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1.
Crit Rev Toxicol ; 49(9): 742-789, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31939687

RESUMO

For a few years, mineral oils and their potential adverse health effects have been a constant issue of concern in many regulatory areas such as food, cosmetics, other consumer products, and industrial chemicals. Analytically, two fractions can be distinguished: mineral oil saturated hydrocarbons (MOSH) and mineral oil aromatic hydrocarbons (MOAH). This paper aims at assessing the bioaccumulative potential and associated histopathological effects of MOSH as well as the carcinogenic potential of MOAH for consumer-relevant mineral oils. It also covers the absorption, distribution, metabolism, and excretion of MOSH and MOAH upon oral and dermal exposures. The use and occurrence of consumer-relevant, highly refined mineral oils in food, cosmetics and medicinal products are summarized, and estimates for the exposure of consumers are provided. Also addressed are the challenges in characterizing the substance identity of mineral oil products under REACH. Evidence from more recent autopsy and biopsy studies, along with information on decreasing food contamination levels, indicates a low risk for adverse hepatic lesions that may arise from the retention of MOSH in the liver. With respect to MOAH, at present there is no indication of any carcinogenic effects in animals dermally or orally exposed to highly refined mineral oils and waxes. Such products are used not only in cosmetics but also in medicinal products and as additives in food contact materials. The safety of these mineral oil-containing products is thus indirectly documented by their prevalent and long-term use, with a simultaneous lack of clinical and epidemiological evidence for adverse health effects.


Assuntos
Cosméticos , Contaminação de Alimentos , Óleo Mineral , Animais , Exposição Ambiental/estatística & dados numéricos , Humanos , Hidrocarbonetos/análise , Hidrocarbonetos Aromáticos/análise
2.
Nat Cell Biol ; 6(2): 97-105, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14743216

RESUMO

Signal transduction pathways are modular composites of functionally interdependent sets of proteins that act in a coordinated fashion to transform environmental information into a phenotypic response. The pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha triggers a signalling cascade, converging on the activation of the transcription factor NF-kappa B, which forms the basis for numerous physiological and pathological processes. Here we report the mapping of a protein interaction network around 32 known and candidate TNF-alpha/NF-kappa B pathway components by using an integrated approach comprising tandem affinity purification, liquid-chromatography tandem mass spectrometry, network analysis and directed functional perturbation studies using RNA interference. We identified 221 molecular associations and 80 previously unknown interactors, including 10 new functional modulators of the pathway. This systems approach provides significant insight into the logic of the TNF-alpha/NF-kappa B pathway and is generally applicable to other pathways relevant to human disease.


Assuntos
Proteínas de Drosophila , NF-kappa B/metabolismo , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Chaperoninas , Cromatografia de Afinidade/métodos , Ativação Enzimática , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Proteínas I-kappa B/isolamento & purificação , Proteínas I-kappa B/metabolismo , MAP Quinase Quinase Quinase 3 , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/metabolismo , Substâncias Macromoleculares , Espectrometria de Massas/métodos , Modelos Biológicos , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , NF-kappa B/genética , NF-kappa B/isolamento & purificação , Proteoma/análise , Interferência de RNA , Receptores do Fator de Necrose Tumoral/metabolismo , Proteínas de Ligação a Tacrolimo/genética , Proteínas de Ligação a Tacrolimo/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/isolamento & purificação , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
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