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    Plasmaspiegels van benzo(a)pyreen na viereneenhalve maand herhaalde orale toediening van benzo(a)pyreen aan de Riv:TOX rat

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    Authors
    Lusthof KJ
    Olling M
    Kroese ED
    Type
    Report
    Language
    nl
    
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    Title
    Plasmaspiegels van benzo(a)pyreen na viereneenhalve maand herhaalde orale toediening van benzo(a)pyreen aan de Riv:TOX rat
    Translated Title
    Plasma levels of benzo(a)pyrene after four and a half months' repeated oral administration of benzo(a)pyrene to the Riv:TOX rat
    Publiekssamenvatting
    In het kader van project '658603 (chronische carcinogeniteitsstudie met benzo(a)pyreen in de rat)' zijn er bij 48 ratten (24 mannelijke en 24 vrouwelijke) na een periode van viereneenhalve maand van regelmatige orale toediening van benzo(a)pyreen bloedmonsters afgenomen. De toediening bestond uit dagelijkse doses van een oplossing van benzo(a)pyreen in soya-olie per maagsonde, gedurende vijf dagen per week. Er waren vier doseringsniveaus: 0,1, 3, 10 en 30 mg per kg lichaamsgewicht. Op tijdstippen tot zes uur na toediening werden twee bloedmonsters per dier afgenomen. De tijdstippen van monstername waren gelijk voor de verschillende doseringsniveaus. De plasmaspiegels waren evenredig met de toegediende dosis tot de macht 1,5 voor mannetjesdieren en tot de macht 1,6 voor vrouwtjesdieren. De gemiddelde blootstelling aan onveranderd benzo(a)pyreen was gelijk voor mannetjes en vrouwtjes bij doseringen van 0,1 mg/kg en 3,0 mg/kg, maar ongeveer twee maal zo groot voor mannetjes dan voor vrouwtjes bij doseringen van 10 en 30 mg/kg. De blootstelling na de laatste dosis van 30 mg/kg was hetzelfde als waargenomen in een 15-daagse studie aan het einde van elk doseringsinterval. De in dit onderzoek verkregen resultaten zullen worden gebruikt in het Physiologically Based Pharmacokinetic (PB-PK) model voor benzo(a)pyreen dat momenteel in ontwikkeling is. Aan de hand daarvan worden de resultaten in samenhang met de waargenoment effecten geinterpreteerd.
    During the carcinogenicity study of oral benzo(a)pyrene in the rat, blood samples were taken from 48 rats (24 male, 24 female) after the last of four and a half months' repeated daily intragastric administrations. The repeated administrations took place once daily, five times weekly ; benzo(a)pyrene was administered by gastric intubation as a solution in soybean oil. The dosing levels were 0.1, 3.0, 10 and 30 mg per kg body weight. After the last dose, two blood samples were taken from each animal at times up to six hours after administration. The sampling times were the same for the different dosing levels. The plasma levels increased proportionally with the dose raised to the power 1.5 for male rats and 1.6 for female rats. The average exposure to unchanged benzo(a)pyrene was the same for males and females at dosing levels of 0.1 and 3.0 mg/kg, but about twice as high for males as compared to females at the dosing levels of 10 and 30 mg/kg. The exposure after the last dose of 30 mg/kg was the same as observed in a two-weeks' study at the end of the dosing interval.
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    HIGB
    URI
    http://hdl.handle.net/10029/258839
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