Mutagenicity/Genotoxicity

OSHA considers that, at excessive levels, ethylene oxide may present reproductive, mutagenic, genotoxic, neurologic, and sensitization hazards. In addition, ethylene oxide is considered by OSHA, lARC, and NTP as a potential human carcinogen. 

For non-threshold effects (e.g., sensitization, mutagenicity, genotoxicity, genotoxic carcinogenicity), the dose-response curve, in the absence of mechanistic evidence to the contrary, is assumed to be linear. 

In the various OECD test guidelines for mutagenicity/genotoxicity testing, the definitions relevant for a specific test are provided in the Annex. 

The OECD, US-EPA, and EU have developed a number of specific test guidelines for in vitro testing of mutagenicity/genotoxicity, see Table 4.15. The EU Annex V methods are generally... 

Test Guidelines Adopted for In Vivo Testing of Mutagenicity/Genotoxicity... 

Overview of In Vivo Mutagenicity/Genotoxicity Test Guideline Studies... 

APIs are chemicals that have been optimized for intended biological effect, minimal undesired side effects, and stability. Stability is essential for long shelf-life. However, this is not always successful as some APIs are also mutagenic, genotoxic, or carcinogenic, such as some compounds used in anti-cancer treatment. After their... 

To exclude substances with mutagenic/genotoxic potential, as a minimum, a combination of two suitable in vitro tests is necessary. 

Depending on the outcome of previous testing on mutagenicity/genotoxicity and systemic exposure, complete carcinogenicity testing might be necessary to exclude these risks. 

Mutagenicity (genotoxicity). A bacterial mutagenicity test that demonstrates the induction of point (gene) mutations is always required. Some mutations result in the development of cancer. 

This hazard class is primarily concerned with chemicals that may cause mutations in the germ cells of humans that can be transmitted to the progeny. However, mutagenicity/genotoxicity tests in vitro and in mammalian somatic cells in vivo are also considered in classifying substances and mixtures within this hazard class. 

Examples of mutagenicity/genotoxicity tests in germ cells are ... 

Mutagenicity (genotoxicity) tests are designed to identify compounds that may induce genetic damage. A standard battery of tests is conducted and include ... 

BHT is a possible carcinogen with the target organ being the lungs. It does not represent a relevant mutagenic/genotoxic risk to humans. 

The use of agrochemicals to improve the growth of or to protect medicinal plants should be applied only when required and only approved plant protection products (such as pesticides and herbicides) should be used at the minimum effective concentration (J4). The investigation into the biological activity of Cyrtanthus suaveolens Schonland (Amaiylhdaceae), a medicinal plant widely used in Southern Africa, lead to the isolation of Captan, a commercial pesticide with known mutagenic, genotoxic and teratogenic activity (27). 

Key words Mutagenicity, Genotoxicity, Carcinogenicity, In vitro assays, Test methods, Hazard identification... 

Negative Substance is negative in all test systems under appropriate in vitro conditions the substance is not mutagenic (genotoxic) in vitro and is predicted not to be mutagenic in vivo [for exceptions, see Tweats et al. (2007a,b)]. 

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