PMID- 19585553 OWN - NLM STAT- MEDLINE DCOM- 20091104 LR - 20171116 IS - 1542-9741 (Electronic) IS - 1542-9733 (Linking) VI - 86 IP - 4 DP - 2009 Aug TI - Reproductive toxicity and pharmacokinetics of di-n-butyl phthalate (DBP) following dietary exposure of pregnant rats. PG - 345-54 LID - 10.1002/bdrb.20199 [doi] AB - Most rodent developmental toxicity studies of dibutylphthalate (DBP) have relied on bolus gavage dosing. This study characterized the developmental toxicity of dietary DBP. Pregnant CD rats were given nominal doses of 0, 100, or 500 mg DBP/kg/day in diet (actual intake 0, 112, and 582 mg/kg/day) from gestational day (GD) 12 through the morning of GD 19. Rats were killed 4 or 24 hr thereafter. DBP dietary exposure resulted in significant dose-dependent reductions in testicular mRNA concentration of scavenger receptor class B, member 1; steroidogenic acute regulatory protein; cytochrome P450, family 11, subfamily a, polypeptide 1; and cytochrome P450 family 17, subfamily a, polypeptide 1. These effects were most pronounced 4 hr after the end of exposure. Testicular testosterone was reduced 24 hr post-exposure in both DBP dose groups and 4 hr after termination of the 500-mg DBP/kg/day exposure. Maternal exposure to 500 mg DBP/kg/day induced a significant reduction in male offspring's anogenital distance indicating in utero disruption of androgen function. Leydig cell aggregates, increased cord diameters, and multinucleated gonocytes were present in DBP-treated rats. Monobutyl phthalate, the developmentally toxic metabolite of DBP, and its glucuronide conjugate were found in maternal and fetal plasma, amniotic fluid, and maternal urine. Our results, when compared to previously conducted gavage studies, indicate that approximately equal doses of oral DBP exposure of pregnant rats, from diet or gavage, result in similar responses in male offspring. CI - Copyright (c) 2009 Wiley-Liss, Inc. FAU - Struve, Melanie F AU - Struve MF AD - CIIT at The Hamner Institutes for Health Sciences, 6 Davis Drive, P.O. Box 12137, Research Triangle Park, NC 27709-2137, USA. FAU - Gaido, Kevin W AU - Gaido KW FAU - Hensley, Janan B AU - Hensley JB FAU - Lehmann, Kim P AU - Lehmann KP FAU - Ross, Susan M AU - Ross SM FAU - Sochaski, Mark A AU - Sochaski MA FAU - Willson, Gabrielle A AU - Willson GA FAU - Dorman, David C AU - Dorman DC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Birth Defects Res B Dev Reprod Toxicol JT - Birth defects research. Part B, Developmental and reproductive toxicology JID - 101155115 RN - 0 (Androgen Antagonists) RN - 0 (Glucuronides) RN - 0 (Phthalic Acids) RN - 0 (Scarb1 protein, rat) RN - 0 (Scavenger Receptors, Class B) RN - 0 (Steroids) RN - 2286E5R2KE (Dibutyl Phthalate) RN - 3XMK78S47O (Testosterone) RN - ZI46LWZ45G (monobutyl phthalate) SB - IM MH - Administration, Oral MH - Amniotic Fluid/chemistry MH - Androgen Antagonists/administration & dosage/pharmacokinetics/*toxicity MH - Animals MH - Biotransformation MH - Body Weight/drug effects MH - Dibutyl Phthalate/administration & dosage/pharmacokinetics/*toxicity MH - Dose-Response Relationship, Drug MH - Female MH - Gas Chromatography-Mass Spectrometry MH - Gene Expression Regulation, Developmental/drug effects MH - Genitalia, Male/drug effects/embryology/pathology MH - Gestational Age MH - Glucuronides/analysis/blood/pharmacokinetics/urine MH - Male MH - Phthalic Acids/*analysis/blood/urine MH - Pregnancy MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley MH - Scavenger Receptors, Class B/drug effects MH - Steroids/biosynthesis MH - Testis/drug effects/embryology/metabolism/pathology MH - Testosterone/biosynthesis EDAT- 2009/07/09 09:00 MHDA- 2009/11/05 06:00 CRDT- 2009/07/09 09:00 PHST- 2009/07/09 09:00 [entrez] PHST- 2009/07/09 09:00 [pubmed] PHST- 2009/11/05 06:00 [medline] AID - 10.1002/bdrb.20199 [doi] PST - ppublish SO - Birth Defects Res B Dev Reprod Toxicol. 2009 Aug;86(4):345-54. doi: 10.1002/bdrb.20199.