Disposition of diiosononyl phthalate and its effects on sexual development of the male fetus following repeated dosing in pregnant rats.
Pregnant Sprague-Dawley rats received 50, 250, and 500 mg/kg/day diisononyl phthalate (DiNP) from GD 12 to 19 via corn oil gavage to study the dose response for effects on fetal male rat sexual development as well as metabolite disposition in the dam and fetus. Monoisononyl phthalate (MiNP), mono(carboxy-isooctyl) phthalate (MCiOP), mono(hydroxyl-isononyl) phthalate (MHiNP), mono(oxo-isononyl) phthalate (MOiNP), and monoisononyl phthalate glucuronide (MiNP-G) were found in all measured tissues. MCiOP was the major metabolite, followed in decreasing order by MiNP, MHiNP, MOiNP, and MiNP-G. Percentage of dose absorbed decreased at 750 mg/kg/day. Testosterone concentration in the fetal testes was reduced at 250 and 750 mg/kg/day. Multinucleated germ cells were increased in the testes of rats at 250 and 750 mg/kg/day. The no observed effect level (NOEL) for this study was 50 mg/kg/day based on increased MNGs and reduced testes testosterone concentration in the fetal rat.
The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA. rclewell@thehamner.org
Rebecca A
RA
Clewell
Mark
M
Sochaski
Kendra
K
Edwards
Dianne M
DM
Creasy
Gabrielle
G
Willson
Melvin E
ME
Andersen
D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D052244:Endocrine Disruptors / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D010795:Phthalic Acids / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D046468:Sexual Development / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000378:metabolism*; D014018:Tissue Distribution
D052244:Endocrine Disruptors; D010795:Phthalic Acids; D013739:Testosterone; C012125:diisononyl phthalate