Ames test activation

The inhalation toxicity of NF on animals has been studied extensively (37—40). These studies provide the basis of emergency exposure limits (EEL) that have been proposed for NE. The NAS—NRC Committee on Toxicology recommends that the EEL for NE be 10 min at 2250 ppm, 30 min at 750 ppm, and 60 min at 375 ppm. Gaseous NE is considered to be innocuous to the skin and a minor irritant to the eyes and mucous membranes. NE does give a weakly positive metabotically activated Ames test but only at concentrations greater than 2% or 10 times the 10 minute EEL. 

Succinic anhydride is extremely irritating to the eyes. It causes skin, mucous membranes, and respiratory tract irritation. It may be a sensiti2er. There is no evidence of carcinogenic activity in male or female tats given 50 or 100 mg/kg succinic anhydride (186) the Ames test is negative (187). LD q in rat 1510 mg/kg. There ate no estabflshed exposure limits for ACGIH TLV or TWA. 

Much toxicological data are available on this red pigment acute oral toxicity in mice, 90-day subchronic toxicological study, acute dermal irritation and corrosion, acute eye irritation and corrosion, anti-tumor effectiveness, micronucleus test in mice, AMES test Salmonella typhimurium reverse mutation assay), estimation of antibiotic activity, and results of estimation of five mycotoxins. A new patent on Arpink Red was filed in 2001 with claims of anti-cancer effects of the anthraquinone derivatives and apphcations in the food and pharmaceutical fields. 

Some toxicity studies were performed analyzing Bfx and Fx mutagenic effects [240-242], For example, Bfx and Bfz nitro-substituted were tested for mutagenicity in Salmonella typhimurium (S. typhimurium) TA 98 and TA 100 strains with and without metabolic activation (Ames test). All the Bfx (10/10) and some of the Bfz (9/15) are mutagenic without activation. Other study has demonstrated benzofuroxan (128, Fig. 20) is mutagenic in the Luria and Del-brueck s fluctuation test, with Klebsiella pneumoniae, and in the Ames test. In another study it has been found that compound 137 (Fig. 21) is not mutagenic to S. typhimurium. 

Some Fx and Fz derivatives have been evaluated for its mutagenicity in the Ames test [115]. For example, Fx 138 and 139 and Fz 140 posses mutagenic activity while Fx 3 (Fig. 8) is not mutagenic in this test. 

H. Czeczot, B. Tudek, J. Kusztelak, T. Sz.ymczyk, B. Dobrowolska, G. Glinkowska, J. Malinowski, and H. Strzeiccka, Isolation and studies of the mutagenic activity in the Ames test of flavonoids naturally occurring in medical herbs. Mutat. Re.s. 240 209 (1990). 

The Ames test involves the reversion from a his— to his+ phenotype in any one of multiple bacterial strains (usually five strains are tested simultaneously). If the addition of test compound to a his— strain of bacteria allows them to grow on histidine deficient media, the obvious conclusion is compound-induced mutagenesis and a high potential hazard for the compound being carcinogenic. This test can also be conducted in the presence or absence of metabolic activation, in order to provide more information on potential risks (i.e., the parent compound may not be mutagenic, but the primary metabolite may present a safety risk). In practice, a positive Ames test almost always leads to discontinuing work on a compound of interest, and so these data are always collected prior to nomination of a compound for development. 

Skin sensitization Ames test To determine the potential to induce skin sensitization reactions To evaluate potential mutagenic activity in a bacterial reverse mutation system with and without metabolic activation... 

Muta-Chromoplate Kit from wastewater, reduction of respiratory activity Modified version of Ames test [55]... 

Several short-term bioassay procedures (3-14) have been developed recently which are applicable to detecting mutagenic and potential carcinogenic activity of organic substances. The SaimoneJla/mammalian mlcrosome assay or Ames Test (13-13] has been the most frequently applied and its efficacy has been well documented. This assay has also been applied to complex mixtures (19-22) to reduce greatly the time... 

Before administration of a NME to man, a mutagenicity test in bacterial cells (Ames test), with and without metabolic activation, and tests for chromosomal aberrations in mammalian cells should be negative. Any positive or equivocal results will require additional tests to be performed before proceeding to man. Studies of embryo-foetal toxicity should be performed before administration of a NME to women of reproductive potential. Studies of fertility, early embryonic development and pre- and post-natal development are not required at this stage of development neither are carcinogenicity studies. 

Coal tar fumes were mutagenic in a modified Ames test." Fumes generated at 316°C contained significantly higher concentrations of PAHs than those generated at 232°C, and the mutagenic activity generally paralleled the PAH content. 

DAB was genotoxic in the comet assay inducing DNA damage in the stomach, colon liver, bladder, lung, and bone marrow. It is also mutagenic to Salmonella in the Ames test. Because of its demonstrated carcinogenicity in animals, human exposure to DAB by any route should be avoided. In recent years, this compound has been used only in laboratories as a model of tumorigenic activity in animals. It is not produced commercially in the United States and is of little occupational health importance. 

Methyl 2-cyanoacrylate was positive in the Ames test with and without activation by metabolic enzymes. ... 

Mutagenesis Oxcarbazepine increased mutation frequencies in the Ames test in vitro in the absence of metabolic activation in 1 of 5 bacterial strains. Oxcarbazepine and MHD produced increases in chromosomal aberrations and polyploidy in the Chinese hamster ovary assay in vitro in the absence of metabolic activation. 

Vamvakas S, Kordowich FJ, Dekant W, et al. 1988a. Mutagenicity of hexachloro-1,3-butadiene and its S-conjugates in the Ames test-role of activation by the mercapturic acid pathway in its nephrocarcinogenicity. Carcinogenesis 9 907-910. 

Strueturally related adduets include the 8-phenol derivatives, 8-(4"-hydroxyphenyl)-dG (8-p-PhOH-dG), and 8-(2"-hydroxyphenyl)-dG (8-o-PhOH-dG) that are generated by reaetion of phenol with excess nitrite.This reaetion generates diazoquinones that break down into hydroxyphenyl radicals that attach covalently to C-8 of dG. Diazoquinones are mutagenic in the Ames test without metabolie aetivation, and it is expected that hydroxyphenyl radicals and the isomeric adducts, 8-p-PhOH-dG and 8-o-PhOH-dG, play a key role in the mutagenie activity of diazoquinones. Careinogenic PAHs, such as benzo[a]pyrene (BP), also form C8-dG adducts (8-BP-dG, Fig. 7). 2,173 hile classical metabolic activation of... 

P. Doze, P.H. Elsinga, E.F. deVries, A. van Waarde, W. Vaalburg, Mutagenic activity of a fluorinated analog of the /l-adrenoceptor ligand carazolol in the Ames test, Nucl. Med. Biol. 27 (2000) 315-319. 

In most instances the test system will be self-evident (e.g., the animal to which the test article is administered or applied). Studies with micro-organisms, however, sometimes present difficulty in defining the test system. In the case of the Ames test, for example, the test system is not merely the colonies of salmonella or yeast, but includes in addition the culture medium, metabolic activation agent (if any), biotin, histidine, and buffer (if any). The last sentence of the definition makes it clear that untreated control groups also meet the definition of test system even though a test or control article is not administered or applied to such groups. 

It was surprising and exciting to find that the oeacetoxy-dibenzylnitrosamine (VII) was a potent mutagen in the Ames test, and since activation by a microsomal fraction was not required for this activity, VII may be an analog of a metabolite ( ). 

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