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INVESTIGATION OF THE ABILITY OF DIISONONYL PHTHALATE (DINP) TO ALTER ANDROGEN-DEPENDENT TISSUE DEVELOPMENT IN SPRAGUE-DAWLEY RATS
Citation:
Ostby, J S., A. K. Hotchkiss, J. R. Furr, AND L. E. Gray Jr. INVESTIGATION OF THE ABILITY OF DIISONONYL PHTHALATE (DINP) TO ALTER ANDROGEN-DEPENDENT TISSUE DEVELOPMENT IN SPRAGUE-DAWLEY RATS. Presented at Triangle Consortium for Reproductive Biology, RTP, NC, January 27, 2001.
Description:
Title: INVESTIGATION OF THE ABILITY OF DIISONONYL PHTHALATE (DINP) TO ALTER ANDROGEN-DEPENDENT TISSUE DEVELOPMENT IN SPRAGUE-DAWLEY RATS.
Authors: J S Ostby 1 , A K Hotchkiss 2 , J R Furr 1 and L E Gray Jr. 1
Sponsor: L Gray Jr.
Institutions: 1. USEPA, NHEERL, RTD, EB, RTP, NC, USA
2. North Carolina State University, NCSU/USEPA Cooperative Training Program, Raleigh, NC, USA
Abstract:
In a structure activity study, we found that perinatal exposure from gestational day (GD) 14 through postnatal day (PND) 3 to 0.75 g bis(2-ethylhexyl)phthalate (DEHP), benzyl butyl phthalate (BBP) and diisononyl phthalate (DINP) produced reproductive malformations in 91% (DEHP), 84% (BBP) and 7.7% (DINP) of the F1 males. In 52 DINP males, malformations included 2 males with permanent nipples, one male with an aspermatogenic fluid-filled testis and agenesis of the ipsilateral epididymis, and another male exhibited bilateral testicular atrophy, small epididymides and hypospermatogenesis. The profile of malformations was similar but of lower incidence than those produced by DEHP and BBP. Also, DINP increased the percent of males with areolas at 13 days of age, but did not significantly reduce male anogenital distance at 2 days of age. Thus, a second study was undertaken using higher dosage levels of DINP to confirm its antiandrogenic action in utero. Although DINP (CAS # 68515-48-0) consists primarily of C9 phthalate esters, the length of the side chain varies from formulation to formulation and it also contains other phthalate esters. In the current study, DINP was administered orally at 0, 1 and 1.5 g/kg dam body weight/2.5 ml corn oil as the vehicle from GD 14 - PND 3. At 2 days of age males exposed to 1.5 g DINP displayed reduced anogenital distance while female anogenital distance was unaffected by treatment. DINP also increased the percentage of males with areolas on PND 13 in a dose related fashion from 14 % in control males to 55 % and 75 % in the 1.0 and 1.5 mg DINP groups. Thus, these results on the neonatal and infantile male rat confirm our previous observation, that DINP alters development of androgen-dependent tissues. Additional observations on these males will be reported, when the in-life phase of the study is completed. This abstract does not necessarily reflect USEPA policy.