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Environ Toxicol Chem ; 35(11): 2753-2764, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27043355

RESUMO

The selection and prioritization of pharmaceuticals and their transformation products for evaluating effects on the environment and human health is a challenging task. One common approach is based on compounds (e.g., mixture composition, concentrations), and another on biology (e.g., relevant endpoint, biological organizational level). Both of these approaches often resemble a Lernaean Hydra-they can create more questions than answers. The present study embraces this complexity, providing an integrated approach toward assessing the potential effects of transformation products of pharmaceuticals by means of mutagenicity, estrogenicity, and differences in the gene expression profiles. Mutagenicity using the tk kinase assay was applied to assess a list of 11 priority pharmaceuticals, namely, atenolol, azithromycin, carbamazepine, diclofenac, ibuprofen, erythromycin, metoprolol, ofloxacin, propranolol, sulfamethoxazole, and trimethoprim. The most mutagenic compounds were found to be ß-blockers. In parallel, the photolabile pharmaceuticals were assessed for their mixture effects on mutagenicity (tk assay), estrogenicity (T47D- KBluc assay), and gene expression (microarrays). Interestingly, the mixtures were mutagenic at the µg/L level, indicating a synergistic effect. None of the photolysed mixtures were statistically significantly estrogenic. Gene expression profiling revealed effects related mainly to certain pathways, those of the p53 gene, mitogen-activated protein kinase, alanine, aspartate, and glutamate metabolism, and translation-related (spliceosome). Fourteen phototransformation products are proposed based on the m/z values found through ultra-performance liquid chromatography-tandem mass spectrometry analysis. The transformation routes of the photolysed mixtures indicate a strong similarity with those obtained for each pharmaceutical separately. This finding reinforces the view that transformation products are to be expected in naturally occurring mixtures. Environ Toxicol Chem 2016;35:2753-2764. © 2016 SETAC.


Assuntos
Antagonistas Adrenérgicos beta/toxicidade , Misturas Complexas/toxicidade , Mutagênicos/toxicidade , Preparações Farmacêuticas/análise , Transcriptoma/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Antagonistas Adrenérgicos beta/análise , Antagonistas Adrenérgicos beta/efeitos da radiação , Animais , Linhagem Celular Tumoral , Misturas Complexas/análise , Misturas Complexas/efeitos da radiação , Perfilação da Expressão Gênica , Humanos , Camundongos , Análise em Microsséries , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mutagênicos/análise , Mutagênicos/efeitos da radiação , Ofloxacino , Preparações Farmacêuticas/efeitos da radiação , Fotólise , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/efeitos da radiação
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