The percutaneous fate of the rodenticide flocoumafen in the rat: role of non-biliary intestinal excretion.
1. Appreciable penetration of radioacticity occurred through rat skin following percutaneous administration of 14C-flocoumafen. At 7 days after dosing 12% of the administered radioactivity remained at the site of application, while 25% was located in the liver as unchanged flocoumafen. 2. Excretion of flocoumafen metabolites via the urine accounted for 10% dose over the 7 day experiment, this is some 30-fold greater than that seen after a single oral dose. 3. Unchanged flocoumafen comprised the major product detected in faeces. Biliary elimination was a very minor route of excretion and did not account for all of the unmodified flocoumafen present in faeces. 4. Considerable amounts of unchanged flocoumafen found associated with the contents of the large intestine after intraperitoneal administration to rats fitted with biliary fistulae indicates that, in the intact rat, flocoumafen enters the intestine by a non-biliary intestinal excretion mechanism.
Shell Research Limited, Sittingbourne Research Centre, Kent, UK.
K R
KR
Huckle
B J
BJ
Morrison
P A
PA
Warburton
D015110:4-Hydroxycoumarins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001345:Autoradiography; D001646:Bile / Q000378:metabolism; D002845:Chromatography / Q000379:methods; D005243:Feces / Q000032:analysis; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D012378:Rodenticides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012869:Skin Absorption; D014018:Tissue Distribution
D015110:4-Hydroxycoumarins; D012378:Rodenticides; C048069:flocoumafen