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Methodology
Dosage estimates of NDPA from the Cardy et al. (1979) study were made based on reference body
weights of 0.380 and 0.229 kg and daily food consumption rates of 0.030 and 0.021 kg for male and
female mice, respectively. The resulting daily dosage calculations are 79 and 92 mg/kg-day for males
and females, respectively, for the groups fed 1000 ppm in their diet, and 316 and 368 mg/kg-day for
males and females, respectively, for the groups fed 4000 ppm in their diet. Fitting a multistage
procedure to the incidence data for transitional-cell carcinoma of the bladder gives upper 95%
confidence bounds on the cancer potency (q 1 * ) of 0.00050 and 0.00048 (mg/kg-day) -1 for male and
female rats, respectively (Crump and Howe (1984)).
Calculation of the cancer potency for animals (q animal ) can be made using q *
1 and the following
relationship, where T is the natural lifespan of the animal (104 weeks) and T e is the experimental
duration (100 weeks):
q animal = q * 1 × (T/T e ) 3
The resulting q animal values of 0.00056 and 0.00050 (mg/kg-day) -1 for male and female rats,
respectively, can be converted to human cancer potency values (q human ) based on the following
relationship, where bw animal is the assumed body weight for the test species and bw human is the assumed
human body weight (reference values from US EPA (1986)):
q human = q animal × (bw h /bw a ) 1/3
The resulting estimates of q human are 0.0032 and 0.0034 (mg/kg-day) -1 .
Daily dosage estimates for animals from the Innes et al.(1969) study were made with estimates of food
consumption rates of 12% and 13% for male and female mice, respectively, based on Gold et al.
(1984). During the oral gavage dosing period (days 7 to 28) it is assumed that a linear threefold
increase in body weight occurs. The method of Crouch (1983) was used to account for variable dosing
during the study period. Calculations of daily dosage are 444 and 476 mg/kg-day for male and female
mice, respectively. Fitting the linear model below to the significant tumor incidence data for hepatomas
in male B6C3F 1 mice results in a cancer potency estimate (q animal ) of 0.0046 (mg/kg-day) -1 . In this
relationship, D is the estimated daily dose, p(T e ) is the probability of dying with a tumor at time T e , and
A is the background (control) tumor incidence.
q =
animal
-ln[1- p(T
e )] - A
D
Conversion of the q animal to q human is achieved as described for the Cardy et al. (1979) data, with an
assumed experimental animal body weight (bw animal ) of 0.03 kg. The resulting q human for this study is
0.061 (mg/kg-day) -1 .
Selection of a reference cancer potency value comes from identification of the most sensitive site,
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