Mutagenicity screening

Acute oral toxicity (rat)3 Ames mutagenicity screening test (Salmonella typhimurium)... 

Ishidate M, Sofuni T, Yoshikawa K, et al. 1984. Primary mutagenicity screening of food additives currently used in Japan. Food Chem Toxicol 22(8) 623-636. 

The Ames salmonella-microsome test is a principal sensitive mutagen screening test. Compounds are tested on the mutants of Salmonella typhimurium for reversion from a histidine requirement back to prototrophy. A positive result is seen by the growth of revertant bacteria (which do not require an external histidine source). A microsomal activation system should be included in this assay. The use of five different bacterial test strains are generally required. 

Some of these problems can be overcome by the use of cell-based systems, in particular, primary hepatocytes. Hepatocytes closely simulate the metabolic systems found in the intact fiver and do not require additional cofactors for optimal enzyme activity. However, apart from greater technical difficulties in obtaining hepatocytes as opposed to S9 fraction, hepatocytes can effectively detoxify particular carcinogens and prevent their detection as mutagens. Despite these difficulties, hepatocytes have a role to play in mutagenicity screening, in both bacterial and mammalian-based systems (Tweats and Gatehouse, 1988). 

Rinkus SJ, Legator MS. 1980. The need for both in vitro and in vivo systems in mutagenicity screening. In de Serres FJ, Hollaender A, eds. Chemical mutagens Principles and methods for their detection. New York, NY Plenum Press, 365-473. 

Shirasu Y, Moriya M, Tezuka H, et a1. 1982. Mutagenicity screening studies on pesticides. In Proceedings of the 3rd Environmental Mutagens and Carcinogens International Conference, Sept. 

McGregor DB. 1981. Tier II mutagenic screening of 13 NIOSH priority compounds Individual compound report methyl bromide. Report to National Institute for Occupational Safety and Health, Cincinnati, OH, by Inveresk Research International Limited, Musselburgh, Scotland. NTIS No. PB83-130211. 

Morimoto, I., F. Watanabe, T. Osawa, T. Okitsu and T. Kada. Mutagenicity screening of crude drugs with Bacillus subtilis rec-assay and Salmonella/micro-some reversion assay. Mutat Res 1982 97 81-102. 

Rockwell, P., and I. Raw. A mutagenic screening of various herbs, spices and food additives. Nutr Cancer 1979 1 10-15. 

Shirasu Y, Moriya M, Kato K, et al. 1976. Mutagenicity screening of pesticides in the microbial system. Mutation Research 40 19-30. 

SOLVENT Choice. Solvent extraction is limited to water immiscible solvents. Solid adsorbents do not have this limitation, so miscible solvents, desirable for subsequent analytical or bioassay purposes, can be used. For example, DMSO is preferred for mutagenicity screening and has been used to elute the adsorbed organic material (211-213, 216, 235, 328). For analytical purposes, acid, base, and neutral eluents can be employed for on-column fractionation of the adsorbed organic solutes (78, 80,196). 

Hazard Identification. The first step is to determine whether a substance is mutagenic. For this purpose, inexpensive and sensitive short-term tests have been developed and are extensively used, nils report discusses the general features of these tests and proposes a specific mutagenicity screening program to detect potential mammalian mutagens. 

Bridges, B.A. Some general principles of mutagenicity screening and a possible framework for testing procedures. Environ. Health Perspect. 6 221-227,... 

Ma, T-H. Tradescantia micronucleus bioassay and pollen tube chromatid aberration test for in situ monitoring and mutagen screening. Environ. Health Perspect. 37 85-90, 1981. 

MacGregor, J.T., and L.E. Sacks. The sporulation system of Bacillus subtilis as the basis of a multigene mutagen screening test. Mutat. Res. 38 271-286,... 

Massey IJ, Aitken MD, Ball LM, Heck PE. Mutagenicity screening of reaction products from the enzyme-catalyzed oxidation of phenolic pollutants. Environ Toxi Chem 1994 11 1743-1752. 

The conduct of animal toxicity studies proceeds concurrently with and in advance of clinical studies. A certain amount of animal toxicity data is required for the IND. This often includes acute toxicity in two rodent species, mutagenicity screening studies, and one-month toxicity studies in a rodent and non-rodent species. After the clinical studies have begun, further animal studies are conducted, usually until the time for the NDA. These would include further mutagenicity studies, reproductive toxicity studies, and long-term toxicity studies, possibly including carcinogenicity studies. 

McCalla DR, Voutsinos D, Olive PL. Mutagen screening with bacteria niridazole and nitrofurans. Mutat Res 1975 31(l) 31-7. 

Ungsurungsu, M., Suthienkal, O., and Paovalo, C., Mutagenicity screening of popular Thai spices, Fd. Chem. Toxicol., 20, 527, 1982. 

Sub-chronic and/or chronic toxicity study Additional mutagenicity screening studies Basic toxicokinetic information... 

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