No-observed-adverse-effect level

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In non-clinical assessment NOAEL (no-observed-adverse-effect level) plays a pivotal role. It is determined or proposed by qualified personnel (pharmacologist, 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". 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] 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 (e.g. alteration of morphology, functional capacity, growth, development or life span) increase in the frequency or severity of any adverse effects in the exposed population when compared to its appropriate control.[2][3]

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.[4][5][6]

This level may be used in the process of establishing a dose-response relationship,[7] a fundamental step in most risk assessment methodologies.[6]

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.[6] 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.'[8]

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References[edit]

  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. ^ "Seton Resource Center". 
  3. ^ "IUPAC glossary of terms used in toxicology - terms starting with N". Environmental Health and Toxicology Specialized Information Services. U.S. Department of Health & Human Services. Retrieved February 18, 2013.  based upon Duffus, J. H.; Nordberg, M.; Templeton, D. M. (2007). "Glossary of terms used in toxicology, 2nd edition (IUPAC Recommendations 2007)". Pure and Applied Chemistry. 79 (7): 1153. doi:10.1351/pac200779071153. 
  4. ^ 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.
  5. ^ "Food Safety and Risk Assessment website". Glasgow Caledonian University. 
  6. ^ 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 : RTP. 42 (3): 265–74. doi:10.1016/j.yrtph.2005.05.004. PMID 15979222. 
  7. ^ 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.". Risk analysis : an official publication of the Society for Risk Analysis. 26 (1): 115–23. doi:10.1111/j.1539-6924.2006.00722.x. PMID 16492185. 
  8. ^ Registries, EPA, OEI, SOR, System Of. "Terms & Acronyms".