Lethal dose

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

A lethal dose (LD) is an indication of the lethality of a given substance or type of radiation. Because resistance varies from one individual to another, the 'lethal dose' represents a dose (usually recorded as dose per kilogram of subject body weight) at which a given percentage of subjects will die.

The most commonly-used lethality indicator is the LD₅₀ (or LD50), a dose at which 50% of subjects will die. LD measurements are often used to describe the power of venoms in animals such as snakes.

Animal-based LD measurements are a commonly-used technique in drug research, although many researchers are now shifting away from such methods.

LD figures depend not only on the species of animal, but also on the mode of administration. For instance, a toxic substance inhaled or injected into the bloodstream may require a much smaller dosage than if the same substance is swallowed.

LD values for humans are generally estimated by extrapolating results from testing on animals or on human cell cultures. One common form of extrapolation involves measuring LD on animals like mice or dogs, converting to dosage per kilogram of biomass, and extrapolating to human norms. While animal-extrapolated LD values are correlated to lethality in humans, the degree of error is sometimes very large. The biology of test animals, while similar to that of humans in many respects, sometimes differs in important aspects. For instance, mouse tissue is approximately fifty times less responsive than human tissue to the venom of the Sydney funnel-web. The square-cube law can also complicate the scaling relationships involved.

Currently, the only known LD₅₀ values obtained directly on humans are from Nazi human experimentation.