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Toxicity and metabolism of trimethylarsine in mice and hamsters
H Yamauchi1, T Kaise, K Takahashi
1Department of Public Health, St. Marianna University School of Medicine, Kawasaki, Japan.
Abstract:
Trimethylarsine (TM-As) proved to be an arsenic compound of low toxicity, with a po LD50 of 7870 mg/kg in mice. A single po dose of 10 mg/kg of TM-As caused no hemolysis, but a single po dose of 750 mg/kg induced mild, transient hemolysis in hamsters. TM-As was very rapidly eliminated into the urine, with a biological half-life of 3.7 hr. TM-As was oxidized in vivo to form trimethylarsine oxide (TMAO) and excreted as such into the urine. TM-As was never demethylated in vivo. A mechanism was demonstrated by which a part of TM-As was eliminated directly into the expired air. We drew a conclusion that TM-As is far less an toxic than arsine, most probably due to its in vivo conversion to TMAO.
Insights
Trimethylarsine (TM-As) exhibits low toxicity and is rapidly excreted, primarily as trimethylarsine oxide (TMAO). This conversion likely explains its reduced toxicity compared to arsine.
Area of Science:
- Toxicology
- Pharmacokinetics
- Environmental Chemistry
Background:
- Arsenic compounds present varied toxicity profiles.
- Understanding the metabolic fate and toxicity of organoarsenic compounds like Trimethylarsine (TM-As) is crucial for risk assessment.
Purpose of the Study:
- To evaluate the toxicity and pharmacokinetic profile of Trimethylarsine (TM-As).
- To investigate the metabolic transformation and excretion pathways of TM-As in vivo.
- To compare the toxicity of TM-As with arsine.
Main Methods:
- Oral administration of TM-As to mice and hamsters to determine LD50 and observe hemolysis.
- Urine and expired air analysis to track TM-As and its metabolites.
- Pharmacokinetic analysis to determine biological half-life.
Main Results:
- TM-As demonstrated low oral toxicity (LD50 7870 mg/kg in mice).
- Mild, transient hemolysis observed in hamsters at high doses (750 mg/kg).
- Rapid urinary excretion with a biological half-life of 3.7 hours.
- In vivo oxidation to trimethylarsine oxide (TMAO), excreted in urine.
- Direct elimination of TM-As via expired air observed.
- No in vivo demethylation of TM-As occurred.
Conclusions:
- TM-As is significantly less toxic than arsine, likely due to its rapid in vivo conversion to TMAO.
- TM-As is efficiently eliminated from the body, primarily through urinary excretion of TMAO.
- The metabolic pathway and rapid excretion contribute to the low toxicity profile of TM-As.