22.4: The Lethal Dose (2024)

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    Learning Objectives
    • Describe the LD50 value and its limitations.
    • Know the LD50 value of various substances.

    The LD50 is a standardized measure for expressing and comparing the toxicity of chemicals. The LD50 is the dose that kills half (50%) of the animals tested (LD = "lethal dose"). The animals are usually rats or mice, although rabbits, guinea pigs, hamsters, and so on are sometimes used. In all these tests, the dose must be calculated relative to the size of the animal. The most common units are milligrams of chemical per kilogram of test animal (mg/kg or ppm). (Table \(\PageIndex{1}\)) provides examples of LD50 values for various substances.

    As a measure of toxicity, lethal dose is somewhat unreliable and results may vary greatly between testing facilities due to factors such as the genetic characteristics of the sample population, animal species tested, environmental factors and mode of administration.

    There can be wide variability between species as well; what is relatively safe for rats may very well be extremely toxic for humans (cf. paracetamol toxicity), and vice versa. For example, chocolate, comparatively harmless to humans, is known to be toxic to many animals. When used to test venom from venomous creatures, such as snakes, LD50 results may be misleading due to the physiological differences between mice, rats, and humans. Many venomous snakes are specialized predators of mice, and their venom may be adapted specifically to incapacitate mice; and mongooses may be exceptionally resistant. While most mammals have a very similar physiology, LD50 results may or may not have equal bearing upon every mammal species, including humans.

    Table \(\PageIndex{1}\): LD50 Values of Various Substances. Source: Wikipedia
    Substance Animal Route LD50 (mg/kg)
    Water rat, oral 90,000
    Sucrose (table sugar) rat, oral 29,700
    Glucose (blood sugar) rat, oral 25,800
    Monosodium glutamate (MSG) rat, oral 16,600
    Cadmium sulfide rat, oral 7,080
    Ethanol (grain alcohol) rat, oral 7,060
    Methanol human, oral 810
    Sodium chloride (table salt) rat, oral 3,000
    Metallic arsenic rat, oral 763
    Arsenic trisulfide rat, oral 185-6400
    Sodium cyanide rat, oral 6.4
    Hydrogen cyanide mouse, oral 3.7
    Ibuprofen rat, oral 636
    Aspirin rat, oral 200
    Caffeine rat, oral 192
    Cocaine mouse, oral 96
    Nicotine rat, oral 50
    Heroin (diamorphine) mouse, intravenous 21.8
    Methamphetamine rat, intraperitoneal 57
    Mercury(II) chloride rat, oral 1
    Strychnine human, oral 1-2
    Sarin mouse, subcutaneous injection 172 microgram/kg
    Ricin (from castor oil plant) rat, oral 20-30
    Botulinum toxin (Botox) human, oral injection, inhalation 1 ng/kg

    (Table \(\PageIndex{2}\)) gives the LD50 values of some insecticides. In each case, the chemical was fed to laboratory rats. Note that the lower the LD50, the more toxic the chemical. Even adjusting for the test animal's weight, the LD50 for one species is often quite different from that for another. Thus any LD50 value gives only a rough estimate of the risk to humans. The way in which the chemical is administered also has a marked effect on LD50 values. The chemical may be fed, injected, applied to the animal's skin, etc., and each method usually generates a different LD50.

    Table \(\PageIndex{2}\): LD50 Values of Pesticides.
    Chemical Category Oral LD50 in Rats (mg/kg)
    Aldicarb ("Temik") Carbamate 1
    Carbaryl ("Sevin") Carbamate 307
    DDT Chlorinated hydrocarbon 87
    Dieldrin Chlorinated hydrocarbon 40
    Diflubenzuron ("Dimilin") Chitin inhibitor 10,000
    Malathion Organophosphate 885
    Methoprene JH mimic 34,600
    Methoxychlor Chlorinated hydrocarbon 5,000
    Parathion Organophosphate 3
    Piperonyl butoxide Synergist 7,500
    Pyrethrin Plant extract 200
    Rotenone Plant extract 60

    Summary

    • The LD50 is the dose that kills half (50%) of the animals tested (LD = "lethal dose"). It is a standardized measure for expressing and comparing the toxicity of chemicals.
    • LD50 values are given for common drugs (e.g. ibuprofen and aspirin), common household ingredients including water, table sugar (sucrose), salt (sodium chloride), insecticides (e.g. DDT and pyrethrin), and harmful drugs (e.g. cocaine and heroin).

    Contributors and Attributions

    22.4: The Lethal Dose (2024)
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