Phthalate acid esters (PAEs), otherwise known as plasticizers, are widely used to impart flexibility and clarity to a variety of plastic formulations. The reproductive and developmental effects of different PAEs vary quite widely. Recently, at least seven PAEs have been selected for a re-review of their reproductive and/or developmental effects, particularly in experimental animals (e.g., rats and mice). The seven PAEs include, butyl benzyl phthalate (BBP), dibutyl phthalate (DBP), dihexyphthalate (DHP), di(2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DnOP), diisononyl phthalate (DINP), and diisodecyl phthalate (DIDP). DINP, DIDP and DnOP do not appear to possess any significant reproductive or developmental toxicity in experimental animals. BBP, DBP and DHP exhibit some degree of reproductive and developmental toxicity in experimental animals, but only at doses that far exceed any reasonable human exposure conditions. Of the seven PAEs, only DEHP has been shown to exert deleterious effects on the testes, particularly in rats and mice. Such deleterious effects are seen primarily following oral dosing with DEHP. In many species, DEHP is metabolized in the G-I tract to the monoester, MEHP. Further metabolism of MEHP can occur, but its degradation is influenced by the route of administration and is species specific. There are numerous studies on the effects of DEHP administration in rodents and in nonrodents that demonstrate adverse effects upon the testes. DEHP and/or MEHP exert adverse effects on cells located within the seminiferous tubules. The proximate reproductive toxicant appears to be MEHP and the specific target cell in the testes appears to be the Sertoli cell. In addition, MEHP may interfere with Leydig cell function. While DEHP and/or MEHP are clearly reproductive toxicants in rodents, there is little likelihood that they adversely affect human reproduction.
