NOAEL (engl. For N o O bserved A dverse E ffect L evel) is a toxicological endpoint in the toxicity determination .
The NOAEL corresponds to the highest dose or exposure concentration of a substance in subchronic or chronic studies in which no significantly increased harmful, treatment-related findings in morphology , function, growth, development or lifespan are observed. In contrast, the NOEL describes the dose at which no effect is observed.
The NOAEL for a substance always relates to a specific biological measurement method with a specific form of application and a specific animal species or a specific cell culture system, so a substance can have different NOAEL values in different processes. Many published NOAEL values refer to subchronic toxicity studies with oral administration in rodents.
The problem with the type of NOAEL determination is that normally only one single value from a given dose series is used in the NOAEL determination. With other, more complex methods such as the benchmark procedure , all values of the entire dose-effect curve are included using statistical methods.
The NOAEL is in pre-clinical pharmaceutical research , since usually starting from the NOAEL of the most sensitive species an important toxicological endpoint via allometric the maximum recommended starting dose scaling and the inclusion of a safety factor (Maximum Recommended Starting Dose, MrsD) for the first application on humans in clinical trials is determined .
The Committee for Hazardous Substances and the MAK Commission of the DFG base their derivation of occupational exposure limits ( AGW ) or MAK values on the NOAEL "for the most sensitive endpoint with health relevance" of a substance. Such a critical endpoint can e.g. B. in the case of the solvent 2-ethylhexanol, the eyelid closing frequency as a physiological marker of sensory irritation.
- Wolfgang Dekant, S. Vamvakas, H. Popa-Henning: Toxikologie. An introduction for chemists, biologists, and pharmacists. 2004, ISBN 978-3-8274-1452-6 .
- FDA Guideline on Starting Dose in Clinical Studies, July 2005
- BekGS 901 Criteria for the Derivation of Occupational Exposure Limits ( Committee for Hazardous Substances ), GMBL 2010 No. 32, pp. 691–696 (May 21, 2010), pdf
- Significance, use and derivation of MAK values (MAK and BAT value list 2014) , pdf
- MAK documentation for 2-ethylhexanol supplement to the MAK documentation 2012, pdf