Benzo[a]Pyrene Ultralow Dose-Response Study

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).

Study Overview

• Status: Completed
• Conditions: Environmental Exposure
• Intervention / Treatment: Drug: [14C]-benzo[a]pyrene

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 Type: Interventional
• Enrollment (Actual): 8
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Corvallis, Oregon, United States, 97331
      • Clinical Research Facility, 407 Linus Pauling Science Center, Oregon State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 25 ng dose; Capsule containing 25 ng (2.7 nCi) [14C]-benzo[a]pyrene (BaP)	Drug: [14C]-benzo[a]pyrene; Oral micro-dose range (25, 50, 100 and 250 ng); Other Names: Carcinogenic PAH environmental pollutant
Experimental: 50 ng dose; Capsule containing 50 ng (2.7 nCi) [14C]-benzo[a]pyrene (BaP)	Drug: [14C]-benzo[a]pyrene; Oral micro-dose range (25, 50, 100 and 250 ng); Other Names: Carcinogenic PAH environmental pollutant
Experimental: 100 ng dose; Capsule containing 100 ng (2.7 nCi) [14C]-benzo[a]pyrene (BaP)	Drug: [14C]-benzo[a]pyrene; Oral micro-dose range (25, 50, 100 and 250 ng); Other Names: Carcinogenic PAH environmental pollutant
Experimental: 250 ng dose; Capsule containing 100 ng (2.7 nCi) [14C]-benzo[a]pyrene (BaP)	Drug: [14C]-benzo[a]pyrene; Oral micro-dose range (25, 50, 100 and 250 ng); Other Names: Carcinogenic PAH environmental pollutant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma and urine benzo[a]pyrene and metabolite levels after oral dose	Plasma and urine levels measured by accelerator mass spectrometry	48 hours

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Oregon State University
• Collaborators: National Institute of Environmental Health Sciences (NIEHS); Pacific Northwest National Laboratory; Lawrence Livermore National Laboratory

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2018
• Primary Completion (Actual): January 1, 2024
• Study Completion (Actual): February 1, 2024

Study Registration Dates

• First Submitted: October 17, 2017
• First Submitted That Met QC Criteria: October 20, 2017
• First Posted (Actual): October 24, 2017

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Benzo[a]pyrene; Accelerator Mass Spectrometry; Polycyclic Aromatic Hydrocarbons
• Other Study ID Numbers: LPI-8233; R01ES028600 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Deidentified samples sent to Lawrence Livermore National Laboratory Deidentified data sent to Pacific Northwest National Laboratory

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No