RESUMO
A battery of in vitro and in vivo tests were conducted on HCFC-141b as a vapour. Bacterial gene mutation assays with Escherichia coli and Salmonella typhimurium were negative in all tester strains. In vitro chromosomal aberration assays were positive on CHO cells but negative on human lymphocytes. Moreover, HCFC-141b was negative in vivo in a mouse micronucleus inhalation assay. On the basis of these data and previously reported genotoxicity testing, HCFC-141b is considered non-genotoxic. Groups of 80 male and 80 female Sprague-Dawley rats were exposed, by inhalation (6 hr/day, 5 days/wk) to vapours of HCFC-141b for 104 wk at target concentrations of 0 (control), 1500, 5000 and 20,000 ppm (increased from 15,000 ppm after 17 wk of exposure). No exposure-related effects of toxicological significance were noted with respect to survival, clinical signs, ophthalmoscopy, haematology, clinical chemistry, urinalysis or organ weight analysis. Reduced food intake and body weight gain were noted in both sexes of the 15,000 ppm group during the first 16 wk; thereafter, body weight gains in all groups were similar although the intergroup differences in body weight remained evident. Reduced food intake persisted in both sexes through wk 52 and in females during the second year of exposure. Treatment-related effects on macroscopic pathology were confined to increased incidences of testicular masses and altered appearance. Microscopic pathology examinations confirmed the testes as the target organ with findings of increased incidences of benign interstitial cell tumours and hyperplasia at 5000 and 20,000 ppm. The no-observable-adverse-effect level (NOAEL) was 1500 ppm. The testicular changes at high exposure levels were considered to be due to a change of the senile hormonal imbalance in geriatric rats and of little significance for the assessment of human health effects.
Assuntos
Clorofluorcarbonetos/toxicidade , Mutagênicos/toxicidade , Administração por Inalação , Animais , Peso Corporal , Células CHO , Carcinógenos/toxicidade , Etano Clorofluorcarbonos , Aberrações Cromossômicas , Cricetinae , Feminino , Humanos , Masculino , Testes para Micronúcleos , Testes de Mutagenicidade , Ratos , Ratos Sprague-Dawley , Medição de Risco , Salmonella typhimurium , Fatores de TempoAssuntos
Testes de Mutagenicidade/normas , Animais , Medula Óssea/efeitos dos fármacos , Carcinógenos/toxicidade , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Dose Letal Mediana , Camundongos , Testes para Micronúcleos/métodos , Testes para Micronúcleos/normas , Testes de Mutagenicidade/métodos , Ratos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
A series of 6 studies has been performed to evaluate the potential genotoxic effect of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H- imidazol-1-yl)ethoxy-methyl]benzo[b]thiophene (sertaconazole, FI 7045, CAS 99592-32-2). From these studies, the reverse mutation assay on Salmonella typhimurium, sex-linked recessive lethal mutations on Drosophila and genetic mutations in cultured mammal cells allowed to study the genetic mutations in prokaryotes and eukaryotes. In vitro and in vivo chromosomal aberrations were studied using human lymphocytes cytogenetic test, micronucleus test and sister chromatid exchange test. The results obtained in these studies, which are complemented one another, demonstrated that sertaconazole did not induce any signs of promutagenic, mutagenic or clastogenic activity or interference with the chromosomal segregation process.
Assuntos
Antifúngicos/toxicidade , Imidazóis/toxicidade , Mutagênicos/toxicidade , Tiofenos/toxicidade , Animais , Células CHO , Células Cultivadas , Aberrações Cromossômicas , Cricetinae , Drosophila melanogaster , Linfócitos/efeitos dos fármacos , Camundongos , Testes de Mutagenicidade , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Troca de Cromátide Irmã/efeitos dos fármacosRESUMO
A glucose isomerase enzyme, obtained from Streptomyces murinus, was produced by a fermentation process and subjected to a series of tests to investigate its safety in use and manufacture. It was not mutagenic (Ames test, using liquid culture) nor did it provoke chromosomal damage (rat bone marrow cytogenetics test). It did not contain (nor did the organism produce) antimicrobial activity or macrolidpolyene antibiotics. It had no teratogenic activity when administered to pregnant rats at 100,000 ppm in the diet. It was without effect upon rats when administered at this dietary concentration for 4 weeks. Dietary administration at 5000, 15,000 or 50,000 ppm to rats for 13 weeks resulted in nephrocalcinosis in females at all dosages (probably a physiological response to the altered calcium:phosphate ratio in the admixed diet) and status spongiosus in the brains of males receiving 50,000 ppm. As the finding of nephrocalcinosis in rats is generally agreed to be of no toxicological importance with regard to the use in man, the dietary concentration of 15,000 ppm was considered to be highest no-effect level. This level corresponds to an intake of some 1000 mg/kg/day, which represents approximately 8000 times the human intake based on a conservative estimation.
Assuntos
Aldose-Cetose Isomerases , Carboidratos Epimerases/toxicidade , Streptomyces/enzimologia , Animais , Aberrações Cromossômicas , Dieta , Feminino , Testes de Mutagenicidade , Nefrocalcinose/induzido quimicamente , Gravidez , Ratos , Ratos Endogâmicos , Salmonella/efeitos dos fármacosRESUMO
41 compounds or mixtures of diverse structure and application have been tested for genotoxic activity. The materials were tested in bacterial mutation assays, in Saccharomyces cerevisiae JD1 for mitotic gene conversion and in a cultured rat-liver cell line for structural chromosome damage. 11 compounds were bacterial mutagens, 4 induced mitotic gene conversion in yeast and 5 were positive in the chromosome assay. 5 of the materials were positive in bacteria only and 2 compounds induced chromosome damage in cultured cells in the absence of mutation in bacteria or gene conversion in yeast. The materials were tested over a 5-year period and the performance and evolution of the 3 assays during this time is evaluated. The results are considered in relation to the structure of the chemicals and the genotoxicity of related compounds.
Assuntos
Mutagênicos , Medicina do Trabalho , Animais , Células Cultivadas , Cromossomos/efeitos dos fármacos , Conversão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Mitose/efeitos dos fármacos , Testes de Mutagenicidade , Ratos , Saccharomyces cerevisiae/efeitos dos fármacos , Salmonella typhimurium/efeitos dos fármacos , Relação Estrutura-AtividadeAssuntos
Carcinógenos/farmacologia , Cricetinae/genética , Cricetulus/genética , Mutagênicos , Especificidade de Órgãos , Animais , Células Cultivadas , Mucosa Gástrica/metabolismo , Marcadores Genéticos , Rim/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Masculino , Mutação , Bexiga Urinária/metabolismoRESUMO
An in vitro chromosome assay has been developed which utilises an epithelial-like cell line derived from rat liver. The cell line, designed RL1, retains sufficient metabolic enzyme activity to detect chromosome damage induced by a variety of chemical mutagens and carcinogens without the incorporation of an extrinsic metabolising system. The cells are grown on standard glass microscope slides, exposed to the test chemical and processed in situ for metaphase analysis. In a small validation study, chromosome damage was detected in cultures exposed to the direct-acting agents, methyl nitronitrosoguanine, 4-nitroquinoline-N-oxide, propylene oxide, epichlorohydrin and 1,2:3,4-diepoxybutane and to compounds requiring metabolic activation, including cyclophosphamide, 2-acetylaminofluorene, 3-methylcholanthrene and 7,12-dimethylbenz[a]anthracene. Negative results were obtained with pyrene and carbon tetrachloride.
Assuntos
Cromossomos/efeitos dos fármacos , Técnicas Citológicas , 4-Nitroquinolina-1-Óxido/farmacologia , Animais , Linhagem Celular , Epicloroidrina/farmacologia , Compostos de Epóxi/farmacologia , Técnicas Genéticas , Fígado , Metilnitronitrosoguanidina/farmacologia , RatosRESUMO
In order to investigate the relationship between mutation and carcinogenesis in vivo, a method has been developed in which somatic mutation can be studied in specific organs of Chinese hamsters after acute dosing with chemical carcinogens. In preliminary experiments an increase in mutation was detected in cultures derived from lung tissue of hamsters after intraperitoneal dosing with the direct-acting mutagen and weak carcinogen, ethyl methanesulphonate, or with diethylnitrosamine, a carcinogen which requires metabolic activation before mutagenic activity can be demonstrated in vitro. Subsequent experiments have shown the induction of mutation in cells dereived from the bladder of animals dosed with diethylnitrosamine or methyl nitrosourea and in a variety of tissues from animals dosed with methane-sulphonates, 2-acetylaminofluorene and 3-methylcholanthrene.