NOAEL

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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.

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  1. ↑ Wolfgang Dekant, S. Vamvakas, H. Popa-Henning: Toxikologie. An introduction for chemists, biologists, and pharmacists. 2004, ISBN 978-3-8274-1452-6 .
  2. ↑ FDA Guideline on Starting Dose in Clinical Studies, July 2005
  3. ↑ 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
  4. ↑ Significance, use and derivation of MAK values ​​(MAK and BAT value list 2014) , pdf
  5. ↑ MAK documentation for 2-ethylhexanol supplement to the MAK documentation 2012, pdf