CClinicalTrials.gg
CompletedNCT03318978Updated May 22, 2025Results posted

Benzo[a]Pyrene Ultralow Dose-Response Study

An Early Phase 1 interventional study of [14C]-benzo[a]pyrene in Environmental Exposure, sponsored by Oregon State University. Completed at 1 site in United States. Open to participants aged 21 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-05-22.

Sponsored by Oregon State University · Early Phase 1, Interventional, and Basic science

Phase
Early Phase 1
Study type
Interventional
Enrollment
8
Allocation
Not applicable
Ages
21 Years to 65 Years
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • Environmental Exposure

Keywords

  • Benzo[a]pyrene
  • Accelerator Mass Spectrometry
  • Polycyclic Aromatic Hydrocarbons
03

Who can participate

Ages eligible
21 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Eligibility criteria

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.)
04

Study design

Phase
Early Phase 1
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
8 participants (actual)

Study arms

  • Experimental
    25 ng dose, 50 ng dose, 100 ng dose, 250 ng dose

    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.

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

Interventions

  • Drug[14C]-benzo[a]pyrene

    Oral micro-dose range (25, 50, 100 and 250 ng)

    Also known as: Carcinogenic PAH environmental pollutant

05

What researchers measure

Primary outcomes

  1. Peak Plasma Concentration Cmax

    Determination of highest concentration 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 peak plasma concentration Cmax.

    Time frame: 0-48 hours for each of the 4 dosing cycles with a washout period of 3 weeks between each dosing cycle

Secondary outcomes

  1. Time at Highest Plasma Concentration Tmax

    Determination of time at which plasma concentration 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, time at highest plasma concentration.

    Time frame: 0-48 hours for each of the 4 dosing cycles with a washout period of 3 weeks between each dosing cycle

  2. Area Under Plasma Concentration Versus Time Curve AUC

    Integration of concentration 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.

    Time frame: 0-48 hours for each of the 4 dosing cycles with a washout period of 3 weeks between each dosing cycle

  3. Rate of Elimination (k1e)

    Determination of constants for rate of elimination 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 k1e.

    Time frame: 0-48 hours for each of the 4 dosing cycles with a washout period of 3 weeks between each dosing cycle

06

Results

Posted May 22, 2025

Participant flow

Participant flow — Overall Study
Milestone25 ng Dose, 50 ng Dose, 100 ng Dose, 250 ng Dose
Started8
Completed7
Not completed1
Withdrew: Withdrawal by subject1

Outcome measures

PrimaryPeak Plasma Concentration Cmax

Determination of highest concentration 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 peak plasma concentration Cmax.

Time frame:
0-48 hours for each of the 4 dosing cycles with a washout period of 3 weeks between each dosing cycle
Reported as:
Mean · fg [14C]-BaP/mL plasma
Peak Plasma Concentration Cmax
fg [14C]-BaP/mL plasma25 ng, 50 ng, 100 ng, and 250 ng Doses
25 ng [14C]-BaP2.51 ± 2.53
50 ng [14C]-BaP5.68 ± 4.70
100 ng [14C]-BaP13.8 ± 9.52
250 ng [14C]-BaP8.99 ± 7.08
SecondaryTime at Highest Plasma Concentration Tmax

Determination of time at which plasma concentration 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, time at highest plasma concentration.

Time frame:
0-48 hours for each of the 4 dosing cycles with a washout period of 3 weeks between each dosing cycle
Reported as:
Median · hour
Time at Highest Plasma Concentration Tmax
hour25 ng Dose, 50 ng Dose, 100 ng Dose, 250 ng Dose
25 ng [14C]-BaP0.5 (0.5 to 4.0)
50 ng [14C]-BaP0.5 (0.5 to 1.0)
100 ng [14C]-BaP0.5 (0.5 to 1.0)
250 ng [14C]-BaP0.5 (0.5 to 3.0)
SecondaryArea Under Plasma Concentration Versus Time Curve AUC

Integration of concentration 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.

Time frame:
0-48 hours for each of the 4 dosing cycles with a washout period of 3 weeks between each dosing cycle
Reported as:
Mean · fg [14C]-BaP/mL plasma x hour
Area Under Plasma Concentration Versus Time Curve AUC
fg [14C]-BaP/mL plasma x hour25 ng Dose, 50 ng Dose, 100 ng Dose, 250 ng Dose
25 ng [14C]-BaP12.2 ± 14.5
50 ng [14C]-BaP19.6 ± 15.7
100 ng [14C]-BaP88.5 ± 14.1
250 ng [14C]-BaP68.6 ± 60.4
SecondaryRate of Elimination (k1e)

Determination of constants for rate of elimination 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 k1e.

Time frame:
0-48 hours for each of the 4 dosing cycles with a washout period of 3 weeks between each dosing cycle
Reported as:
Mean · hour(-1)
Rate of Elimination (k1e)
hour(-1)25 ng Dose, 50 ng Dose, 100 ng Dose, 250 ng Dose
25 ng [14C]-BaP12.2 ± 14.5
50 ng [14C]-BaP19.6 ± 15.7
100 ng [14C]-BaP88.5 ± 14.1
250 ng [14C]-BaP68.6 ± 64.0

Adverse events

Collected over 48.5 hours for each of 4 dosing cycles with a 3-week washout period between each dosing cycle. Participants were assessed for adverse events 15 minutes prior to the [14c]-BaP dose administration (time= 0 hour) until 15 minutes after the final blood sample collection time point (time = 48 hour) and removal of the peripheral IV catheter.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
25 ng Dose, 50 ng Dose, 100 ng Dose, 250 ng Dose0/7 (0%)0/7 (0%)0/7 (0%)

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)25 ng Dose, 50 ng Dose, 100 ng Dose, 250 ng Dose
<=18 years0
Between 18 and 65 years8
>=65 years0
Sex: Female, Male
Sex: Female, Male(Participants)25 ng Dose, 50 ng Dose, 100 ng Dose, 250 ng Dose
Female3
Male5
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)25 ng Dose, 50 ng Dose, 100 ng Dose, 250 ng Dose
Hispanic or Latino0
Not Hispanic or Latino8
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)25 ng Dose, 50 ng Dose, 100 ng Dose, 250 ng Dose
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White7
More than one race1
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)25 ng Dose, 50 ng Dose, 100 ng Dose, 250 ng Dose
United States8
07

Study locations

1 site
  • Clinical Research Facility, 407 Linus Pauling Science Center, Oregon State University
    Corvallis, Oregon 97331, United States
08

References and documents

Study documents

  • Protocol, analysis plan and consent form · Sep 13, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — Deidentified samples sent to Lawrence Livermore National Laboratory Deidentified data sent to Pacific Northwest National Laboratory

09

Registry details

Key details

Study ID
NCT03318978
Lead sponsor
Oregon State University
Collaborators
National Institute of Environmental Health Sciences (NIEHS), Lawrence Livermore National Laboratory, Pacific Northwest National Laboratory
Responsible party
David Williams (Helen P. Rumbel Professor for Cancer Prevention, Oregon State University) — Principal investigator
First posted
Oct 24, 2017
Start date
Apr 17, 2018
Primary completion
Jan 1, 2024
Completion
Feb 1, 2024
Results posted
May 22, 2025
Last update
May 22, 2025

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in May 2025. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion