Ultralow Dose PAH Binary Mixture Study
关键词
抽象
描述
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.
日期
| 最后验证: | 02/29/2020 |
| 首次提交: | 08/07/2018 |
| 提交的预估入学人数: | 08/13/2018 |
| 首次发布: | 08/14/2018 |
| 上次提交的更新: | 03/29/2020 |
| 最近更新发布: | 03/31/2020 |
| 实际学习开始日期: | 09/30/2018 |
| 预计主要完成日期: | 11/30/2020 |
| 预计完成日期: | 11/30/2022 |
状况或疾病
干预/治疗
Drug: 50 ng dose
Drug: 50 ng dose plus 1250 ng phenanthrene
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| Experimental: 50 ng dose Capsule containing 50 ng (5.4 nCi) [14C]-benzo[a]pyrene (BaP) | Drug: 50 ng dose Oral micro-dose (50 ng) (5.4 nCi) |
| Experimental: 50 ng dose plus 1250 ng phenanthrene Capsule containing 50 ng (5.4 nCi) [14C]-benzo[a]pyrene (BaP) and 1250 phenanthrene | Drug: 50 ng dose plus 1250 ng phenanthrene Oral micro-dose of 50 ng (5.4 nCi) [14C]-benzo[a]pyrene plus 1250 ng phenanthrene |
资格标准
| 有资格学习的年龄 | 21 Years 至 21 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | 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 |
结果
主要结果指标
1. Plasma and urine 14C-BaP and 14C-BaP metabolite levels after oral dose [48 hours]
次要成果指标
1. Peak plasma concentration of 14C-BaP Cmax [48 hours]
2. Time at highest plasma concentration of 14C-BaP Tmax [48 hours]
3. Area under plasma concentration of 14C-BaP versus time curve AUC [48 hours]
4. Rate of elimination of 14C-BaP [48 hours]
5. Metabolites of 14C-BaP in plasma [48 hours]
6. Metabolites of 14C-BaP in urine [48 hours]
