The no-observed-adverse-effect level (NOAEL) denotes the level of exposure of an

organism An organism is any life, living thing that functions as an individual. Such a definition raises more problems than it solves, not least because the concept of an individual is also difficult. Many criteria, few of them widely accepted, have be ...

, found by

experiment An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs whe ...

observation Observation in the natural sciences is an act or instance of noticing or perceiving and the acquisition of information from a primary source. In living beings, observation employs the senses. In science, observation can also involve the percep ...

, 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 A mouse (: mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

, prior to initiation of human trials in order to establish a safe clinical starting dose in humans. The

OECD The Organisation for Economic Co-operation and Development (OECD; , OCDE) is an international organization, intergovernmental organization with 38 member countries, founded in 1961 to stimulate economic progress and international trade, wor ...

publishes guidelines for Preclinical Safety Assessments, in order to help scientists discover the NOAEL.

Synopsis

Some adverse effects in the exposed population when compared to its appropriate control might include alteration of

morphology Morphology, from the Greek and meaning "study of shape", may refer to: Disciplines *Morphology (archaeology), study of the shapes or forms of artifacts *Morphology (astronomy), study of the shape of astronomical objects such as nebulae, galaxies, ...

, functional capacity, growth, development or life span. The NOAEL is determined or proposed by qualified personnel, often a

pharmacologist Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur between ...

or a

toxicologist Toxicology is a scientific discipline (academia), discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnos ...

. 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 In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually used ...

. 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. In

toxicology Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating ex ...

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.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. . The NOAEL level may be used in the process of establishing a dose-response relationship, a fundamental step in most

risk assessment Risk assessment is a process for identifying hazards, potential (future) events which may negatively impact on individuals, assets, and/or the environment because of those hazards, their likelihood and consequences, and actions which can mitigate ...

methodologies.

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).

US EPA definition

The

United States Environmental Protection Agency The Environmental Protection Agency (EPA) is an independent agency of the United States government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it began operation on De ...

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. 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.'

References

Concentration indicators Environmental policy in the United States Food law Food safety Food and Drug Administration Toxicology United States Environmental Protection Agency {{med-toxic-stub

Synopsis

Synonyms

US EPA definition

See also

References