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Male or female C57Bl/6 mice (50/sex/group) were exposed to 60 or 240 ppm NDBA in their drinking
water from age 10-12 weeks until moribund or dead (Bertram and Craig, 1970). The incidence of
bladder carcinomas in males was 17/47 and 36/45 at the 60 and 240 ppm concentrations, respectively.
Females developed bladder carcinomas with an incidence of 2/42 and 8/45 for the 60 and 240 ppm
groups, respectively. Esophageal papillomas were found in 45/47 and 40/42 for males and 40/42 and
45/45 for females at the 60 and 240 ppm groups, respectively. No data on unexposed controls were
presented.
Male and female Syrian Golden Hamsters (5/sex/group) were given single doses of 400, 800, or 1600
mg/kg NDBA by gavage; groups of 20 males or females served as controls (Althoff et al., 1973).
Animals were observed for their lifespan and were killed when moribund. Mean survival times were
affected in a dose-dependent manner; controls survived 63.5 weeks, and low-, medium- and high-dose
groups survived for 59.6, 54.5, and 49.3 weeks, respectively. Respiratory neoplasms (unspecified
type) were found in 0/40, 3/10, 5/10 and 7/10 hamsters of the control, low-, medium-, and high-dose
groups, respectively. In a later study, Althoff et al. (1974) exposed groups of 20 (10/sex/group) male
and female Syrian Golden hamsters to 0, 29, 58, 116, 232, or 464 mg/kg NDBA once pre week for
life. In this study, the incidences of respiratory neoplasms were 0/20, 0/20, 0/19, 2/16, 12/20, and
8/16 for the groups exposed to 0, 29, 58, 116, 232, or 464 mg/kg NDBA, respectively.
Several studies in mice, rabbits and hamsters have shown NDBA to be carcinogenic following
subcutaneous injection (Fuji et al., 1977; Flaks et al., 1973; Althoff et al., 1973 & 1974; Reznik et
al., 1976; Cohen et al., 1975).
IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
The study by Bertram and Craig (1970) was used by CDHS (1988) to derive the cancer potency for
NDBA. The upper bound estimate of cancer potency from these data is the most reliable upper bound
from dose-response data in sensitive species.
The upper 95% bound on the multistage polynomial could not be determined from the tumor incidence
data in two other studies: Althoff et al. (1974) and Okajima et al. (1971). The potency estimates from
the studies by Lijinsky and Reuber (1983), and Takayama and Imaizumi (1971) both rely on
assumptions about the time of sacrifice and corrections for less than lifetime dosing.
Methodology
The study by Bertram and Craig (1970) showed that several organ sites developed tumors in both
sexes of mice exposed to NDBA. The combined incidence of bladder and esophageal neoplasms in
male mice was used for the potency estimate. These data depict the most reliable dose-response for
the most sensitive site and species.
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