to DNA in rapidly dividing cells like cancer cells is a primary feature of both their therapeutic
effects and toxicities. Admittedly, it may be well worth a theoretical risk of developing cancer 20 years
after taking medication to cure a current case of cancer, however, a number of drugs whose therapeutic
benefits are directed at less serious health conditions are also known to have carcinogenic effects in
humans or in animal cancer bioassays. Some potentially carcinogenic pharmaceuticals are listed in
Table 13.19.
Not only are many of the drugs listed in Table 13.19 commonly prescribed, but the single daily
doses of these chemicals are large relative to the doses of chemicals one is typically concerned with
when evaluating environmental pollutants. Thus, the theoretical risks associated with even limited
therapy may approach or exceed the theoretical risks posed by the environmental contamination we
are often concerned about when remediating sites that contain these contaminants.
13.10 CANCER TRENDS AND THEIR IMPACT ON EVALUATION OF CANCER
CAUSATION
Human Cancer Trends in the United States
As mentioned regarding smoking, the incidence of cancer in this nation has remained stable, or
declined, for most types of cancer according to the American Cancer Society. The greatest exception
is, of course, lung cancer in both males and females. A 1998 report from the National Cancer Institute
(NCI) (see Table 13.20) indicated that after increasing 1.2 percent per year from 1973 to 1990,
incidence for all cancers combined declined in the United States an average of 0.7 percent from 1990
to 1995. Cancer mortality similarly declined about 0.5 percent per annum for the same period
(1990–1995). Cancers of the lung, breast, prostate, and colon–rectum accounted for over half of the
new cases. Cancer of the lung, both incidence and mortality, is actually showing a slight decline while
in women, such cancers (and the resultant mortality) are still on the increase. Incidence and mortality