Wester R C, Maibach H I, Bucks D A, Guy R H
Toxicol Appl Pharmacol. 1983 Mar 30;68(1):116-9. doi: 10.1016/0041-008x(83)90360-5.
Prediction of exposure and toxic potential of pesticides such as malathion are routinely based upon acute exposure and single-dose percutaneous absorption determination. What has become obvious with pesticide exposure such as the malathion spraying for the medfly is that chronic daily exposure is the more relevant situation. Our objective was to determine the percutaneous absorption of chronically applied malathion in man and to compare chronic absorption to single-dose absorption. The experimental design was to first topically apply [14C]malathion to human male volunteers. This procedure was followed by repeated administration of nonradioactive malathion to the same site of application (ventral forearm). [14C]Malathion was reapplied (Day 8) when urinary excretion of radioactivity from the first application reached minimum detectable levels. The first [14C]malathion absorption was compared to the second [14C]malathion application. The percutaneous absorption from the first [14C]malathion application was 4.48 +/- 1.3% (SD) of the applied dose. The absorption from the second [14C]malathion administration was 3.53 +/- 1.0%, a value not significantly (p greater than 0.05) different from the first application. Therefore, for malathion the single-dose application data are relevant for predicting the toxic potential for longer-term exposure.
对诸如马拉硫磷等农药的暴露和毒性潜力的预测通常基于急性暴露和单剂量经皮吸收测定。对于诸如为防治地中海实蝇而喷洒马拉硫磷这类农药暴露而言,显而易见的是,慢性每日暴露才是更相关的情况。我们的目标是测定长期施用的马拉硫磷在人体中的经皮吸收情况,并将慢性吸收与单剂量吸收进行比较。实验设计是首先将[14C]马拉硫磷局部涂抹于男性志愿者身上。此步骤之后,在相同涂抹部位(前臂腹侧)重复施用非放射性马拉硫磷。当首次施用的放射性物质的尿排泄量达到最低可检测水平时(第8天),重新施用[14C]马拉硫磷。将首次[14C]马拉硫磷的吸收情况与第二次[14C]马拉硫磷施用情况进行比较。首次[14C]马拉硫磷施用后的经皮吸收量为施用剂量的4.48±1.3%(标准差)。第二次[14C]马拉硫磷施用后的吸收量为3.53±1.0%,该值与首次施用相比无显著差异(p大于0.05)。因此,对于马拉硫磷而言,单剂量施用数据与预测长期暴露的毒性潜力相关。