Document OE04jaR02wQ4D668n7koZx6DK

ARY26-02M0 =oir ER 7 MECHANISM OF TOXICITY OF A UNIQUE PESTICIDE * = ETHYLPERFLUOROOCTANE SULFONAMIDE (NEPFOS), NEB. Efe ITS METABOLITE PERFLUOROOCTANE 'SULFONAMIDE "Z3 (PFOS) TO ISOLATED RABBIT RENAL CORTICAL MITG-. i ; CHONDRIA (RCM). TJ Cross and RG Schnell=: 8 mann. Dept. Physiol./Pharmacol., Coll. Vety 3 Med., University of Georgi, a, Athens, GA. E TE i L NEPFOS is currently being evaluated as a pest{i-.232 cide for the red imported fire ant. Previous=:f studies from `this laboratory: showed that a"=i early effect of NEPFOS and PFOS on rabbit renal:i:i=s proximal tubules wasa- concentration-dependen$=:i7: (5-200 uM) increase in ouabain-insensitive res: 3 piration (RESP). The goal of this study was to "=: determine whether the increased RESP resulted EH from uncoupling of oxidative phosphorylation (0X 8 PHOS). NEPFOS (5-100 uM) and PFOS {0.5-50 ul) "HE increased state 4 RESP of RCM respiring on pyru- vate/malate or succinate in the absence of 3 phosphate acceptor or in the presence of oligo: mycin, an inhibitor of FOF1-ATPase. The effect of NEPFOS (200 uM), PFOS (100 uM), and the known protonophore FCCP (luM), on proton movement by RCM was examined. Immediately on addition, PFOS and, FCCP, but not NEPFOS, dissipated the proton gradient. These results show that PFOS acts as a protonophore and -uncouples OX PHOS by this `mechanism. The `lack of proton movement bY "iz. If "3 = 4 : 1 J "NEPFOS `suggests that NEPFOS -may need to be ~=metabolized to *PFOS to produce cytotoxicity and ~uncoupling of 0X PHOS. {Supported by VMES, "Univ. Georgia). 8 STRACT Feom MarCH1987 SUT MEETING. BESTCOPY AVAILABLE 01007