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Table 1.
Incidence of liver and mammary gland tumors among female CD rats exposed to
practical grade 2,4-dinitrotoluene (2,4-DNT) in feed for 24 months
(Lee et al., 1978).
treatment level
tumor incidence
(ppm) liver 1 mammary gland 2 combined
0 0/31 11/31 11/31
15 3/43 12/43 13/43
100 3/35 18/35 18/35
700 30/42 34/43 35/43
1
Tumor incidence includes neoplastic nodules and hepatocellular carcinoma of the liver.
2
Tumor incidence includes adenoma, fibroadenoma, fibroma, or adenocarcinoma of the mammary
gland.
The National Cancer Institute (NCI, 1978) conducted a study exposing Fischer rats and B6C3F 1 mice
to practical-grade 2,4-DNT (>95% pure). Male and female Fischer rats (50/sex/group) were exposed
to feed containing 0.02% or 0.008% 2,4-DNT (time-weighted concentrations). Control groups
consisted of 25 rats/sex for the high-dose group and 50 rats/sex for the low-dose group. The treatment
period was 78 weeks long and the observation period continued for 26 weeks. Among treated male
rats in both high- and low-dose groups, the incidence of benign fibroma of the skin and subcutaneous
tissue was increased over controls (high-dose: 13/49 treated vs. 0/25 control, p = 0.003; low-dose:
7/49 treated vs. 0/46 control, p = 0.008 by Fisher’s exact test). Among treated female rats in the highdose
group, the incidence of fibroadenoma of the mammary gland was increased over control animals
(23/50 treated vs. 4/23 control, p = 0.016).
In the same study (NCI, 1978), male and female B6C3F 1 mice (50/sex/group) were treated with diet
containing 0.04% or 0.008% 2,4-DNT (time-weighted concentrations). Groups of 50 mice/sex served
as controls for the high- and low-dose groups. The treatment period lasted 78 weeks and the animals
were observed for an additional 13 weeks. No significant increase in tumor incidence was observed
among treated animals.
Ellis et al. (1979) (also reported by Lee et al.,1985) exposed male and female CD (Sprague-Dawley)
rats (38/sex/group) to 0, 15, 100, or 700 ppm 2,4-DNT in feed. At 12 months, 8 rats/group were
sacrificed for necropsy; the remainder were sacrificed at 24 months. Cumulative deaths during the
course of the study ranged from 55 to 100% in male rats and 60 to 97% in female rats, including control
animals. Histopathological outcomes of animals that died during the course of the experiment (but after
52 weeks) were included in the final incidence data along with the incidence data among survivors.
Tumors showing statistically significant increases (p < 0.05 by Fisher’s exact test) were hepatocellular
carcinomas and mammary gland tumors among female rats in the highest dose group. Hepatocellular
carcinomas were reported in 18/34 treated high-dose female rats vs. 0/23 control rats (p = 4.3 × 10 -6 ).
Mammary gland tumors, including both benign and malignant tumors of epithelial or mesenchymal origin,
were reported in 33/35 treated high-dose female rats vs. 11/23 control rats (p < 0.0001).
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