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Ellis et al.(1979) (also reported by Hong et al., 1985) exposed male and female CD-1 mice
(38/sex/group) to 0, 100, 700, or 5000 ppm 2,4-DNT in feed as described in the rat study above.
Since over 70% of the mice in the highest dose group died before 12 months, these animals were not
included in the analysis. Mortality among the remaining dose groups and controls ranged from 70 to
85%. Tumor incidence data were drawn from animals surviving at least 12 months. A significantly
increased incidence of renal tumors was found among male mice in the 700 ppm 2,4-DNT dose group
(19/28 treated vs. 0/33 control; p = 1.32 × 10 -9 , Fisher’s exact test). Renal tumor types included
cystic papillary adenomas, solid renal cell carcinomas, and cystic papillary carcinomas. No significantly
increased tumor incidence was reported among female mice.
Ellis et al. (1979, 1985) treated beagle dogs (6/sex/group) with 2,4-DNT in gelatin capsules daily for 2
years at dose rates of 0, 0.2, 1.5, or 10 mg/kg body weight. The highest dose was lethal to five of the
12 treated animals. Throrough examination of all animals upon sacrifice showed no evidence of
carcinogenicity of 2,4-DNT.
The Chemical Industry Institute of Toxicology (CIIT, 1982) exposed male and female F344 rats
(130/sex/dose) to technical grade DNT (76% 2,4-DNT and 19% 2,6-DNT) feed such that daily
dosing was 0, 3.5, 10.0, and 35.0 mg/kg-day. The entire high-dose group was sacrificed at 55 weeks
due to significantly reduced survival. Twenty rats (/sex) were examined histopathologically at this time.
The animals in the remaining dose groups were sacrificed at the scheduled time of 104 weeks. The
incidences of hepatocellular carcinoma and neoplastic nodules of the liver are reported in Table 1.
Cholangiocarcinomas were also reported in 3/20 high-dose male rats (at 55 weeks) and 2/23 mid-dose
male rats (at 104 weeks).
Table 1.
Tumor incidence in male and female F344 rats exposed to technical grade
dinitrotoluene (DNT) in feed (CIIT, 1982).
tumor type males (mg/kg-day) females (mg/kg-day)
0 3.5 10.0 35.0 * 0 3.5 10.0 35.0 *
hepatocellular 1/61 9/70 22/23 20/20 0/57 0/61 40/68 11/20
carcinoma
neoplastic nodules 9/61 11/70 16/23 5/20 5/57 12/61 53/68 12/20
* All the high-dose group animals were sacrificed at 55 weeks due to significantly reduced survival.
Histopathological examinations were performed on 20 rats/sex.
Leonard et al. (1987) exposed 20 male CDF(F344)/CrlBR rats to 2,4-DNT in the diet for 12 months
such that daily dose rate was 27 mg/kg-day. No evidence of carcinogenicity was found, however, the
study was short in duration and the number of animals was small.
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