Ultralow Dose PAH Binary Mixture 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 50 ng dose (5.4 nCi) alone or with 1250 ng phenanthrene.
Metabolite profiles and kinetics of elimination 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:

- Age 21-65 (inclusive)

- If female, 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)

Exclusion Criteria:

- 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.)

- Regular use of indole-3-carbinol or DIM dietary supplements