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Threshold dose is a dose of drug barely adequate to produce a biological effect in an animal. In dose-response assessment, the term ‘threshold dose’ is refined into several terminologies, such as NOEL, NOAEL, and LOAEL.
The lowest-observed-adverse-effect level (LOAEL), or the lowest-observed-adverse-effect concentration (LOAEC), is the lowest concentration or amount of a substance found by experiment or observation that causes an adverse alteration of morphology, function, capacity, growth, development, or lifespan of a target organism distinguished from normal organisms of the same species under defined ...
The United States Environmental Protection Agency defines NOAEL as 'an exposure level at which there are no statistically or biologically significant increases in the frequency or severity of adverse effects between the exposed population and its appropriate control; some effects may be produced at this level, but they are not considered as adverse, or as precursors to adverse effects. [5]
This level was thus identified at the lowest observed adverse effect level (LOAEL). A NOAEL of 0.5 mg/kg was estimated by dividing the LOAEL by a three-fold uncertainty factor. The NOAEL was then divided by the standard 10-fold inter- and 10-fold intraspecies uncertainty factors to arrive at the RfD of 0.005 mg/kg/day.
A threshold model or linear no-threshold model may be more appropriate, depending on the circumstances. A recent critique of these models as they apply to endocrine disruptors argues for a substantial revision of testing and toxicological models at low doses because of observed non- monotonicity , i.e. U-shaped dose/response curves.
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A proposed alternative is the use of so-called ECx – the concentration(s) showing x% effect (e.g. an EC 50 in a survival experiment indicates the concentration where 50% of the test animals would die in that experiment).
Florida has the country’s highest number of exonerations at 30 and will likely soon have the lowest jury threshold for a death sentence at 8-4.
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