title: Meta-analysis of data from human ex vivo placental perfusion studies on genotoxic and immunotoxic agents within the integrated European project NewGeneris.
abstract: In the E.U. integrated project NewGeneris, we studied placental transport of thirteen immunotoxic and genotoxic agents in three ex vivo placental perfusion laboratories. In the present publication, all placental perfusion data have been re-analyzed and normalized to make them directly comparable and rankable. Antipyrine transfer data differed significantly between the studies and laboratories, and therefore normalization of data was necessary. An antipyrine normalization factor was introduced making the variance significantly smaller within and between the studies using the same compound but performed in different laboratories. Non-normalized (regular) and normalized data showed a good correlation. The compounds were ranked according to their transplacental transfer rate using either antipyrine normalized AUC120 or transfer index (TI120(%)). Normalization generated a division of compounds in slow, medium and high transfer rate groups. The transfer rate differed slightly depending on the parameter used. However, compounds with passage similar to antipyrine which goes through the placenta by passive diffusion, and good recovery in media (no accumulation in the tissue or adherence to equipment) were highly ranked no matter which parameter was used. Antipyrine normalization resulted in the following ranking order of compounds according to AUC(120NORM) values: NDMA ≥ EtOH ≥ BPA ≥ IQ ≥AA ≥ GA ≥ PCB180 ≥ PhIP ≥ AFB1 > DON ≥ BP ≥ PCB52 ≥ TCDD. As the variance in all parameters within a study decreased after antipyrine normalization, we conclude that this normalization approach at least partially corrects the bias caused by the small methodological differences between studies.
authors.affiliation: Department of Public Health, University of Copenhagen, Øster Farimagsgade 5, 1014 Copenhagen, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Mose
authors.forename: L
authors.initials: L
authors.lastname: Mathiesen
authors.forename: V
authors.initials: V
authors.lastname: Karttunen
authors.forename: J K S
authors.initials: JK
authors.lastname: Nielsen
authors.forename: E
authors.initials: E
authors.lastname: Sieppi
authors.forename: M
authors.initials: M
authors.lastname: Kummu
authors.forename: T A
authors.initials: TA
authors.lastname: Mørck
authors.forename: K
authors.initials: K
authors.lastname: Myöhänen
authors.forename: H
authors.initials: H
authors.lastname: Partanen
authors.forename: K
authors.initials: K
authors.lastname: Vähäkangas
authors.forename: L E
authors.initials: LE
authors.lastname: Knudsen
authors.forename: P
authors.initials: P
authors.lastname: Myllynen
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics; D000983:Antipyrine / Q000493:pharmacokinetics; D019540:Area Under Curve; D002492:Central Nervous System Depressants / Q000493:pharmacokinetics; D000431:Ethanol / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics; D000922:Immunotoxins / Q000493:pharmacokinetics*; D009153:Mutagens / Q000493:pharmacokinetics*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011804:Quinolines / Q000493:pharmacokinetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002492:Central Nervous System Depressants; D007093:Imidazoles; D000922:Immunotoxins; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D000431:Ethanol; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D000983:Antipyrine