home edit2 whole TSD November 2002 PDF format - OEHHA

In an inhalation study, Torkelson et al. (1974) exposed groups of 288 male or female Wistar rats to
111 ppm 1,4-dioxane for 7 hours/day, 5 days/week, for 2 years. Control rats (192 male or female
rats) were exposed to filtered room air. Weight gain among males and females was not affected by
dioxane treatment compared with controls. Survival rates were not significantly different between
control and treated rats. Similarly, the tumor incidence was not significantly different with dioxane
treatment. The estimated equivalent dose rate from the inhalation study was 100 mg/kg/day, based on
default values for rat body weight and breathing rate. This estimated dose is much lower than that used
in the drinking water studies described above.
Male and female Swiss-Webster mice (30/sex/group) were exposed dermally to an unspecified
concentration of dioxane in acetone 3 times/week (King et al., 1975). Dioxane was tested either as a
complete carcinogen for 60 weeks, or as a promoter, following a single exposure to DMBA followed
by 59-week exposure to dioxane. Control mice were treated with the acetone vehicle alone or with
DMBA. Dioxane was a significant promoter of skin carcinomas compared to controls treated with
DMBA only. However, no significant increase in skin papillomas or carcinomas was observed in the
test for complete carcinogenicity.
The tumor-intitiating properties of dioxane were investigated using the tumor promoter 12-Otetradecanoylphorbol-13-acetate
(TPA) in Sencar mice (40 females/group) (Bull et al., 1986). Mice
were exposed to a single oral, topical, or subcutaneous dose of 1,000 mg/kg dioxane, followed by TPA
in acetone 3 times per week for up to 52 weeks. No significant increase in skin tumor incidence was
reported in the mice, however, tumor incidence was not reported and length of observation was not
specified.
IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
Five studies (Argus et al., 1965; Hoch-Ligeti et al., 1969; Argus et al., 1973; Kociba et al., 1974;
and NCI, 1978) allow the estimation of cancer potency values for dioxane. Of these studies, only the
Kociba et al. (1974) and NCI (1978) studies were considered for the determination of the cancer
potency factor for dioxane.
In the Argus et al. (1965) study, 26 adult male Wistar rats were given drinking water containing 1%
dioxane for 63 weeks. The estimated dose of dioxane by the authors was 300 mg/day. The incidence
of liver hepatomas (6/26) in the treated animals was significantly higher than in untreated control animals
(0/9) but not significantly different from historical control animals. The cancer incidence in the treated
animals is considered biologically significant, but is not quantitatively suitable for use as the basis of a
cancer potency factor for dioxane.
The Hoch-Ligeti et al. (1969) and Argus et al. (1973) study failed to demonstrate significant
differences in tumor incidences between treated and control rats. The trend for increasing tumors was
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