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

Author:
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.
Source:
Food and chemical toxicology 2018 v.115 pp. 136-147
ISSN:
0278-6915
Subject:
United States Environmental Protection Agency, absorption, adults, benzo(a)pyrene, carbon, carcinogenicity, carcinogens, dietary exposure, dietary restriction, food matrix, humans, mass spectrometry, models, neoplasms, pharmacokinetics, polycyclic aromatic hydrocarbons, questionnaires, radionuclides, salmon, smoked salmon, toxicology
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 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.
Agid:
5918142