Mutagenicity studies, Ames test

Not mutagenic according to Ames test, cytogenicity study and gene mutation assay. 

Physicochemical properties requked include melting/boiling point, vapor pressure, solubiUty, and flammabiUty/explosion characteristics. The toxicological studies include acute toxicity tests, oral, inhalation, and dermal skin and eye kritation skin sensiti2ation subacute toxicity, oral, inhalation, and dermal and mutagenicity tests. In vitro reverse mutation assay (Ames test) on Salmonella typhimurium and/or E.scherichia coli and mammalian cytogenic test. In vivo mouse micronucleus test. 

Studies on the reproductive function (three generations) and intrauterine development of rat showed no impairment of the rate of fertility and no sign of any teratogenic effect. The Ames test on mutagenicity was negative [101]. 

Some toxicity studies were performed analyzing Bfx and Fx mutagenic effects [240-242], For example, Bfx and Bfz nitro-substituted were tested for mutagenicity in Salmonella typhimurium (S. typhimurium) TA 98 and TA 100 strains with and without metabolic activation (Ames test). All the Bfx (10/10) and some of the Bfz (9/15) are mutagenic without activation. Other study has demonstrated benzofuroxan (128, Fig. 20) is mutagenic in the Luria and Del-brueck s fluctuation test, with Klebsiella pneumoniae, and in the Ames test. In another study it has been found that compound 137 (Fig. 21) is not mutagenic to S. typhimurium. 

H. Czeczot, B. Tudek, J. Kusztelak, T. Sz.ymczyk, B. Dobrowolska, G. Glinkowska, J. Malinowski, and H. Strzeiccka, Isolation and studies of the mutagenic activity in the Ames test of flavonoids naturally occurring in medical herbs. Mutat. Re.s. 240 209 (1990). 

FMC. 1992b. Durad 550B. Salmonella/mammalian-microsome plate incorporation mutagenicity assay (Ames Test). Study No. 191-1222. FMC Corporation, Philadelphia, PA. 

Genotoxic Effects. The Ames test with Salmonella typhimurium with and without s9 liver fractions from male Syrian golden hamsters or Sprague-Dawley rats indicates that hydrogen sulfide is not a mutagen (EPA 1984). A summary of genotoxicity studies is presented in Table 2-3. 

In vitro models could be used to study the molecular mechanisms involved in the process of neoplastic transformation and as screening tools for the classification of the carcinogenic potential of a substance. Among the in vitro tests available to the scientific community, the CTA may represent an important tool for the identification of carcinogens, particularly those that are not identifiable by classic mutagenicity tests such as the Ames test. 

Before administration of a NME to man, a mutagenicity test in bacterial cells (Ames test), with and without metabolic activation, and tests for chromosomal aberrations in mammalian cells should be negative. Any positive or equivocal results will require additional tests to be performed before proceeding to man. Studies of embryo-foetal toxicity should be performed before administration of a NME to women of reproductive potential. Studies of fertility, early embryonic development and pre- and post-natal development are not required at this stage of development neither are carcinogenicity studies. 

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