Nanomaterials and mutations
Mutations are changes to the genetic material of cells or organisms and the ability to cause these changes is called mutagenicity. Like any other chemical, a nanomaterial may also cause mutations and mutagenicity is a key area that can be used to evaluate the potentially harmful effects of chemicals.
Mutagenicity testing generally looks at two mechanisms: gene mutation – changes in the DNA of a single gene, or chromosomal aberration.
Chromosomal aberration can be structural where chromosomes break or are rearranged, or numerical where the number of chromosomes changes. These can lead to a variety of genetic disorders and birth defects.
A range of tests needed to assess mutagenicity
A single test cannot detect all mutagenic mechanisms so a battery of tests is usually required.
The test battery that is currently recommended for nanomaterial mutagenicity includes a mammalian cell gene mutation test and a mammalian cell micronucleus test or chromosomal aberration test.
Adapting test guidelines for nanomaterials
The OECD has given several recommendations to properly assess nanomaterials in vitro:
- Nanomaterials should be well-characterised in the test medium.
- Cells growing in suspension are more sensitive than adherent cell lines and should be used.
- The ability for nanomaterials to penetrate different cells should be demonstrated. Only cells that can efficiently internalise nanomaterials should be used for testing.
- The highest concentration should be limited to 100 μg/mL or 100 μg/cm2 (higher doses are not physiologically relevant and can interfere with scoring due to high deposition on cells).
- Several methods can be used to disperse nanomaterials, but the NANoREG protocol is a well-established method.
Nanomaterials that turn up negative in the battery of in vitro mutagenicity tests should be considered non-mutagenic. If one of the in vitro tests show a positive result or if it is not appropriate to test the nanomaterial in vitro, a follow-up in vivo test, so testing with a living organism, should be done. This helps to verify whether mutagenicity observed in an in vitro system can be reproduced in an in vivo system.
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