PRINCIPLES OF TOXICOLOGY

TABLE 13.10 The Poor Correlation in Organ Sites among Positive Rodent Tests
Site of Cancer N Rats/Mice Percent N Mice/Rats Percent
Liver 25/33 75 25/78 32
Lung 2/7 29 2/18 11
Hematopoietic system 3/14 21 3/11 27
Kidney (tubular cells) 3/21 14 3/4 75
Mammary gland 4/18 22 4/7 57
Forestomach 8/14 57 8/15 53
Thyroid gland 7/16 44 7/9 78
Zymbal gland 2/12 17 2/2 100
Urinary bladder 2/12 17 2/3 67
Skin 3/11 27 3/3 100
Clitoral/Preputial gland 0/7 — 0/3 —
Circulatory system 2/4 50 2/10 20
Adrenal medulla 0/4 — 0/4 —
Total 61/173 35 61/167 37
Source: Adapted from Haseman and Lockhart (1993).
analysis but compares the data from a subsequent update of the original study as well, illustrating that
as the number of chemicals tested expands, the agreement in results across species does not seem to
be changing.
From this analysis it is evident that when a chemical induces cancer in one of these two rodent
species, it is also carcinogenic in the other species less than 50 percent of the time. This lack of
concordance between these two phylogenetically similar species raises a concern voiced by many
scientists when such data are extrapolated to humans without also considering mechanistic and
pharmacokinetic data from both species that might help explain why such large differences exist.
A similar problem arises when the issue of identifying the correct target organ is considered. A
recent analysis of the predictivity of the target organ for a carcinogen when extrapolating across two
rodent species found one could predict the correct target organ about only about 37 percent of the time
(Table 13.10). So, it would appear that not only is the assumption that a positive response in animals
can be assumed to predict the human response, but the likelihood that the correct target has been
identified would also seem to be of some question.
13.8 OCCUPATIONAL CARCINOGENS
13.8 OCCUPATIONAL CARCINOGENS 301
Although the first occupational carcinogen was identified by Sir Percival Pott in 1775, it was not until
1970 with the passage of the Occupational Safety and Health Act and establishment of the Occupational
Safety and Health Administration (OSHA) that the United States had enforcement authority granted
to an agency to regulate the use of substances that were considered carcinogenic in the workplace.
Prior to 1970, the source that was widely considered the most authoritative was the American
Conference of Governmental Industrial Hygienists (ACGIH) and industry relied on this organization
to regulate worker exposure to chemicals and agents. The other event occurring about this time that
has shaped our current view of occupational carcinogens was the emergence of the cancer bioassay.
The development and continued use of this bioassay over the years has identified many hundreds of
industrial chemicals as having carcinogenic activity, at least in high-dose animal tests, many of which
had never before been suspected of human carcinogenic activity. As certain chemicals or groups of
chemicals became identified as carcinogens, this, in turn, brought to bear new pressures on industries
as lower exposure levels or alternative chemicals were sought to reduce the possible risks associated