Benzo[a]Pyrene Ultralow Dose-Response Study

Early Phase 1

Completed

• Conditions: Environmental Exposure
• Interventions: Drug: [14C]-benzo[a]pyrene

• Registration Number: NCT03318978
• Lead Sponsor: Oregon State University

Brief Summary

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).

Detailed 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.

Study Timeline

• Study First Submitted: 2017-10-17
• Study First Submitted QC: 2017-10-20
• Study First Posted: 2017-10-24
• Study Start: 2018-04-17
• Primary Completion: 2024-01-01
• Status Verified: 2024-02
• Study Completion: 2024-02-01
• Last Update Submitted: 2024-02-14
• Last Update Posted: 2024-02-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

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.)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
50 ng dose	[14C]-benzo[a]pyrene	Capsule containing 50 ng (2.7 nCi) \[14C\]-benzo\[a\]pyrene (BaP)
100 ng dose	[14C]-benzo[a]pyrene	Capsule containing 100 ng (2.7 nCi) \[14C\]-benzo\[a\]pyrene (BaP)
25 ng dose	[14C]-benzo[a]pyrene	Capsule containing 25 ng (2.7 nCi) \[14C\]-benzo\[a\]pyrene (BaP)
250 ng dose	[14C]-benzo[a]pyrene	Capsule containing 100 ng (2.7 nCi) \[14C\]-benzo\[a\]pyrene (BaP)

Primary Outcome Measures

Name	Time	Method
Plasma and urine benzo[a]pyrene and metabolite levels after oral dose	48 hours	Plasma and urine levels measured by accelerator mass spectrometry

Secondary Outcome Measures

Name	Time	Method
Peak plasma concentration Cmax	48 hours	Determination of highest concentration in plasma
Time at highest plasma concentration Tmax	48 hours	Determination of time at which plasma concentration is highest
Area under plasma concentration versus time curve AUC	48 hours	Integration of concentration over time
Rate of elimination	48 hours	Determination of constants for rate of elimination from plasma
Metabolites in plasma	48 hours	Determination of plasma metabolites
Metabolites in urine	48 hours	Determination of urinary metabolites

Trial Locations

Locations (1)

Clinical Research Facility, 407 Linus Pauling Science Center, Oregon State University; 🇺🇸 Corvallis, Oregon, United States