Absorption and mass balance of piperonyl butoxide following an 8-h dermal exposure in human volunteers

Dermal absorption, metabolism and excretion of piperonyl butoxide (PBO) was studied using C-14-PBO either by itself as a 3% (w/w) solution in isopropy l alcohol or as a 4% (w/w) solution in an aqueous end-use formulation. Each of these two formulations were tested on four young, healthy male voluntee rs, using a single topical application on the ventral forearm under non-occ lusive conditions for an 8-h period. The application sites were thoroughly cleaned with cotton swabs moistened with isopropyl alcohol, then rinsed wit h isopropyl alcohol. Blood from the ipsilateral and contralateral arms, uri ne and feces were collected at selected intervals during the 8-h applicatio n and through a 120-h post-application period. The application area was als o tape-stripped to determine if any of the test material accumulated in the stratum corneum. These samples provided data which permitted insight into the kinetics of penetration and elimination processes of PBO. The absorptio n of PBO either by itself or formulated was very poor, as demonstrated by t he radioactivity excreted in the urine, and radioactivity in the ipsilatera l plasma. When dosed by itself, approximate to 1.78% of the dose was excret ed in the urine. In contrast, only 0.47% of the formulated PBO was excreted in the urine. Trace radioactivity was detected in the feces from both form ulations. The absorbed radioactivity was rapidly eliminated in the urine. T here was no evidence of accumulation of PBO in the skin as evidenced by low amounts of radioactivity in the tape-strippings. The majority of the appli ed radioactivity was recovered from the skin surface. Total recovery of the applied radioactivity was 100.86 and 104.22% for PBO and the formulated pr oduct respectively. Absorbed PBO was completely metabolized to at least thr ee major metabolites prior to its excretion in the urine. The three metabol ites represented over 70% of the excreted radioactivity for PBO. The HPLC r etention times for these metabolites are different than that seen in rats. The structures of these metabolites have not been elucidated. (C) 1999 Else vier Science Ireland Ltd. All rights reserved.