Toxicokinetiek van benzo(a)pyreen bij de Riv:TOX rat na herhaalde orale toediening
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Series / Report no.
Open Access
Type
Report
Language
nl
Date
1995-11-30
Research Projects
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Journal Issue
Title
Toxicokinetiek van benzo(a)pyreen bij de Riv:TOX rat
na herhaalde orale toediening
Translated Title
Toxicokinetics of benzo(a)pyrene in the Riv:TOX
rat after repeated oral administration
Published in
Abstract
Aan 12 mannelijke en 12 vrouwelijke Riv:TOX ratten werd
in een periode van 15 dagen op 5 achtereenvolgende dagen per week oraal
benzo(a)pyreen (per maagsonde, 30 mg/kg) toegediend, in de vorm van een
oplossing in soja-olie. Bij de ene helft van de dieren werd er bloed
afgenomen over een periode van 12 uur op de eerste dag van toediening (dag
1) en op dag 12, bij de andere helft van de dieren op dag 5 en dag 15. Uit
de resultaten blijkt, dat de gemiddelde en maximale plasmaspiegels (C-max en
AUC) van benzo(a)pyreen afnemen en de t-max toeneemt na herhaalde dagelijkse
toediening. Deze effecten berusten waarschijnlijk op een inductie van de
leverenzymen welke verantwoordelijk zijn voor het metabolisme van
benzo(a)pyreen alswel op een afname van de absorptie. Geen uitspraak kan
nog worden gedaan over wat de relatieve bijdrage van elk van de processen
is. Na het doseringsvrije interval herstellen de plasmaspiegels van
benzo(a)pyreen zich gedeeltelijk, maar zij blijven lager dan op de eerste
dag van toediening. De plasmaspiegels van benzo(a)pyreen waren op dag 5 en
dag 12 (beide na vijf dagelijkse toedieningen) gemiddeld 73% hoger bij de
mannetjes dan bij de vrouwtjesdieren. Dit sexeverschil was na de eerste
dosering niet aanwezig. Vergelijking met de resultaten van de eerder
uitgevoerde studie BaP04, waarin de ratten gevast werden voor toediening,
suggereert dat de absorptie van benzo(a)pyreen toeneemt in aanwezigheid van
voedsel.
Benzo(a)pyrene was administered once daily (30 mg/kg) by gavage to 12 male and 12 female Riv:TOX rats, for 15 days on five successive days per week, in the form of a solution in soy oil. Blood samples were taken over a period of 12 hours on the first day of administration (day 1) and on day 12 from half of the animals, and on day 5 and day 15 from the other half of the animals. The results show that de mean and maximum plasma concentrations of benzo(a)pyrene decrease after repeated administration and that the t-max increases. These phenomena are probably caused by an induction of liver enzymes and also by a decreasing absorption of benzo(a)pyreen from the gut. The relative contributions of both processes are yet unknown. After the dosing-free interval of two days the plasma concentrations recover to values that are higher than on the last day of the dosing period, but still lower than after the first dose. In male rats, the plasma levels of benzo(a)pyrene on day 5 and day 12 (both after a five days' administration) were on average 73% higher than in female rats. This gender difference was not present after the first dose. Comparison with the results from the previous study BaP04, where the rats were fasted for 12 h before oral administration, suggests that the absorption of benzo(a)pyrene increases in the presence of food.
Benzo(a)pyrene was administered once daily (30 mg/kg) by gavage to 12 male and 12 female Riv:TOX rats, for 15 days on five successive days per week, in the form of a solution in soy oil. Blood samples were taken over a period of 12 hours on the first day of administration (day 1) and on day 12 from half of the animals, and on day 5 and day 15 from the other half of the animals. The results show that de mean and maximum plasma concentrations of benzo(a)pyrene decrease after repeated administration and that the t-max increases. These phenomena are probably caused by an induction of liver enzymes and also by a decreasing absorption of benzo(a)pyreen from the gut. The relative contributions of both processes are yet unknown. After the dosing-free interval of two days the plasma concentrations recover to values that are higher than on the last day of the dosing period, but still lower than after the first dose. In male rats, the plasma levels of benzo(a)pyrene on day 5 and day 12 (both after a five days' administration) were on average 73% higher than in female rats. This gender difference was not present after the first dose. Comparison with the results from the previous study BaP04, where the rats were fasted for 12 h before oral administration, suggests that the absorption of benzo(a)pyrene increases in the presence of food.
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