Antifertility and Mutagenic Effects in Mice from Parenteral Administration of Di-2-ethylhexyl Phthalate (DEHP)

The subcutaneous administration of 1-10 mg of undiluted di-(2-ethylhexyl)phthalate di-(2-ethylhexyl)phthalate (DEHP) to adult male ICR mice on d 1, 5, and 10 was followed by mating, one to one, with untreated adult virgin females. A single mating at d 21 resulted in a reduction in the incidence of pregnancies in the DEHP-treated groups. On the other hand, repeated matings with fresh females starting on d 2, 6, 11, 16, and 21, and at weekly intervals through 8 wk, revealed no perceptible effect of DEHP on the incidence of pregnancy. Examination of surgically exposed uteri and ovaries of pregnant females on d 13 of gestation revealed an increase in the incidence of preimplantation losses and early fetal deaths in the DEHP-treated groups; consequently, there were fewer viable fetuses per pregnancy. Mutagenic indices for DEHP, calculated as percent ratios of (1) preimplantation losses/implantations per pregnancy and (2) early fetal deaths/implantations per pregnancy, suggested a dominant lethal mutation effect in the treated mice. These effects tend to be more pronounced on the postmiotic stage of germ-cell development.