Toxicity mammalian mutagenicity test

It must be emphasized that the dominant lethal assay should be applied together with other in vivo- mammalian mutagenicity tests, notably in vivo cytogenetics, karyotype analysis of bone marrow, and the host-mediated assay, in addition to ancillary submammalian tests. Such mammalian systems can be simply and practically incorporated in the course of routine toxicity testing. 

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. 

Preliminary Cytotoxicity Testing. An essential first step is to carry out a preliminary study to evaluate the toxicity of the test material to the indicator cells, under the conditions of the main mutagenicity test. When selecting dose levels, the solubility of the test compound, the resulting pH of the media, and the osmolality of the test solutions all need to be considered. The latter two parameters have been known to induce false positive effects in in vitro mammalian tests (Brusick, 1986). The experimental procedure is carried out as follows. 

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. 

In addition to references on these topics, a separate reference section is devoted to other E P materials. Information related to human health effects is emphasized in this article. Included are the mostly qualitative accounts, by industrial or military physicians, of human intoxication documentation of mammalian toxicity expts and the results of microbial mutagenicity testing, a comparatively recent development. Brief summaries have been presented of the results of tests on aquatic organisms because of their sensitivity to the pollutants that surround them, such organisms provide responses indicative of water quality... 

The leaves and fruits of Cassia angustifolia and Cassia senna (senna) contain laxative anthranoid derivatives. Mutagenicity testing of sennosides has produced negative results in several bacterial and mammalian systems, except for a weak effect in Salmonella typhimurium strain TA102 (1,2). No evidence of reproductive toxicity of sennosides has been found in rats and rabbits (3). 

S-9 A metabolic activation mixture that is used with many in vitro genetic-toxicity tests to provide for the conversion of promutagens into mutagens the enzymatic activities of an S-9 mixture are those of a post-mitochondrial supernatant (i.e., microsomal and cytosolic enzymes) derived from a mammalian liver homogenate the expression "S-9" originally referred to supernatant from centrifugation at 9,000 rpm. 

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