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

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.

Authors:
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Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1503550
Report Number(s):
PNNL-SA-132485
Journal ID: ISSN 0278-6915
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Food and Chemical Toxicology
Additional Journal Information:
Journal Volume: 115; Journal Issue: C; Journal ID: ISSN 0278-6915
Publisher:
Elsevier
Country of Publication:
United States
Language:
English

Citation Formats

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., and Williams, David E. Pharmacokinetics of [14C]-Benzo[a]pyrene (BaP) in humans: Impact of Co-Administration of smoked salmon and BaP dietary restriction. United States: N. p., 2018. Web. doi:10.1016/j.fct.2018.03.003.
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. Pharmacokinetics of [14C]-Benzo[a]pyrene (BaP) in humans: Impact of Co-Administration of smoked salmon and BaP dietary restriction. United States. doi:10.1016/j.fct.2018.03.003.
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., and Williams, David E. Tue . "Pharmacokinetics of [14C]-Benzo[a]pyrene (BaP) in humans: Impact of Co-Administration of smoked salmon and BaP dietary restriction". United States. doi:10.1016/j.fct.2018.03.003.
@article{osti_1503550,
title = {Pharmacokinetics of [14C]-Benzo[a]pyrene (BaP) in humans: Impact of Co-Administration of smoked salmon and BaP dietary restriction},
author = {Hummel, Jessica M. and Madeen, Erin P. and Siddens, Lisbeth K. and Uesugi, Sandra L. and McQuistan, Tammie and Anderson, Kim A. and Turteltaub, Kenneth W. and Ognibene, Ted J. and Bench, Graham and Krueger, Sharon K. and Harris, Stuart and Smith, Jordan and Tilton, Susan C. and Baird, William M. and Williams, David E.},
abstractNote = {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.},
doi = {10.1016/j.fct.2018.03.003},
journal = {Food and Chemical Toxicology},
issn = {0278-6915},
number = C,
volume = 115,
place = {United States},
year = {2018},
month = {5}
}