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    PBPK simulated DNA adduct formation: Relevance for the risk assessment of benzo(a)pyrene

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    Authors
    Zeilmaker MJ
    Eijkeren JCH van
    Kroese ED
    Series/Report no.
    RIVM Rapport 658603009
    Language
    en
    
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    Title
    PBPK simulated DNA adduct formation: Relevance for the risk assessment of benzo(a)pyrene
    Translated Title
    De toepassing van PBPK simulaties van de vorming van DNA adducten bij de risicoschatting van benzo(a)pyreen
    Publiekssamenvatting
    In a previous report a Physiologically Based PharmacoKinetic (PBPK) model for Benzo(a)Pyrene (B(a)P) is described (Zeilmaker et al., 1998). This model simulates, after chronic exposure, the distribution of B(a)P in the body and the metabolism of B(a)P, including the formation of (a limited number of) DNA adducts in the liver. This study explores the effect of using PBPK simulated DNA adduct formation, instead of the administered dose of B(a)P, as the starting point for the calculation of the life-long dose rate which is associated with an acceptable tumor response in humans, i.e. the so-called 'Virtual Safe Dose'(VSD).The results of this study suggest that the VSD which is calculated on the basis of the accumulation of B(a)P DNA adducts in the liver is one order of magnitude lower than the VSD which is calculated on the basis of the administered amount of B(a)P
    In een voorgaand rapport is een fysiologisch-kinetisch model (UPBPKL model) voor de orale blootstelling aan B(a)P beschreven (Zeilmaker et al., 1998). Dit model simuleert, na orale blootstelling, de verdeling van B(a)P in het lichaam en het metabolisme van B(a)P, inclusief de vorming van (een beperkt aantal) DNA adducten in de lever. Dit rapport beschrijft een verkennende studie naar de mogelijkheid om, in plaats van de toegediende hoeveelheid B(a)P, de door het model gesimuleerde vorming van DNA adducten als uitgangspunt te gebruiken voor de berekening van het voor de mens acceptabel geachte blootstellingsniveau voor B(a)P, de z.g.n. UVirtual Safe DoseL(VSD).De resultaten van deze studie suggereren dat de VSD die berekend wordt op basis van de vorming van B(a)P DNA adducten n orde grootte lager is dan de VSD die berekend wordt op basis van de toegediende hoeveelheid B(a)P
    Publisher
    Rijksinstituut voor Volksgezondheid en Milieu RIVM
    URI
    http://hdl.handle.net/10029/10240
    Collections
    RIVM official reports

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