Mutagenicity testing

Although in vitro mutagenicity tests suggest that some nitrofurans in general provoke a positive response, use of in vivo mammalian systems has produced equivocal or negative results. 

Pyridine Chronic Toxicology. AH mutagenicity tests have been negative and (1) is not considered a carcinogen or potential carcinogen. There have been no reports of adverse health effects on long-term exposure to (1) at low concentrations. 

B. J. Kilbey, M. Legator, W. Nicols, and C. Ramel, eds.. Handbook of Mutagenicity Test Procedures, Elsevier Scientific Publishing Company,... 

Safety is assessed by subjecting the antioxidant to a series of animal toxicity tests, eg, oral, inhalation, eye, and skin tests. Mutagenicity tests are also carried out to determine possible or potential carcinogenicity. Stabilizers are being granulated and Hquid products are receiving greater acceptance to minimize the inhalation of dust and to improve flow characteristics. 

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. 

Inhalation toxicity does not present a hazard because of low vapor pressure. DGEBPA-based resins have been reported to cause minimal eye irritation (44). Systemic toxicity has not been noted in experiments where DGEBPA-based resins have been fed to laboratory animals. Mutagenic activity has not been shown in animals, but in vitro mutagenicity tests have yielded variable results (44). 

T. G. PuUin, Integrated Mutagenicity Testing Program on SeperalEpoyj Compounds, The Dow Chemical Company, 1977. 

Genotoxic Effects. Endosulfan has been evaluated for genotoxicity in a variety of in vivo and in vitro assays. As summarized in Tables 2-4 and 2-5, the results of these assays have been positive and negative, but the majority of mutagenicity tests reported positive results. Certain studies were unsatisfactory, as indicated below. 

Ames B.N., McCann J. Yamasaki E. (1975) Methods for detecting carcinogens and mutagens with the Salmonella/mammalian microsome mutagenicity test. MutatRes, 31, 347-364. 

Maron DM, BN Ames (1983) Revised methods for the Salmonella mutagenicity test. Mutat Res 113 173-215. 

Subcllnlcal effects clinical laboratory test alteration (liver function, nerve conduction velocity), mutagenicity testing, cytogenetic testing Requires estimation of eventual likelihood of clinical disease predicted by subcllnlcal abnormalities ... 

Ciba-Geigy Ltd. 1978a. Salmonella/mammalian-microsome mutagenicity test with TK 10 509 (REOFOS 95). Experiment No. 78-2506. Ciba-Geigy Limited, Basle, Switzerland. NTIS OTS0507280. 

Haworth S, Lawlor T, Mortelmans K, et al. 1983. Salmonella mutagenicity test results for 250 chemicals. Environ Mutagen Suppl 1 3-142. 

TEST allows for estimates of the value for several toxicity endpoints [29] 96 h Fathead minnow LC50, 48 h Daphnia magna LC50, 48 h Tetrahymena pyriformis IGC50, Oral rat LD50, bioaccumulation factor, developmental toxicity, and Ames mutagenicity. TEST also estimates several physical properties... 

In vitro models could be used to study the molecular mechanisms involved in the process of neoplastic transformation and as screening tools for the classification of the carcinogenic potential of a substance. Among the in vitro tests available to the scientific community, the CTA may represent an important tool for the identification of carcinogens, particularly those that are not identifiable by classic mutagenicity tests such as the Ames test. 

ECHA (2008) REACH Guidance on information requirements and chemical safety assessment, Chapter R.7a Endpoint specific guidance. See chapter R7.7.1 Mutagenicity testing. Available at http //guidance.echa.europa.eu/docs/guidance document/information requirements r7a en.pdf vers=20 08 08... 

Only four plant species, i.e., Vicia faba, Allium cepa, Pisum sativum and Triticum turgidum, responded adequately to the Feulgen procedure, and were considered for use in the successive experiments. These species, together with the corresponding mutagenic compounds used and the mutagenicity tests adopted (see below in Sect. 2.4.) are listed in Table 4. 

Table 4. Plant species positive to the Feulgen method, mutagenicity coumpounds used and mutagenic tests applied ...

Plant species Mutagenic compound Mutagenicity test... 

Among the mutagens tested on each plant species (Table 4), those that produced evident clastogenic alterations were (a) MH on V faba, A. cepa, P. sativum, and T. turgidum, (b) COL on V. faba and A. cepa, and (c) ALA on T. turgidum. The effects measured for MH and ALA on T. turgidum, and for 2,4-D and GLY on V faba and A. cepa, were not statistically significant, thus the related data will not be considered further in this section. 

Chung KT, FlukGE, Andrews AE (1981) Mutagenicity testing of some commonly used dyes. Appl Environ Microbiol 42(4) 641-648... 

Mutagenicity tests are usually carried out in vitro and in vivo, often using both prokaryotic and eukaryotic organisms. A well-known example is the Ames test, which assesses the ability of a drug to induce mutation reversions in E. coli and Salmonella typhimurium. 

Macgregor, J.T., D.H. Gould, A.D. Mitchell, and G.P. Sterling. 1979. Mutagenicity tests of diflubenzuron in the micronucleus test in mice, the L5178Y mouse forward mutation assay, and the Ames Salmonella reverse mutation test. Mutat. Res. 66 45-53. 

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