Genetic toxicology

National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 

Charlotte Auerbach and colleagues in 1946 described studies (actually conducted in 1941) that demonstrated that mustard gas could induce mutations and that these were similar at the whole-organism level in Drosophila to those induced by X-rays. Thus, research began in the new area of chemical mutagenesis that ran in parallel with radiation mutagenesis studies. 

The next event of particular signihcance to the held of genetic toxicology was the development, by William Russell in 1951, of a mouse mutagenesis assay that could 

Molecular and Biochemical Toxicology, Fourth Edition, edited by Robert C. Smart and Ernest Hodgson Copyright 2008 John Wiley Sons, Inc. 

2 GENETIC TOXICOLOGY AND RISK ASSESSMENT (GENERAL CONSIDERATIONS) 

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D. Bmsick, Principles of Genetic Toxicology, Plenum Press, New York, 1980. 

Hoffmann, G. R. (1996). Genetic toxicology. In Casarett and DonlTs Ib.xicology The Basic Science of Poisons (C. D. Klaasseii, Ed.), p. 281. McGraw-hfill, New York. 

Severn, D.J. (1982) Exposure assessment for agricultural chemicals, in Genetic Toxicology, and Agricultural Perspective, Fleck, R.A. and Hollander, A., Eds., Plenum Press, New York, pp. 235-242. 

Zelikoff JT, Li JH, Hartwig A, et al. 1988. Genetic toxicology of lead compounds. Carcinogenesis 9 1727-1732. 

Natarajan, A.T. and Obe, G. (1982). Mutagenicity testing with cultured mammalian cells cytogenetic assays. In Mutagenicity, New Horizons in Genetic Toxicology, (Heddle, J.A., Ed.). Academic Press, New York, pp. 172-213. 

OECD (1983). OECD Guidelines for the Testing of Chemicals. No. 475. Genetic toxicology in vivo mammalian bone marrow cytogenetic test chromosomal analysis. Adopted 4 April 1984. 

Parry, J.M., Arlett, C.F. and Ashby, J. (1985). An overview of the results of the in vivo and in vitro test systems used to assay the genotoxicity of BZD, DAT, DAB and CDA in the second UKEMS study. In Comparative Genetic Toxicology The Second UKEMS Collaborative Study, (Parry, J.M. and Arlett, C.F., Eds.). Macmillan, London, pp. 597-616. 

The weight of evidence from in vivo and in vitro genetic toxicology tests, in vivo liver function studies, and the two-stage tumor promotion assay is adequate to conclude that chlordecone is a promotor rather than an initiator of carcinogenesis. While the evaluation of mirex in an in vivo tumor promoter... 

FDA, Guidance for Industry Recommended Approaches to the Integration of Genetic Toxicology Study Results, November 2004, Available at http / /www.fda.gov/cder/guidance. 

Following the first demonstration of the deleterious effect of radiation and ultimately that of chemicals on genetic material, numerous test systems have been used to study the induction of DNA damage, chromosomal aberrations, and mutations. This broad spectrum of activity resulted in the birth of genetic toxicology. The test organisms include prokaryotes (e.g., bacteria, fungi) and eukaryotes (e.g., yeast, fruit flies, plants, mammals). 

Richard H.C. San Genetic Toxicology, BioReliance, Rockville, Maryland, U.S. 

Number of replicates Counting method Criteria for positive results Summary of individual study findings Study validity Study outcome Genetic toxicology summary Genetic toxicology conclusions... 

Cohen MM, Shiloh Y. (1977-78). Genetic toxicology of lysergic acid diethylamide (LSD-25). Mutation Res. 47(3-4) 183-209. 

Genotoxicity. No definite conclusions can be reached from the in vitro human cell and whole animal genetic toxicology studies that have been performed with fuel oils. Data from bacterial in vitro assays are inconsistent (see Section 2.4, Genotoxic Effects). A study of the genotoxicity/mutagenicity of commercially available fuel oils and the various component petroleum streams used in their formulation would be of value. 

Genetic Toxicology Group, Department of Nutrition and Food Science, Massachusetts Institute of Technology, Gambridge, MA 02139... 

W. N. Choy, Genetic Toxicology and Cancer Risk Assessment, Marcel Dekker, New York,... 

D. Y. Lai and L.-T. Woo, Structure-activity relationships (SAR) and its roles in cancer risk assessment, in Genetic Toxicology and Cancer Risk Assessment, ed. W. N. Choy, Marcel Dekker, New York, 2001, pp. 73-91. 

Genetic Toxicology Sex-Linked Recessive Ixthal Test in Drosophila melanogaster (Updated Guideline, adopted 4 April 1984)... 

Genetic Toxicology In Vitro Sister Chromatid Exchange Assay in Mammahan Cells (Original Guideline, adopted 23 October 1986)... 

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