RESUMO
The environmental fate and effects of pioglitazone prescribed for the treatment of type 2 diabetes were evaluated in an environmental risk assessment following the European Medicines Agency (EMA) "Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use"; EMEA/CHMP/SWP/4447/00. A predicted environment concentration (PEC) for surface water was estimated at 0.023µgL(-1), (action limit of 0.01µgL(-1)) triggering a comprehensive battery of laboratory evaluations. Pioglitazone and its major metabolites were determined not to significantly adsorb to sewage solids, were not persistent in the aquatic environment, did not bioaccumulate and were non-toxic to aquatic organisms. Pioglitazone does not pose an unacceptable risk to groundwater supplies, with concentrations not anticipated to be a risk to aquatic organisms or human drinking water supplies. Pioglitazone does not pose a risk of secondary poisoning.
Assuntos
Hipoglicemiantes/análise , PPAR gama/agonistas , Tiazolidinedionas/análise , Poluentes Químicos da Água/análise , Animais , Clorófitas/efeitos dos fármacos , Cyprinidae/metabolismo , Daphnia/efeitos dos fármacos , Água Doce/química , Sedimentos Geológicos/química , Hipoglicemiantes/metabolismo , Hipoglicemiantes/toxicidade , Cinética , Pioglitazona , Medição de Risco , Tiazolidinedionas/metabolismo , Tiazolidinedionas/toxicidade , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade , Poluição Química da Água/estatística & dados numéricosRESUMO
A standardized bioassay using the face fly, Musca autumnalis L. (Diptera: Muscidae), was developed to test the lethal and sublethal toxicity of parasiticide residues in livestock dung. The repeatability of this test was assessed for the parasiticide ivermectin in seven tests performed in four laboratories in Germany and France. Additional results of limit tests were provided by two laboratories from the UK. Test results had an acceptable range of heterogeneity. The calculated effect concentration at which 50% emergence was observed (EC50) averaged 4.65+/-2.17 (Standard Deviation (SD) microg ivermectin/kg fresh dung (range: 1.20-7.7)). Effects on emergence were, with one exception, not observed below the No Observed Effect Concentration (NOEC) ranging between 1.11 and 3.33microg ivermectin/kg. No effect on development time was observed. We conclude that the face fly is suitably sensitive, and the methods sufficiently repeatable, to support use of this standardized bioassay by the international community in the registration of new veterinary pharmaceuticals. Following these considerations, this species was accepted as a possible test organism in a recently published OECD Guideline (No. 228).
