Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. IPN 2508, Col. San Pedro Zacatenco, 07360, Ciudad de México, Mexico.
Facultad de Química, Universidad Nacional Autónoma de México, 04510, Ciudad de México, Mexico.
Arch Toxicol. 2021 Mar;95(3):935-947. doi: 10.1007/s00204-021-02975-8. Epub 2021 Jan 20.
Temephos (Tem) is the larvicide of choice to control mosquito transmission of dengue, Zika, and chikungunya. The toxicokinetic and toxicological information of temephos is very limited. The aim of this work was to determine the toxicokinetics and dosimetry of temephos and its metabolites. Male Wistar rats were orally administered temephos (300 mg/kg) emulsified with saline solution and sacrificed over time after dosing. Temephos and its metabolites were analyzed in blood and tissues by high performance liquid chromatography-diode array detector. At least eleven metabolites were detected, including temephos-sulfoxide (Tem-SO), temephos-oxon (Tem-oxon), temephos-oxon-sulfoxide (Tem-oxon-SO), temephos-oxon-SO-monohydrolyzed (Tem-oxon-SO-OH), 4,4´-thiodiphenol, 4,4´-sulfinyldiphenol, and 4,4´-sulfonyldiphenol or bisphenol S (BPS). The mean blood concentrations of temephos were fitted to a one-compartment model for kinetic analysis. At 2 h, the peak was reached (t = 0.38 h), and only trace levels were detected at 36 h (t = 8.6 h). Temephos was detected in all tissues and preferentially accumulated in fat. Temephos-sulfone-monohydrolyzed (Tem-SO-OH) blood levels remained constant until 36 h and gradually accumulated in the kidney. Tem-oxon was detected in the brain, liver, kidney, and fat. Clearance from the liver and kidney were 7.59 and 5.52 ml/min, respectively. These results indicate that temephos is well absorbed, extensively metabolized, widely distributed and preferentially stored in adipose tissue. It is biotransformed into reactive metabolites such as Tem-oxons, Tem-dioxons, and BPS. Tem-SO-OH, the most abundant metabolite of temephos, could be used as an exposure biomarker for toxicokinetic modeling. These results could provide critical insight into the dosimetry and toxicity of temephos and its metabolites.
敌百虫（Tem）是控制登革热、寨卡病毒和基孔肯雅热蚊媒传播的首选杀幼虫剂。关于敌百虫的毒代动力学和毒理学信息非常有限。这项工作的目的是确定敌百虫及其代谢物的毒代动力学和剂量学。雄性 Wistar 大鼠经口给予敌百虫（300mg/kg）乳化生理盐水，并在给药后不同时间点处死。通过高效液相色谱-二极管阵列检测器分析血液和组织中的敌百虫及其代谢物。至少检测到 11 种代谢物，包括敌百虫亚砜（Tem-SO）、敌百虫氧肟（Tem-oxon）、敌百虫氧肟亚砜（Tem-oxon-SO）、敌百虫氧肟亚砜单水解（Tem-oxon-SO-OH）、4,4´-硫代二苯酚、4,4´-亚磺酰基二苯酚和 4,4´-磺酰基二苯酚或双酚 S（BPS）。敌百虫的平均血液浓度拟合为动力学分析的单室模型。在 2 小时时达到峰值（t=0.38 小时），在 36 小时时仅检测到痕量水平（t=8.6 小时）。敌百虫在所有组织中均有检测到，并且优先在脂肪中积累。敌百虫砜单水解（Tem-SO-OH）的血液水平在 36 小时内保持不变，并逐渐在肾脏中积累。Tem-oxon 存在于大脑、肝脏、肾脏和脂肪中。肝脏和肾脏的清除率分别为 7.59 和 5.52ml/min。这些结果表明，敌百虫吸收良好，广泛代谢，广泛分布，优先储存在脂肪组织中。它被生物转化为反应性代谢物，如 Tem-oxons、Tem-dioxons 和 BPS。敌百虫最丰富的代谢物 Tem-SO-OH 可作为毒代动力学建模的暴露生物标志物。这些结果可以为敌百虫及其代谢物的剂量学和毒性提供重要的见解。
