Journal Article
Disposition of diiosononyl phthalate and its effects on sexual development of the male fetus following repeated dosing in pregnant rats
Clewell, RA; Sochaski, M; Edwards, K; Creasy, DM; Willson, G; Andersen, ME
Reproductive Toxicology
ISSN: 0890-6238
EISSN: 1873-1708
PERGAMON-ELSEVIER SCIENCE LTD
Reprod Toxicol. 2013, Jan; 35:56-69. [Reproductive toxicology (Elmsford, N.Y.)]
Pregnant Sprague-Dawley rats received 50, 250, and 500mg/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 750mg/kg/day. Testosterone concentration in the fetal testes was reduced at 250 and 750mg/kg/day. Multinucleated germ cells were increased in the testes of rats at 250 and 750mg/kg/day. The no observed effect level (NOEL) for this study was 50mg/kg/day based on increased MNGs and reduced testes testosterone concentration in the fetal rat.
Phthalate; DiNP; Gestation; Metabolism; Testosterone; Developmental effects
