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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 disposition of methyl bromide following a single acute administration. Male Fischer-344 rats were given 250 mumol 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 14CO2, with 46% of the dose exhaled as 14CO2. 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 (less than 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 14CO2 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.
Insights
The excretion of methyl bromide in rats depends on the administration route. Oral dosing leads to urinary excretion, while i.p. injection results in exhalation of 14CO2, with significant biliary excretion and reabsorption observed.
Area of Science:
- Environmental Science
- Toxicology
- Pharmacokinetics
Background:
- Methyl bromide is a soil fumigant used for disinfection.
- Understanding its metabolic fate is crucial for risk assessment.
Purpose of the Study:
- To investigate the excretion and tissue distribution of methyl bromide after acute administration.
- To determine the influence of administration route on methyl bromide disposition.
Main Methods:
- Male Fischer-344 rats received [14C] methyl bromide orally or via i.p. injection.
- Urine, feces, expired air, and tissues were analyzed for 14C content over 72 hours.
- Bile duct-cannulated rats were used to assess biliary excretion.
Main Results:
- Intraperitoneal administration resulted in 46% of the dose exhaled as 14CO2.
- Oral administration led to 43% of the dose excreted in urine.
- Biliary excretion accounted for 46% of an oral dose within 24 hours, with significant gut reabsorption indicated.
- Liver and kidney showed the highest retention of 14C at 72 hours (14-17% of the dose).
Conclusions:
- The route of methyl bromide administration significantly impacts its excretion pathways.
- Biliary excretion and subsequent enterohepatic reabsorption are key factors in methyl bromide disposition following oral intake.