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      Elimination and accumulation of the rodenticide flocoumafen in rats following repeated oral administration.

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          Abstract

          1. Following multiple oral administration of 14C-flocoumafen to rats at 0.02 and 0.1 mg/kg per week, appreciable cellular accumulation was seen in the liver. 2. Residues in the liver increased with dose throughout the duration of the experiment (14 weeks) at the low dose, but reached a plateau after 4 weeks at the high dose. The major component was unchanged flocoumafen together with a minor polar metabolite seen also in faeces. 3. The data suggest the presence in rat liver of a saturable high-affinity binding site for flocoumafen and a second binding site of lower affinity. 4. Lethal anticoagulant action occurs only when the binding sites have become saturated. 5. A range of haematological and clinical chemistry measurements failed to predict the onset of anticoagulant toxicity seen in the high dose treatment group. 6. Flocoumafen was not extensively metabolised; at the low dose, approximately 30% of the cumulative administered dose was eliminated in the faeces within 3 days of each dosing, mainly as unchanged rodenticide. At the high dose, this value ranged from 18% after the first dose to 59% after the tenth dose. 7. Two more polar metabolites and a lipophilic compound were minor products in faeces. Amounts of the polar products increased with cumulative dosage received. The urinary route of elimination was a very minor one (less than 1.6%) at both doses.

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          Author and article information

          Affiliations
          [1 ] Shell Research, Ltd., Sittingbourne Research Centre, Kent, UK.
          Journal
          Xenobiotica
          Xenobiotica; the fate of foreign compounds in biological systems
          Informa UK Limited
          0049-8254
          0049-8254
          Dec 1988
          : 18
          : 12
          10.3109/00498258809042269
          3245237

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