A comparative assessment of phthalate effects on gonadal steroidogenesis in male rats.

Abstract

Although it is a known endocrine disrupting chemical (EDC) of the male reproductive tract that is ubiquitous in the environment, di (2-ethylhexyl) phthalate (DEHP) has remained the most utilized industrial plasticizer on Earth. Government regulations that are based on public health concerns, however, have promoted the search for an alternative to DEHP in consumer products. In the present study, we evaluated diisononyl phthalate (DINP), a structural analog of DEHP, as a potential replacement chemical for DEHP. To accomplish this goal, we compared the individual (0, 5, 10, or 15 µg/L) and combined (5 µg/L DINP + 5 µg/L DEHP; DINP+DEHP) effects of these chemicals on the serum concentrations and testicular production of testosterone (T) and estradiol (E2) in weanling male Long-Evans rats. We performed two sets of 14- and 28-day experiments, i.e., 14-dA and 28-dA and 14-dB and 28-dB, during which rats were exposed to DINP, DEHP, or DINP+DEHP in drinking water (Table 1). The results of experiments 14-dA and 28-dA demonstrated that exposure to DEHP, but not to DINP or DINP+DEHP, affected testicular T and E2 production in male rats. Results from the second set of experiments showed that DINP and DEHP individually affected serum E2 concentration and testicular E2 production, but only DEHP and DINP+DEHP exposures affected testicular T production in male rats. Furthermore, the data showed that DINP exerted an additive effect on the cellular effects of DEHP. Collectively, the results of our study demonstrated that DINP caused a lesser testicular toxicity in prepubertal male rats than DEHP, but the results also showed that the prepubertal rat testis is targeted by DINP, which affected serum T and E2 secretion after 14- and 28 day-exposures. Future studies will identify the molecular mechanisms associated with the estrogenic and antiandrogenic effects of DINP and/or DEHP in prepubertal male rats.