Five experiments were conducted in male Sprague-Dawley rats regarding the k
inetic of urinary excretion of I-hydroxypyrene (1-OHP) following i.v., oral
and dermal exposure to 0.5-50 mu mol/kg pyrene either as a single substanc
e or as mixture of various polycyclic aromatic hydrocarbons (PAH). Frequent
urine collections over 48 h after exposure and a tissue versus time distri
bution experiment using [C-14]pyrene allowed to define the kinetic profile
of both pyrene and 1-OHP. For all exposure routes, there is a linear relati
onship over two orders of magnitude between the dose of pyrene and the urin
ary excretion of 1-OHP. Differences in biliary/urinary 1-OHP excretion rati
o in canulated rats (3) versus faecal/urinay 1-OHP excretion ratio in non-c
anulated rats (0.6) indicate major enterohepatic recirculation of the metab
olite. Half-lives of both pyrene and 1-OHP in all measured tissues were all
comprised between 3.1 and 5.4 h, and 5.2-6.7 h, respectively, so that no l
ong term accumulation would be predicted from these values for any tissue.
Binary and ternary mixtures involving naphthalene and benzo(a)pyrene in add
ition to pyrene has no influence on the urinary excretion profile of 1-OHP.
All these observations led to the proposal of a dynamic compartment model
of pyrene and metabolite flows indicating that following rapid initial dist
ribution to fatty tissues, pyrene is rapidly biotransformed into various me
tabolites and undergoes major enterohepatic recycling. Part of the initiall
y formed and part of the recirculated 1-OHP eventually undergoes urinary ex
cretion such that close to 60% of pyrene is eliminated as metabolites in ur
ine by 24 h after injection while 20% is excreted in the faeces over the sa
me period. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.