Age-dependent response of the rat testes to di(2-ethylhexyl) phthalate

Spermatogenesis starts soon after birth in the Sprague-Dawley rat but is not fully established until about 56 days of age. When high oral doses of the plasticizer di(2-ethylhexyl) phthalate (DEHP) were given to rats of different ages, testicular damage was observed in immature but not in mature animals. Plasma concentration and urinary excretion data suggested that the gastrointestinal absorption of the DEHP-derived metabolite mono(2-ethylhexyl) phthalate was higher in young animals. Young rats were not more susceptible than older for repeated intravenous infusions of DEHP. It is suggested that the age-related difference observed in testicular response after oral administration of DEHP may be due to pharmacokinetic rather than tissue sensitivity differences. It is concluded that in assessing risks of testicular injuries in children exposed to DEHP, additional studies are required using species in which testicular development is more similar to that of humans.