RESUMEN
Abstract Introduction: Monitoring water quality in mobile dialysis (MD) services, assessing critical points and characterizing the risks inherent in the process, is essential to avoid risks to the patient's health. This study evaluated the microbiological quality of water in the MD of 36 hospitals with intensive treatment in the city of Rio de Janeiro. Methods: 204 water samples were collected from the points of entry to the network (NET), post-osmosis (PO) and dialysis solution (DS). The samples were evaluated for heterotrophic bacteria count, pathogen search, presence of endotoxins and aluminum content. Results: Bacterial contamination at 3 collection points in 36 hospitals was 30% (32/108); 42% from DS, 31% from PO and 17% from NET, with the presence of Pseudomonas aeruginosa, Stenotrophomonas maltophilia , Burkholderia cepacia and Ralstonia pickettii in the 3 points. Endotoxin concentrations above 0.25 EU/mL occurred in 77% of the samples (17/22) analyzed in the PO. In the aluminum content, values above 0.01 mg/L were presented in 47% (7/15) of PO samples and 27% (4/15) of NET samples. There is no specific legislation for water used in the MD; therefore, the limits of the RDC of the National Health Surveillance Agency (Anvisa) 11/2014 were used; which regulates conventional hemodialysis services. Conclusion: The results highlight the importance of evaluating water quality in MD services to ensure patient safety and support the sanitary monitoring of this process as a healthcare promoter.
Resumo Introdução: Monitorar a qualidade da água nos serviços de diálise móvel (DM), avaliando os pontos críticos e caracterizando os riscos inerentes ao processo, é fundamental para evitar riscos à saúde do paciente. Este estudo avaliou a qualidade microbiológica da água na DM de 36 hospitais com tratamento intensivo no município do Rio de Janeiro. Métodos: Foram coletadas 204 amostras de água dos pontos de entrada da rede (REDE), pós-osmose (PO) e solução de diálise (SD). As amostras foram avaliadas quanto à contagem de bactérias heterotróficas, pesquisa de patógenos, presença de endotoxinas e teor de alumínio. Resultados: A contaminação bacteriana, em 3 pontos de coleta nos 36 hospitais, foi de 30% (32/108), sendo 42% provenientes da SD, 31% da PO e 17% da REDE, com presença de Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Burkholderia cepacia e Ralstonia pickettii nos 3 pontos. Concentrações de endotoxina acima de 0,25 EU/mL ocorreram em 77% das amostras (17/22) analisadas na PO. No teor de alumínio, os valores acima de 0,01 mg/L foram apresentados em 47% (7/15) das amostras da PO e 27% (4/15) das amostras da REDE. Não existe uma legislação específica para água utilizada na DM; logo, foram utilizados os limites da RDC da Agência Nacional de Vigilância Sanitária (Anvisa) 11/2014, que regulamenta os serviços de hemodiálise convencional. Conclusão: Os resultados ressaltam a importância da avaliação da qualidade da água nos serviços de DM para garantir a segurança do paciente e subsidiar o monitoramento sanitário desse processo como um promotor de saúde.
RESUMEN
INTRODUCTION: Monitoring water quality in mobile dialysis (MD) services, assessing critical points and characterizing the risks inherent in the process, is essential to avoid risks to the patient's health. This study evaluated the microbiological quality of water in the MD of 36 hospitals with intensive treatment in the city of Rio de Janeiro. METHODS: 204 water samples were collected from the points of entry to the network (NET), post-osmosis (PO) and dialysis solution (DS). The samples were evaluated for heterotrophic bacteria count, pathogen search, presence of endotoxins and aluminum content. RESULTS: Bacterial contamination at 3 collection points in 36 hospitals was 30% (32/108); 42% from DS, 31% from PO and 17% from NET, with the presence of Pseudomonas aeruginosa, Stenotrophomonas maltophilia , Burkholderia cepacia and Ralstonia pickettii in the 3 points. Endotoxin concentrations above 0.25 EU/mL occurred in 77% of the samples (17/22) analyzed in the PO. In the aluminum content, values above 0.01 mg/L were presented in 47% (7/15) of PO samples and 27% (4/15) of NET samples. There is no specific legislation for water used in the MD; therefore, the limits of the RDC of the National Health Surveillance Agency (Anvisa) 11/2014 were used; which regulates conventional hemodialysis services. CONCLUSION: The results highlight the importance of evaluating water quality in MD services to ensure patient safety and support the sanitary monitoring of this process as a healthcare promoter.
Asunto(s)
Diálisis Renal , Microbiología del Agua , Brasil , Soluciones para Diálisis , Humanos , Unidades de Cuidados IntensivosRESUMEN
Chronic exposure to benzene is a risk factor for hematological malignancies. Gasoline-station workers are exposed to benzene in gasoline, via both inhalation and dermal contact (attendants and managers) or inhalation (workers in the on-site convenience stores and offices). We have studied the exposure of these workers to benzene and the resulting genotoxic and immunotoxic effects. Levels of urinary trans, trans-muconic acid were higher among gasoline-station workers than among office workers with no known exposure to benzene (comparison group). Among the exposed workers, we observed statistically significant biological effects, including elevated DNA damage (comet assay); higher frequencies of micronuclei and nuclear buds (CBMN assay); lower levels of T-helper lymphocytes and naive Th lymphocytes; lower CD4 / CD8 ratio; and higher levels of NK cells and memory Th lymphocytes. Both groups of exposed workers (inhalation and inhalation + dermal routes) showed similar genotoxic and immunotoxic effects.
Asunto(s)
Benceno/toxicidad , Gasolina/toxicidad , Sistema Inmunológico/efectos de los fármacos , Exposición Profesional , Adulto , Anciano , Contaminantes Ocupacionales del Aire/toxicidad , Brasil/epidemiología , Ensayo Cometa , Estudios Transversales , Daño del ADN/efectos de los fármacos , Daño del ADN/inmunología , Femenino , Humanos , Sistema Inmunológico/metabolismo , Inmunomodulación/efectos de los fármacos , Exposición por Inhalación/efectos adversos , Exposición por Inhalación/análisis , Recuento de Linfocitos , Masculino , Pruebas de Micronúcleos , Persona de Mediana Edad , Pruebas de Mutagenicidad , Exposición Profesional/efectos adversos , Exposición Profesional/análisis , Exposición Profesional/estadística & datos numéricos , Estrés Fisiológico/efectos de los fármacos , Estrés Fisiológico/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/patología , Adulto JovenRESUMEN
BACKGROUND: Only benznidazole (Bnz) (1) and nifurtimox (Nfx) (2) are licensed for the treatment of Chagas disease although their safety and efficacy profile are far from ideal. Farmanguinhos from Fiocruz has developed seven nitroimidazole compounds (4-10) analogs of megazol (3). OBJECTIVES: To evaluate whether the genotoxic effect of 3 was abolished in the seven nitroimidazoles (4-10) analogs using the in vitro alkaline comet assay (CA) and the in vitro cytokinesis-block micronucleus assay (CBMN) in whole human blood cells (WHBC) and correlate this effect with their trypanocidal activity using bloodstream trypomastigote forms of Trypanosoma cruzi. METHODS: The toxicity of 3-10 to WHBC in the in vitro CA was determined using the fluorescein diacetate/ethidium bromide assay. DNA damage in the in vitro CA was evaluated according to tail size in four classes (0-3) and methyl methane-sulfonate (MMS) was used as a positive control. The cytotoxicity of 3-10 to WHBC in the CBMN was measured using the cytokinesis-block proliferation index and the replication index. The number of the micronucleate cells in 2,000 binucleate cells by experimental group was determined. Mitomycin C and N-deacetyl-N-methylcolchicine were used as positive controls. FINDINGS: Compound 3 showed a significant DNA strand break effect through the in vitro CA and highly significant clastogenic and/or aneugenic effect in the CBMN. Compounds 5, 6, 8, 9 and 10 showed negative results in the CBMN and positive results in the in vitro CA, while the inverse effect was observed for 4 and 7. MAIN CONCLUSIONS: Compound 10 was the most promising to proceed with the development as a drug candidate in the treatment of Chagas disease showing absence of chromosomal cytogenetic damage and high activity against T. cruzi, about two times higher than 3 and the clinical drug 1.
Asunto(s)
Nitroimidazoles/toxicidad , Tripanocidas/toxicidad , Células Sanguíneas/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayo Cometa/métodos , Daño del ADN , Humanos , Pruebas de Micronúcleos/métodos , Nifurtimox/química , Nifurtimox/toxicidad , Nitroimidazoles/química , Valores de Referencia , Reproducibilidad de los Resultados , Tiadiazoles/química , Tiadiazoles/toxicidad , Factores de Tiempo , Tripanocidas/química , Trypanosoma cruzi/efectos de los fármacosRESUMEN
BACKGROUND Only benznidazole (Bnz) (1) and nifurtimox (Nfx) (2) are licensed for the treatment of Chagas disease although their safety and efficacy profile are far from ideal. Farmanguinhos from Fiocruz has developed seven nitroimidazole compounds (4-10) analogs of megazol (3). OBJECTIVES To evaluate whether the genotoxic effect of 3 was abolished in the seven nitroimidazoles (4-10) analogs using the in vitro alkaline comet assay (CA) and the in vitro cytokinesis-block micronucleus assay (CBMN) in whole human blood cells (WHBC) and correlate this effect with their trypanocidal activity using bloodstream trypomastigote forms of Trypanosoma cruzi. METHODS The toxicity of 3-10 to WHBC in the in vitro CA was determined using the fluorescein diacetate/ethidium bromide assay. DNA damage in the in vitro CA was evaluated according to tail size in four classes (0-3) and methyl methane-sulfonate (MMS) was used as a positive control. The cytotoxicity of 3-10 to WHBC in the CBMN was measured using the cytokinesis-block proliferation index and the replication index. The number of the micronucleate cells in 2,000 binucleate cells by experimental group was determined. Mitomycin C and N-deacetyl-N-methylcolchicine were used as positive controls. FINDINGS Compound 3 showed a significant DNA strand break effect through the in vitro CA and highly significant clastogenic and/or aneugenic effect in the CBMN. Compounds 5, 6, 8, 9 and 10 showed negative results in the CBMN and positive results in the in vitro CA, while the inverse effect was observed for 4 and 7. MAIN CONCLUSIONS Compound 10 was the most promising to proceed with the development as a drug candidate in the treatment of Chagas disease showing absence of chromosomal cytogenetic damage and high activity against T. cruzi, about two times higher than 3 and the clinical drug 1.
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Tripanocidas/uso terapéutico , Tripanocidas/farmacología , Nitroimidazoles/uso terapéutico , Técnicas In Vitro/métodos , Pruebas de Mutagenicidad/métodosRESUMEN
Megazol (7) is a 5-nitroimidazole that is highly active against Trypanosoma cruzi and Trypanosoma brucei, as well as drug-resistant forms of trypanosomiasis. Compound 7 is not used clinically due to its mutagenic and genotoxic properties, but has been largely used as a lead compound. Here, we compared the activity of 7 with its 4H-1,2,4-triazole bioisostere (8) in bloodstream forms of T. brucei and T. cruzi and evaluated their activation by T. brucei type I nitroreductase (TbNTR) enzyme. We also analysed the cytotoxic and genotoxic effects of these compounds in whole human blood using Comet and fluorescein diacetate/ethidium bromide assays. Although the only difference between 7 and 8 is the substitution of sulphur (in the thiadiazole in 7) for nitrogen (in the triazole in 8), the results indicated that 8 had poorer antiparasitic activity than 7 and was not genotoxic, whereas 7 presented this effect. The determination of Vmax indicated that although 8 was metabolised more rapidly than 7, it bounds to the TbNTR with better affinity, resulting in equivalent kcat/KM values. Docking assays of 7 and 8 performed within the active site of a homology model of the TbNTR indicating that 8 had greater affinity than 7.
Asunto(s)
Animales , Humanos , Masculino , Ratones , Nitrorreductasas/efectos de los fármacos , Tiadiazoles , Triazoles , Tripanocidas , Trypanosoma brucei brucei/efectos de los fármacos , Trypanosoma brucei brucei/enzimología , Ensayo Cometa , Daño del ADN/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Nitrorreductasas/metabolismo , Pruebas de Sensibilidad Parasitaria , Relación Estructura-Actividad , Tiadiazoles/química , Tiadiazoles/metabolismo , Tiadiazoles/farmacología , Tiadiazoles/toxicidad , Triazoles/química , Triazoles/metabolismo , Triazoles/farmacología , Triazoles/toxicidad , Tripanocidas/química , Tripanocidas/farmacología , Tripanocidas/toxicidad , Trypanosoma cruzi/efectos de los fármacosRESUMEN
Megazol (7) is a 5-nitroimidazole that is highly active against Trypanosoma cruzi and Trypanosoma brucei, as well as drug-resistant forms of trypanosomiasis. Compound 7 is not used clinically due to its mutagenic and genotoxic properties, but has been largely used as a lead compound. Here, we compared the activity of 7 with its 4H-1,2,4-triazole bioisostere (8) in bloodstream forms of T. brucei and T. cruzi and evaluated their activation by T. brucei type I nitroreductase (TbNTR) enzyme. We also analysed the cytotoxic and genotoxic effects of these compounds in whole human blood using Comet and fluorescein diacetate/ethidium bromide assays. Although the only difference between 7 and 8 is the substitution of sulphur (in the thiadiazole in 7) for nitrogen (in the triazole in 8), the results indicated that 8 had poorer antiparasitic activity than 7 and was not genotoxic, whereas 7 presented this effect. The determination of Vmax indicated that although 8 was metabolised more rapidly than 7, it bounds to the TbNTR with better affinity, resulting in equivalent kcat/KM values. Docking assays of 7 and 8 performed within the active site of a homology model of the TbNTR indicating that 8 had greater affinity than 7.
Asunto(s)
Nitrorreductasas/efectos de los fármacos , Tiadiazoles , Triazoles , Tripanocidas , Trypanosoma brucei brucei/efectos de los fármacos , Trypanosoma brucei brucei/enzimología , Animales , Ensayo Cometa , Daño del ADN/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Humanos , Masculino , Ratones , Nitrorreductasas/metabolismo , Pruebas de Sensibilidad Parasitaria , Relación Estructura-Actividad , Tiadiazoles/química , Tiadiazoles/metabolismo , Tiadiazoles/farmacología , Tiadiazoles/toxicidad , Triazoles/química , Triazoles/metabolismo , Triazoles/farmacología , Triazoles/toxicidad , Tripanocidas/química , Tripanocidas/farmacología , Tripanocidas/toxicidad , Trypanosoma cruzi/efectos de los fármacosRESUMEN
A cor e a aparência dos alimentos são os primeiros atributos fundamentais, se não os mais importantes a serem avaliados pelos consumidores no momento da sua aquisição. Os alimentos podem ser mais nutritivos, seguros e econômicos, no entanto, se não forem atraentes, sua aquisição não ocorrerá. O salmão é basicamente um peixe branco que se torna rosado pela ingestão do camarão. O pigmento vermelho armazenado presente no músculo ou na casca do camarão e que se acumula no tecido adiposo é adquirido pela ingestão das algas e dos organismos unicelulares pelos camarões do mar. Os carotenóides utilizados nas indústrias alimentícia, farmacêutica, de cosméticos e de ração são corantes naturais responsáveis pelas cores amarela, laranja e vermelha. O salmão criado em aqüicultura não tem acesso aos organismos citados acima, entretanto é adicionada à sua ração a astaxantina (ATX), substância que confere a cor rosada à sua carne. A ATX (3,3'-dihidroxi-beta,beta-caroteno-4,4'-diona) é um pigmento carotenóide oxigenado, que confere a característica de coloração rosa-avermelhada a alguns peixes, crustáceos, aves e microrganismos. A ATX apresenta potente atividade na eliminação de radicais livres e na proteção quanto à peroxidação de lipídios e quanto aos danos causados pela oxidação das membranas celulares e de tecidos.
The color and appearance of food are the first fundamental attributes, if not the most important, to beevaluated by consumers at the time of its acquisition. The food can be more nutritious, safer and moreeconomical, however, if it is not attractive, its acquisition will not occur. Basically, salmon is a white fishthat becomes pink by eating shrimp. The stored red pigment existing in the shrimp muscle or shell, which isaccumulated in the adipose tissue, is acquired through the ingestion of algae and unicellular organisms bythe marine shrimps. The carotenoids employed in the food, pharmaceutical, cosmetics and feed industriesare natural colorants responsible for providing yellow, orange and red colors. As the salmon raised inaquaculture do not have access to the organism above mentioned, the astaxanthin (ATX), a substance thatgives a pinkish color to salmon meat, is added to their feed. ATX (3,3'-dihydroxy-beta,beta-carotene-4,4'-dione) is a oxygenated carotenoid pigment which confers the characteristic reddish-pink colorationto certain fish, crustaceans, birds and microorganisms. The ATX has potent activity in removing the freeradicals and protecting against the lipid peroxidation and the damage caused by oxidation of cell andtissues membranes.
Asunto(s)
Carotenoides , Colorantes de Alimentos , SalmónRESUMEN
The color and appearance of food are the first fundamental attributes, if not the most important, to be evaluated by consumers at the time of its acquisition. The food can be more nutritious, safer and more economical, however, if it is not attractive, its acquisition will not occur. Basically, salmon is a white fish that becomes pink by eating shrimp. The stored red pigment existing in the shrimp muscle or shell, which is accumulated in the adipose tissue, is acquired through the ingestion of algae and unicellular organisms by the marine shrimps. The carotenoids employed in the food, pharmaceutical, cosmetics and feed industries are natural colorants responsible for providing yellow, orange and red colors. As the salmon raised in aquaculture do not have access to the organism above mentioned, the astaxanthin (ATX), a substance that gives a pinkish color to salmon meat, is added to their feed. ATX (3,3'-dihydroxy-beta,beta-carotene-4, 4'-dione) is a oxygenated carotenoid pigment which confers the characteristic reddish-pink coloration to certain fish, crustaceans, birds and microorganisms. The ATX has potent activity in removing the free radicals and protecting against the lipid peroxidation and the damage caused by oxidation of cell and tissues membranes.(AU)
A cor e a aparência dos alimentos são os primeiros atributos fundamentais, se não os mais importantes a serem avaliados pelos consumidores no momento da sua aquisição. Os alimentos podem ser mais nutritivos, seguros e econômicos, no entanto, se não forem atraentes, sua aquisição não ocorrerá. O salmão é basicamente um peixe branco que se torna rosado pela ingestão do camarão. O pigmento vermelho armazenado presente no músculo ou na casca do camarão e que se acumula no tecido adiposo é adquirido pela ingestão das algas e dos organismos unicelulares pelos camarões do mar. Os carotenóides utilizados nas indústrias alimentícia, farmacêutica, de cosméticos e de ração são corantes naturais responsáveis pelas cores amarela, laranja e vermelha. O salmão criado em aqüicultura não tem acesso aos organismos citados acima, entretanto é adicionada à sua ração a astaxantina (ATX), substância que confere a cor rosada à sua carne. A ATX (3,3'-dihidroxi-beta,beta-caroteno-4,4'-diona) é um pigmento carotenóide oxigenado, que confere a característica de coloração rosa-avermelhada a alguns peixes, crustáceos, aves e microrganismos. A ATX apresenta potente atividade na eliminação de radicais livres e na proteção quanto à peroxidação de lipídios e quanto aos danos causados pela oxidação das membranas celulares e de tecidos.(AU)
Asunto(s)
Animales , Salmón , Carotenoides/análisis , Colorantes de Alimentos/análisis , Industria de Alimentos , Palinuridae , Braquiuros , CrustáceosRESUMEN
Nos últimos dez anos, a ocorrência de doenças e de agravos à saúde, e mesmo óbitos, em pacientes que fizeram uso de medicamentos manipulados reacendeu o debate sobre a qualidade desse tipo de medicamento no Brasil. O presente estudo efetuou a descrição do perfil dos medicamentos alopáticos manipulados pelas farmácias comunitárias existentes na época do estudo, com Autorização Especial concedida pela Anvisa (Portaria SVS/MS nº 344/98), e localizadas no município de Nova Friburgo (RJ).Esta investigação foi realizada por meio de pesquisa documental das características consideradas relevantes para o estudo. Foram avaliados os registros do mês de novembro de 2006 dos livros de receituário das farmácias autorizadas a manipular substâncias sujeitas a controle especial, totalizando-se 12.253 fórmulas. Foram verificadas baixa frequência de medicamentos manipulados considerados farmacopeicos (< 1,0%)e alta frequência da forma farmacêutica em cápsula (83%); e que a manipulação destas como mono droga estava concentrada em 15 fármacos, representando classes terapêuticas de grande importância clínica, tais como: antidepressivo, anorexígeno, antipsicótico e anti-hipertensivo. O perfil dos medicamentos manipulados avaliados poderia representar, em termos de saúde pública, potencial risco sanitário quanto à segurança e à eficácia.
Asunto(s)
Autorización de Funcionamiento , Farmacias , Química FarmacéuticaRESUMEN
Nos últimos dez anos, a ocorrência de doenças e de agravos à saúde, e mesmo óbitos, em pacientes que fizeram uso de medicamentos manipulados reacendeu o debate sobre a qualidade desse tipo de medicamento no Brasil. O presente estudo efetuou a descrição do perfil dos medicamentos alopáticos manipulados pelas farmácias comunitárias existentes na época do estudo, com Autorização Especial concedida pela Anvisa (Portaria SVS/MS nº 344/98), e localizadas no município de Nova Friburgo (RJ). Esta investigação foi realizada por meio de pesquisa documental das características consideradas relevantes para o estudo. Foram avaliados os registros do mês de novembro de 2006 dos livros de receituário das farmácias autorizadas a manipular substâncias sujeitas a controle especial, totalizando-se 12.253 fórmulas. Foram verificadas baixa frequência de medicamentos manipulados considerados farmacopeicos (< 1,0%) e alta frequência da forma farmacêutica em cápsula (83%); e que a manipulação destas como monodroga estava concentrada em 15 fármacos, representando classes terapêuticas de grande importância clínica, tais como: antidepressivo, anorexígeno, antipsicótico e anti-hipertensivo. O perfil dos medicamentos manipulados avaliados poderia representar, em termos de saúde pública, potencial risco sanitário quanto à segurança e à eficácia.(AU)
In the last ten years, the occurrence of diseases and health injuries, including deaths, in patients who had taken medicines prepared in community pharmacies have brought back into notice the quality of medicines in Brazil. This work analyzed the profile of the allopathic medicines prepared by the community pharmacies, existing at those time and located in Nova Friburgo city, Rio de Janeiro, by the Special Authorization granted by the National Health Surveillance Agency Anvisa (Regulation SVS/MS no. 344/98). This investigation was performed by means of a documental research on the characteristics considered as relevant to the study. For this purpose, the data recorded in November of 2006 were evaluated, extracted from the Prescriptions Books of the pharmacies which had been licensed to prepare the controlled substances. A total of 12,253 formulas were assessed; a low prevalence of officinal formulas (< 1%) and a high prevalence of medicines in capsules type (83%) were found. The capsules formulations were composed by only one active component, and they were converged on 15 substances, for preparing antidepressant, anorexigenic, antipsychotic and antihypertensive drugs. From the public health aspect, the assessed medicines profile might represent a potential sanitary risk for their safety and efficacy.(AU)
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Buenas Prácticas de Manipulación , Comercialización de Medicamentos , Escalas de Preparación , Farmacias/legislación & jurisprudencia , Química Farmacéutica/legislación & jurisprudencia , Legislación de Medicamentos , DocumentaciónRESUMEN
A ε-caprolactama (CAP) é um monômero precursor de polímeros denominados nylon 6. Esses polímeros destinam-se à produção de tapetes, vestuário e materiais plásticos tais como equipamentos, sistemas e componentes automotivos, conectores, além de embalagens plásticas. Resíduos de CAP podem migrar de embalagens plásticas de nylon 6 para os alimentos. Diante disso, foi de interesse realizar uma revisão dos efeitos relativos à exposição à CAP e o seu impacto sobre a saúde humana. Estudos epidemiológicos indicam a possibilidade da CAP causar inflamações oculares e cutâneas, além de irritações no sistema respiratório. Pode ocorrer ainda hipotensão, taquicardia, palpitações, rinorréia, ressecamento nasal, efeitos geniturinários e sobre a reprodução como distúrbios nas funções menstrual e ovariana, e complicações no parto; além de problemas neurológicos e hematológicos. Estudos com animais são consistentes com tais relatos. Os estudos de genotoxicidade in vitro e in vivo por via oral e intraperitoneal mostram em sua grande maioria, resultados negativos, bem como ausência de efeitos carcinogênicos em ratos e camundongos e sobre o desenvolvimento e reprodução em ratos e coelhos.
ε -Caprolactam (CAP) is a precursor monomer of nylon 6 polymers. Nylon 6 is used in the manufacture of carpets, clothes and plastic materials, such as equipment, systems and automotive components, connectors and plastic packaging. CAP residues can migrate from nylon 6 plastic packaging to foods. Given this fact, this review was realized concerning the effects of CAP exposure and its impact on human health. Epidemiological studies indicate that CAP could cause ocular, cutaneous and respiratory irritations, as well as hypotension, tachycardia, palpitations, rhinorrhea, nose dryness, neurological and blood problems, and genitourinary and reproductive effects, such as alterations in ovarian-menstrual functions and pregnancy/birth complications. Animal studies are consistent with such reports; however, the majority of in vitro and in vivo genotoxicity studies by oral and intraperitoneal routes show negative results, including the absence of carcinogenicity in rats and mice and developmental and reproductive effects in rats and rabbits.
Asunto(s)
Humanos , Ratones , Ratas , Caprolactama/toxicidad , Embalaje de Productos , Carcinógenos/análisis , FarmacocinéticaRESUMEN
Face ao objetivo fundamental deste trabalho de estabelecer e padronizar teste capaz de detectar e avaliar quantitativamente a presença de resíduos não-inativados de toxina pertussis (TP) em vacina pertussis (VP) e/ou tríplice (DTP), selecionamos a cultura de células CHO, pois, além de se enquadrar perfeitamente na regra dos 3 Rs, principalmente em termos de possível substituição do teste in vivo, é amplamente usada como linhagem celular modelo para o estudo dos efeitos celulares da TP comparativamente com os causados pela toxina colérica (TC), de características químicas e biológicas muito semelhantes à TP. Assim, as alterações morfológicas de aglomeração celular (efeito clustering) ou de alongamento celular induzidos, respectivamente, pela TP e TC, foram quantificadas e os seus mecanismos de ação estudados, confirmando-se o da TC e propondo-se o da TP, concluindo-se, ao contrário do até agora supostamente admitido, que são epifenômenos mediados por segundos mensageiros diferentes, pois confirmamos o papel do AMPc no alongamento e sugerimos o envolvimento do GMPc no clustering, demonstrando, outrossim, a participação fundamental do Oligômero B, fração molecular da TP, neste fenômeno morfológico, além de apresentarmos evidências sugestivas da participação de proteínas intracelulares diretamente conectadas com o citoesqueleto, tais como, a actina, tubulina e integrinas, na formação do clustering. Finalmente, a correlação entre os níveis de resíduos de TP - não inativada nas vacinas VP e DTP, encontradas in vivo através do Teste de Sensibilização à Histamina e in vitro em células CHO, definitivamente demonstrou a validade deste último teste, não só como complementar aos testes in vivo, mas também como possível substituto destes últimos no Controle de Qualidade das vacinas DTP. Ressalte-se que nas concentrações de TP capazes de induzir o clustering, não mostraram efeitos citotóxicos, avaliados através da análise do crescimento celular, da eficiência de clonagem, do índice mitótico e do ensaio cometa.