PLATFORM SESSION 13. TOXICOLOGY
Monday, August 2, 2004
2:00 PM–4:00 PM
Chair: Leon Earl Gray, Jr.
Co-Chair: Nigel Noriega
(320) PERIPUBERTAL DEHP EXPOSURE INHIBITS ANDROGEN SENSITIVE TISSUE DEVELOPMENT AND DELAYS PUBERTY IN MALE SPRAGUE-DAWLEY RATS.
Noriega, Nigel 1, Furr, Johnathan1, Lambright, Christy1, Wilson, Vickie1, Gray, L. Earl1, 1 EPA, Research Triangle Park, NC
ABSTRACT- The plasticizer Di (2-ethylhexyl) phthalate (DEHP) may present reproductive risk by demasculinizing prenatal and juvenile males. The current study was designed to assess DEHP effects throughout pubertal development in Sprague-Dawley rats. Subsets of males were dosed from PND 23-43 and 23-44 with DEHP at 0, 100, 300 and 900 mg/kg-bw/day. Reduced bodyweight in 900 mg/kg-bw/day group appeared associated with a temporary growth rate reduction noted in the first 2 days of dosing. At 100, 300 and 900 mg/kg-bw/day, liver weight was elevated and adrenal weight was reduced (P < 0.05) compared to controls. In both 300 and 900 mg/kg-bw/day groups, testis, seminal vesicle, Cowper ′s gland, and levator ani + bulbocavernosus muscle weights were reduced (P < 0.05). Epididymal weights were reduced (P < 0.01) in the highest dose group. Testicular testosterone (T) production was decreased by 38 % in 300 mg/kg-bw/day animals (P = 0.01) and 73% (P < 0.0001) in the 900 mg/kg-bw/day animals. Testicular T production in response to chorionic gonadotropin stimulus was also reduced by 25 % (P = 0.03) and 75 % (P =0.0002) in 300 and 900 mg/kg-bw/day animals respectively. Serum testosterone was reduced by 52 % (P = 0.04) in the highest dose group. At the time of first necropsy, where half of the male study population was sacrificed, 68.8 % of all controls, and 81.3% of 100 mg/kg-bw/day males showed complete preputial separation, compared to 37.5 % and 12.5 % of all males dosed with 300 and 900 mg/kg-bw/day respectively. Females dosed daily from PND 23 (concurrently with males) with either corn oil or 900 mg/kg-bw/day DEHP showed no differences in time to vaginal opening. Peripubertal DEHP exposure inhibited testicular development. Resulting reductions in T production and androgen sensitive tissue weights, as well as delays in time to completion of male puberty are consistent with published results of prenatal and juvenile phthalate exposure studies in rats. These data do not support the hypothesis that DEHP exposure promotes precocial pubertal development by elevating T. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.
KEY WORDS: dehp, androgen, phthalate, puberty