Bioassays genotoxicity tests

Limited carcinogenicity data for chlorine dioxide and chlorite do not indicate a particular cancer concern, but adequate animal cancer bioassays have not been performed. Genotoxicity testing has produced mixed results. Chlorine dioxide and chlorite do not appear to be reproductive toxicants. 

F. K. Ennever, T. J. Noonan, and H. S. Rosenkranz, Mutagenesis, 2, 73 (1987). The Prediction of Animal Bioassays and Short-term Genotoxicity Tests for Carcinogenicity and Non-carcinogenicity to Humans. 

As performance data has become available on these strains, ICH (1997) has incorporated their use into pharmaceutical testing guidelines in lieu of the second rodent species tests (that is, to replace the long-term mouse bioassay when the traditional rat study has been performed). FDA has stated that they would accept such studies when performed in a validated model. In fact, CBER has accepted such studies as a sole carcinogenicity bioassay in some cases where there was negative traditional genotoxicity data and strong evidence of a lack of a mechanistic basis for concern. 

One especially successful method of testing complex mixtures is bioassay-directed fractionation followed by chemical identification of active compounds. Until now this method has mainly been used for the testing and identification of genotoxic compounds in environmental mixtures such as extracts of air particulates, exhaust condensates, and cooked foods. In this approach, each fraction is bioassayed untd the major class of specihc chemical(s) responsible for the activity can be isolated and chemically characterized, which make a risk assessment of the mixture possible. 

Fortunately, a number of in situ, short-term bioassays to detect genotoxic and related effects have become available. These include a variety of measured endpoints such as aneuploids, chromosal aberrations, DNA damage, dominant lethal mutation, gene mutation, inhibition of intercellular communication, micronuclei, mitotic recombination and gene conversions, and sister chromatid exchange and cell transformation (IARC, 1989). A detailed discussion of these tests is beyond the scope of this book. However, such tests are important from our perspective as atmospheric chemists because, as we shall see, they can be used to detect biologically active compounds in very complex mixtures, and hence serve to focus chemical analysis efforts (IARC, 1989, p. 20). We emphasize in advance the... 

Selection of representative bioassays is crucial for successful application of the pT-scale. Sub-cellular tests such as enzyme assays may not be sufficiently relevant in their indicative power of environmental hazard instead of tests using cells or whole organisms. Future refinements to the pT-scale might be the incorporation of additional genotoxicity or immunotoxicity tests to a test battery to augment its diagnostic power in terms of hazard assessment. 

Seven bioassays a) acute bacterial test (Vibrio fischeri) b) algal test (Pseudokirchneriella subcapitata) c) acute crustacean test (Daphnia magna) d) acute fish test (Pimephales promelas) e) SOS chromotest (Escherichia coli PQ 3 7) f) genotoxicity Mutatox test (Vibrio fischeri mutant) g) fluctuation AMES test (Salmonella typhimurium his- TA 98, 100, 1535, 1537) Tire cmmbs 1) Unspecifiedfiltration of water extracts for the first four tests 2) Soxhlet extraction for the three last tests... 

A total of 45 different species were employed, but authors did not always specify their choice of species. Ideally, bioassays should have some basic characteristics, as defined by Giesy and Hoke (1989). An adequate battery of bioassays needs in principle to measure various types (acute, chronic, genotoxic) and levels (lethal, sublethal) of ecotoxicity, without any redundancy, with test species belonging to different trophic levels or characterized by different ecological and biological traits (Ducrot et al., 2005). Another important aspect in the selection of bioassays for a test... 

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