PHARMACOLOGY

 GENOTOXICITY ::

Genotoxic compounds in the absence of other data is presumed to be trans -species carcinogens implying a hazard to humans Such compounds need not be Subjected to long -term carcinogenicity studies However if such a drug is intended to be administered for chronic illnesses or otherwise over a long period of time -a chronic toxicity study (up to one year) may be necessary to detect early tumorigenic effects Genotoxicity tests are in vitro and in vivo tests conducted to detect compounds which induce genetic damage directly or indirectly These tests should enable a hazard identification with respect to damage to DNA and its fixation 

            The various standard tests that are generally conducted include test for gene mutation bacteria in vitro tests and in vivo tests other genotoxicity tests e.g. tests for measurement of DNA adducts DNA strand breaks DNA repair or recombination serve as options in addition to the standard battery for further investigation of genotoxicity test results obtained in the standard battery only under extreme conditions in which one or more tests comprising the standard battery cannot be employed for technical reasons alternative validated test can serve as substitutes provided sufficient scientific justification should be provided to support the argument that a given standard battery test is not appropriate 

In-vitro tests ::

In-vitro studies include Ames Salmonella assay and chromosomal aberrations (CA) in cultured cells In -vivo studies should include micronucleus assay (MNA) or CA in rodent bone marrow Data analysis of CA should include analysis of gaps