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Several factors have been suggested to account for the difference in carcinogenicity between the gavage
and inhalation studies, including the strains of animal used, the differences in the actual dose received by
the animal, and the pharmacokinetic differences in rates of formation and/or retention of reactive
metabolites in target organs for different routes of administration (US EPA, 1985; CDHS, 1985;
Hooper et al., 1980).
Theiss et al. (1977) conducted a pulmonary tumor bioassay in mice with EDC. Groups of twenty mice
received intraperitoneal (ip) injections of either 0, 20, 40 or 100 mg/kg EDC three times weekly for a
total of 24 injections per mouse. The mice were sacrificed 24 weeks after the first injection. The lungs
were subsequently examined for surface adenomas. Although the incidence of lung tumors increased
with dose, none of the groups had a significantly greater number of pulmonary adenomas than did
vehicle-treated control mice (Theiss et al., 1977).
Van Duuren et al. (1979) conducted a bioassay of EDC and one of its suspected metabolite,
chloroacetaldehyde, using the two-stage mouse skin test on female Swiss mice. The results of this study
indicated that neither EDC nor chloroacetaldehyde induced a statistically significant increase of
papillomas or carcinomas of the skin, although dermal application of EDC was associated with a
significant increase in the number of mice with benign lung papillomas (Van Duuren et al., 1979).
In summary, EDC has been demonstrated to increase the incidence of tumors in rats and mice, both
local to, and distant from, the initial site of chemical contact.
IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
EDC has caused statistically significant increases in tumor incidences in both rats and mice in several
different laboratories by different routes of exposure. The State of California Scientific Advisory Panel
for Proposition 65 has identified EDC as a compound known to the State to cause cancer. EDC has
been classified by the US EPA and IARC as a B2 and 2B carcinogen, respectively. CDHS (1985)
used the tumor incidence data from the NCI (1978) carcinogenesis bioassay for developing a
quantitative risk assessment.
Methodology
DHS staff performed several different analyses to generate estimates of cancer potency of EDC in
humans using the NCI tumor data. The Crump polynomial model was applied to data which
summarizes the tumor incidence observed, time-dependent analyses were performed to take into
account early death of treated animals, crude adjustments were made to take into account the saturable
pharmacokinetics of EDC, and a physiologically-based pharmacokinetics model (PBPK) was applied
to correct for the differing effects of species, routes, and dose levels on the pharmacokinetics of EDC.
Due to the lack of data on the metabolism and disposition of EDC in humans and the inherent
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