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there was a slight increase in fibrosarcomas of the integumentary system, this was not considered by
NTP to be a significant carcinogenic response. DMBA pretreatment had no additional effect.
DHS staff members agreed with IARC (1982) that there is adequate evidence to support a conclusion
that TCDD is carcinogenic to rats and mice and that TCDD should be considered a potential
carcinogen to humans. The NTP bioassays (NTP 1980a) of HexaCDDs also indicated that the mixture
used was tumorigenic.
IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
Several human epidemiological studies of PCDD exposure reviewed in the dioxin TAC document
(CDHS, 1986) reported results which suggested an increase in cancer incidence or mortality associated
with PCDD exposure (Hardell and Sandstrom, 1979; Ericksson et al., 1981; Zack and Gaffey, 1983).
However, these and the other studies described in the dioxin TAC document suffer from a number of
limitations. The characterization of exposure to PCDD/PCDF were at best, uncertain. Usually the
exposure occurred at a time when there were no sensitive measures of exposure levels. Exposure was
often based on job title, self-reported use of substances which may have had PCDD contamination, or
exposure to an event thought to have liberated PCDDs. Additionally, none of the human exposures
described have been solely to PCDDs or PCDFs, but rather to a mixture of chemicals. PCDDs were
only trace contaminants of other toxic chemicals. Many of the occupationally exposed subjects were
exposed only briefly (e.g., during an accidental release), or worked in a possibly contaminated
environment for a short time. For example, more than 75% of the workers studied by Ott et al. (1980)
had been exposed for less than one year. Finally, many of the discussed studies, including the four US
cohorts, have been hampered by small samples. Studies of only a few hundred subjects lack sufficient
power to detect small increases in the risk of rare tumors. For these reasons, DHS staff members
concluded that the epidemiologic data available at the time the dioxin TAC document was written
provided insufficient information to conclude whether or not PCDDs or PCDFs are human carcinogens.
CDHS (1986) found that the most sensitive species, sex, and site for the induction of cancer by TCDD
is the male mouse with hepatocellular adenomas or carcinomas (NTP, 1982a). This response is an
order of magnitude greater than the least sensitive species, sex, and site examined, the female mouse
subcutaneous fibromas. It is interesting to note that there is less than a four-fold difference in the unit
risk between animal species for liver tumors. CDHS therefore developed an inhalation cancer unit risk
value for TCDD based on the NTP (1982a) male mouse hepatocellular adenoma/carcinoma tumor
data. CDHS also developed an inhalation cancer unit risk value for HexaCDD based on the most
sensitive species, sex, and site for the induction of cancer. The data set chosen was the NTP (1980b)
female rat liver neoplastic nodule or hepatocellular carcinoma incidence data as evaluated by
Hildebrandt (1983).
Methodology
GLOBAL79 was used to fit a linearized multistage procedure to the NTP (1982a) male mouse
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