ArticleJournal of pharmacokinetics and pharmacodynamics2013
Understanding the linked kinetics of benzo(a)pyrene and 3-hydroxybenzo(a)pyrene biomarker of exposure using physiologically-based pharmacokinetic modelling in rats.
Article in Journal of pharmacokinetics and pharmacodynamics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 11 citations in OpenAlex.
- Fat depot-specific accumulation of benzo(a)pyrene metabolites in rats fed with western diet and its implications for colon cancer.Toxicology reports · 2026Article
- Benzo(a)pyrene-induced cytotoxicity, cell proliferation, DNA damage, and altered gene expression profiles in HT-29 human colon cancer cells.Cell biology and toxicology · 2021Article
- Predicting the in vivo developmental toxicity of benzo[a]pyrene (BaP) in rats by an in vitro-in silico approach.Archives of toxicology · 2021Article
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2 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
3-hydroxybenzo(a)pyrene (3-OHBaP) in urine has been proposed as a biomarker of occupational exposure to polycyclic aromatic hydrocarbons. However, to reconstruct exposure doses in workers from biomarker measurements, a thorough knowledge of the kinetics of the benzo(a)pyrene (BaP) and 3-OHBaP given different routes of exposure is needed. A rat physiologically-based pharmacokinetic model of BaP and 3-OHBaP was built. Organs (tissues) represented as compartments were based on in vivo experimental data in rats. Tissue: blood partition coefficients, permeability coefficients, metabolism rates, excretion parameters, and absorption fractions and rates for different routes-of-entry were obtained directly from published in vivo time courses of BaP and 3-OHBaP in blood, various tissues and excreta of rats. The latter parameter values were best-fitted by least square procedures and Monte Carlo simulations. Sensitivity analyses were then carried out to ensure the stability of the model and the key parameters driving the overall modeled kinetics. This modeling pointed out critical determinants of the kinetics: (1) hepatic metabolism of BaP and 3-OHBaP elimination rate as the most sensitive parameters; (2) the strong partition of BaP in lungs compared to other tissues, followed by adipose tissues and liver; (3) the strong partition of 3-OHBaP in kidneys; (4) diffusion-limited tissue transfers of BaP in lungs and 3-OHBaP in lungs, adipose tissues and kidneys; (5) significant entero-hepatic recycling of 3-OHBaP. Very good fits to various sets of experimental data in rats from four different routes-of-entry (intravenous, oral, dermal and inhalation) were obtained with the model.
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