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The comparative metabolism of diisopropyl methylphosphonate in mink and rats
D J Weiss1, R S Geary, W Wustenberg
1Department of Veterinary Pathobiology, University of Minnesota, St. Paul 55108.
Abstract:
This study reports the metabolism of carbon-14labeled diisopropyl methylphosphonate (DIMP) in mink and rats, undertaken to better understand the dose-related mortality reported for mink in a previous study. In both male and female mink and rats, DIMP was rapidly absorbed after oral administration; it was metabolized by a saturable pathway to a single metabolite, isopropyl methylphosphonate (IMPA), which was rapidly excreted, primarily in the urine (90%). Fecal radioactivity, also identified as IMPA, was 1.7-3.1% of the administered dose. Female rats had a slower rate of conversion of DIMP to IMPA and less total excretion of IMPA than male rats. Metabolism of DIMP administered intravenously was not very different from that given orally in both species. These data indicate that mink absorb, metabolize, and excrete DIMP (as IMPA) in a manner very similar to mice, rats, and dogs.
Insights
Mink and rats rapidly absorb, metabolize, and excrete diisopropyl methylphosphonate (DIMP) as isopropyl methylphosphonate (IMPA). This metabolism pathway is similar across species, aiding understanding of DIMP toxicity.
Area of Science:
- Toxicology
- Pharmacokinetics
- Environmental Science
Background:
- Previous studies reported dose-related mortality in mink exposed to diisopropyl methylphosphonate (DIMP).
- Understanding the metabolic fate of DIMP is crucial for assessing its toxicological profile.
- Comparative metabolism studies are essential for interspecies risk assessment.
Purpose of the Study:
- To investigate the absorption, metabolism, and excretion (ADME) of carbon-14 labeled diisopropyl methylphosphonate (DIMP) in mink and rats.
- To elucidate the metabolic pathway of DIMP and identify its primary metabolite.
- To compare the DIMP metabolic profile in mink and rats with other species.
Main Methods:
- Oral and intravenous administration of carbon-14 labeled diisopropyl methylphosphonate (DIMP) to male and female mink and rats.
- Quantification of radioactivity in urine and feces.
- Identification of the major metabolite using analytical techniques.
Main Results:
- DIMP was rapidly absorbed and metabolized to isopropyl methylphosphonate (IMPA) via a saturable pathway in both species.
- IMPA was primarily excreted in urine (approximately 90%), with minor amounts in feces (1.7-3.1%).
- Female rats exhibited a slower conversion rate of DIMP to IMPA and lower total IMPA excretion compared to male rats.
Conclusions:
- Mink, rats, mice, and dogs share similar DIMP absorption, metabolism, and excretion pathways.
- The primary metabolite of DIMP is IMPA, which is rapidly excreted.
- These findings provide a basis for understanding DIMP-related mortality and inform risk assessments.