Benzo[a]Pyrene Ultralow Dose-Response Study

Oregon State University (OSU)

Status and phase: Completed; Early Phase 1

Conditions: Environmental Exposure

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

Study type: Interventional

Funder types: Other; Other U.S. Federal agency; NIH

Identifiers

NCT03318978

R01ES028600 (U.S. NIH Grant/Contract)

LPI-8233

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 4 oral doses of 25, 50, 10 and 250 ng (2.7-27 nCi).

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 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.

Enrollment: 8 patients

Sex: All

Ages: 21 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.)

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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8 participants in 1 patient group

25 ng dose, 50 ng dose, 100 ng dose, 250 ng dose

Experimental group

Description:

Cycle 1: Capsule containing 25 ng (2.7 nCi) \[14C\]-benzo\[a\]pyrene (BaP). Cycle 2: Capsule containing 50 ng (2.7 nCi) \[14C\]-benzo\[a\]pyrene (BaP). Cycle 3: Capsule containing 100 ng (2.7 nCi) \[14C\]-benzo\[a\]pyrene (BaP). Cycle 4: Capsule containing 250 ng (2.7 nCi) \[14C\]-benzo\[a\]pyrene (BaP). At least 3 weeks will pass between cycles as a washout period.

Treatment:

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