Ame test

The results of the Ames test for mutagenesis Indicate that many ruthenium compounds Introduce serious lesions into cellular genetic material so that an error-prone DNA repair mechanism is Induced. These results are similar to those obtained for clsplatln (M) and suggest that these complexes probably bind directly to nuclear DNA. In concert with this, many of the ruthenium complexes also Inhibit cellular DNA synthesis (H, ), another property also noted for the cls-platlnum drugs. Unfortunately, however, there Is no correlation between either of these studies and the antitumor activity of ruthenium compounds tested In animal systems. 

A high percentage of the compounds tested, which would be expected to function as Ru(III)-prodrugs, have exhibited antitumor activity In rats. An exception to this are those complexes containing blpyrldyl or o-phenanthrollne ligands which strongly stabilize the lower valent state and which 

ACS Symposium Series American Chemical Society Washington, DC, 1980. 

Compound Time (Hrs) Tumor Blood Muscle (Tumor/Tissue Ratios in Liver Kidney Parentheses) TCI 

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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. 

The long latent periods involved in development of cancers make correlation of chemical exposures and disease extremely difficult. This can be countered pardy with tests on naturally short-Hved animals. Tests on bacteria, eg, the Ames test, may permit rapid detection of cancer potential, although there is no direct relationship between the results of bacterial tests and the effects of the tested chemicals on humans (56). 

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. 

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. 

In order to expedite the launch of a new chemical and allow further time to complete the toxicological package for full registration, a "limited announcement" is normally used. This requkes only parts of the full toxicological packages, usually acute toxicity and Ames test. Consequentiy, it is less expensive ( 20,000) and quicker (90 days) than full registration. However, only 1 t or less of the chemical per year is allowed to be sold in the EEC. 

S u/woue//j/mammalian microsome assay (Ames test)... 

The Ames test measures the reversion from mutant to wild type form (back-mutation) in a culture of Salmonella. The test is used to screen large numbers of compounds for their potential mutagenicity. 

Alternative Splicing Alzheimer s Disease Ames Test Amiloride... 

Studies on the reproductive function (three generations) and intrauterine development of rat showed no impairment of the rate of fertility and no sign of any teratogenic effect. The Ames test on mutagenicity was negative [101]. 

Figure 4.7 An explanation of the bacterial reverse-mutation test (the Ames test).

Kitchin KT, Brown JL, Kulkami AP. 1993. Predicting rodent carcinogenicity of Ames test false positives by in vivo biochemical parameters. Mutat Res 290 155-164. 

II 1 -100 kg p.a. Public (including as part of a formulation) As Category I + Ames test... 

These principles of reverse mutation are utilized in one important method, the Ames test (section 4.4.2), which is used to detect compounds that act as mutagens or carcinogens (most carcinogens are mutagens). 

The Ames test is used to sereen a wide variety of chemieals for potential eareinogenicity... 

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