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Toxicol Ind Health ; 25(1): 5-13, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19318500

RESUMO

The Royal Australian Air Force (RAAF) has reported that personnel involved in F-111 fuel tank maintenance were concerned that exposure to a range of chemicals during the period 1977 to mid-1990s was the cause of health problems, including cancer. Particular concern was directed at SR-51, a desealant chemical mixture containing the following four solvents: aromatic 150 solvent (Aro150), dimethylacetamide, thiophenol (TP), and triethylphosphate. The present study examined the mutagenic potential of SR-51 using a range of well-known mutagen and genotoxin assays. The tests used were i) a modified version of the Ames test, ii) the mouse lymphoma assay, iii) the comet assay (a single-cell gel electrophoresis assay), and iv) a mouse micronucleus test. The modified Ames test used mixed bacterial strains in liquid suspension media. The Ames test results showed that SR-51 (tested up to the cytotoxic concentration of 36 microg/ml, 30 min incubation) in the presence and absence of S9 metabolic activation was not mutagenic. The mouse lymphoma assay used cultured mouse lymphoma cells in a microwell suspension method. The mouse lymphoma assay was also negative with SR-51 (tested up to the cytotoxic concentration of 22.5 microg/ml, 3 h incubation) in the presence and absence of S9 metabolic activation. The Comet assay, using cultured mouse lymphoma cells, showed no evidence of DNA damage in cells exposed up to the cytotoxic concentration of SR-51 at 11.25 microg/ml. The in-vivo mouse micronucleus test was undertaken in wild-type C57Bl6J male mice dosed orally with SR-51for 14 days with a single daily dose up to 360 mg/kg/day (the maximum-tolerated dose). No increases were observed in micronuclei (MN) frequency in bone marrow collected (24 h after final dose) from SR-51-treated mice compared to the number of MN observed in bone marrow collected from untreated mice. Tissues collected from treated mice at necropsy demonstrated a significant increase in spleen weights in the high dose mice. Gas chromatography analysis of SR-51 identified more than 40 individual components and an oxidation product, diphenyldisulfide derived from TP under conditions of mild heating. In conclusion, there was no evidence that SR-51 is mutagenic.


Assuntos
Acetamidas/toxicidade , Dano ao DNA , DNA/efeitos dos fármacos , Mutagênicos/toxicidade , Exposição Ocupacional/efeitos adversos , Organofosfatos/toxicidade , Fenóis/toxicidade , Solventes/toxicidade , Compostos de Sulfidrila/toxicidade , Acetamidas/química , Acetamidas/classificação , Animais , Linhagem Celular Tumoral , Cromatografia Gasosa , Ensaio Cometa , Leucemia L5178 , Masculino , Camundongos , Testes para Micronúcleos , Testes de Mutagenicidade , Mutagênicos/química , Mutagênicos/classificação , Mutação/efeitos dos fármacos , Mutação/genética , Tamanho do Órgão/efeitos dos fármacos , Organofosfatos/química , Organofosfatos/classificação , Fenóis/química , Fenóis/classificação , Ratos , Ratos Sprague-Dawley , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismo , Solventes/química , Solventes/classificação , Baço/efeitos dos fármacos , Baço/patologia , Compostos de Sulfidrila/química , Compostos de Sulfidrila/classificação
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