Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
J Pharm Sci ; 110(7): 2743-2752, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33647275

RESUMEN

Therapeutic proteins are among the most widely prescribed medications, with wide distribution and complex supply chains. Shipping exposes protein formulations to stresses that can trigger aggregation, although the exact mechanism(s) responsible for aggregation are unknown. To better understand how shipping causes aggregation, we compared populations of aggregates that were formed in a polyclonal antibody formulation during live shipping studies to populations observed in accelerated stability studies designed to mimic both the sporadic high g-force and continuous low g-force stresses encountered during shipping. Additionally, we compared the effects on aggregation levels generated in two types of secondary packaging, one of which was designed to mitigate the effects of large g-force stresses. Aggregation was quantified using fluorescence intensity of 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid (bis-ANS) dye, size exclusion high performance liquid chromatography (SECHPLC), and flow imaging microscopy (FIM). FIM was also combined with machine learning methods to analyze particle morphology distributions. These comparisons revealed that the morphology distributions of aggregates formed during live shipping resemble distributions that result from low g-force events, but not those observed following high g-force events, suggesting that low g-force stresses play a predominant role in shipping-induced aggregation.


Asunto(s)
Anticuerpos , Proteínas , Aprendizaje Automático , Agregado de Proteínas
2.
J Toxicol Environ Health A ; 81(16): 774-791, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29985787

RESUMEN

Fischer-Tropsch (FT) Synthetic Paraffinic Kerosene (SPK) jet fuel is a synthetic organic mixture intended to augment petroleum-derived JP-8 jet fuel use by the U.S. armed forces. The FT SPK testing program goal was to develop a comparative toxicity database with petroleum-derived jet fuels that may be used to calculate an occupational exposure limit (OEL). Toxicity investigations included the dermal irritation test (FT vs. JP-8 vs. 50:50 blend), 2 in vitro genotoxicity tests, acute inhalation study, short-term (2-week) inhalation range finder study with measurement of bone marrow micronuclei, 90-day inhalation toxicity, and sensory irritation assay. Dermal irritation was slight to moderate. All genotoxicity studies were negative. An acute inhalation study with F344 rats exposed at 2000 mg/m3 for 4 hr resulted in no abnormal clinical observations. Based on a 2-week range-finder, F344 rats were exposed for 6 hr per day, 5 days per week, for 90 days to an aerosol-vapor mixture of FT SPK jet fuel (0, 200, 700 or 2000 mg/m3). Effects on the nasal cavities were minimal (700 mg/m3) to mild (2000 mg/m3); only high exposure produced multifocal inflammatory cell infiltration in rat lungs (both genders). The RD50 (50% respiratory rate depression) value for the sensory irritation assay, calculated to be 10,939 mg/m3, indicated the FT SPK fuel is less irritating than JP-8. Based upon the proposed use as a 50:50 blend with JP-8, a FT SPK jet fuel OEL is recommended at 200 mg/m3 vapor and 5 mg/m3 aerosol, in concurrence with the current JP-8 OEL.


Asunto(s)
Aerosoles/toxicidad , Queroseno/toxicidad , Exposición Profesional/análisis , Parafina/toxicidad , Administración por Inhalación , Animales , Médula Ósea/efectos de los fármacos , Femenino , Hidrocarburos/toxicidad , Masculino , Ratones , Pruebas de Micronúcleos , Pruebas de Mutagenicidad , Conejos , Ratas , Ratas Endogámicas F344 , Pruebas de Toxicidad
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA