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Why is LD50 so important for toxicity assessment?
In toxicology, the unit commonly used to evaluate the toxicity of substances is the median lethal dose (LD50), whose name is derived from the English "lethal dose, 50%". This metric measures the dose that would kill half of the subjects in a given test. This value is usually expressed in milligrams per kilogram of body weight, such as "mg/kg." Therefore, the lower the LD50 value, the more toxic the substance is.
Based on the results of the LD50 test, this unit is able to effectively compare the acute toxicity of different substances.
The concept of LD50 was first proposed by John William Trevan in 1927. This test is usually done on animals such as mice. With the advancement of technology, many organizations have begun to seek alternative methods without animal testing. For example, in 2011, the U.S. Food and Drug Administration (FDA) approved an alternative testing method for the cosmetic drug Botox.
The way to measure LD50 is usually based on the substance and environment used. For example, for toxic substances in water, it is expressed in terms of its environmental concentration, that is, LC50 (lethal concentration per cubic meter or per liter). Although the 50% lethal benchmark of LD50 avoids the ambiguity of extreme measurements, it does not mean that all individuals will die at this dose - some individuals may die at a lower dose or at a higher dose. dose to survive.
Therefore, LD50 is not only a measure of the toxicity of a substance, but also related to many factors such as testing methods, animal species, and testing environment.
Although LD50 provides an objective indicator of toxicity, it also has its limitations. For example, differences in toxicity between species are often significant. Some substances may be relatively safe in humans but extremely toxic in other species. For example, chocolate is not dangerous to humans, but it is deadly to many animals, such as dogs and cats.
Aside from LD50, we also need to consider other toxicity indicators, such as LD1 (the dose that is 1% lethal) and LD99 (the dose that is 99% lethal), which can be used for toxicity assessment in specific situations. In addition, the effects of different routes of administration can also affect the lethal dose. Oral administration is generally less toxic than intravenous administration, so the LD50 data should be labeled with the mode of administration, such as “LD50 i.v.”
The spectrum of toxicity is very broad. A substance like botulinum toxin has an LD50 value of just 1 ng/kg, while water has an LD50 of over 90 g/kg, meaning the difference in toxicity is over 100 billion times greater. The huge difference in these values suggests that we should have more precise standards when comparing the toxicity of substances. For example, many scholars have begun to use the therapeutic index, that is, the ratio of LD50 to effective dose (ED50), to more reasonably compare the safety of different substances.
Thinking about the combination of ethics and science makes the LD50 test no longer the only evaluation standard, and more humane evaluation methods can be explored in the future.
In the field of biological warfare, the infectious dose (ID50) is also of concern because it describes how much exposure to a pathogen must occur to cause infection. The complexity of this measurement further challenges the way we are accustomed to measuring toxicity. At the same time, LD50 results may vary greatly between different laboratories, which is related to the environmental factors of the test, the genetic characteristics of the sample, and the species of the animal.
So taken together, although LD50 is an important toxicity indicator, its results do not always fully reflect the actual radiation of a certain substance. So, in the face of more and more new substances and their potential risks, how should we balance the contradiction between scientific development and moral ethics?
