Median Lethal Dose Definition

The median lethal dose, or LD50, is a term used in toxicology as a measurement of a lethal dose of a substance (e.g., pathogen, medication, toxic substance, etc.). Specifically, the LD50 represents the dose at which a substance is lethal for 50% of tested subjects. This value is then used as an indicator of a substance’s relative toxicity. Thus, a substance with a high LD50 would have a low toxicity, while a substance with a low LD50 would have a high toxicity. This information is highly useful when designing regulations. One example is the use of the LD50 for radiation exposure to determine safe limits for workers at a nuclear power plant (pictured below). Thus, such information is critical for maintaining the safety of workers and ensuring that the level of radiation exposure is maintained well below that of the LD50.

Radiation Doses and Regulatory Limits

Median Lethal Dose Limitations

While the LD50 is a useful indicator of toxicity, there are also some inherent limitations associated with this method. Such drawbacks include:

  1. Variability between testing facilities, which can produce unreliable results.
  2. Genetic variability in the tested subjects. Thus, depending on the sample population, the LD50 may vary.
  3. The route of delivery (e.g., intravenous, intermuscular, subcutaneous, etc.).
  4. Animal species used for testing. For example, a substance that is innocuous in one species could be lethal in another (e.g., chocolate is lethal to dogs but safe for humans).

Quiz

1. A substance with a low LD50 is considered to be: (Multiple Choice)
A. Lethal at a lower dose
B. Lethal at a higher dose
C. Highly toxic
D. Minimally toxic

Answer to Question #1
A and C are correct. Since the LD50 measures the dose which is lethal to 50% of tested subjects, the lower the lethal dose, the greater the toxicity of the substance.

References

  • Crome, P. (1993). The toxicity of drugs used for suicide. Acta Psychiatr Scand. 371:33-7.
  • MacVittie et al. (2015). The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship. Health Phys. 109(5):342-66.
  • Yagmur et al. (2015). Determination of the Median Lethal Dose and Electrophoretic Pattern of Hottentotta saulcyi (Scorpiones, Buthidae) Scorpion Venom. J Arthropod Borne Dis. 9(2):238-45.