Long-term carcinogenesis bioassays are the most valued and predictive
means for identifying potential carcinogenic hazards of various
agents to humans. Agents may be chemicals, chemical mixtures,
multiple chemicals, combinations of chemicals, residues and
contaminants, commercial products and formulations, and various
exposure circumstances. Life-styles, dietary factors, and occupational
exposure circumstances are very difficult, but not totally impossible,
to evaluate experimentally. Historically, the first chemical
bioassay took place in the early part of this century: Yamagiwa
and Ichikawa
1 in 1915, showed that coal tar applied experimentally
to rabbit ears caused skin carcinomas. Since then, nearly 1500-2000
bioassays of one sort or another have been carried out. Importantly,
however, some of these bioassays must be considered inadequate
for judging the absence of carcinogenicity, since there were
various limitations on the way they were performed: too few
animals, too short a duration, too low exposure concentrations,
too limited pathology, as examples. Thus, each bioassay must
be critically evaluated, especially those reported to be
negative,
because "false negatives" are certainly more hazardous to human
health than are "false positives". Likewise, one must be careful
not to discount bioassay results simply because a target organ
in rodents may not have a direct counterpart in humans (e.g.,
Zymbal glands
2), or because an organ site in rodents may not
be a major site of cancers in humans (e.g., mouse liver). The
design and conduct of a bioassay is not simple, however, and
one must be fully aware of possible pitfalls as well as viable
and often necessary alternatives. Similarly, evaluating results
and interpreting findings must be approached with the utmost
objectivity and consistency. These and other select issues,
controversies, and uncertainties possibly encountered in long-term
bioassays are covered in this paper. One fact remains abundantly
clear: for every known human carcinogen that has been tested
adequately in laboratory animals, the findings of carcinogenicity
are concordant.
