Identification of metabolites of octamethylcyclotetrasiloxane (D-4) in raturine

Octamethylcyclotetrasiloxane (D-4) is an industrial chemical of significant commercial importance. In this study, its major urinary metabolites were i dentified. The urine samples described here were collected from male and fe male Fischer rats (F-344) administered [C-14]D-4 i.v. The metabolite profil e was obtained using an HPLC system equipped with a radioisotope detector. HPLC analysis was performed on a C18 column, using an acetonitrile/water mo bile phase. The HPLC radiochromatogram revealed two major and at least five minor metabolites. The two major metabolites, constituting 75 to 85% of th e total radioactivity, were identified as dimethylsilanediol [Me2Si(OH)(2)] and methylsilanetriol [MeSi(OH)(3)]. Formation of MeSi(OH)(3) clearly esta blished demethylation at the silicon-methyl bonds of D-4. No parent D-4 was present in urine. The minor metabolites identified were tetramethyldisilox ane-1,3-diol [Me2Si(OH)-O-Si(OH)Me-2], hexamethyltrisiloxane-1,5-diol [Me2S i(OH)-OSiMe2-O-Si-(OH)Me-2], trimethyldisiloxane-1,3,3-triol [MeSi(OH)(2)-O Si(OH)Me-2], dimethyldisiloxane-1,1,3,3-tetrol [MeSi(OH)(2)-O-Si(OH)(2)Me], and dimethyldisiloxane-1,1,1,3,3-pentol [Si(OH)(3)-O-Si(OH)(2)Me]. The str uctural assignments were based on gas chromatography-mass spectrometry anal ysis of the tetrahydrofuran metabolite extracts, which were derivatized usi ng bis(trimethylsiloxy)triflouroacetamide, a trimethylsilylating agent. The structures were confirmed by synthesizing C-14-labeled standards and compa ring their HPLC radiochromatograms with the corresponding components in the rat urine. GC-MS spectral comparisons of the trimethylsilylated derivatize d standards and urinary components also were made to further confirm their identities. Finally, several of the urinary metabolites were fractionated u sing HPLC, and GC-MS comparisons were again made for positive structural id entification. The pathways for metabolite formation are not yet understood, but a mechanistic hypothesis has been proposed to account for the various metabolites observed thus far.