Disposition of [ 14C] methyl bromide in fischer-344 rats after oral or intraperitoneal administration

Abstract

Methyl bromide is used as a disinfectant to fumigate soil. The intent of our study was to determine the diposition of methyl bromide following a single acute administration. Male Fischer-344 rats were given 250 μmol of [ 14C] methyl bromide/kg body wt by either oral or i.p. administration. Urine, feces and expired air were collected and at the end of 72 h the rats were sacrificed and tissues analyzed to determine 14C excretion and tissue distribution. After i.p. administration of methyl bromide, the dominant route of excretion was exhalation of 14CO 2, with 46% of the dose exhaled as 14CO 2. In contrast, urinary excretion of 14C was the major route of elimination (43% of the dose) when methyl bromide was given orally. Very little of the 14C appeared in the feces (<3% of the dose) regardless of route of administration. In rats with bile duct cannulations, 46% of an oral dose appeared in the bile over a 24-h period. Collection of bile significantly decreased the exhalation of 14CO 2 and 14C excreted in urine compared to controls. At 72 h after oral or i.p. administration, 14–17% of the 14C remained in the rats, with liver and kidney being the major organs of retention. Results indicate that route of administration can affect the pathways for excretion. In addition, excretion of 14C in bile, coupled with the low levels of radioactivity found in the feces, indicates that reabsorption of biliary metabolites from the gut plays a significant role in the disposition of [ 14C] methyl bromide.