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animals and the second generation treated group consisted of 66 animals. Among first and second
generation animals, an increased incidence of lung tumors was found (first generation: 44/62 treated vs.
20/62 control, p = 10 -5 ; second generation: 44/66 treated vs. 15/69 control, p = 10 -8 ).
Terao et al. (1978) exposed 4 week old male Wistar rats to feed containing NDMA and/or
sterigmatocystin (STG) for 54 weeks. Five exposure groups included 10 ppm STG alone, 10 ppm STG
and 1 ppm NDMA, 1 ppm STG and 10 ppm NDMA, 10 ppm NDMA, and a group receiving basal
diet alone. Animals were sacrificed at 69 weeks with the exception of one animal from each group
sacrificed after 5 weeks of exposure. Rats in all groups exposed to NDMA showed an increased
incidence of Leydig-cell tumors (p = 0.002). Liver tumors were not observed in the group receiving
NDMA alone; however, liver tumor incidence was elevated in the group receiving STG alone and in the
group receiving 10 ppm STG and 1 ppm NDMA.
Arai et al. (1979) exposed 6 week old male and female Wistar rats (7 to 17/sex/group) to feed
containing 0, 0.1, 1 or 10 ppm NDMA for 96 weeks. Food intake was monitored. Treated female
animals were found to have a higher incidence of nodular hyperplastic liver lesions (p < 0.05, Fisher’s
exact test).
Griciute et al. (1981) treated 8 week old male and female C57BL mice with NDMA (0.03 mg) and/or
ethanol (0.8 ml) in 0.2 ml water by intragastric intubation for 50 weeks. Control animals received only
water. Survivors were sacrificed at 80 weeks. No liver tumors developed in animals receiving ethanol
alone. Among animals receiving NDMA alone, the incidence of malignant liver tumors was increased
over controls (14/37 treated males, p = 10 -5 ; 16/29 treated females, p < 10 -6 ). Among animals
receiving both NDMA and ethanol, the incidence of forebrain olfactory neuroepithelioma was increased
(24/66 treated vs. 0/66 control; p < 0.001). No tumors of this type were observed in animals receiving
NDMA or ethanol alone.
Peto et al. (1982, 1984) exposed Colworth rats (60/sex/group) to NDMA in drinking water at 15
concentrations ranging from 0.033 to 16.896 ppm for life. A group of 240 animals receiving only
drinking water served as controls. Additional treatment groups of 6 animals/group were sacrificed at 6
and 12 months. Water consumption for male and female rats was 41 ml/kg and 72 ml/kg, respectively.
Among exposed animals, the incidence of fatal liver neoplasms (see Table 1) was significantly increased
over controls (p≤0.005) and the increase was found to be dose-related. Other tumors with trends
toward increased incidence include tumors of the lung (p =0.004), skin (p =0.001),
lymphatic/hematopoietic tissues (p =0.032), and seminal vesicles (p =0.004).
Lijinski and Reuber (1984) exposed 7-8 week old female Fischer 344 rats (20/group) to NDMA in
drinking water at concentrations of 13 and 5.5 mg/l for 5 days/week for 30 weeks. Animals were
observed for life. Hepatocellular carcinomas, hemangiosarcomas, and neoplastic nodules were
observed in treated animals. Significantly increased incidence of liver tumors of all types was observed
in both low-dose (14/20 treated vs. 2/20 controls; p = 10 -4 ) and high-dose (19/20 treated vs. 2/20
controls; p < 10 -5 ) animals.
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