Little Pro on 2016-04-24
Mutagenicity refers to the induction of permanent transmissible changes in the amount or structure of the genetic material of cells or organisms. These changes may involve a single gene or gene segment, a block of genes or chromosomes. The genetic change is referred to as a mutation and the agent causing the change as a mutagen.
Genotoxicity is similar to mutagenicity except that genotoxic effects are not necessarily always associated with mutations. All mutagens are genotoxic, however, not all genotoxic substances are mutagenic.
Mutations can either occur in germ cells or somatic cells. If the mutation occurs in a germ cell the effect is heritable. There is no effect on the exposed person; rather the effect is passed on to future generations. If the mutation occurs in a somatic cell, it can cause altered cell growth (e.g. cancer) or cell death (e.g. teratogenesis) in the exposed person.
No Observed Adverse Effect Level (NOAEL) cannot be obtained from mutagenicity/genotoxicity studies due to study design and different mode of action. It is generally assumed that even a small dose of mutagenic (genotoxic) chemicals may have a potential adverse effect. In general, the advice given by risk assessors in Europe has been to keep exposure to such compounds at the lowest possible level - ALARA principle (“as low as reasonably achievable”).
All known germ cell mutagens are also mutagenic in somatic cells in vivo. Substances that are mutagenic in somatic cells may produce heritable effects if they, or their active metabolites, have the capability of interacting with the genetic material of germ cells. Substances that do not induce mutations in somatic cells in vivo would not be expected to be germ cell mutagens.
There is considerable evidence of a positive correlation between the mutagenicity of substances in vivo and their carcinogenicity in long-term studies with animals
GHS hazard class Germ Cell Mutagenicity is primarily concerned with chemicals that may cause mutations in germ cells of humans that can be transmitted to the progeny. However, in vivo genotoxicity to somatic cells are also considered.
The table below summarizes GHS classification criteria for germ cell mutagenicity.
|Category 1A||Chemicals known to induce or regarded as if they induce heritable mutations in human germ cells
Known to induce heritable mutations –positive evidence from human epidemiological studies.
Mixtures containing ≥ 0.1% of such a category 1A mutagen.
|Category 1B||Chemicals known to induce or regarded as if they induce heritable mutations in human germ cells
Regard as if they induce heritable mutations – positive results from in vivo heritable germ cell or somatic cell mammalian mutagenicity tests, or positive results showing mutagenic effects in the germ cells of humans without demonstration of transmission to progeny.
Mixtures containing ≥ 0.1% of such a category 1B mutagen.
|Category 2||Chemicals that may induce heritable mutations in human germ cells
Positive evidence obtained from in vivo somatic cell mutagenicity or somatic cell genotoxicity tests in mammals and in some cases with support from in vitro experiments
Mixtures containing ≥ 1% of such a category 2 mutagen.
There are both in vitro and in vivo mutagenicity/genotoxicity studies for germ cells and somatic cells. Usually, in vitro studies are employed the first. The most basic test for mutageniciy is the Ames test - an in vitro gene mutation study in bacteria. If there is any positive result within in vitro tests, in vivo mutagenicity studies are required for further confirmation.
For an adequate evaluation of the genotoxic potential, usually 3 endpoints need to be assessed: gene mutation, structural chromosome aberrations, and numerical chromosome aberrations.
The table below summarizes commonly used in vitro and in vivo mutagenicity/genotoxicity studies. The studies marked in bold below are often required for chemical hazard identification and risk assessment.
|Type||Germ Cells||Somatic Cells|
You have learned the definition of mutagenicity and genotoxicity, the difference between germ cells and somatic cells, GHS classification criteria for germ cell mutagenicity and testing guidelines.
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