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).
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
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
8
Oral micro-dose range (25, 50, 100 and 250 ng)
Clinical Research Facility, 407 Linus Pauling Science Center, Oregon State University
Corvallis, Oregon, United States
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
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
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
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
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