Metabolism of pyridalyl in rats: excretion, distribution, and biotransformation of dichloropropenyl-labeled pyridalyl.
Metabolism of pyridalyl [2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl ether] labeled at position 2 of the dichloropropenyl group with 14C was investigated after single oral administration to male and female rats at 5 and 500 mg/kg. Absorbed 14C was excreted into feces (68-79%), urine (8-14%), and expired air (6-10%) in all of the groups. Regarding 14C-tissue residues on the seventh day after administration, fat showed the highest levels at 0.98-2.34 ppm and 219-221 ppm with the low and high doses, respectively. 14C-Residues in other tissues accounted for 0.03-0.32 ppm at the low dose and 3-70 ppm at the high dose. The percentages of the 14C-residue in fat were 1.50-3.16% of the dose, and those of muscle and hair and skin were also relatively high, accounting for 0.49-1.20%. Total 14C-residues in the whole body were 2.95-6.80% of the dose. Fecal metabolites in male rats treated with 500 mg/kg pyridalyl were purified by a combination of chromatographic techniques, and chemical structures of 8 metabolites were identified by NMR and MS spectrometry. The biotransformation reactions in rats were proposed to be as follows: (1) epoxidation of the double bond in the dichloropropenyl group followed by hydration, dehydrochlorination, decarboxylation, and/or mercapturic acid conjugation; (2) CO2 formation after O-dealkylation of pyridalyl and its metabolites; (3) hydroxylation of C3 in the pyridyl ring; (4) O-dealkylation of the pyridyloxy and the trimethylene groups; (5) dehydrochlorination and hydration in the dichloropropenyl group.
Nagahori
Hirohisa
H
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 1-98, 3-Chome, Kasugade-Naka, Konohana-Ku, Osaka 554-8558, Japan. nagahori@sc.sumitomo-chem.co.jp
Tomigahara
Yoshitaka
Y
Isobe
Naohiko
N
Kaneko
Hideo
H
D000273:Adipose Tissue / Q000737:chemistry; D000818:Animals; D001944:Breath Tests; D002250:Carbon Radioisotopes; D005243:Feces / Q000737:chemistry; D005260:Female; D006197:Hair / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D009132:Muscles / Q000737:chemistry; D010647:Phenyl Ethers / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D051381:Rats; D012867:Skin / Q000737:chemistry; D014556:Urine / Q000737:chemistry
D002250:Carbon Radioisotopes; D010647:Phenyl Ethers; C418569:S 1812