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Toxicity Testing in Animals

Toxicity Testing in Animals

Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...

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Immunological protecion against dixin toxicity.

D H Schmidt, V P Butler

The Journal of Clinical Investigation

|April 1, 1971

Summary

This summary is machine-generated.

Digoxin toxicity was studied in rabbits. Digoxin-specific antibodies protected rabbits from lethal doses, preventing adverse effects seen in non-immunized animals.

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Area of Science:

Pharmacology
Toxicology
Immunology

Background:

Digoxin is a cardiac glycoside used to treat heart conditions.
Understanding digoxin's lethal dose and the potential for antibody-mediated protection is crucial for clinical safety.

Purpose of the Study:

To determine the lethal dose of digoxin in rabbits.
To investigate the protective effect of digoxin-specific antibodies against digoxin toxicity.

Main Methods:

Administered varying doses of digoxin to non-immunized and immunized rabbits.
Monitored survival rates and toxic effects, including arrhythmia.
Measured digoxin-specific antibody titers in immunized rabbits.

Main Results:

A dose of 0.5 mg/kg digoxin was lethal to non-immunized rabbits within 1 hour.
Rabbits immunized with digoxin-albumin conjugates survived higher doses (0.6-0.9 mg/kg).
Digoxin administration led to a significant fall in digoxin-specific antibody titers.

Conclusions:

Digoxin-specific antibodies confer protection against lethal doses of digoxin in rabbits.
The protective effect is specific to digoxin immunization, as unrelated antigens did not confer protection.
This suggests a potential therapeutic strategy for digoxin overdose using antibody-based interventions.