Comparative in vitro-in vivo percutaneous penetration of the fungicide ortho-phenylphenol

Comparative in vitro-in vivo percutaneous penetration of the fungicide ortho-phenylphenol

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

2002

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).

Health
Dermal penetration
In vitro-in vivo comparison
Ortho-phenylphenol
Risk assessment
2 hydroxybiphenyl
2-phenylphenol
Biphenyl derivative
Fungicide
Animal tissue
Biotransformation
Controlled study
Human
Human tissue
In vitro study
In vivo study
Male
Nonhuman
Skin absorption
Skin culture
Skin penetration
Thickness
Toxicokinetics
Urinary excretion
Adult
Animal
Comparative study
Dose response
Epidermis
Intradermal drug administration
Membrane
Metabolism
Outbred strain
Permeability
Swine
Wistar rat
Administration, Cutaneous
Adult
Animal
Animals, Outbred Strains
Biphenyl Compounds
Comparative Study
Dose-Response Relationship, Drug
Epidermis
Female
Fungicides, Industrial
Human
In Vitro
Male
Membranes
Permeability
Rats
Rats, Wistar
Skin Absorption
Support, Non-U.S. Gov't
Swine
Animals
Humans
Sus scrofa

http://resolver.tudelft.nl/uuid:a5f050dc-91af-4ae8-8633-f9efc662df1d

https://doi.org/10.1006/rtph.2001.1530

236596

0273-2300

Regulatory Toxicology and Pharmacology, 35 (2 I), 198-208

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