No-observed-adverse-effect level

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 of the tested protocol. In drug development, the NOAEL of a new drug is assessed in laboratory animals, such as mice, prior to initiation of human trials in order to establish a safe clinical starting dose in humans. The OECD publishes guidelines for Preclinical Safety Assessments, in order to help scientists discover the NOAEL.[1]

Synopsis

Some adverse effects in the exposed population when compared to its appropriate control might include alteration of morphology, functional capacity, growth, development or life span. The NOAEL is determined or proposed by qualified personnel, often a pharmacologist or a toxicologist.

The 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 are 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.[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]

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

Synonyms

The NOAEL is also known as NOEL (no-observed-effect level) as well as NEC (no-effect concentration) and NOEC (no-observed-effect concentration).[7][8]

US EPA definition

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.'[9]

See also

References
  1. Deshpande, P.; Mohan, V.; Ingavale, D.; Mane, J.; Pore, M.; Thakurdesai Phd, P. (2017). "Preclinical Safety Assessment of Furostanol Glycoside-Based Standardized Fenugreek Seed Extract in Laboratory Rats". Journal of Dietary Supplements. 14 (5): 521–541. doi:10.1080/19390211.2016.1272659. PMID 28156165. S2CID 25932512.
  2. 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.
  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. 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 (Submitted manuscript). 26 (1): 115–23. CiteSeerX 10.1.1.555.7381. doi:10.1111/j.1539-6924.2006.00722.x. PMID 16492185. S2CID 24406585.
  7. "ECOLOGICAL RISK ASSESSMENT AND ASSESSMENT OF EFFECTS ON NONHUMAN BIOTA TECHNICAL SUPPORT DOCUMENT NEW NUCLEAR – DARLINGTON" (PDF). Vol. NK054-REP-07730-00022 Rev 000. September 2009.
  8. "Northwest Area Noxious Weed Control Program: Environmental Impact Statement". United States. Bureau of Land Management. December 1985.
  9. Registries, EPA, OEI, SOR, System Of. "Terms & Acronyms".{{cite web}}: CS1 maint: multiple names: authors list (link)
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