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there are several bioassays or large differences exist between potency values calculated from available
data sets.
Carcinogenicity bioassays using mice and/or rats will often use an exposure duration of approximately
two years. For standard risk assessments, this is the assumed lifespan for these species. Animals in
experiments of shorter duration are at a lower risk of developing tumors than those in the standard
bioassay; thus potency is underestimated unless an adjustment for experimental duration is made. In
*
estimating potency, short duration of an experiment was taken into account by multiplying q 1 by a
correction factor equal to the cube of the ratio of the assumed standard lifespan of the animal to the
duration of the experiment (T e ). This assumes that the cancer hazard would have increased with the
third power of the age of the animals had they lived longer:
q animal = q 1
*
* (104 weeks/T e ) 3
In some cases excess mortality may occur during a bioassay, and the number of initial animals subject to
late occurring tumors may be significantly reduced. In such situations, the above described procedure
can, at times, significantly underestimate potency. A time-dependent model fit to individual animal data
(i.e., the data set with the tumor status and time of death for each animal under study) may provide
better potency estimates. When Gold et al. indicated that survival was poor for a selected data set, a
time-dependent analysis was attempted if the required data were available in the Tox Risk (Crump et
al., 1991) data base. The Weibull multistage model (Weibull-in-time; multistage-in-dose) was fit to the
individual animal data.
To estimate human cancer potency, q animal values derived from bioassay data were multiplied by an
interspecies scaling factor (K; the ratio of human body weight (bw h ) to test animal body weight (bw a ),
taken to the 1/3 power (Anderson et al., 1983)):
K = (bw h /bw a ) 1/3
Thus, cancer potency = q human = K * q animal
Body Weight and Surface Area Dose Scaling
Both body weight scaling and surface area scaling have been proposed for the purpose of computing
human equivalent doses from applied animal doses when extrapolating human cancer unit risks from
animal cancer bioassay data. Crouch and Wilson (1979) compared cancer potencies for several
chemical carcinogens between rats and/or mice and humans and concluded that body weight scaling
was appropriate. Surface area scaling assumes that 1) body weight scaling alone does not completely
account for interspecies toxicity sensitivity differences (because it does not account for toxicokinetic
differences); 2) metabolic processes that are a key factor in toxicity sensitivity are related to surface
area (since heat loss from a warm-blooded animal is roughly proportional to surface area). A formula
for the computation of estimated surface area has been derived from the geometric formula that
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