Human in vivo Pharmacokinetics of [¹⁴C]Dibenzo[def,p]chrysene by Accelerator Mass Spectrometry Following Oral Micro-Dosing Public Deposited

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  • Human in vivo Pharmacokinetics of [14C]Dibenzo[def,p]chrysene by Accelerator Mass Spectrometry Following Oral Micro-Dosing
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  • 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.
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  • Madeen, E., Corley, R. A., Crowell, S., Turteltaub, K. W., Ognibene, T., Malfatti, M., ... & Williams, D. E. (2014). Human in vivo Pharmacokinetics of [¹⁴C]Dibenzo[def,p]chrysene by Accelerator Mass Spectrometry Following Oral Micro-Dosing. Chemical Research in Toxicology. doi:10.1021/tx5003996
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  • description.provenance : Approved for entry into archive by Erin Clark(erin.clark@oregonstate.edu) on 2014-12-01T21:42:26Z (GMT) No. of bitstreams: 2kruegers796466136.zip: 1037834 bytes, checksum: 8200d8f7f9607f02d40e5a925f6df5f2 (MD5)CRT DBC Madeen et al tx-2014-003996 revised accepted manuscript.docx: 1180292 bytes, checksum: e52db299886c164d496fbe4a83706b49 (MD5)
  • description.provenance : Made available in DSpace on 2014-12-01T21:42:26Z (GMT). No. of bitstreams: 2kruegers796466136.zip: 1037834 bytes, checksum: 8200d8f7f9607f02d40e5a925f6df5f2 (MD5)CRT DBC Madeen et al tx-2014-003996 revised accepted manuscript.docx: 1180292 bytes, checksum: e52db299886c164d496fbe4a83706b49 (MD5) Previous issue date: 2014-11-24
  • description.provenance : Submitted by Open Access (openaccess@library.oregonstate.edu) on 2014-11-26T21:36:16ZNo. of bitstreams: 1CRT DBC Madeen et al tx-2014-003996 revised accepted manuscript.docx: 1180292 bytes, checksum: e52db299886c164d496fbe4a83706b49 (MD5)

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