Determination of the effect of tridiphane on the pharmacokinetics of [14C]-atrazine following oral administration to male Fischer 344 rats.
The absorption, distribution, metabolism and excretion of [14C]-atrazine was studied in male Fischer 344 rats administered a 30 mg [14C]-atrazine/kg of body weight oral dose with or without pretreatment with a non-radiolabeled oral dose of 60 mg tridiphane/kg of body weight. The objective of this study was to determine whether tridiphane had any meaningful effect on the pharmacokinetics and/or metabolism of atrazine in the rat. The 14C plasma time-course exhibited a mono-exponential decrease with an absorption and elimination half-life of approximately 3 h and 11 h, respectively for both treatment groups. In addition, at 72 h after the administration of [14C]-atrazine, approximately 93% of the administered radioactivity was recovered and the primary route of excretion was via the urine (67%) for both treatment groups. The feces accounted for approximately 18% of the dose, and less than 10% remained in the carcass, skin, and red blood cells (RBCs). The urine excreted in the first 24 h post-dosing contained approximately 57% of the administered radioactivity for both treatment groups. There were no appreciable differences in the metabolite distribution between treatment groups, and the major urinary metabolite of atrazine was found to be 2-chloro-4,6-diamino-1,3,5-triazine (II; 64-67%). Additionally, S-(2-amino-4-methylethylamino-1,3,5-triazin-6-yl)-mercapturi c acid (V; 13-14%), and S-(2,4-diamino-1,3,5-triazin-6-yl)-mercapturic acid (III; 9%) were tentatively identified based upon similar HPLC retention times as seen with synthesized standards. These data indicate that there are no meaningful differences in the absorption, distribution, metabolism, and excretion between rats administered only [14C]-atrazine and those administered both tridiphane and [14C]-atrazine. Therefore, it can be concluded that tridiphane has no meaningful effect on the pharmacokinetics and/or metabolism of atrazine in the rat.
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Mammalian and Environmental Toxicology Research Laboratory, Dow Chemical Company, Midland, MI 48674.
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Langvardt
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Kastl
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Osborne
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D000284:Administration, Oral; D000818:Animals; D001280:Atrazine / Q000378:metabolism / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D004852:Epoxy Compounds / Q000378:metabolism / Q000494:pharmacology* / Q000652:urine; D004988:Ethers, Cyclic / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D006540:Herbicides / Q000378:metabolism / Q000494:pharmacology* / Q000652:urine; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D006540:Herbicides; D001280:Atrazine; C051460:tridiphane