RESUMO
This study describes the within- and between-laboratory reproducibility (WLR and BLR) of a Time-to-Toxicity (TTT) approach for chemicals based on the SkinEthic™ HCE tissue construct, capable to distinguish chemicals that do not require classification for serious eye damage/eye irritation (No Cat.) from chemicals that require classification for eye irritation (Cat. 2), and serious eye damage (Cat. 1). The WLR and BLR was assessed with three participating laboratories. Each laboratory tested 40 coded chemicals in three independent runs. The predictive capacity of the method was assessed on a larger set of 150 chemicals (70 liquids and 80 solids) by combining the results of this study with the results of the test method developer. The WLR for the 20 liquids ranged from 85% to 95% with a BLR of 90%. For the 20 solids, a WLR and BLR of 100% was obtained. The test method developer obtained a WLR of 80% and 95%, based on 50 liquids and 48 solids tested in three independent runs, respectively. Regarding the predictive capacity, the SkinEthic™ HCE TTT test method identified 80.8% Cat. 1, 69.2% Cat. 2, and 74.9% No Cat. correctly. An independent peer review panel concluded that based on all available data, the relevance and reliability of the SkinEthic™ HCE TTT has been demonstrated for discriminating the three UN GHS eye hazard categories.
Assuntos
Epitélio Corneano/efeitos dos fármacos , Irritantes/classificação , Irritantes/toxicidade , Testes de Toxicidade/métodos , Alternativas aos Testes com Animais , Humanos , Laboratórios , Reprodutibilidade dos Testes , Nações UnidasAssuntos
Anti-Hipertensivos/efeitos adversos , Nefropatias/induzido quimicamente , Losartan/efeitos adversos , Escleroderma Sistêmico/induzido quimicamente , Síndrome de Abstinência a Substâncias/etiologia , Doença Aguda , Anti-Inflamatórios/efeitos adversos , Causalidade , Feminino , Humanos , Hipertensão/tratamento farmacológico , Nefropatias/sangue , Nefropatias/diagnóstico , Angiografia por Ressonância Magnética , Pessoa de Meia-Idade , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/diagnóstico , Esteroides , Síndrome de Abstinência a Substâncias/sangue , Síndrome de Abstinência a Substâncias/diagnóstico , Ultrassonografia DopplerRESUMO
[formula: see text] Oxidation of 2,3-disubstituted 1,4-dioxenes 3 with m-chloroperbenzoic acid in methanol followed by nucleophilic addition of allyltrimethylsilane in the presence of TiCl4 afforded dienes 5, which have been converted to oxabicyclo[4.2.1] nonenes 8 in excellent yield by olefin ring-closing metathesis reaction.