Absorption, tissue distribution, excretion, and metabolism of clothianidin in rats.
Absorption, distribution, excretion, and metabolism of clothianidin [(E)-1-(2-chloro-1,3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine] were investigated after a single oral administration of [nitroimino-(14)C]- or [thiazolyl-2-(14)C]clothianidin to male and female rats at a dose of 5 mg/kg of body weight (bw) (low dose) or 250 mg/kg of bw (high dose). The maximum concentration of carbon-14 in blood occurred 2 h after administration of the low oral dose for both labeled clothianidins, and then the concentration of carbon-14 in blood decreased with a half-life of 2.9-4.0 h. The orally administered carbon-14 was rapidly and extensively distributed to all tissues and organs within 2 h after administration, especially to the kidney and liver, but was rapidly and almost completely eliminated from all tissues and organs with no evidence of accumulation. The orally administered carbon-14 was almost completely excreted into urine and feces within 2 days after administration, and approximately 90% of the administered dose was excreted via urine. The major compound in excreta was clothianidin, accounting for >60% of the administered dose. The major metabolic reactions of clothianidin in rats were oxidative demethylation to form N-(2-chlorothiazol-5-ylmethyl)-N'-nitroguanidine and the cleavage of the carbon-nitrogen bond between the thiazolylmethyl moiety and the nitroguanidine moiety. The part of the molecule containing the nitroguanidine moiety was transformed mainly to N-methyl-N'-nitroguanidine, whereas the thiazol moiety was further metabolized to 2-(methylthio)thiazole-5-carboxylic acid. With the exception of the transiently delayed excretion of carbon-14 at the high-dose level, the rates of biokinetics, excretion, distribution, and metabolism of clothianidin were not markedly influenced by dose level and sex.
Yokota
Tokunori
T
Agricultural Research Laboratories, Technical Division, Sumitomo Chemical Takeda Agro Company, Ltd., 10 Wadai, Tsukuba, Ibaraki 300-4247, Japan. Yokota_Tokumori@sumi-take.co.jp
Mikata
Kazuki
K
Nagasaki
Hiromi
H
Ohta
Kazunari
K
D000818:Animals; D002250:Carbon Radioisotopes / Q000032:analysis / Q000097:blood / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005243:Feces / Q000737:chemistry; D005260:Female; D006146:Guanidines / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D007306:Insecticides / Q000493:pharmacokinetics*; D008297:Male; D000073943:Neonicotinoids; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D006146:Guanidines; D007306:Insecticides; D000073943:Neonicotinoids; D013844:Thiazoles; C480342:clothianidin