Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Mexico City, Mexico.
Laboratorio de Contaminación y Toxicología Ambiental, Secretaría de Investigación y Posgrado, Universidad Autónoma de Nayarit, Tepic, Mexico.
Crit Rev Toxicol. 2022 Feb;52(2):113-124. doi: 10.1080/10408444.2022.2065967. Epub 2022 May 24.
Temephos (,,','-tetramethyl ,'-thiodi--phenylene bis(phosphorothioate)) is a larvicide belonging to the family of organophosphate pesticides used for the control of different vectors of diseases, such as dengue, Zika, chikungunya, and dracunculiasis. The aim of this review was to discuss the available published information about temephos toxicokinetics and toxicity in mammals. Temephos is quickly absorbed in the gastrointestinal tract, distributed to all organs, and then it accumulates mainly in adipose tissue. It is metabolized by -oxidation, oxidative desulfuration, and hydrolysis reactions, with the possible participation of cytochrome P450 (CYP). Temephos is mainly eliminated by feces, whereas some of its metabolites are eliminated by urine. The World Health Organization classifies it as class III: slightly dangerous with a NOAEL (no-observed adverse effect level) of 2.3 mg/kg/day for up to 90 days in rats, based on brain acetylcholinesterase (AChE) inhibition. A LOAEL (lowest observable adverse effect level) of 100 mg/kg/day for up to 44 days in rats was proposed based on cholinergic symptoms. However, some studies have shown that temephos causes toxic effects in mammals. The inhibition of the enzyme acetylcholinesterase (AChE) is one of its main demonstrated effects; however, this larvicide has also shown genotoxic effects and some adverse effects on male reproduction and fertility, as well as liver damage, even at low doses. We performed an extensive review through several databases of the literature about temephos toxicokinetics, and we recommend to revisit current assessment of temephos with the new available data.
硫丹(,,','-四甲基,'-硫代二亚苯基双(膦酸酯))是一种拟除虫菊酯类杀虫剂,用于控制登革热、寨卡病毒、基孔肯雅热和麦地那龙线虫等不同疾病的传播媒介。本综述的目的是讨论有关硫丹在哺乳动物体内的毒代动力学和毒性的现有已发表信息。硫丹在胃肠道中被迅速吸收,分布到所有器官,然后主要在脂肪组织中积累。它通过β-氧化、氧化脱硫和水解反应代谢,可能涉及细胞色素 P450(CYP)。硫丹主要通过粪便排泄,而其一些代谢物通过尿液排泄。世界卫生组织将其归类为 III 类:在大鼠中,每天 2.3mg/kg 连续 90 天,未见不良作用水平(NOAEL)为 2.3mg/kg/day,基于大脑乙酰胆碱酯酶(AChE)抑制。基于胆碱能症状,在大鼠中每天 100mg/kg 连续 44 天的最低可观察不良作用水平(LOAEL)为 100mg/kg/day。然而,一些研究表明硫丹会对哺乳动物造成毒性作用。酶乙酰胆碱酯酶(AChE)的抑制是其主要表现之一;然而,这种杀虫剂还表现出遗传毒性作用,以及对雄性生殖和生育能力的一些不良影响,甚至在低剂量下也会对肝脏造成损害。我们通过几个文献数据库对硫丹的毒代动力学进行了广泛的综述,我们建议根据新的可用数据重新评估当前对硫丹的评估。