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Table 1.
Tumor incidence in rats exposed to 1,4-dichlorobenzene (DCB) in air for 76 weeks
(Loeser and Litchfield, 1983)
Concentration of 1,4-DCB Combined Tumors (males) Combined Tumors (females)
0 ppm 39/60 55/61
75 ppm 31/60 54/61
500 ppm 35/60 53/58
A parallel experiment was conducted using groups of 75 Swiss mice of either sex (Loeser and
Litchfield, 1983). In this experiment, female mice were exposed to 0, 75, or 500 ppm 1,4 – DCB for 5
hours/day, 5 days/week, for 57 weeks. A similar experiment in male mice was terminated due to high
mortality due to fighting and respiratory infections. As with the rats, no significant increase in any tumor
type was detected.
The National Toxicology Program (NTP, 1987) studied the carcinogenicity of 1,4 - DCB in male and
female F344 rats and B6C3F1 mice via chronic (103 week) oral intubation. Male rats were given 0,
150, or 300 mg/kg 1,4 - DCB for 5 days/week for 103 weeks. Male and female mice, and female rats
were given 0, 300, or 600 mg/kg for the same duration. Sentinel animals were killed periodically to test
for infectious pathogenic agents. The survival of male rats given 300 mg/kg was significantly lower than
controls after 97 weeks, but the survival of treated female rats was unchanged from controls. The timeweighted
average doses in the study were 0, 214, and 428 mg/kg/day for the mice, and 0, 107, and
214 mg/kg/day for the rats. Male rats treated with 1,4-DCB displayed nephropathy and mineralization
and hyperplasia of renal tubules. The incidence of renal tubular adenocarcinomas was also dosedependently
increased in the male rats (1/50, 3/50, or 7/50 for the 0, 107, or 214 mg/kg groups,
respectively). A significant dose-dependent increase in the incidence of mononuclear cell leukemia
(5/50, 7/50, or 11/50 for the 0, 107, or 214 mg/kg groups, respectively) was observed in the male rats.
Additionally, an increasing trend in the incidence of mesothelioma was observed in the male rats (1/50,
0/50, 4/50, for the 0, 107, or 214 mg/kg groups, respectively).
Mice of both sexes exposed to 1,4 - DCB had significantly increased incidence of hepatocellular
adenomas and carcinomas (NTP, 1987). In addition, four male mice exposed to 428 mg/kg were
found to have hepatoblastomas, a rare hepatocellular carcinoma. The incidence of follicular thyroid cell
adenomas was increased in female mice exposed to 428 mg/kg (p < 0.038). As with the male rats,
male mice showed evidence of kidney tubule damage when treated with 1,4 - DCB. Females were not
similarly affected.
NTP concluded from these data that 1,4 - DCB was carcinogenic to male rats, but not female rats. In
addition, NTP concluded that the increased incidence of hepatocellular adenomas and carcinomas was
evidence of carcinogenicity in male and female mice.
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