GENOTOXIC

Teratogenic effects have been noted with 2- and 4-aminophenol in the hamster, but 3-aminophenol was without effect in the hamster and rat (129,130). 4-Aminophenol is known to inhibit DNA synthesis and alter DNA stmcture in human lymphoblasts (131,132) and is mutagenic in mouse micronuclei tests (133). The aminophenols have been shown to be genotoxic, as evidenced by the induction of sister chromatid exchanges (134,135), but they also exert a protective effect against DNA interaction with other noxious chemicals (136). After assessment of available data a recent report stated that the aminophenols were safe as cosmetic ingredients in their present uses and concentrations (137). 

Literature reports iadicate that sodium sorbate causes weak genotoxic effects such as chromosomal aberrations and mutations ia mammalian cells (172,173). This effect is thought to be caused by oxidative products of sodium sorbate ia stored solutions (173—175). The main oxidation product of sodium sorbate, 4,5-oxohexenoate, is mutagenic ia a Salmonella mammahan-microsome test (176). Sorbic acid and potassium sorbate were not genotoxic under the same test procedures (167,172,174—177). 

A further consensus developed within the scientific community regarding the relative carcinogenicity of the different types of asbestos fibers. There is strong evidence that the genotoxic and carcinogenic potentials of asbestos fibers are not identical in particular mesothelial cancer is mostiy, if not exclusively, associated with amphibole fibers (43). 

The key to hexavalent chromium s mutagenicity and possible carcinogenicity is the abiHty of this oxidation state to penetrate the cell membrane. The Cr(VI) Species promotes DNA strand breaks and initiates DNA—DNA and DNA-protein cross-links both in cell cultures and in vivo (105,112,128—130). The mechanism of this genotoxic interaction may be the intercellular reduction of Cr(VI) in close proximity to the nuclear membrane. When in vitro reductions of hexavalent chromium are performed by glutathione, the formation of Cr(V) and glutathione thiyl radicals are observed, and these are beHeved to be responsible for the formation of the DNA cross-links (112). 

OSHA considers that, at excessive levels, ethylene oxide may present reproductive, mutagenic, genotoxic, neurologic, and sensitization hazards. In addition, ethylene oxide is considered by OSHA, lARC, and NTP as a potential human carcinogen. 

The first application is related to tire molecular interaction between surface-liirked DNA and pollutants or dmgs, in order to develop a simple device for rapid screening of toxic compounds or better to try to quantify the genotoxicity of a specific sample. 

Muragenicuy, genotoxicity Rats, mice, bacterial strains, yeasts Few days Potential to cause mutations, chromosomal damage, and... 

However, for some type of adverse effects, such as genotoxicity, carcinogenicity, and respiratory sensitization, it may not be possible from present knowledge to define this threshold of activity, so we may conclude that any level of exposure might carry some finite risk. In this case, OELs should be established at levels sufficiently low to avoid risks these are called pragmatic OELs. 

Recently, 202 and 203 were found to significantly reduce the mutation frequency induced by BaP in vivo as well (00UP3). Previously, flie same group had pointed out that some genotoxic effects could result from UV irradiation of tryptophan, but this had not been attributed to lipophilic substances like 202 and 203 (94MI5). 

Antoch M, Kondratov R, Takahashi J (2005) Circadian clock genes as modulators of sensitivity to genotoxic stress. Cell Cycle 4901-907... 

S1 C(R1) Dose Selection for Carcinogenicity Studies of Pharmaceuticals Limit Dose S2A Guidance on Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals S2B Genotoxicity A Standard Battery for Genotoxicity Testing of Pharmaceuticals Toxicokinetics and Pharmacokinetics... 

Genotoxicity studies are required to identify compounds that can induce genetic damage ranging from single point gene mutations to gross alterations of chromosomal structure. Such effects are taken as indicative of the potential to cause cancer or heritable defects in humans. A standard battery of three types of test is recommended ... 

GL23 Safety genotoxicity Studies to evaluate the safety of residues of veterinary drug in human food genotoxicity testing... 

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