Print Email Facebook Twitter Comparative in vitro-in vivo percutaneous penetration of the fungicide ortho-phenylphenol Title Comparative in vitro-in vivo percutaneous penetration of the fungicide ortho-phenylphenol Author Cnubben, N.H.P. Elliott, G.R. Hakkert, B.C. Meuling, W.J.A. van de Sandt, J.J.M. TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO Publication year 2002 Abstract The validity of in vitro and in vivo methods for the prediction of percutaneous penetration in humans was assessed using the fungicide ortho-phenylphenol (OPP) (log Po/w 3.28, MW 170.8, solubility in water 0.7 g/L). In vivo studies were performed in rats and human volunteers, applying the test compound to the dorsal skin and the volar aspect of the forearm, respectively. In vitro studies were performed using static diffusion cells with viable full-thickness skin membranes (rat and human), nonviable epidermal membranes (rat and human), and a perfused pig ear model. For the purpose of conducting in vitro/in vivo comparisons, standardized experimental conditions were used with respect to dose (120 μg OPP/cm2), vehicle (60% aqueous ethanol), and exposure duration (4 h). In human volunteers, the potentially absorbed dose (amount applied minus dislogded) was 105 μg/cm2, while approximately 27% of the applied dose was excreted with urine within 48 h. In rats these values were 67 μg/cm2 and 40%, respectively. In vitro methods accurately predicted human in vivo percutaneous absorption of OPP on the basis of the potential absorbed dose. With respect to the other parameters studied (amount systemically available, maximal flux), considerable differences were observed between the various in vitro models. In viable full-thickness skin membranes, the amount systemically available and the potentially absorbed dose correlated reasonably well with the human in vivo situation. In contrast the Kp/maximal flux considerably underestimated the human in vivo situation. Although epidermal membranes overestimated human in vivo data, the species differences observed in vivo were reflected correctly in this model. The data generated in the perfused pig ear model were generally intermediate between viable skin membranes and epidermal membranes. © 2002 Elsevier Science (USA). Subject HealthDermal penetrationIn vitro-in vivo comparisonOrtho-phenylphenolRisk assessment2 hydroxybiphenyl2-phenylphenolBiphenyl derivativeFungicideAnimal tissueBiotransformationControlled studyHumanHuman tissueIn vitro studyIn vivo studyMaleNonhumanSkin absorptionSkin cultureSkin penetrationThicknessToxicokineticsUrinary excretionAdultAnimalComparative studyDose responseEpidermisIntradermal drug administrationMembraneMetabolismOutbred strainPermeabilitySwineWistar ratAdministration, CutaneousAdultAnimalAnimals, Outbred StrainsBiphenyl CompoundsComparative StudyDose-Response Relationship, DrugEpidermisFemaleFungicides, IndustrialHumanIn VitroMaleMembranesPermeabilityRatsRats, WistarSkin AbsorptionSupport, Non-U.S. Gov'tSwineAnimalsHumansSus scrofa To reference this document use: http://resolver.tudelft.nl/uuid:a5f050dc-91af-4ae8-8633-f9efc662df1d DOI https://doi.org/10.1006/rtph.2001.1530 TNO identifier 236596 ISSN 0273-2300 Source Regulatory Toxicology and Pharmacology, 35 (2 I), 198-208 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.