Germ cell mutagenicity of γ-ethyl-γ-phenyl-butyrolactone (EPBL) detected in the CF1 mouse-dominant lethal study

Abstract Female and male CF1 mice weighing 25–30 g were given 0, 50, 100 or 200 mg/kg of γ-ethyl-γ-phenyl-butyrolactone (EPBL) for 5 days intraperitoneally. In the male-dominant lethal phase, males treated with EPBL were mated with untreated females following a 7-day mating schedule with three consecutive mating events. In the female-dominant lethal phase, females treated with EPBL were caged with untreated males. The above dosages and schedule treatments were used. The incidence of pregnancy of females mated on days 1–7 and 8–14 after males were given 200 mg/kg of EPBL and of females given 200 mg/kg when mated to untreated males was decreased. Upon examining surgically exposed uteri and ovaries of pregnant females during the first phase, on gestation days 13–15, an increased incidence of pre-implantation losses with 200 mg/kg of EPBL and an increased incidence of post-implantation losses with 100 and 200 mg/kg was observed. In addition, an increased frequency of pre- and post-implantation losses was seen in females treated with 200 mg/kg. These results support the conclusion that EPBL is a germ cell mutagen and its effects are more pronounced during the post-meiotic stage.