Toxicokinetics of temephos after oral administration to adult male rats

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_{1/2 abs} = 0.38 h), and only trace levels were detected at 36 h (t_{1/2 elim} = 8.6 h). Temephos was detected in all tissues and preferentially accumulated in fat. Temephos-sulfone-monohydrolyzed (Tem-SO₂-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-SO₂-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.

Biomarkers; Metabolism; Organophosphorus pesticides; Temephos; Toxicokinetics.