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TRANSGENERATIONAL EFFECTS OF DEHP IN THE MALE RAT
Citation:
Gray Jr., L E., J. R. Furr, J. Brock, N. J. Barlow, AND J S. Ostby. TRANSGENERATIONAL EFFECTS OF DEHP IN THE MALE RAT. Presented at Society of Toxicology, Salt Lake City, UT, March 09 - 13, 2003.
Description:
Abstract
TITLE: Transgenerational Effects of Di(2-ethylhexyl) Phthalate in the Male Rat. AUTHORS (ALL): Gray, Leon Earl1; Barlow, Norman J2; Furr, Johnathan R1; Brock, John 3; Silva, Manori J3; Barr, Dana B3; Ostby, Joseph S1
SPONSOR NAME:
INSTITUTIONS (ALL): 1. ORD, NHEERL, RTD, EB, USEPA, Research Triangle Park, NC, USA; 2. CIIT, RTP, NC, USA; 3. CDC, Atlanta, GA, USA;
ABSTRACT BODY:
Phthalate esters such as di(2-ethylhexyl)- (DEHP), di(n-butyl)-, and benzyl butyl phthalate are widely used plasticizers that have been implicated in adverse developmental reproductive effects. They alter sexual differentiation by altering fetal Leydig cell development and hormone synthesis which in turn, results in abnormalities of the testis, gubernacular ligaments, epididymis and other androgen-dependent tissues. In spite of these concerns, studies of DEHP including relatively low dosage levels with developmental exposure and examination of sensitive endpoints in an adequate number of adult offspring have not been published. The current study was designed to begin to address these data gaps. Pregnant SD rats were dosed by gavage with DEHP from gestational day (GD) 8 to day 17 of lactation with 0, 11, 33, 100 or 300 mg/kg/d. On GD 18, two dams per group were euthanized and amniotic fluid was collected for analysis of MEHP levels. In half of the males (PUB cohort), dosing was continued from 18 to 63-65 days of age while the rest (IUL cohort) were not dosed directly. The PUB cohort was necropsied at 63-65 days of age while the IUL cohort was necropsied at full maturity. The 300 mg/kg/d, IUL group displayed permanent reductions in anogenital distance and reproductive organ weights, and permanent nipples. In the high dose group, about 25% of the males displayed testicular and/or epididymal abnormalities. These abnormalities also were displayed at a low incidence in the 11, 33 and 100 mg/kg/d dose groups along with subtle reductions in reproductive organ weights. In the PUB group, puberty (100 and 300) and reproductive organ weights (300 mg) were affected. Liver and adrenal weights were affected in all dose groups including 11 mg/kg/d (by one-tailed t-test), the lowest dose tested. Amniotic fluid levels of MEHP are being analyzed and a second study is reexaming the low dose effects of IUL DEHP exposure. Abstract of a proposed presentation and does not necessarily reflect EPA, CDC or CIIT policies.