Lethal Dose 50
NOEL (no-observed-effect-level)
Acceptable Daily Intake (ADI)
Dose Response Curve
Lethal Dose 50
In toxicology, the LD50 (abbreviation for "Lethal Dose, 50%") or median lethal dose of a toxic substance or radiation is the dose required to kill half the members of a tested population. LD50 figures are frequently used as a general indicator of a substance's acute toxicity. The test was created by J.W. Trevan in 1927[1] but is now being phased out in favor of the Fixed Dose Procedure.
http://en.wikipedia.org/wiki/LD50
Some examples of lethal dose 50:NaCl 40g/kg
Caffeine 200mg/kg
Tetrodoxin 25 microgram/kg
Botulotoxin 100ng/kg
NOEL (no-observed-effect-level)
The greatest concentration or amount of a substance. found by experiment or observation, that causes no alterations of morphology, functional capacity, growth, development or lifespan of target organisms distinguishable from those observed in normal (control) organisms of the same species and strain under the same defined conditions of exposure.
Derived from: http://www.iupac.org/goldbook/N04209.pdf
Acceptable Daily Intake (ADI)
What is an ADI?
The Acceptable Daily Intake is defined as the amount of a food additive that can be ingested daily in the diet without appreciable risk on the basis of all facts known at the time. "Without appreciable risk" refers to the practical certainty that injury will not result, even after a lifetime of experience.
Who determines the ADI?
Basically, scientific expert committees that advise national and international regulatory authorities. The concept was first introduced in 1957 by the Council of Europe and later the Joint Expert Committee on Food Additives (JECFA) of the United Nations Food and Agricultural Organization and World Health Organization. Since then, many other committees and governments have adopted the ADI concept, including the U.S. Food and Drug Administration.
What is the purpose of an ADI?
The ADI is a practical approach to determining the safety of food additives and is a means of achieving some uniformity of approach in regulatory control. It serves to ensure that the actual human intake of a substance is well below toxic levels.How is the ADI determined?
It is based on a scientific review of all available toxicological data on a specific additive D both observations in humans and tests in animals. Laboratory tests in animals determine the maximum dietary level of the additive that is without demonstrable toxic effects, i.e., the "No Observable Effect Level" (NOEL). This level is then extrapolated to man by dividing the no-effect level by a large factor, often 100. This results in a substantially lower level for man, and thus a large margin of safety.
Why is a safety margin necessary?
For two main reasons. First, the NOEL is determined in animals not humans. It is therefore prudent to adjust for possible differences by assuming that man is more sensitive than the most sensitive test animal. Second, the reliability of toxicity tests is limited by the number of animals tested. Such tests cannot represent the diversity of the human population, subgroups of which may show different sensitivities (e.g., children, the old, the ill). Once again it is prudent to adjust for these differences.
What safety margin is normally tested?
Traditionally a safety factor of 100 has been used, based on a 10-fold factor allowed for each of the above reasons. The 100-fold factor (10x10) is not a constant, however, and may be varied according to the characteristics of the additive, the extent of the toxicology data and the conditions of use.
How exact a value is an ADI?
The ADI is an estimated value based on experimental data determined over a lifetime of exposure in animals and derived with a somewhat arbitrary safety factor. It should be regarded as a biological guide to be applied with flexibility, rather than an absolute unalterable constant.
Is it correct then, than an ADI does not represent a toxic dose?
Yes. The ADI is an acceptable level D as the name implies. It is not a toxic dose because of the large safety factor which has been used. Even levels marginally greater than the ADI do not necessarily reflect toxic levels. They simply lessen the safety factor applied.
Is it acceptable for an individual to exceed the ADI on any given day?
Yes, because all you do is slightly reduce the safety margin. For example, if one day you consume even twice the ADI, all you are doing is reducing the safety margin from 100 to 50 for that single day.
http://www.ific.org/publications/qa/adiqa.cfm
Dose Response Curve
http://www.elmhurst.edu/~chm/onlcourse/chm110/outlines/doserespon.html
A dose-response curve is a simple X-Y graph relating the magnitude of a stressor (e.g. concentration of a pollutant, amount of a drug, temperature, intensity of radiation) to the response of the receptor (e.g. organism under study). The response is usually death (mortality), but other effects (or endpoints) can be studied.
The measured dose (usually in milligrams, micrograms, or grams per kilogram of body-weight) is generally plotted on the X axis and the response is plotted on the Y axis. Commonly, it is the logarithm of the dose that is plotted on the X axis, and in such cases the curve is typically sigmoidal, with the steepest portion in the middle.
The first point along the graph where a response above zero is reached is usually referred to as a threshold-dose. For most beneficial or recreational drugs, the desired effects are found at doses slightly greater than the threshold dose. At higher doses still, undesired side effects appear and grow stronger as the dose increases. The stronger a particular substance is, the steeper this curve will be. In quantitative situations, the Y-axis usually is designated by percentages, which refer to the percentage of users registering a standard response (which is often death, when the 50% mark refers to LD50). Such a curve is referred to as a quantal dose response curve, destinguishing it from a graded dose response curve, where response is continuous.
Problems exist regarding non-linear relationships between dose and response, thresholds reached and 'all-or-nothing' responses. These inconsistencies can challenge the validity of judging causality solely by the strength or presence of a dose-response relationship.
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