Geno toxicity

The vast majority of in vivo tests show no geno-toxicity of mono- and dialkyltins. Results from in vitro tests are variable, with little indication of DNA reactivity. There are, however, indications of clastogenicity and effects on spindle formation in mitosis in vitro. 

Cemeli E, ED Wagner, D Anderson, SD Richardson, MI Plewa (2006) Modulation of the cytoxicity and geno-toxicity of the drinking water disinfection byproduct iodoacetic acid by suppressors of oxidative stress. Environ Sci Technol 40 1878-1883. 

Numerous studies have demonstrated that degradation products of (3-carotene exhibit deleterious effects in cellular systems (Alija et al., 2004, 2006 Hurst et al., 2005 Salerno et al., 2005 Siems et al., 2003). A mixture of (3-carotene degradation products exerts pro-apoptotic effects and cytotoxicity to human neutrophils (Salerno et al., 2005 Siems et al., 2003), and enhances the geno-toxic effects of oxidative stress in primary rat hepatocytes (Alija et al., 2004, 2006), as well as dramatically reduces mitochondrial activity in a human leukaemic cell line, K562, and RPE 28 SV4 cell line derived from stably transformed fetal human retinal pigmented epithelial cells (Hurst et al., 2005). As a result of degradation or enzymatic cleavage of (3-carotene, retinoids are formed, which are powerful modulators of cell proliferation, differentiation, and apoptosis (Blomhoff and Blomhoff, 2006). 

Amundson SA et al. Fluorescent cDNA microarray hybridisation reveals complexity and heterogeneity of cellular geno-toxic stress responses. Oncogene 1999 18 3666-3672. 

Andrae U. Evidence for the involvement of cytochrome P-450-dependent mono-oxygenase(s) in the formation of geno-toxic metabolites from N-hydroxyurea. Biochem Biophys Res Commun 1984 118 409-415. 

Murthy MS Induction of gene conversion in diploid yeast by chemicals Correlation with mutagenic action and its relevance in geno-toxicity screening. Mutat Res 1979 64 1-17. 

The pathway of delivery seems to be an important determinant in the geno-toxicity of nickel compounds in vitro. Regarding X-chromosome fragmentation in CHO cells [306, 444], nickel chloride was reported to be ineffective by contrast to crystalline NiS. Delivery and uptake by phagocytosis of NiCl2, artificially encapsulated in liposomes, induced fragmentation. 

The applicability of Eq. (45) to a broad range of biological (i.e., toxic, geno-toxic) structure-activity relationships has been demonstrated convincingly by Hansch and associates and many others in the years since 1964 [60-62, 80, 120-122, 160, 161, 195, 204-208, 281-285, 289, 296-298]. The success of this model led to its generalization to include additional parameters in attempts to minimize residual variance in such correlations, a wide variety of physicochemical parameters and properties, structural and topological features, molecular orbital indices, and for constant but for theoretically unaccountable features, indicator or dummy variables (1 or 0) have been employed. A widespread use of Eq. (45) has provided an important stimulus for the review and extension of established scales of substituent effects, and even for the development of new ones. It should be cautioned here, however, that the general validity or indeed the need for these latter scales has not been established. 

Reactive chemicals are used to manufacture drugs and a proportion of these are geno-toxic. A draft guideline has been issued by the Europe and CHMP that seeks to control patient exposure to most genotoxic contaminants to below a Threshold of Toxicological concern of 1.5 xg/day. This is based on modelling data on known human carcinogens where such concentrations for specific compoimds would not be expected to increase human cancer above 1 per 10 exposed individuals. ... 

Administered by gavage for 1.5 years, allyl chloride was not carcinogenic to rats but caused a low incidence of squamous cell carcinomas of the forestomach in mice. It is geno-toxic in a number of in vitro assays and is a direct alkylating agent." The lARC has determined that there is inadequate evidence in experimental animals for the carcinogenicity of allyl chloride and that it is not classifiable as to its carcinogenicity to humans. ... 

Wild D, Eckhardt K, Harnasch D, et al Geno-toxicity study of CS (ottZ o-chlorobenzylidene-malononitrile) in Salmonella, Drosophila and mice. Arch Toxicol 54 167-170, 1983... 

Chlorodibromomethane was not geno-toxic in vivo but gave positive results in a number of in vitro assays. ... 

Chlorpyrifos was not carcinogenic in rats fed up to 3.0mg/kg/day for 2 years.Although many studies reported negative results, geno-toxic effects, including induction of micronuclei, increases in sister chromatid exchanges and chromosomal aberrations, have been reported in some smdies. ... 

BHT has given primarily negative results in a large number of in vivo and in vitro geno-toxic assays. ... 

Equivocal results have been found in geno-toxic assays, but endosulfan was mutagenic and clastogenic and induced effects on cell cycle kinetics in various in vivo and in vitro tests. ... 

Ethyl acrylate was negative in most geno-toxic assays. 

There was no evidence of carcinogenicity in rats or mice exposed to 0.01, 0.05, or 0.2 ppm for 6 hours/day for 2 years. Pigmentation of the respiratory epithelium occurred in both species, and squamous metaplasia of the laryngeal epithelium occurred in female rats. Geno-toxic assays have been uniformly negative. 

No effect on fertility was seen in male rats treated orally." Hexylene glycol was not geno-toxic in a variety of assays." ... 

Methyl parathion is not strongly geno-toxic it has produced both positive and negative results in both eukaryotic and prokaryotic assays. ... 

Chronic exposure to hepatotoxic doses of DMN has also been found to suppress humoral and cellular immunity in mice. DMN is geno-toxic in a wide variety of assays inducing DNA synthesis, chromosomal aberrations, sister chromatid exchange, and bacterial mutations. " The formation of DNA adducts by metabolites of DMN may play a critical role in the carcinogenic process."... 

The possible carcinogenicity of nitrous oxide has been studied in dentists and chairside assistants with occupational exposures. No effect was observed in male dentists, but a 2.4-fold increase in cancer of the cervix in heavily exposed female assistants was reported. Other epidemiological reports of workers exposed to waste anesthetic gases have been negative. Carcinogenic bioassays in animals have yielded negative results. Nitrous oxide was not geno-toxic in a variety of assays. ... 

Propionic acid does not appear to be geno-toxic. In vitro mutagenicity assays with propionic acid, using Salmonella typhimurium or Saccharcmyces cerevisiae, were negative with or without metabolic activation. ... 

Batt KJ, Healy CE, Kneiss JJ, et al Geno-toxicity testing of tributyl phosphate. Environ Mol Mutagen 19(20) 5, 1992... 

DeMerlis CC, Schoneker DR, Borzelleca JF. A subchronic toxicity study in rats and geno-toxicity tests with an aqueous ethylcellulose dispersion. Food Chem Tox 2005 43 1355. 

Neomycin is particularly ototoxic and nephrotoxic when given parenterally. As with gentamicin and kanamycin, the nephrotoxicity may be reversible but the ototoxicity is usually irreversible and deafness may occur following oral administration, instillation into cavities, or topical use. It may block neuromuscular action and respiratory depression has been reported. Local treatments may cause hypersensitivity, rashes, pruritus, and anaphylaxis. Neomycin is not geno-toxic. 

Parathion methyl 6-24 300-420 Rat, 2-year diet, NOAEL 2-mg/kg diet Rat embriotoxicity and feto-toxicity at 1 mg/kg. Some test have demonstrated certain evidence of geno-toxicity. 6.6-7.6 2.7-6.9 0.291 Insecticide, acaricide... 

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