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Van Duuren et al. (1972) report on two experimental approaches to evaluate the carcinogenicity of
bis(2-chloroethyl)ether; a subcutaneous injection study and an initiation study by dermal application.
ICR/Ha Swiss mice (30 females) were injected weekly with 1 mg BCEE for 68 days. No tumors
remote from the injection site were observed. Two sarcomas were noted at the injection site (2/30) but
were not found to be statistically different from controls (0/30) (p > 0.05 by Fisher’s Exact Test).
Van Duuren et al. (1972) also treated ICR/Ha Swiss mice (20 females/group) with a single dose of 1
mg BCEE applied to the skin followed by three applications/week of the tumor promoter phorbol
myristate acetate (PMA) in acetone for life. Control groups included animals not treated with BCEE
and animals treated with BCEE but without the promoter. Skin papillomas were noted among animals
treated with both BCEE and PMA, but the incidence was not significantly higher than among control
animals (3/20 treated, 2/20 controls; p>0.05 by Fisher’s Exact Test). No tumors were observed
among animals treated only with BCEE.
Theiss et al. (1977) injected A/St mice (20 males) intraperitoneally with 8, 20, or 40 mg/kg BCEE 3
times/week for 8 weeks. After 24 weeks all surviving mice were sacrificed and examined only for lung
tumors. The incidence of tumors among treated animals was not found to be significantly higher than
among controls.
Table 1. Incidence of tumors in rats treated with bis(2-chloroethyl)ether *
(Innes et al.,1969).
Tumor Incidence
Strain X
Strain Y
Tumor Type/Treatment female male female male
hepatomas treated 4/18 ** 14/16 ** 0/18 9/17 **
control 0/87 8/79 1/82 5/90
pulmonary tumors treated 0/18 0/16 0/18 2/16
control 3/83 5/79 3/92 10/90
lymphomas treated 0/18 2/16 0/18 0/17
control 4/87 5/79 4/82 1/90
* F 1 generation mice were administered 100 mg/kg body weight bis(2-chloroethyl)ether by oral gavage
from day 7 to 28 of life and subsequently in feed at a concentration of 300 ppm for 76 weeks
(calculated dose is 39 mg/kg-day). Surviving mice were sacrificed at 80 weeks.
** statistically significant increase in incidence (p < 0.001 by Fisher’s exact test)
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