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espectively (all statistically significant). None were observed in controls. The female rats also had
statistically significant increases in hepatocellular carcinomas (5/25, time-adjusted, high dose).
Hemangiosarcomas were found in male and female rats and the incidences were statistically significant in
the males (11/50, low dose). Squamous cell carcinomas of the stomach were found in 45/50, 29/49,
46/49, and 28/50 of the low-dose males, high-dose males, low-dose females, and high-dose females,
respectively (all statistically significant, p < 0.001). None were observed in controls. Male and female
mice had statistically significant incidences of alveolar/bronchiolar adenomas (10/47, high-dose males;
10/43, low-dose females).
IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
Epidemiologic studies of EDB carcinogenicity in humans have been suggestive but inconclusive, or of
insufficient power to detect an effect. In animals, however, EDB is a potent carcinogen causing tumors
in rats and mice of both sexes at multiple sites via various routes of exposure. CDHS (1985) based
their risk assessment on the inhalation bioassays in rats and mice reported by NTP (1982). CDHS
(1988) also based an oral EDB cancer potency on the NCI (1978) gavage male and female rat and
mouse forestomach squamous cell carcinoma incidence data.
Methodology
CDHS (1985) fitted the Weibull-multistage, multistage, and probit models to data from the NTP
inhalation study (NTP, 1982) which describes tumor incidence at two sites: tumors at the site of first
chemical contact (nasal malignancies in male rats), and tumors at a remote site (hemangiosarcomas in
female mice). For continuous lifetime exposures to 10 parts per trillion (ppt) in air, CDHS estimated
essentially zero risk under the probit model, and for the Weibull-multistage and multistage models, risks
of 1.0 to 5.5 excess cancers per million exposed. These estimates correspond to potencies of 0.05 -
0.25 (mg/kg-day) -1 [1.4 - 7 × 10 -5 (µg/m 3 ) -1 ]. Particular estimates depended upon the model used, the
tumor selected (rat nasal malignancies or mice hemangiosarcomas), and whether the upper 95%
confidence limit or maximum likelihood estimate of potency was used. Potency estimates derived from
distant site (hemangiosarcomas) and local site (nasal malignancies) did not differ substantially.
CDHS (1988), under Proposition 65, recommended that a “best value” cancer potency factor of 0.25
(mg/kg-day) -1 be used for EDB inhalation. This potency was obtained using the NTP (1982) male rat
nasal tumor data (Weibull-multistage, 95% upper confidence limit). This potency corresponds to a unit
risk of 7.1 × 10 -5 (µg/m 3 ) -1 .
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