| Abstract |
- Dibenzo(def,p)chrysene (DBC), (also known as dibenzo[a,l]pyrene), is a high molecular weight
polycyclic aromatic hydrocarbon (PAH) found in the environment, including food, produced by
the incomplete combustion of hydrocarbons. DBC, classified by IARC as a 2A probable human
carcinogen, has a relative potency factor (RPF) in animal cancer models 30-fold higher than
benzo[a]pyrene. No data are available describing disposition of high molecular weight (>4 rings)
PAHs in humans to compare to animal studies. Pharmacokinetics of DBC was determined in 3
female and 6 male human volunteers following oral micro-dosing (29 ng, 5 nCi) of [14C]-DBC.
This study was made possible with highly sensitive accelerator mass spectrometry (AMS),
capable of detecting [14C]-DBC equivalents in plasma and urine following a dose considered of
de minimus risk to human health. Plasma and urine were collected over 72 h. The plasma Cmax
was 68.8 ± 44.3 fg*mL-1 with a Tmax of 2.25 ± 1.04 h. Elimination occurred in two distinct
phases; a rapid (α)-phase, with a T1/2 of 5.8 ± 3.4 h and apparent elimination rate constant (Kel)
of 0.17 ± 0.12 fg*h-1 followed by a slower (β)-phase, with a T1/2 of 41.3 ± 29.8 h and apparent
Kel of 0.03 ± 0.02 fg*h-1. In spite of the high degree of hydrophobicity (log Kow of 7.4), DBC was
eliminated rapidly in humans, as are most PAHs in animals, compared to other hydrophobic
persistent organic pollutants such as, DDT, PCBs and TCDD. Preliminary examination utilizing
a new UHPLC-AMS interface, suggests the presence of polar metabolites in plasma as early as
45 min following dosing. This is the first in vivo dataset describing pharmacokinetics in humans
of a high molecular weight PAH and should be a valuable addition to risk assessment paradigms.
- To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work. This is the publisher’s final pdf. The published article is copyrighted by the American Chemical Society and can be found at: https://doi.org/10.1021/tx5003996
- Keywords: accelerator mass spectrometry, human micro-dosing, polycyclic aromatic hydrocarbon, pharmacokinetics, dibenzo(def\, p)chrysene
- Keywords: accelerator mass spectrometry, human micro-dosing, polycyclic aromatic hydrocarbon, pharmacokinetics, dibenzo(def\, p)chrysene
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