Effects of co-administration of di(2-ethylhexyl) phthalate and testosterone on several parameters in the testis and pharmacokinetics of its mono-de-esterified metabolite

The administration of 1 g/kg di(2-ethylhexyl)phthalate (DEHP) or 5 mg/kg testosterone for 1 week did not affect the testicular and prostatic gland weights in rats. However, co-administration of DEHP and testosterone induced severe testicular atrophy accompanied by a decrease of zinc concentration in the testis and reduction of the activity of testicular specific lactate dehydrogenase isozyme. These changes were similar to the results of high dose administration of DEHP alone. Values of biological half-life and area under the concentration-time curve (AUC) of mono(2-ethylhexyl)phthalate, the main metabolite of DEHP, in testes after a single co-administration of DEHP (p.o.) and testosterone (i.p.) were higher than those after DEHP administration alone. Results suggest that the co-administration of DEHP and testosterone enhanced the adverse effects of DEHP on testes as the result of changes in pharmacokinetic values of MEHP.