Ultralow Dose PAH Binary Mixture Study

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.

Study Overview

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

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 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.

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

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Corvallis, Oregon, United States, 97331
      • 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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 50 ng dose and 50 ng dose plus 1250 ng phenanthrene; Cycle 1: Capsule containing 50 ng (5.4 nCi) [14C]-benzo[a]pyrene (BaP). Cycle 2: Capsule containing 50 ng (5.4 nCi) [14C]-benzo[a]pyrene (BaP) and 1250 phenanthrene. At least 3 weeks will pass between cycles as a washout period.	Drug: [14C]-benzo[a]pyrene; Oral micro-dose (50 ng) (5.4 nCi); Other Names: Carcinogenic PAH environmental pollutant; Drug: [14C]-benzo[a]pyrene plus phenanthrene; Oral micro-dose of 50 ng (5.4 nCi) [14C]-benzo[a]pyrene plus 1250 ng phenanthrene; Other Names: Binary mixture of carcinogenic PAH and non-carcinogenic PAH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration of 14C-BaP Cmax	Determination of highest concentration of 14C-BaP in plasma. Blood samples collected at 0 (baseline), 0.25, 0.5, 1, 2, 3, 4, 8, 24, and 48 hour after dosing. All time points were used to determine Cmax.	0-48 hours for each of 2 dosing cycles, with a washout period of 3 weeks between the dosing cycles
Time at Highest Plasma Concentration of 14C-BaP Tmax	Determination of time at which plasma concentration of 14C-BaP is highest. Blood samples collected at 0 (baseline), 0.25, 0.5, 1, 2, 3, 4, 8, 24, and 48 hour after dosing. All time points were used to determine Tmax.	0-48 hours for each of 2 dosing cycles, with a washout period of 3 weeks between the dosing cycles

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under Plasma Concentration of 14C-BaP Versus Time Curve AUC	Integration of concentration of 14C-BaP in plasma over time. Blood samples collected at 0 (baseline), 0.25, 0.5, 1, 2, 3, 4, 8, 24, and 48 hour after dosing. All time points were used to determine AUC.	0-48 hours for each of 2 dosing cycles, with a washout period of 3 weeks between the dosing cycles
Rate of Elimination of 14C-BaP (Half Life)	Determination of constants for rate of elimination of 14C-BaP from plasma. Blood samples collected at 0 (baseline), 0.25, 0.5, 1, 2, 3, 4, 8, 24, and 48 hour after dosing. All time points were used to determine half-life.	0-48 hours for each of 2 dosing cycles, with a washout period of 3 weeks between the dosing cycles

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): October 1, 2018
• Primary Completion (Actual): January 1, 2024
• Study Completion (Actual): February 1, 2024

Study Registration Dates

• First Submitted: August 8, 2018
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (Actual): August 15, 2018

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 21, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Benzo[a]pyrene; Accelerator Mass Spectrometry; Polycyclic Aromatic Hydrocarbons; Phenanthrene
• Other Study ID Numbers: LPI-8554; 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