This study aimed at gaining more insights into the impact of pesticide coexposure on the toxicokinetics of biomarkers of exposure. This was done by conducting an in vivo experimental case-study with binary mixtures of lambda-cyhalothrin (LCT) and captan and by assessing its impact on the kinetic profiles of LCT biomarkers of exposure. Groups of male Sprague–Dawley rats were exposed orally by gavage to LCT alone (2.5 or 12.5 mg/kg bw) or to a binary mixture of LCT and captan (2.5/2.5 or 2.5/12.5 or 12.5/12.5 mg/kg bw). In order to establish the temporal profiles of the main metabolites of LCT, serial blood samples were taken, and excreta (urine and feces) were collected at predetermined intervals up to 48 h post-dosing. Major LCT metabolites were quantified in these matrices: 3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropane carboxylic (CFMP), 3-phenoxybenzoic acid (3-PBA), 4-hydroxy-3-phenoxybenzoic acid (4-OH3PBA). There was no clear effect of coexposure at the low LCT dose on the kinetics of CFMP and 3-PBA metabolites, based on the combined assessment of temporal profiles of these metabolites in plasma, urine and feces; however, plasma levels of 3-PBA were diminished in the coexposed high-dose groups. A significant effect of coexposure on the urinary excretion of 4-OH3PBA was also observed while fecal excretion was not affected. The temporal profiles of metabolites in plasma and in excreta were further influenced by the LCT dose. In addition, the study revealed kinetic differences between metabolites with a faster elimination of 3-PBA and 4-OH3BPA compared to CFMP. These results suggest that the pyrethroid metabolites CFMP and 3-PBA, mostly measured in biomonitoring studies, remain useful as biomarkers of exposure in mixtures, when pesticide exposure levels are below the reference values. However, the trend of coexposure effect observed in the benzyl metabolite pathway (in particular 4-OH3BPA) prompts further investigation.

这项研究旨在获得更多关于农药共同暴露对接触生物标志物毒物动力学的影响的见解。这是通过对lambda-cyhalothrin（LCT）和captan的二元混合物进行体内实验案例研究，并评估其对暴露的LCT生物标志物动力学特征的影响来完成的。雄性Sprague–Dawley大鼠组通过管饲法单独口服LCT（2.5或12.5 mg / kg bw）或LCT和Captan的二元混合物（2.5 / 2.5或2.5 / 12.5或12.5 / 12.5 mg / kg bw）口服。 。为了建立LCT主要代谢产物的时间分布，需要采集一系列血样，并在给药后48小时内以预定间隔收集排泄物（尿液和粪便）。在以下基质中定量了主要的LCT代谢产物：3-（2-氯-3,3,3-三氟丙-1-烯基）-2，2-二甲基-环丙烷羧酸（CFMP），3-苯氧基苯甲酸（3-PBA），4-羟基-3-苯氧基苯甲酸（4-OH3PBA）。根据血浆，尿液和粪便中这些代谢物的时间变化曲线的综合评估，在低LCT剂量下共同暴露对CFMP和3-PBA代谢物的动力学没有明显影响。然而，在高剂量组中，3-PBA的血浆水平降低了。共排毒对4-OH3PBA的尿排泄也有显着影响，而粪便排泄不受影响。LCT剂量进一步影响血浆和排泄物中代谢物的时间分布。此外，该研究还揭示了与CFMP相比，3-PBA和4-OH3BPA消除更快的代谢物之间的动力学差异。这些结果表明拟除虫菊酯代谢物CFMP和3-PBA 当农药暴露水平低于参考值时，通常在生物监测研究中进行的大多数测量仍可作为混合物中暴露的生物标志物。然而，在苄基代谢途径（特别是4-OH3BPA）中观察到的共同暴露效应趋势提示了进一步的研究。