RESUMO
The Ames MPF™ is a miniaturized, microplate fluctuation format of the Ames test. It is a standardized, commercially available product which can be used to assess mutagenicity in Salmonella and E. coli strains in 384-well plates using a color change-based readout. Several peer-reviewed comparisons of the Ames MPF™ to the Ames test in Petri dishes confirmed its suitability to evaluate the mutagenic potential of a variety of test items. An international multicenter study involving seven laboratories tested six coded chemicals with this assay using five bacterial strains, as recommended by the OECD test guideline 471. The data generated by the participating laboratories was in excellent agreement (93%), and the similarity of their dose response curves, as analyzed with sophisticated statistical approaches further confirmed the suitability of the Ames MPF™ assay as an alternative to the Ames test on agar plates, but with advantages with respect to significantly reduced amount of test substance and S9 requirements, speed, hands-on time and, potentially automation.
Assuntos
Escherichia coli , Salmonella typhimurium , Escherichia coli/genética , Salmonella typhimurium/genética , Mutagênicos/toxicidade , Mutagênese , Testes de Mutagenicidade/métodosRESUMO
The frog embryo teratogenesis assay Xenopus (FETAX) test is a development toxicity screening test. Due to the small amount of compound needed and the capability to study organogenesis in a short period of time (96 h), FETAX test constitutes an efficient development toxicity alert test when performed early in drug safety development. The test is conducted on fertilized Xenopus laevis mid-blastula-stage eggs over the organogenesis period. Compound teratogenic potential is determined after analysis of the mortality and malformation observations on larvae. In parallel, FETAX test provides also information concerning embryotoxic effect based on larva length.
Assuntos
Bioensaio/métodos , Testes de Toxicidade/métodos , Animais , Embrião não Mamífero/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/metabolismo , Teratogênicos/toxicidade , Xenopus laevis/embriologiaRESUMO
Frog embryo teratogenesis assay on Xenopus (FETAX) has been routinely used in our laboratory for the last 12 years as a routine developmental toxicity screening test for pharmaceutical candidate compounds. To date, out of more than 400 candidates tested in FETAX, around 60 have also been evaluated in mammalian embryotoxicity studies according to standard ICH protocols.Compound teratogenic potential in both FETAX and mammalian embryotoxicity studies is determined after analysis of the developmental toxicity characterized by embryotoxicity, growth delay, and/or potential to induce malformations. Based on this experience, the predictivity of FETAX is 81% with a minimal proportion of false positive results.
Assuntos
Teratologia/métodos , Xenopus laevis/embriologia , Animais , Embrião de Mamíferos/anormalidades , Embrião de Mamíferos/efeitos dos fármacos , Embrião não Mamífero/anormalidades , Embrião não Mamífero/efeitos dos fármacos , Feminino , Feto/anormalidades , Feto/efeitos dos fármacos , Masculino , Coelhos , Ratos , Teratogênicos/toxicidade , Teratologia/legislação & jurisprudênciaRESUMO
The Frog Embryo Teratogenesis Assay Xenopus (FETAX) test is a development toxicity screening test. Due to the small amount of compound needed and the capability to study organogenesis in a short period of time (96 h), FETAX test constitutes an efficient development toxicity alert test when performed early in drug safety development. The test is conducted on fertilized Xenopus laevis mid-blastula stage eggs over the organogenesis period. Compound teratogenic potential is determined after analysis of the mortality and malformation observations on larva. In parallel, FETAX test provides also information concerning embryotoxic effect based on larva length.