Carcinogenicity
Dermal application in C3H/JAX
mice for 18–20 months at 30% in acetone resulted in no mice
with tumors. All mice had died by 20 months. When applied
in C3H/HeJ mice for up to 24 months at 50% in acetone for
the first 15 months and 25% in acetone for the rest of the
study, there were again no skin tumors. In another test
in C3H mice at 50 and 10% in acetone, there were 5/80 with skin tumors at 50% level and 0/40 with skin tumors at
10%. When a 1:1 mixture of this compound and
ERL 2774 was applied at 50% and 10% in acetone to the
same two strains of mice, there were 51/80 and 19/40,
respectively, C57BL/6 mice with skin tumors. The sample
of ERL 2774 tested was shown to have 10% of an epoxidized
polyglycol (molecular weight 7500) and up to 5000 ppm
phenyl glycidyl ether present. Nothing is known of the
toxicity potential of the epoxidized polyglycol, but phenyl
glycidyl ether is known to cause nasal carcinoma in rats
following chronic inhalation.
The compound has been shown to be positive in the
Ames test for bacterial mutagenesis, positive in a cell
transformation assay in Chinese hamster ovary cells, and
negative for induction of DNA repair in cultured human
leukocytes.
