Related Experiment Videos
Toxicokinetics of trimethyltin in four inbred strains of mice
J E Ekuta1, A H Hikal, J C Matthews
1Department of Pharmacology, School of Pharmacy, The University of Mississippi, University 38677, USA.
Abstract:
Sixteen week old male AKR/J, Balb/cByJ, C57B1/6J and DBA/2J mice received single i.p. injections of trimethyltin (TMT). The toxic effects were weight loss, hyperexcitability, tremor, clonic-tonic convulsion, posterior paresis and death. The minimum toxic dose was 1.8 mg/kg, for the AKR strain and 2.3 mg/kg for the other strains. The highest non-lethal dose was 2.7 mg/kg for the AKR, DBA/2 and C57B1/6 strains and 3.0 mg/kg for the Balb/c strain. Blood levels of TMT peaked within 1 h and declined with half-lives of approximately 1.5 days. Blood levels of TMT were lower in the C57B1/6 mice due to greater tissue binding of TMT in C57B1/6 mice. Some of the toxic endpoints showed different rank orders among the strains, leading us to conclude that more than one biological process is responsible for the acute toxic effects of TMT in mice.
Insights
Trimethyltin (TMT) causes acute toxicity in mice, with varying sensitivity across strains. Different biological processes likely contribute to TMT
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Trimethyltin (TMT) is a neurotoxicant known to induce a range of adverse effects.
- Understanding strain-specific susceptibility to TMT is crucial for preclinical research and risk assessment.
Purpose of the Study:
- To investigate the acute toxic effects of trimethyltin (TMT) in four different strains of male mice.
- To determine the dose-response relationship and identify strain-specific differences in TMT toxicity.
Main Methods:
- Four strains of 16-week-old male mice (AKR/J, Balb/cByJ, C57B1/6J, DBA/2J) were administered single intraperitoneal injections of TMT.
- Observed toxic effects included weight loss, hyperexcitability, tremors, convulsions, paresis, and mortality.
- Blood TMT levels were monitored over time to determine pharmacokinetic parameters.
Main Results:
- Minimum toxic doses ranged from 1.8 mg/kg (AKR/J) to 2.3 mg/kg (other strains).
- Highest non-lethal doses varied by strain, with Balb/cByJ showing higher tolerance.
- Blood TMT levels peaked within 1 hour and had a half-life of approximately 1.5 days; C57B1/6J mice exhibited lower blood levels due to increased tissue binding.
Conclusions:
- Acute TMT toxicity manifests differently across mouse strains, indicating varying susceptibility.
- The observed differences in toxic endpoints and pharmacokinetic profiles suggest that multiple biological mechanisms underlie TMT's acute effects.
- Strain-specific responses highlight the importance of considering genetic background in TMT toxicity studies.