No-observed-adverse-effect level

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The no-observed-adverse-effect level (NOAEL) denotes the level of exposure of an organism, found by experiment or observation, at which there is no biologically or statistically significant increase in the frequency or severity of any adverse effects (e.g. alteration of morphology, functional capacity, growth, development or life span) in the exposed population when compared to its appropriate control. In non-clinical assessment, NOAEL plays a pivotal role. It is determined or proposed by qualified personnel (pharmacologist or toxicologist) depending on the study, drug indications and its pharmacological therapeutics side/adverse effects. NOAEL could be defined as "the highest experimental point that is without adverse effect," meaning that under laboratory conditions, it is the level where there is no side-effects. It either does not provide the effects of drug with respect to duration and dose, or it does not address the interpretation of risk based on toxicologically relevant effects.[1] To say detail the NOAEL does not describe the duration, dose, or risk involved and is therefore more of a threshold marker. This is also known as highest no-effect level, or HNEL.[2]

In toxicology it is specifically the highest tested dose or concentration of a substance (i.e. a drug or chemical) or agent (e.g. radiation), at which no such adverse effect is found in exposed test organisms where higher doses or concentrations resulted in an adverse effect.[3][4][5]

This level may be used in the process of establishing a dose-response relationship,[6] a fundamental step in most risk assessment methodologies.[5]

In drug development, NOAEL of a new drug is assessed in laboratory animals drugs prior to initiation of clinical trials to establish a safe clinical starting dose in human trials.

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] In an experiment with several NOAELs, the regulatory focus is primarily on the highest one, leading to the common usage of the term NOAEL as the highest exposure without adverse effects.'[7]

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  1. ^ Engelhardt JA, Dorato MA (August 2005). "The no-observed-adverse-effect-level in drug safety evaluations: Use, issues, and definition(s)". Regul Toxicol Pharmacol. 42 (3): 265–274. doi:10.1016/j.yrtph.2005.05.004. PMID 15979222.
  2. ^ Marie, S.; Piggott, J.R., eds. (July 2013). Handbook of Sweeteners (1991 ed.). New York, New York, USA: Springer. p. 279. ISBN 978-1475753820. Archived from the original on February 5, 2018. Retrieved February 5, 2018.
  3. ^ Faustman, E.M., Omenn, G.S. Risk assessment. (2001) In: C. D. Klaassen (ed.): Casarett & Doull's Toxicology, 6. ed., McGraw-Hill, New York, pp. 92–94. ISBN 0-07-134721-6.
  4. ^ "Food Safety and Risk Assessment website". Glasgow Caledonian University. Archived from the original on 2006-09-28.
  5. ^ a b c Dorato, MA; Engelhardt, JA (August 2005). "The no-observed-adverse-effect-level in drug safety evaluations: use, issues, and definition(s)". Regulatory Toxicology and Pharmacology. 42 (3): 265–74. doi:10.1016/j.yrtph.2005.05.004. PMID 15979222.
  6. ^ Dakeishi, M; Murata, K; Tamura, A; Iwata, T (February 2006). "Relation between benchmark dose and no-observed-adverse-effect level in clinical research: Effects of daily alcohol intake on blood pressure in Japanese salesmen" (PDF). Risk Analysis : An Official Publication of the Society for Risk Analysis (Submitted manuscript). 26 (1): 115–23. CiteSeerX doi:10.1111/j.1539-6924.2006.00722.x. PMID 16492185.
  7. ^ Registries, EPA, OEI, SOR, System Of. "Terms & Acronyms".