Ultralow Dose PAH Binary Mixture Study

Oregon State University (OSU)

Status and phase

Completed

Early Phase 1

Conditions

Environmental Exposure

Treatments

Drug: [14C]-benzo[a]pyrene plus phenanthrene

Drug: [14C]-benzo[a]pyrene

Study type

Interventional

Funder types

Other

Other U.S. Federal agency

NIH

Identifiers

NCT03631667

LPI-8554

R01ES028600 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Evaluation of the pharmacokinetics for [14C]-benzo[a]pyrene ([14C]-BaP) and metabolites in plasma and urine over 48 hours following a 50 ng dose (5.4 nCi) alone or with 1250 ng phenanthrene.

Full description

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.

Enrollment

5 patients

Sex

All

Ages

21 to 65 years old

Volunteers

Accepts Healthy Volunteers

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