What is ld50 and ed50
Ayesha Dudekula. Marjun Lagbang. DRx Mishra. Arun Suresh. Show More. Views Total views. Actions Shares. No notes for slide. Dose is the amount of a substance administered at one time.
Other parameters are needed to characterize the exposure to xenobiotics. The most important are the number of doses frequency total time period of the treatment. Xenobiotics can travel into the body through the skin, eyes, lungs, and digestive tract. Exposure to a xenobiotic can occur in any environment where a substance can enter the: Skin through dermal absorption air and water.
Respiratory tract through inhalation. Digestive tract through ingestion. Age and body size usually are connected, particularly in children. This relationship is important because a person's body size can affect the burden that a substance has on it. For example, a mg dose of acetaminophen is typical for adults but it would be toxic to young children.
One way to compare the effectiveness of a dose and its toxicity is to assess the amount of a substance administered with respect to body weight. Another important aspect is the time over which a dose is administered. That is especially important for exposures that occur over several days or that are chronic. In Katzung, the therapeutic index is defined as. The official IUPC documents don't seem to have any sort of gospel answer, and every piece of literature seems to have some arbitrary way of defining this concept.
These pharmacologists' authority as experts Wiley gave them a chapter from their Encyclopedia of Clinical T rials suggests that one should at least be vaguely aware of how they define this concept:.
All of these variants are probably valid on some level, but the exam-going CICM trainee would probably be better off treating Katzung as the definitive official source for this sort of thing. As such, the von Zastrow definition is used for the purposes of the diagrams here. For real-life bedside clinical purposes, this therapeutic index concept leaves much to be desired. In contrast, Birkett called this a therapeutic range , and describes it using an example rather than offering any exam-worthy definition.
The therapeutic range, he says, is the range of drug concentrations " which gives a therapeutic effect The concept of the "therapeutic window" is perhaps more reasonable and flexible than the therapeutic index. Again, it has no formal definition, but most authors describe it as the dose range over which drug is effective and relatively non-toxic in most of the population.
The von Zastrow definition quoted above is actually not seen very often in the literature because it fails to define what an acceptable minimum is one percent of the population? The units of LD50 and LC50 are listed as follows:. No Observed Adverse Effect Level NOAEL is the highest exposure level at which there are no biologically significant increases in the frequency or severity of adverse effect between the exposed population and its appropriate control; some effects may be produced at this level, but they are not considered adverse effects.
NOAEL are typically obtained from repeated dose toxicity studies 28d repeated dose toxicity study, 90d repeated dose toxicity study or chronic toxicity and reproductive toxicity studies. NOAELs are very important. Lowest Observed Adverse Effect Level LOAEL is the lowest exposure level at which there are biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control group. Sometimes, only LOAEL can be obtained from repeated dose toxicity studies 28d repeated dose toxicity study, 90d repeated dose toxicity study or chronic toxicity and reproductive toxicity studies due to study design.
However, higher assessment factors need to be applied. It is generally recognized that some chemicals non-threshold carcinogens will cause carcinogenic risks even at the smallest exposure concentration. Thus T25 and BMD10 are used.
Since different chemicals cause different toxic effects, comparing the toxicity of one with another is hard. We could measure the amount of a chemical that causes kidney damage, for example, but not all chemicals will damage the kidney. We could say that nerve damage is observed when 10 grams of chemical A is administered, and kidney damage is observed when 10 grams of chemical B is administered. However, this information does not tell us if A or B is more toxic because we do not know which damage is more critical or harmful.
Therefore, to compare the toxic potency or intensity of different chemicals, researchers must measure the same effect. One way is to carry out lethality testing the LD 50 tests by measuring how much of a chemical is required to cause death.
This type of test is also referred to as a "quantal" test because it is measures an effect that "occurs" or "does not occur". In , J. Trevan attempted to find a way to estimate the relative poisoning potency of drugs and medicines used at that time. He developed the LD 50 test because the use of death as a "target" allows for comparisons between chemicals that poison the body in very different ways.
Since Trevan's early work, other scientists have developed different approaches for more direct, faster methods of determining the LD Acute toxicity is the ability of a chemical to cause ill effects relatively soon after one oral administration or a 4-hour exposure to a chemical in air. In nearly all cases, LD 50 tests are performed using a pure form of the chemical. Mixtures are rarely studied. The chemical may be given to the animals by mouth oral ; by applying on the skin dermal ; by injection at sites such as the blood veins i.
Researchers can do the test with any animal species but they use rats or mice most often. Other species include dogs, hamsters, cats, guinea-pigs, rabbits, and monkeys. In each case, the LD 50 value is expressed as the weight of chemical administered per kilogram body weight of the animal and it states the test animal used and route of exposure or administration; e. If the lethal effects from breathing a compound are to be tested, the chemical usually a gas or vapour is first mixed in a known concentration in a special air chamber where the test animals will be placed.
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