Evaluation of the pharmacokinetics for [14C]-benzo[a]pyrene ([14C]-BaP) and metabolites in plasma and urine over 48 hours following 4 oral doses of 25, 50, 10 and 250 ng (2.7-27 nCi).

The pharmacokinetics for [14C]-BaP and metabolites will be assessed by UHLPC-Accelerator Mass Spectrometry (AMS, Lawrence Livermore National Laboratory) in plasma and urine collected over 48 hours following oral doses of 25, 50, 100 or 250 ng (2.7-27 nCi). Metabolite profiles and kinetics of elimination over this dose range are predicted to be consistent with a BaP physiologically based pharmacokinetic (PBPK) model developed by Pacific Northwest National Laboratory (PNNL). A non-smoker, not exposed occupationally, receives 270-700 ng of BaP daily; about 95% dietary. The WHO has set an estimated safe daily lifetime (70 year/70 Kg individual, cancer endpoint) exposure to BaP of 42-350 ng. This protocol represents de minimus risk.

Inclusion Criteria:

• Inclusion criteria for women:

  • Age 21-65 (inclusive)
  • Must be post-menopausal or have had surgical sterilization to eliminate any possibility for fetal exposure
  • Willing to defer blood donation for one month before, throughout, and one month after completion of study activities
  • Willing to avoid consuming cruciferous vegetables, I3C or DIM supplements, smoked or cured meat or cheeses, or charcoal-grilled meats for 2 weeks prior to and during each study cycle (gas grilled foods acceptable)

Inclusion criteria for men:

• Age 21-65 (inclusive)
• Willing to defer blood donation for one month before, throughout, and one month after completion of study activities
• Willing to avoid consuming cruciferous vegetables, I3C or DIM supplements, smoked or cured meat or cheeses, or charcoal-grilled meats for 2 weeks prior to and during each study cycle (gas grilled foods acceptable)

Exclusion Criteria:

Exclusion criteria for both men and women:

• Smoker (tobacco or other substances) or use of smokeless tobacco in past 3 months or living with smoker
• Regular use of medications that affect gut motility or nutrient absorption (e.g. cholestyramine, sucralfate, orlistat, pro- or anti-motility agents)
• History of gastrointestinal surgery (e.g. bariatric surgery, cholecystectomy) or gastrointestinal disorder (Crohn's disease, celiac disease, IBS, or colitis)
• Current or history of kidney or liver disease
• Prior high-dose 14C exposure from medical tests. (micro-dose 14C exposure not exclusionary)
• Occupational PAH exposure (e.g. roofers, asphalt pavers, fire-fighters, etc.)

Deidentified samples sent to Lawrence Livermore National Laboratory Deidentified data sent to Pacific Northwest National Laboratory

48.5 hours for each of 4 dosing cycles with a 3-week washout period between each dosing cycle. Participants were assessed for adverse events 15 minutes prior to the [14c]-BaP dose administration (time= 0 hour) until 15 minutes after the final blood sample collection time point (time = 48 hour) and removal of the peripheral IV catheter.

The definitions of adverse event and serious adverse event used to determine incidence are consistent with clinicaltrials.gov definitions. Each participant was verbally asked about the occurrence of adverse events at each clinical visit by the research nurse.

Deidentified samples will be analyzed by AMS at Lawrence Livermore National Laboratory and the pharmacokinetics determine at Pacific Northwest National Laboratory.