Preliminary interlaboratory comparison of the ex vivo dual human placental perfusion system.
As a part of EU-project ReProTect, a comparison of the dual re-circulating human placental perfusion system was carried out, by two independent research groups. The detailed placental transfer data of model compounds [antipyrine, benzo(a)pyrene, PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine) and IQ (2-amino-3-methylimidazo(4,5-f)quinoline] has been/will be published separately. For this project, a comparative re-analysis was done, by curve fitting the data and calculating two endpoints: AUC(120), defined as the area under the curve between time 0 and time 120 min and as t(0.5), defined as the time when the fetal to maternal concentration ratio is expected to be 0.5. The transport of the compounds from maternal to fetal circulation across the perfused placenta could be ranked in the order of antipyrine>IQ>PhIP in terms of both t(0.5) and AUC(120) by both partners. For benzo(a)pyrene the curve fitting failed. These prevalidation results give confidence for harmonization of the placental perfusion system to be used as one of the test methods in a panel for reproductive toxicology to model placental transfer in humans.
Myllynen
Päivi
P
Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Oulu, Oulu, Finland. paivi.myllynen@oulu.fi
Mathiesen
Line
L
Weimer
Marc
M
Annola
Kirsi
K
Immonen
Elina
E
Karttunen
Vesa
V
Kummu
Maria
M
Mørck
Thit Juul
TJ
Nielsen
Jeanette Kolstrup Søgaard
JK
Knudsen
Lisbeth Ehlert
LE
Vähäkangas
Kirsi
K
D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007753:Laboratories / Q000592:standards; D008431:Maternal-Fetal Exchange; D010477:Perfusion / Q000379:methods / Q000592:standards; D010920:Placenta / Q000378:metabolism*; D021041:Placental Circulation; D011247:Pregnancy; D015203:Reproducibility of Results; D012098:Reproduction / Q000187:drug effects; D018675:Toxicity Tests / Q000379:methods / Q000592:standards
D004785:Environmental Pollutants