Pharmacokinetics of [14C]-Benzo[a]pyrene (BaP) in humans: Impact of Co-Administration of smoked salmon and BaP dietary restriction. (May 2018)

• Record Type: Journal Article
• Authors: Hummel, Jessica M.; Madeen, Erin P.; Siddens, Lisbeth K.; Uesugi, Sandra L.; McQuistan, Tammie; Anderson, Kim A.; Turteltaub, Kenneth W.; Ognibene, Ted J.; Bench, Graham; Krueger, Sharon K.; Harris, Stuart; Smith, Jordan; Tilton, Susan C.; Baird, William M.; Williams, David E.
• Is Part Of: Food and chemical toxicology. Volume 115(2018)
• Page Start: 136
• Page End: 147
• Publication Date: 2018-05
• Subjects: Pharmacokinetics -- Benzo[a]pyrene -- Accelerator mass spectrometry -- Dietary polycyclic aromatic hydrocarbons; ADME absorption distribution metabolism and excretion -- AFB1 aflatoxin B1 -- AMS accelerator mass spectrometry -- ATDSR Agency for Toxic Substances and Disease Registry -- BaP benzo[a]pyrene -- BaPeq benzo[a]pyrene equivalents -- BLOD below the limit of detection -- BLOQ below the limit of quantitation -- BMI body mass index -- CTUIR Confederated Tribes of the Umatilla Indian Reservation -- CYP cytochrome P450 -- DBC dibenzo[def, p]chrysene -- EPA Environmental Protection Agency -- FDA Food and Drug Administration -- IARC International Agency for Research on Cancer -- IND investigative new drug -- IRB institutional review board -- JECFA Joint FAO/WHO expert committee on food additives -- LDAL lowest daily allowable level -- LLNL Lawrence Livermore National Laboratory -- LOD limit of detection -- OSU Oregon State University -- PAH polycyclic aromatic hydrocarbon -- PBMCs peripheral blood mononuclear cells -- PBPK physiologically based pharmacokinetics -- PK pharmacokinetics -- RPF relative potency factor; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2018.03.003
• Languages: English
• ISSNs: 0278-6915

Abstract

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 [ 14 C]-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 [ 14 C]-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 [ 14 C]-BaP. Co-administration of smoked salmon, containing a complex mixture of PAHs with an RPF of 460 ng BaPeq, 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. Graphical abstract: Highlights: [ 14 C]-BaP pharmacokinetics in humans in presence or absence of smoked salmon with a complex mixture of PAHs was performed. The results call into question the validity of the Relative Potency Factor Approach for oral cancer risk for PAHs. Unsmoked salmon with no detectable PAHs had similar pharmacokinetics of [ 14 C]-BaP supporting a food matrix effect. Physiologically-based pharmacokinetics and risk assessments with rodent models use doses much higher than human exposure. This dataset is useful for further analysis of cancer risk in humans following exposure to environmentally relevant levels.