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.
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
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
8
Oral micro-dose (50 ng) (5.4 nCi)
Oral micro-dose of 50 ng (5.4 nCi) \[14C\]-benzo\[a\]pyrene plus 1250 ng phenanthrene
Oregon State University
Corvallis, Oregon, United States
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.
Time frame: 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.
Time frame: 0-48 hours for each of 2 dosing cycles, with a washout period of 3 weeks between the dosing cycles
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.
Time frame: 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.
Time frame: 0-48 hours for each of 2 dosing cycles, with a washout period of 3 weeks between the dosing cycles
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