A measure of the
acute toxicity of
chemicals, developed in 1927; LD stands for
lethal dose. The amount of a substance which when administered to
test animals, usually
rats or
mice, causes the death of half of them. Expressed as
weight of the
chemical administered per
kilogram body weight of the test animal, and animal used and method of administration or exposure:
LD50 (oral, rat) - 5 mg/kg
LD50 (dermal, rabbit) - 10 g/kg.
Useful because different
poisons or
medicines may have effects of similar intensity but on different
tissues or
organ systems, so a test is needed that produces an
identical effect, namely
death.
An LD50 test is performed by administering gradually increasing dosages to successive test populations over a set time frame, usually 14 days, until 50% of the subjects die, after which surviving animals are killed.
The LC50 test is another measure of acute toxicity, but of concentrations in air or water rather than an administered dosage, and is expressed in parts per million (ppm) or milligrams per cubic meter, and the test animal, and the duration of exposure:
LC50 (rat) - 500 ppm/4 hr
LC50 (rabbit) - 5 mg/m3/2 hr.
LD50 is
controversial today, for several reasons. The test consumes a large number of animals and to those not
inured to
laboratory use of animals, seems cruel. It gives little or no information about
cause of death. Its
reliability is very sensitive to test conditions. Most telling, variations in species-to-species sensitivity call into question the test's relevance for
human toxicity. For example,
acetaminophen has an LD50 in mice of about 300 mg/kg due to liver
necrosis, but in rats the LD50 is about 1000 mg/kg with little liver damage evident.
Nevertheless, use of the LD50 test is widespread not only as a measure of chemical toxicity, but to:
classify substances for regulatory purposes including safe transportation and labelingprovide information for treatment of acute intoxications standardize certain biological productsset dose levels for subsequent toxicity studiesprovide comparative information on dose response curvesprovide data for evaluation and validation of alternative test methods.