Benzo[a]Pyrene Ultralow Dose-Response Study

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.)