Benzo[a]Pyrene Ultralow Dose-Response Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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Benzo[a]Pyrene Ultralow Dose-Response Study

Conditions
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Environmental Exposure

Intervention / Treatment
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* Drug: [14C]-benzo[a]pyrene


Participation Criteria
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Eligibility Criteria
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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.)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Benzo[a]pyrene, Accelerator Mass Spectrometry, Polycyclic Aromatic Hydrocarbons