The potential for human exposure to pyrethroid pesticides has prompted pharmacodynamic and pharmacokinetic research to better characterize risk. This work tested the hypothesis that blood and brain concentrations of the pyrethroid bifenthrin are predictive of neurotoxic effects. Adult male Long Evans rats received a single oral dose of bifenthrin dissolved in corn oil. Using figure-eight mazes, motor activity was measured for 1h at 4- and 7-h following exposure to bifenthrin (0-16mg/kg or 0-9mg/kg, respectively; n=4-8/group). Whole blood and brains were collected immediately following motor activity assays. Bifenthrin concentrations in blood and brain were quantified using HPLC/MS/MS. Bifenthrin exposure decreased motor activity from 20% to 70% in a dose-dependent manner at both time points. The relationship between motor activity data and administered dose, and blood and brain bifenthrin concentrations were described using a sigmoidal E(max) model. The relationships between motor activity and administered dose or blood concentrations were different between the 4- and 7-h time points. The relationship between motor activity and brain concentration was not significantly different between the two time points. These data suggest that momentary brain concentration of bifenthrin may be a more precise dose metric for predicting behavioral effects because the relationship between brain concentration and locomotor activity is independent of the time of exposure.

中文翻译：

---

拟除虫菊酯联苯菊酯的组织浓度与大鼠神经毒性的相关性。

人类接触拟除虫菊酯农药的可能性促使药效学和药代动力学研究更好地表征风险。这项工作检验了以下假设：拟除虫菊酯联苯菊酯的血液和大脑浓度可预测神经毒性作用。成年雄性 Long Evans 大鼠接受单次口服剂量的溶解在玉米油中的联苯菊酯。使用八字形迷宫，在接触联苯菊酯（分别为 0-16mg/kg 或 0-9mg/kg；n=4-8/组）后 4 小时和 7 小时测量运动活动 1 小时。在运动活动测定后立即收集全血和大脑。使用 HPLC/MS/MS 对血液和大脑中的联苯菊酯浓度进行定量。联苯菊酯暴露在两个时间点均以剂量依赖性方式将运动活动从 20% 降低至 70%。使用 sigmoidal E(max) 模型描述了运动活动数据和给药剂量以及血液和脑联苯菊酯浓度之间的关系。运动活动与给药剂量或血液浓度之间的关系在 4 小时和 7 小时时间点之间是不同的。两个时间点之间的运动活动和大脑浓度之间的关系没有显着差异。这些数据表明，联苯菊酯的瞬时脑浓度可能是预测行为影响的更精确剂量指标，因为脑浓度和运动活动之间的关系与暴露时间无关。运动活动与给药剂量或血液浓度之间的关系在 4 小时和 7 小时时间点之间是不同的。两个时间点的运动活动和大脑浓度之间的关系没有显着差异。这些数据表明，联苯菊酯的瞬时脑浓度可能是预测行为影响的更精确剂量指标，因为脑浓度和运动活动之间的关系与暴露时间无关。运动活动与给药剂量或血液浓度之间的关系在 4 小时和 7 小时时间点之间是不同的。两个时间点之间的运动活动和大脑浓度之间的关系没有显着差异。这些数据表明，联苯菊酯的瞬时脑浓度可能是预测行为影响的更精确剂量指标，因为脑浓度和运动活动之间的关系与暴露时间无关。