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to the small sample size and short exposure period of the study, the authors concluded that the negative
results were not conclusive.
Animal Studies
Male Wistar rats (n = 26) were given drinking water containing 1% dioxane for 63 weeks (Argus et al.,
1965). A group of 9 rats given untreated water were used as controls. Six hepatomas, one kidney
tumor, and one case of leukemia were found in the treated animals. One lymphosarcoma was found in
the control group. The increased incidence of cancer in the treated animals was not statistically
significant (p < 0.05). However, due to the small size of the control group, this study was of very
limited sensitivity, and therefore inconclusive.
Another drinking water study in male rats was conducted by Hoch-Ligeti et al. (1969) and further
reported on by Argus et al. (1973). In this study, male Charles River rats (30 per group) were given 0,
0.75, 1.0, 1.4, or 1.8% dioxane in their drinking water from 2-3 months of age for 13 months. Animals
were killed 16 months following treatment or earlier if tumors in the nasal cavity were observed.
Survival data was not reported. Nasal histological examinations were only performed on animals with
grossly visible tumors. The incidence of tumors found in this study are presented in Table 1.
Table 1.
Tumor incidence in male Charles River rats exposed to 1,4-dioxane in drinking water
(Hoch-Ligeti et al., 1969; Argus et al., 1973).
Tumor Incidence
1,4-Dioxane
Concentration (%) 0 0.75 1.0 1.4 1.8
Hepatocarcinomas 0/30 0/30 0/30 2/30 2/30
Nasal tumors 0/30 1/30 1/30 2/30 2/30
Hepatic tumors (total) NR 4/30 8/30 16/30 25/30
NR = Not reported
Kociba et al. (1974) studied the effects of dioxane in the drinking water of male and female Sherman
rats. Rats (60/sex/group) were exposed to 0, 0.01, 0.1, or 1.0% dioxane for 2 years. Actual dosages
of dioxane were estimated using drinking water consumption and body weight data. The dosages were
0, 9, 94, or 1015 mg/kg/day for the males, and 0, 14, 148, or 1599 mg/kg/day in females. Because the
tumor incidence data are averaged for the combined male and female responses, the doses were also
averaged. Mortality in the combined high dose group was 45% after 1 year of exposure, compared
with 12% in the control group. The tumor incidence data is summarized in Table 2.
King et al. (1975) exposed male and female B6C3F1 mice (50/sex/group) to dioxane in the drinking
water for 40-43 weeks. Concentrations of dioxane used were 0, 0.5, or 1.0 %. No tumors were
observed in any group at the end of the treatment period. According to IARC (1976), the duration of
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