The no-observed-adverse-effect level (NOAEL) denotes the level of exposure of an
organism
In biology, an organism () is any life, living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms are classified by taxonomy (biology), taxonomy into groups such as Multicellular o ...
, 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 wh ...
or
observation
Observation is the active acquisition of information from a primary source. In living beings, observation employs the senses. In science, observation can also involve the perception and recording of data via the use of scientific instruments. Th ...
, 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; french: Organisation de coopération et de développement économiques, ''OCDE'') is an intergovernmental organisation with 38 member countries, founded in 1961 to stimulate ...
publishes guidelines for
Preclinical Safety Assessment
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phase ...
s, 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
Growth may refer to:
Biology
* Auxology, the study of all aspects of human physical growth
* Bacterial growth
* Cell growth
* Growth hormone, a peptide hormone that stimulates growth
* Human development (biology)
* Plant growth
* Secondary grow ...
, development or life span. The NOAEL is determined or proposed by qualified personnel, often a
pharmacologist
Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemic ...
or a
toxicologist
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 ...
.
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, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
. 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 expos ...
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
Broadly speaking, a risk assessment is the combined effort of:
# identifying and analyzing potential (future) events that may negatively impact individuals, assets, and/or the environment (i.e. hazard analysis); and
# making judgments "on the ...
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 executive agency of the United States federal government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it ...
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.'
See also
*
Lowest-observed-adverse-effect level
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, ...
*
Measures of pollutant concentration Measures of pollutant concentration are used to determine risk assessment in public health.
Industry is continually synthesizing new chemicals, the regulation of which requires evaluation of the potential danger for human health and the environm ...
References
Concentration indicators
Environmental policy in the United States
Food law
Food safety
Food and Drug Administration
Toxicology
United States Environmental Protection Agency
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