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IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
Two studies, Innes et al. (1969) and NCI (1979), have been deemed adequate for the derivation of
cancer potencies. Both demonstrate statistically significant increases in tumor incidence among 2,4,6-
trichlorophenol exposed animal populations. Innes et al. (1969) show increased incidence of reticulum
cell sarcomas in male B6C3F 1 mice and heptomas in female B6C3F 1 mice. The NCI (1979) study
shows increased incidence of hepatomas in both male and female B6C3F 1 mice, and leukemia in male
Fischer F344 rats. The US EPA estimate of cancer potency of 2,4,6-trichlorophenol derived from the
rat study is lower than that for mice (US EPA, 1988 and below). Since selection of the potency value is
made on the basis of the most sensitive species, site, and study in the absence of evidence that the data
are not representative, tumor induction in B6C3F 1 mice has been chosen as the basis for derivation of a
cancer potency value for 2,4,6-trichlorophenol.
Methodology
The multistage Doll-Armitage model polynomial was fit to tumor incidence data from Innes et al.(1969)
and NCI (1979) (Armitage and Doll, 1954). Dosage estimates for the studies were based on food
intake assumptions of 12% and 13% of body weight for male and female mice, respectively (Gold,
1984). In the NCI (1979) study, final dose values were calculated to be 1200 and 600 mg/kg-day for
high- and low-dose females, and 1356 and 678 mg/kg-day for high- and low-dose males. In the Innes
et al.(1969) study, dosage estimates were based on the method of Crouch to account for variation in
dosing during the course of the experiment (Crouch, 1983). Dosage estimates were calculated to be
32.5 and 34.7 mg/kg-day for male and female mice, respectively. Using a multistage polynomial, the
cancer potency was derived using the probability of dying with a tumor from a given dose and the
background lifetime cancer incidence (Crump and Howe, 1984). The upper 95% confidence bound on
the cancer potency was termed q * 1 . Estimates of q * 1 for tumor induction in B6C3F 1 mice are
presented in Table 4.
*
Calculation of the cancer potency in 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 (Innes et al., T e = 104 weeks; NCI, T e = 78 weeks):
q animal = q 1 * × (T/T e ) 3
The resulting q animal can be converted to human cancer potency (q human ) based on the following
relationship, where bw animal is the assumed body weight for the test species (Innes et al. (1969),
bw animal = 0.030 kg; NCI (1979), bw animal = 0.04 kg-males and 0.035 kg-females) and bw human is the
assumed human body weight (70 kg):
q human = q animal × (bw h /bw a ) 1/3
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