Mutagenicity assay

The results of the mutagenicity assay indicated that neither 26a nor 30a demonstrated a positive response with these tester strains at any concentration in either the presence or the absence of Aroclor-induced rat liver S9, indicating that neither of these compounds demonstrate any mutagenicity. This is an important finding in the field of cancer research. 

---

Formaldehyde is not considered a teratogen and has not been reported to cause adverse reproductive effects (138,139). vitro mutagenicity assays... 

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

Dunkel VC, Zieger E, Brusick D, et al. 1984. Reproducibility of microbial mutagenicity assays 1. Tests with Salmonella typhimurim and Escherichia coli using a standardized protocol. Environ Mutagen 6 (Suppl. 2) 1-254. 

Mortelmans K, Zeiger E The Ames Salmo-nella/microsome mutagenicity assay. Mutat Res 2000 455 29-60. 

Simon, V.F. 1979a. In vitro mutagenicity assays of chemical carcinogens and related compounds with Salmonella typhimurium. J. Natl. Cancer Inst. 62 893-899. 

Simmon VF, Kauhanen K. 1978. In vitro microbiological mutagenicity assays of hexachloroethane. Cincinnati, OH U.S. Environmental Protection Agency, National Environmental Research Center, Water Supply Research Laboratory. 

Ashwood-Smith, M.J. (1980). Stability of frozen microsome preparations for use in the Ames Salmonella mutagenicity assay. Mutation Res. 69 199-200. 

Carver, J.H., Machado, M.L. and MacGregor, J.A. (1985). Petroleum distillates suppress in vitro metabolic activation Higher (S9) required in the Salmonella/microsome mutagenicity assay. Environ. Mutagen. 7 369-380. 

Clive, D. (1987). Historical overview of the mouse lymphoma TK+/, mutagenicity assay. In Mammalian Cell Mutagenesis, (Moore, M.M., Demarini, D.M., De Serres, F.J. and Tindall, K.R., Eds.). Banbury Report 28. Cold Spring Harbor Laboratory, NY, pp. 25-36. 

DeSerres, F.J. and Shelby, M.D. (1979). Recommendations on datas production and analysis using the Salmonella/microsome mutagenicity assay. Mutation Res. 64 159-165. 

Some modifications to current in vivo testing methods both can and should be adopted. A current example of this would be in medical devices where a substantial portion of the requirements under the governing regulatory (ISO 10993) can be met with in vitro alternatives (cytogenicity, muscle cell implantation, the limulus test for pyrogens, and in vitro mutagenicity assays). 

Dirven HA, Theuws JL, Jongeneelen FJ, et al. 1991. Non-mutagenicity of 4 metabolites of di(2-ethylhexyl)phthalate (DEHP) and 3 structurally related derivatives of di(2-ethylhexyl)adipate (DEHA) in the salmonella mutagenicity assay. Mutat Res 260 121-130. 

Stott, W.T. and Sinnhuber, R.O. Trout hepatic enzyme activation of aflatoxin-B] in a mutagen assay system and inhibitory effects of PCBs. Bull. Environ. Contam. Toxicol. (1978) 19, 35. 

Positive results in one or more mutagenicity assays do not necessarily translate into human risks. FDA has issued a guidance document on approaches and considerations when positive mutagenicity studies are encountered.18 Among these considerations are the performances of additional studies. Mechanistic studies may show that such responses would not occur in the human cell population, or the concentrations at which positive responses occurred may far exceed any concentration of drug that may occur in the clinical setting. Many marketed drugs have produced some type of positive response in these studies and yet it has been concluded that no human risk is present or the potential risk is not known. See Chapter 15 for more details. 

Clive D, Johnson KO, Spector JFS, et al. 1979. Validation and characterization of the L5178Y/TK+/-mouse lymphoma mutagen assay system. Mutat Res 59 61-108. 

Dunkel VC, Zeiger E, Brusick D, et al. 1985. Reproducibility of microbial mutagenicity assays. II. Testing of carcinogen and noncarcinogens in Salmonella typhimurium and Escherichia coli. Environ Mutagen (SuppI 5) 7 1-248. 

Nakajima M, Kawakami T, Niino T, Takahashi Y, Onodera S (2009) Aquatic fate of sunscreen agents octyl-4-methoxycinnamate and octyl-4-dimethylaminobenzoate in model swimming pools and the mutagenic assays of their chlorination byproducts. J Health Sci 55(3) 363-372... 

Hannigan MP, Cass GR, Penman BW, Crespi CL, Busby JWF, Lafleur AL, Thilly WG, Simoneit BRT (1998) Bioassay-directed chemical analysis of Los Angeles airborne particulate matter using a human ceil mutagenicity assay. Environ Sci Technol 32 3502-3514... 

Anderson D. 1976. Paradichlorobenzene Estimation of its mutagenic potential in the Salmonella typhimurium plate incorporation mutagenicity assay. ICI Report No. CTL/P/298. November. 

Blackburn GR, Deitch RA, Schreiner CA, et al. 1986. Predicting carcinogenicity of petroleum distillation fractions using a modified Salmonella mutagenicity assay. Cell Biol Toxicol 2 63-84. 

Prival MJ. 1983. The Salmonella mutagenicity assay Promises and problems. Ann NY Acad Sci 407 154-163. 

BA s metabolites are genotoxic in the Ames mutation test and caused unscheduled DNA synthesis in primary rat hepatocytes. In an in vivo mutagenic assay, male CD rats (6/group) were dosed three times with BA over a 24-hour interval by intratracheal instillation. Lung cells were enzymatically separated and used to determine the frequency of DNA adducts, sister chromatid exchanges (SCEs), and micronuclei. BA induced DNA adducts, SCEs, and micronuclei in this rat lung cell system. 

Conflicting results have been reported in bacterial mutagen assays diisopropylamine was not genotoxic in DNA repair assays in vitro ... 

---