Pharmacokinetics of [14C]-Benzo[a]pyrene (BaP) in humans: Impact of Co-Administration of smoked salmon and BaP dietary restriction

Jessica M Hummel; Erin P Madeen; Lisbeth K Siddens; Sandra L Uesugi; Tammie McQuistan; Kim A Anderson; Kenneth W Turteltaub; Ted J Ognibene; Graham Bench; Sharon K Krueger; Stuart Harris; Jordan Smith; Susan C Tilton; William M Baird; David E Williams

doi:10.1016/j.fct.2018.03.003

Pharmacokinetics of [¹⁴C]-Benzo[a]pyrene (BaP) in humans: Impact of Co-Administration of smoked salmon and BaP dietary restriction

Food Chem Toxicol. 2018 May:115:136-147. doi: 10.1016/j.fct.2018.03.003. Epub 2018 Mar 5.

Authors

Affiliations

¹ Department of Nutrition and Dietetics, Oregon State University, Corvallis, OR, USA; Superfund Research Program, Oregon State University, Corvallis, OR, USA.
² Superfund Research Program, Oregon State University, Corvallis, OR, USA; Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA.
³ Superfund Research Program, Oregon State University, Corvallis, OR, USA; Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA; Linus Pauling Institute, Oregon State University, Corvallis, OR, USA.
⁴ Linus Pauling Institute, Oregon State University, Corvallis, OR, USA.
⁵ Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA, USA.
⁶ Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, Livermore, CA, USA.
⁷ Confederated Tribes of the Umatilla Indian Reservation, Nixyáawii Governance Center, Pendelton, OR, USA.
⁸ Superfund Research Program, Oregon State University, Corvallis, OR, USA; Chemical Biology and Exposure Science, Pacific Northwest National Laboratory, Richland, WA, USA.
⁹ Superfund Research Program, Oregon State University, Corvallis, OR, USA; Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA; Linus Pauling Institute, Oregon State University, Corvallis, OR, USA. Electronic address: david.williams@oregonstate.edu.

Abstract

Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH), is a known human carcinogen. In non-smoking adults greater than 95% of BaP exposure is through diet. The carcinogenicity of BaP is utilized by the U.S. EPA to assess relative potency of complex PAH mixtures. PAH relative potency factors (RPFs, BaP = 1) are determined from high dose animal data. We employed accelerator mass spectrometry (AMS) to determine pharmacokinetics of [¹⁴C]-BaP in humans following dosing with 46 ng (an order of magnitude lower than human dietary daily exposure and million-fold lower than animal cancer models). To assess the impact of co-administration of food with a complex PAH mixture, humans were dosed with 46 ng of [¹⁴C]-BaP with or without smoked salmon. Subjects were asked to avoid high BaP-containing diets and a 3-day dietary questionnaire given to assess dietary exposure prior to dosing and three days post-dosing with [¹⁴C]-BaP. Co-administration of smoked salmon, containing a complex mixture of PAHs with an RPF of 460 ng BaP_eq, reduced and delayed absorption. Administration of canned commercial salmon, containing very low amounts of PAHs, showed the impacts on pharmacokinetics were not due to high amounts of PAHs but rather a food matrix effect.

Keywords: Accelerator mass spectrometry; Benzo[a]pyrene; Dietary polycyclic aromatic hydrocarbons; Pharmacokinetics.

MeSH terms

Adult
Aged
Animals
Benzo(a)pyrene / metabolism
Benzo(a)pyrene / pharmacokinetics*
Carbon Radioisotopes / analysis
Carcinogens / metabolism
Carcinogens / pharmacokinetics*
Cooking
Female
Fish Products / adverse effects
Fish Products / analysis*
Food Safety
Humans
Male
Middle Aged
Polycyclic Aromatic Hydrocarbons / metabolism
Polycyclic Aromatic Hydrocarbons / pharmacokinetics
Salmon / metabolism*
Young Adult

Substances

Carbon Radioisotopes
Carcinogens
Polycyclic Aromatic Hydrocarbons
Benzo(a)pyrene
Carbon-14

Abstract

MeSH terms

Substances

Grants and funding