RESUMO
Relative sensitivity of in vitro biocompatibility test systems was explored. Cellular responses of 12 standardized cell lines to 20 materials representing a range of toxicity were measured. Each cell line and material combination was tested in duplicate using four different culture methods, and each culture plate was examined by two graders. Results of the tissue culture assays were compared to those obtained for the same materials in vivo using a 5-day rabbit intramuscular implant assay. Methods involving measurement of cellular growth (colony counts or percent of confluence) in serum-fortified media extracts of test samples were generally more sensitive and discriminating than those in which test materials were placed directly in cell cultures (measurement of zone of growth inhibition). There was good agreement between graders for all test methods. Antibiotics were not used in the test program. Based upon sensitivity, reproducibility, ability to discriminate materials, and grader agreement, 4 of the 12 cell lines and 2 of the 4 test methods appeared most suitable for screening and evaluation of materials. Agreement of results using these four cell lines with intramuscular implantation tests for the 30 materials ranged from 60 to 90%.
Assuntos
Materiais Biocompatíveis , Animais , Materiais Biocompatíveis/toxicidade , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Estudos de Avaliação como Assunto , Humanos , Camundongos , Próteses e Implantes , CoelhosAssuntos
Dietilexilftalato/farmacologia , Ácidos Ftálicos/farmacologia , Animais , Carcinógenos , Fenômenos Químicos , Química , Dietilexilftalato/metabolismo , Dietilexilftalato/toxicidade , Feminino , Feto/efeitos dos fármacos , Humanos , Absorção Intestinal , Cinética , Mutagênicos , Gravidez , Reprodução/efeitos dos fármacos , Distribuição TecidualRESUMO
Laboratory screening of a series of halogenated methyl isopropyl ethers revealed sevoflurane (fluoromethyl-1,1,1,3,3,3,-hexafluroro-2-propyl ether) as a potent nonexplosive inhalational anesthetic agent. Sevoflurance, a pleasant-smelling liquid, boils at 58.5 degrees C at 760 torr and has a vapor pressure of 200 torr at 25 degrees C. It is nonflammable in air and has lower flammability limits of 11 vols percent in O2 and 10 vols percent in N2O. Sevoflurane exhibits limited chemical reactivity in vitro; it is subject to slight but measurable hydrolysis, and reacts with soda lime to form traces of related ethers. It provides rapid anesthetic induction and recovery consistent with its low distribution coefficients (blood:gas, 0.6; corn oil:gas, 41.6; olive oil:gas, 53.4). In dogs, anesthetic concentrations of sevoflurane did not produce spontaneous cardiac arrhythmias and did not sensitize the heart to epinephrine. Electroencephalographic patterns were similar to those observed during anesthesia with halothane. In rats, small increases in the urinary excretion of inorganic fluoride ion occurred during the first 24 hours after anesthesia. Subacute studies in dogs and rats, using closed-circle absorption with soda lime, revealed no toxicologically significant changes in animals anesthetized frequently for 2 weeks. Sevoflurane appears to be a unique volatile anesthetic agent worthy of further study.