The Metabolism of CIS - and Trans - Decalin in Fischer 344 Rats.

Abstract

Abstract : A study by Inman et al. showed that the Air force Cruise Missile fuel JP-10, a C10 cyclic hydrocarbon with the chemical name exo-2,3,3a,4,5,6,7,7a-octahydro-4,7-methano-1H-indene (I), produced kidney lesions in Fischer 344 male rates. using 14C labeled JP-10, Inman found the hydrocarbon was distributed throughout the rat's body. A metabolic study of JP-10 shsoed the presence of the alcohol exo-5-hydroxy-exo-2,3,3a,4,5,6,7,7a-octahydro-4,7-methano-1H-indene (II) in the urine. Homogenization and extraction of the rat's kidney resulted in the isolation of the ketone, 5-keto-exo-2,3,3a, 4,5,6,7,7a-octahydro-4,7-methano-1H-indene (III). No ketone was found in the urine. Based upon the work of Inman, it was hypothesized that the metabolites of high-boiling cyclic hydrocarbons may provide valuable information regarding the renal toxicity mechanism. It was proposed that the metabolism of other cyclic hydrocarbons be examined to see if a commonality of metabolism yielded similar toxic effects. The first chemical to be examined was decalin (IV). Male and female Fischer 344 rats were administered cis- and trans-decalin intragastrically. The male rats were more affected than the female rats as evidenced by reduced weight gain and appearances of hyalin droplet formation in the proximal tubules. Urine studies in both male and female rats showed that cis-decalin was metabolized to cis, trans-1-decalol, cis, cis-1-decalol and cis, cis-2-decalol while trans-decalin was converted to trans, trans-1-decalol and trans, cis-2-decalol. Kidney extracts of male Fischer 344 rats showed the presence of 2-decalones. Keywords: Decalin(decahydronaphthalene).