home edit2 whole TSD November 2002 PDF format - OEHHA

Table 2:
Results of the NTP (1982) inhalation bioassay of EDB in B6C3F 1 mice.
Tumor Sex Control 10 ppm 40 ppm
Lung:
Alveolar/bronchiolar carcinomas or
adenomas
Alveolar/bronchiolar carcinomas or
adenomas
Circulatory system:
M 0/41 3/48 23/46 a
F 4/49 11/49 41/50 a
Hemangioma or hemangiosarcoma M 0/45 0/50 4/50
F 0/50 12/50 a 27/50 a
Subcutaneous tissue fibrosarcoma F 0/50 5/50 c 11/50 a
Mammary gland adenocarcinoma F 2/50 14/50 a 8/50 e
Nasal cavity carcinoma or adenoma F 0/50 0/50 8/50 b
a p = 0.001; b p = 0.003; c p = 0.028; e p = 0.046
A chronic inhalation bioassay was conducted by NIOSH to evaluate the effect of disulfiram on
carcinogenic and other toxic effects of EDB. The findings have been reported in several publications
(Plotnick, 1978; Wong et al., 1982). The study exposed four groups of 48 male and four groups of 48
female Sprague-Dawley rats to room air or 20 ppm EDB for 7 hours/day for 5 days/week over an 18-
month period. Diets which contained 0.05% disulfiram were given to one set of controls and EDB
exposed rats.
Male rats receiving EDB exposure had significantly higher tumor incidences in spleen, adrenals, and
subcutaneous tissues than either the control or disulfiram tested rats. Also a significant finding was the
high incidence of hemangiosarcoma in the spleen of male rats exposed to EDB. Tumors were also
found in the liver, kidneys, and lungs in these animals. Female rats exposed to EDB also showed
significantly high tumor incidences in the spleen (hemangiosarcoma), adrenals, and mammary glands.
Tumors were also found in the liver. The number of rats with tumors were 15/96, controls on normal
diet; 13/96 controls, on disulfiram diet; 54/96, EDB-exposed on normal diet; and 90/96, EDB-exposed
on disulfiram diet. The tumor incidence by site was not available.
Osborne-Mendel rats and B6C3F 1 mice were administered various levels of EDB in corn oil by
stomach tube 5 days/week (NCI, 1978). Time-weighted averages for the high and the low dose
groups were 41 and 38 mg/kg/day for male rats, 39 and 37 mg/kg/day for female rats, and 107 and 62
mg/kg/day for male and female mice, respectively (50 animals/sex/group). The responses were
compared with two control groups (20 animals/group), of which one received corn oil and the other had
no treatment. In rats, squamous cell carcinomas of the forestomach were observed in 45/50, 33/50,
40/50, and 29/50 of the low-dose males, high-dose males, low-dose females, and high-dose females,
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