What is the difference between ld50 and ed50

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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. Dose Estimates Dose-response curves are used to derive dose estimates of chemical substances. This difference occurs because giving chemicals to animals by mouth is much easier and less expensive than other techniques.

However, the results of oral studies are important for drug studies, food poisonings, and accidental domestic poisonings. Oral occupational poisonings might occur by contamination of food or cigarettes from unwashed hands, and by accidental swallowing.

In general, the smaller the LD 50 value, the more toxic the chemical is. The opposite is also true: the larger the LD 50 value, the lower the toxicity. The LD 50 gives a measure of the immediate or acute toxicity of a chemical in the strain, sex, and age group of a particular animal species being tested. Changing any of these variables e. The LD 50 test was neither designed nor intended to give information on long-term exposure effects of a chemical.

Once you have an LD 50 value, it can be compared to other values by using a toxicity scale. Confusion sometimes occurs because several different toxicity scales are in use. These tables differ in both the numerical rating given to each class and the terms used to describe each class. It is important to reference the scale you used when classifying a compound.

It is also important to know that the actual LD 50 value may be different for a given chemical depending on the route of exposure e. For example, some LD 50 s for dichlorvos, an insecticide commonly used in household pesticide strips, are listed below:.

Differences in the LD 50 toxicity ratings reflect the different routes of exposure. The toxicity rating can be different for different animals.

The data above show that dichlorvos is much less toxic by ingestion in pigs or dogs than in rats. Using Table 1, dichlorvos is moderately toxic when swallowed oral LD 50 and extremely toxic when breathed inhalation LC 50 in the rat.

Using Table 2, dichlorvos is considered very toxic when swallowed oral LD 50 by a rat. In general, if the immediate toxicity is similar in all of the different animals tested, the degree of immediate toxicity will probably be similar for humans. When the LD 50 values are different for various animal species, one has to make approximations and assumptions when estimating the probable lethal dose for man.

Tables 1 and 2 have a column for estimated lethal doses in man. Special calculations are used when translating animal LD 50 values to possible lethal dose values for humans. Safety factors of 10, or are usually included in such calculations to allow for the variability between individuals and how they react to a chemical, and for the uncertainties of experiment test results.

The LD 50 is only one source of toxicity information. For a more thorough picture of the immediate or acute toxicity of a chemical, additional information should be considered such as the lowest dose that causes a toxic effect TDLO , the rate of recovery from a toxic effect, and the possibility that exposure to some mixtures may result in increasing the toxic effect of an individual chemical.

The literature seems to use the terms "therapeutic index" and "therapeutic ratio" in a way which might suggest that they are synonymous, even though there is an SAQ in the local anaesthetic primary exam which asked the candidates to interpret each term separately. Fortunately, CICM examiners have not yet plagiarised this question. 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?

Ten percent? Some related terms become confluent with the therapeutic window in the literature.