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2.4.1.1 Question 1.1
Оглавление| Question | Answer |
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| Note 1 provides general guidance on the relationship of ICH M7 with ICH Q3A and Q3B. The use of both “mutagenic potential” and “genotoxic potential” in Note 1 is confusing. Are these terms considered interchangeable? | No. The terms “mutagenic potential” and “genotoxic potential” are not interchangeable. Mutagenic potential refers to the ability of a compound to induce point mutations (i.e. bacterial reverse mutation assay), while genotoxic potential refers to both mutagenic and clastogenic potential. ICH M7 focuses specifically on mutagenicity. |
Throughout the ICH M7 guideline it is emphasized that the focus is on DNA reactive substances that have a potential to directly cause DNA damage when present at low levels leading to mutations and therefore potentially cause cancer. These types of mutagenic substances are usually detected in a bacterial reverse mutation assay (i.e. the Ames test). The guideline further states that other types of genotoxicants that are nonmutagenic (i.e. clastogenic) typically have threshold mechanisms and usually do not pose carcinogenic risk in humans at the level ordinarily present as impurities. This will be discussed later in Sections 3 and 6.
