Validated Non-animal Alternatives
|
Methods
|
Test Purpose
|
Validation Authority
|
OECD TG
|
| In vitro Mammalian Cell Micronucleus Test |
Alternative to the in vitro chromosome aberration assay for genotoxicity testing |
ECVAM
|
OECD TG 487
|
| Bacterial Reverse Mutation Test (Ames Test) |
Genotoxicity testing - using bacterial cells |
|
OECD TG 471
|
| Genetic Toxicology: Saccharomyces Cerevisiae Gene Mutation Assay |
Genotoxicity testing - using bacterial cells |
|
OECD TG 480
|
| Genetic Toxicology: Saccharomyces Cerevisiae Mitotic Recombination Assay |
Genotoxicity testing - using bacterial cells |
|
OECD TG 481
|
| In Vitro Mammalian Chromosome Aberration Test |
Genotoxicity testing - using mammalian cells |
|
OECD TG 473
|
| In Vitro Mammalian Cell Gene Mutation Test |
Genotoxicity testing - using mammalian cells |
|
OECD TG 476
|
| Genetic Toxicology: In Vitro Sister Chromatid Exchange Assay in Mammalian Cells |
Genotoxicity testing - using mammalian cells |
|
OECD TG 479
|
| Genetic Toxicology: DNA Damage and Repair, Unscheduled DNA Synthesis in Mammalian Cells In Vitro |
Genotoxicity testing - using mammalian cells |
|
OECD TG 482
|
Following a weight-of-evidence retrospective validation, the ESAC endorsed the in vitro micronucleus test as a scientifically valid alternative to the in vitro chromosome aberration assay for genotoxicity testing (ESAC Statement, Nov. 17, 2006). The ESAC statement clarified their endorsement as follows: "To facilitate test guideline development and regulatory acceptance, a standardised test protocol and performance standards need to be defined. The in vitro [micronucleus test] can then be considered for regulatory use as part of the tier 1 genotoxicity test battery." The in vitro mammalian cell micronucleus test detects two types of chemical-induced changes to dividing cells: chromosome breakage (clastogens) and changes in chromosomal numbers (aneugens).
The ECVAM/INVITTOX database contains seven additional genotoxicity testing protocols, but neither ECVAM nor ICCVAM has formally validated these methods.
Although the OECD encourages the validation of test methods prior to their adoption as Test Guidelines (TGs), validation is not a prerequisite for the adoption of TGs. Except for the in vitro micronucleus test, the in vitro genotoxicity test methods incorporated into OECD TGs have not been formally validated by ECVAM or ICCVAM.
In vitro genotoxicity/mutagenicity test methods based on bacterial cells are TG 471, 480, and 481. In vitro genotoxicity/mutagenicity test methods based on mammalian cells are TG 473, 476, 479, 482, and 487.
Additional information on in vitro methods for genotoxicity testing can be found on AltTox at: Toxicity Endpoints & Tests: Genotoxicity.
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