Transplacental transfer of monomethyl phthalate and mono(2-ethylhexyl) phthalate in a human placenta perfusion system.
The transplacental passage of monomethylphtalate (mMP) and mono (2-ethylhexyl) phthalate (mEHP) was studied using an ex vivo placental perfusion model with simultaneous perfusion of fetal and maternal circulation in a single cotyledon. Umbilical cord blood and placental tissue collected both before and after perfusion were also analyzed. Placentas were obtained immediately after elective cesarean section and dually perfused in a recirculation system. mMP or mEHP was added to maternal perfusion medium to obtain concentrations at 10 and 25 microg/L, respectively. The placental transfer was followed analyzing samples from fetal and maternal perfusion media by liquid chromatography-mass spectrometry-mass spectrometry (LC-MS-MS). Four perfusions with mMP indicated a slow transplacental transfer, with a feto-maternal ratio (FM ratio) of 0.30 +/- 0.03 after 150 min of perfusion. Four perfusions with mEHP indicated a very slow or nonexisting placental transfer. mEHP was only detected in fetal perfusion media from two perfusions, giving rise to FM ratios of 0.088 and 0.20 after 150 min of perfusion. Detectable levels of mMP, mEHP, monoethylphthalate (mEP), and monobutylphthalate were found in tissue. Higher tissue levels of mMP after perfusions with mMP compared to perfusions with mEHP suggest an accumulation of mMP during perfusion. No tendency for accumulation of mEHP was observed during perfusions with mEHP compared to perfusions with mMP. Detectable levels of mEHP and mEP were found in umbilical cord plasma samples. mMP and possibly other short-chained phthalate monoesters in maternal blood can cross the placenta by slow transfer, whereas the results indicate no placental transfer of mEHP. Further studies are recommended.
Mose
Tina
T
Department of Environmental and Occupational Health, Institute of Public Health, University of Copenhagen, Denmark. t.mose@pubhealth.ku.dk
Knudsen
Lisbeth E
LE
Hedegaard
Morten
M
Mortensen
Gerda K
GK
D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange; D008954:Models, Biological; D010477:Perfusion; D010795:Phthalic Acids / Q000097:blood / Q000493:pharmacokinetics*; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy
D010795:Phthalic Acids; C517284:monomethyl phthalate; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate