Genotoxicity

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As genotoxicity refers to the effects of chemical substances , the changes in the genetic material ( deoxyribonucleic acid ) of cells trigger. This term is a purely experimental way of looking at how substances behave in experiments ( in vitro ) . Substances which have been tested positive for genotoxicity do not necessarily have to be mutagenic or carcinogenic . The determination of the genotoxicity of a substance is part of the toxicity determination of a substance.

As part of drug development, pharmaceutical companies are required to carry out a risk assessment of the occurrence of potentially genotoxic impurities in the drug. Such impurities can originate from the synthesis of the medicinal substance or, under certain circumstances, also arise during further processing of the medicinal substance. The risk assessment must be submitted to the competent authority with the application for approval of a medicinal product; in the case of medicinal products that have already been approved, a risk assessment may also be necessary in some cases. With the exception of substances from a few groups of substances known to be highly carcinogenic ( N- nitrosamines , aflatoxins , azoxy compounds ), a daily intake of a maximum of 1.5 micrograms of a potentially genotoxic compound is generally considered to be a toxicologically acceptable risk. This value, derived from animal experiments, carries the risk that one in 100,000 treated patients will develop cancer in the course of their life (assuming a lifespan of 70 years). If specific pharmacological-toxicological data are known for a substance occurring as an impurity, this may also justify higher exposure . The maximum allowable amount of such substances, which the patient by the drug intake exposing (daily permitted daily exposure ; English: permitted daily exposure PDE) is then calculated on the basis of that concentration limits to which in animal experiments no harmful effects can be seen, the so-called NOAEL ( no observed adverse effect level ).

The Ames test is used to identify and quantify mutagenic substances .

See also

Individual evidence

  1. ↑ For the definition see: Glossary ( Memento of July 18, 2013 in the Internet Archive ) Source: FDA (USA).
  2. ↑ Guideline on the Limits of Genotoxic Impurities. (PDF; 57 kB), European Medicines Agency June 28, 2006.