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1.
J Food Sci ; 85(4): 1361-1370, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32147842

RESUMO

The effects of surface application of amino acids on the formation of heterocyclic amines (HCAs) and meat quality properties were evaluated in pan-fried beef patties (230 °C/15 min). Tryptophan, lysine, leucine, and proline at three concentrations, 0.05%, 0.20%, and 0.50% (w/w), were tested. The meat crusts were analyzed for HCA content using liquid chromatography-tandem mass spectrometry. Results showed that surface application of all tested amino acids significantly reduced total HCA content (P < 0.05), and the interaction of amino acid type and concentration significantly affected (P < 0.05) both individual and total HCA formation. Tryptophan at 0.50% reduced total HCAs the most (0.92 ng/g, 93% inhibition), followed by 0.50% lysine (1.94 ng/g, 84% inhibition), while leucine (3.95 ng/g, 64% inhibition) and proline (4.71 ng/g, 56% inhibition) were less effective at 0.50%. In addition, applying amino acids to meat surface significantly influenced (P < 0.05) pH and surface color change of beef crusts; particularly, lysine at 0.20% and 0.50% increased pH and a* (redness) but reduced b* (yellowness), while tryptophan and leucine at 0.50% increased L* (whiteness). No significant effect was observed on cooking loss. Adding amino acids at 0.50% affected (P < 0.05) formation of aldehydes and pyrazines (as the key flavor compounds of fried beef). Overall, the results of this study suggested that adding amino acids to ground beef patties could effectively mitigate mutagenic HCA formation during cooking.


Assuntos
Aminas/metabolismo , Aminoácidos/administração & dosagem , Culinária/métodos , Carne Vermelha/análise , Aminas/química , Aminoácidos/química , Animais , Bovinos , Cromatografia Líquida , Compostos Heterocíclicos , Mutagênicos/análise , Extratos Vegetais/farmacologia
2.
Am J Clin Nutr ; 111(6): 1244-1251, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32077920

RESUMO

BACKGROUND: Red and processed meat, recognized carcinogens, are risk factors for colorectal neoplasia, including polyps, the precursor for colorectal cancer. The mechanism is unclear. One possible explanation is the mutagenic activity of these foods, perhaps due to generation during cooking [e.g., heterocyclic amine (HCA) intake]. Few studies have evaluated meat intake and sessile serrated lesion (SSL) risk, a recently recognized precursor, and no study has evaluated meat cooking methods and meat-derived mutagens with SSL risk. OBJECTIVE: We evaluated intakes of meat, meat cooking methods, and inferred meat mutagens with SSL risk and in comparison to risk of other polyps. METHODS: Meat, well-done meat, and inferred meat mutagen intakes were evaluated. Polytomous logistic regression models were used to estimate ORs and 95% CIs among cases (556 hyperplastic polyp, 1753 adenoma, and 208 SSL) and controls (3804) in the large colonoscopy-based, case-control study, the Tennessee Colorectal Polyp Study. RESULTS: The highest quartile intakes of red meat (OR: 2.38; 95% CI: 1.44, 3.93), processed meat (OR: 2.03; 95% CI: 1.30, 3.17), well-done red meat (OR: 2.19; 95% CI: 1.34, 3.60), and the HCA 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQX; OR: 2.48; 95% CI: 1.49, 4.16) were associated with increased risk of SSLs in comparison to the lowest quartile intake. CONCLUSIONS: High intakes of red and processed meats are strongly and especially associated with SSL risk and part of the association may be due to HCA intake. Future studies should evaluate other mechanism(s) and the potential for primary prevention.


Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Culinária/métodos , Exposição Dietética/efeitos adversos , Carne/análise , Mutagênicos/efeitos adversos , Aminas/efeitos adversos , Aminas/análise , Aminas/metabolismo , Estudos de Casos e Controles , Neoplasias Colorretais/epidemiologia , Exposição Dietética/análise , Feminino , Temperatura Alta , Humanos , Masculino , Pessoa de Meia-Idade , Mutagênicos/análise , Mutagênicos/metabolismo , Fatores de Risco , Tennessee/epidemiologia
3.
J Chromatogr A ; 1609: 460512, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31542208

RESUMO

The simultaneous use of nitrite and sorbate as preservatives in meat products may produce mutagenic compounds such as the ethylnitrolic acid and 2-methyl-1,4-dinitro-pyrrole. We developed a sensitive analytical method with high metrological reliability. After assessing several extraction approaches and chromatographic separation modes, a modified Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) approach was chosen for sample preparation, which were analyzed by reversed-phase liquid chromatography (with C18 as stationary phase) coupled to tandem mass spectrometry. After validation, we confirmed that this method is fit-for-purpose, since it was applied to the analysis of several meat products. Limits of detection were set from 5 to 20 µg kg-1. Satisfactory results were obtained for both compounds, such as precision (CV > 20%) and recoveries (77-92%). This method determine these carcinogenic compounds in processed meats, contributing to the preservation of public health and the improvement of food regulation and control.


Assuntos
Métodos Analíticos de Preparação de Amostras , Hidroxilaminas/análise , Produtos da Carne/análise , Mutagênicos/análise , Nitrilos/análise , Pirróis/química , Espectrometria de Massas em Tandem/métodos , Calibragem , Cromatografia Líquida , Cromatografia de Fase Reversa , Reprodutibilidade dos Testes
4.
Chemosphere ; 238: 124574, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31445332

RESUMO

Waste landfills represent a global problem, which is more pronounced in developing countries because of the lack of resources to implement procedures that include separation and waste processing. The aim of this research was to analyze leachate and ground waters samples at the site, upstream and downstream from the landfill during different year seasons on a registered non-hazardous waste dump and to conduct physico-chemical and biological assays to determine potential risk for the ecosystem. Potential cytotoxic, prooxidative and mutagenic effects of leachates and water samples were evaluated on human laryngeal cell line (HEp2). Leachates collected at landfill site caused genotoxic effect and had a higher pH, chemical oxygen demand (COD), biochemical oxygen demand (BOD) and elevated concentrations of phosphorus, chloride, nitrogen compounds and sulphate. Genotoxicity of the leachate was increased in samples collected in dry and warm period of the year. These results are in accordance to the physico-chemical analysis which revealed that during summer period, because of intense degradation process at high temperatures increased concentrations of different chemicals can be found in leachate. Groundwater collected downstream and upstream from landfill did not show statistically significant (geno)toxic effect, irrespective of the sampling season. Chemical analysis revealed that all compounds in groundwater were below permitted values. Purification process at landfill is effective and compounds that reach groundwater do not represent a toxicological threat.


Assuntos
Água Subterrânea/química , Mutagênicos/análise , Eliminação de Resíduos/métodos , Instalações de Eliminação de Resíduos , Poluentes Químicos da Água/análise , Análise da Demanda Biológica de Oxigênio , Ecossistema
5.
Environ Geochem Health ; 42(7): 2163-2178, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31848784

RESUMO

Concerns over the health effects of exposure to particulate matter of aerodynamic diameter of less than 2.5 µm (PM2.5) led the South African Government to establish the national standard for PM2.5 in the year 2012. However, there is currently no exposure limit for polycyclic aromatic hydrocarbons (PAHs) and PM2.5-bound PAHs. The understanding of the concentration levels and potential health risks of exposure to PM2.5-bound PAHs is important in ensuring a suitable risk assessment and risk management plans. This study, therefore, determined the concentration levels and carcinogenic and mutagenic health risks of PM2.5-bound PAHs. A hundred and forty-four PM2.5 samples were collected over 4 months during the winter and summer seasons of 2016 in an industrial area. The concentrations of 16 PAHs were analysed by gas chromatography-mass spectrometry, and their carcinogenic and mutagenic risks were determined using the Human Health Risk Assessment model. The mean winter (38.20 ± 8.4 µg/m3) and summer (22.3 ± 4.1 µg/m3) concentrations of PM2.5 levels were lower than the stipulated 40 µg/m3 daily limit. The daily inhalation and ingestion exposure to PAHs for all age groups were higher than the daily exposure through the dermal contact. Children and adults are more likely to inhale and ingest PAHs in PM2.5 than infants. The excess cancer risk and excess mutagenic risk values were below the priority risk level (10-4). There is a potential risk of 1-8 per million persons developing cancer from exposure to benzo[a]anthracene, benzo[a]pyrene, indeno[1,2,3-cd]pyrene, and dibenz[a,h]anthracene over a lifetime of 70 years.


Assuntos
Poluentes Atmosféricos/química , Carcinógenos Ambientais/análise , Mutagênicos/análise , Material Particulado/química , Hidrocarbonetos Policíclicos Aromáticos/química , Poluentes Atmosféricos/análise , Cidades , Humanos , Indústrias , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Medição de Risco , Estações do Ano , África do Sul
6.
J Food Sci ; 84(12): 3866-3875, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31750949

RESUMO

This work aimed includes performing the sclerotia chemical profile and evaluates their biological effects on mutagenesis, oxidative stress, cancer, and malaria. A chemical profile was determined by ultraperformance liquid chromatography mass spectrometry (UHPLC-HRMS) analysis dereplicating norditerpenoid dilactone, sclerolide, and other compounds. The GI50 values to cancer cells (19.8 to 277.6 µg/mL) were higher than normal (16.05 µg/mL), meaning high cytotoxicity. Regarding the oxidative stress, the results showed that the all AcOET fraction concentrations tested on IMR90 noncancer cell increased reactive oxygen species (ROS) production in more intense way (by fivefold) than in tested cancer cells. The in vivo study showed an increase of the following biomarkers (by 296.00%): % DNA in comet tail in peripheral blood and liver cells; micronucleated erythrocytes and colon cells and lipid serum peroxidation. These results indicate the sclerotia as genotoxic and mutagenic agent and its contamination may lead to fungal toxic effects with a risk to human health.


Assuntos
Antimaláricos , Ascomicetos/química , Produtos Biológicos , Sobrevivência Celular/efeitos dos fármacos , Mutagênicos , Antimaláricos/análise , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Produtos Biológicos/análise , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Espectrometria de Massas , Mutagênicos/análise , Mutagênicos/isolamento & purificação , Mutagênicos/farmacologia , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo
7.
Mutat Res ; 847: 403025, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31699346

RESUMO

An aneuploidy workgroup was established as part of the 7th International Workshops on Genotoxicity Testing. The workgroup conducted a review of the scientific literature on the biological mechanisms of aneuploidy in mammalian cells and methods used to detect chemical aneugens. In addition, the current regulatory framework was discussed, with the objective to arrive at consensus statements on the ramifications of exposure to chemical aneugens for human health risk assessment. As part of these efforts, the workgroup explored the use of adverse outcome pathways (AOPs) to document mechanisms of chemically induced aneuploidy in mammalian somatic cells. The group worked on two molecular initiating events (MIEs), tubulin binding and binding to the catalytic domain of aurora kinase B, which result in several adverse outcomes, including aneuploidy. The workgroup agreed that the AOP framework provides a useful approach to link evidence for MIEs with aneuploidy on a cellular level. The evidence linking chemically induced aneuploidy with carcinogenicity and hereditary disease was also reviewed and is presented in two companion papers. In addition, the group came to the consensus that the current regulatory test batteries, while not ideal, are sufficient for the identification of aneugens and human risk assessment. While it is obvious that there are many different MIEs that could lead to the induction of aneuploidy, the most commonly observed mechanisms involving chemical aneugens are related to tubulin binding and, to a lesser extent, inhibition of mitotic kinases. The comprehensive review presented here should help with the identification and risk management of aneugenic agents.


Assuntos
Rotas de Resultados Adversos , Aneuploidia , Doenças Genéticas Inatas/induzido quimicamente , Mitose/efeitos dos fármacos , Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Neoplasias/induzido quimicamente , Animais , Aurora Quinase B/antagonistas & inibidores , Aurora Quinase B/fisiologia , Carcinógenos/toxicidade , Aberrações Cromossômicas/induzido quimicamente , Segregação de Cromossomos/efeitos dos fármacos , Cromossomos/efeitos dos fármacos , Genes Reporter , Doenças Genéticas Inatas/genética , Células Germinativas/efeitos dos fármacos , Células Germinativas/ultraestrutura , Humanos , Camundongos , Testes para Micronúcleos , Microtúbulos/efeitos dos fármacos , Mitose/fisiologia , Testes de Mutagenicidade/normas , Mutagênicos/análise , Neoplasias/genética , Não Disjunção Genética/efeitos dos fármacos , Gestão de Riscos/legislação & jurisprudência , Moduladores de Tubulina/toxicidade
8.
Ecotoxicol Environ Saf ; 183: 109552, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31442804

RESUMO

To study source-specific carcinogenicity and mutagenicity of polycyclic aromatic hydrocarbons (PAHs) under diverse anthropogenic activities, PM2.5-bound PAHs were detected in Beijing in four periods. PAHs in Asia-Pacific Economic Cooperation meeting (APEC) was much lower than that in after-APEC period. The highest PAHs concentration was in heating period (303 ng/m3). Sources were quantified by Positive Matrix Factorization (PMF). In heating period, due to high emissions, weak diffusion, low degradation and evaporation, high contributions of all sources were observed, and both absolute and relative contributions of coal combustion increased. Changed contributions in during-APEC and after-APEC periods implied effectiveness of reinforced emission control, especially for coal combustion and vehicles. Furthermore, variations of sources-specific carcinogenicity and mutagenicity were investigated. In non-heating period, contributions of gasoline exhaust (38.4% TEQ: Toxic Equivalent Quantity, 33.7% MEQ: Mutagenic Equivalent Quantity) and diesel exhaust (53.8% TEQ, 57.9% MEQ) dominated both carcinogenic and mutagenic risks. Coal combustion sharply increased in heating period, attributing 27.5% TEQ and 21.7% MEQ. In during-APEC period, all contributions to carcinogenicity and mutagenicity were lower than those in after-APEC period, but "others" linked with regional transport contributed increased fractions (above 20%). Sources-specific carcinogenicity and mutagenicity under diverse anthropogenic activities, especially for APEC meeting with reinforced control, gave a new insight into assessment of control measures based on health risks.


Assuntos
Poluentes Atmosféricos/análise , Carcinógenos/análise , Monitoramento Ambiental/métodos , Mutagênicos/análise , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Atmosféricos/toxicidade , Pequim , Carcinógenos/toxicidade , China , Carvão Mineral/análise , Carvão Mineral/toxicidade , Calefação , Atividades Humanas , Mutagênicos/toxicidade , Tamanho da Partícula , Material Particulado/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Emissões de Veículos/análise , Emissões de Veículos/toxicidade
9.
Artigo em Inglês | MEDLINE | ID: mdl-31357106

RESUMO

A molecularly imprinted polymer (MIP) with specific adsorption for patulin was successfully polymerized by precipitation polymerization using 2-oxindole (2-oxin) and 6-hydroxynicotinic acid (6-HNA) as dummy template molecules, methylacrylic acid (MAA) as a functional monomer, trimethylolpropane trimethacrylate (TRIM) as a crosslinker, 2,2-azobis-(2-methylpropionitrile) (AIBN) as a initiator, and methanol as a porogen solvent. The molecularly imprinted solid phase extraction (MI-SPE) column was prepared using the polymer as a sorbent and applied for the selective extraction of patulin from real samples. The results showed that the MI-SPE method had high selectivity and specific adsorption towards patulin with mean recoveries ranged between 81.3% and 106.3% and a relative standard deviation (RSD) < 4.5%. Additionally, the developed MI-SPE method coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) exhibited good linearity in the range of 1-100 ng mL-1 with correlation coefficients (R2) >0.998. The limits of detection (LODs, S/N = 3) were 0.05-0.2 ng g-1, and the limits of quantification (LOQs, S/N = 10) were 0.2-0.5 ng g-1. The developed method showed a better purification and higher patulin recovery for real samples than the quick, easy, cheap, effective, rugged, safe "QuEChERS" method.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Contaminação de Alimentos/análise , Patulina/análise , Patulina/isolamento & purificação , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Adsorção , Impressão Molecular , Mutagênicos/análise , Mutagênicos/isolamento & purificação , Polímeros/síntese química , Polímeros/química , Extração em Fase Sólida/instrumentação
10.
Artigo em Inglês | MEDLINE | ID: mdl-31287381

RESUMO

A major challenge in the safety assessment of food contact materials (FCM) is the evaluation of unknown non-intentionally added substances (NIAS). Even though consumer exposure levels may be quantitatively low, these substances are considered to be of high toxicological concern if they act as DNA reactive mutagens. From a safety assessment perspective, it is therefore important to detect their presence in FCM migrates. The present study applied the Ames MPF assay to assess the mutagenicity of migrates obtained from 30 food contact material samples out of 3 categories: plastics, composite materials and coatings. As a food simulant, 95% ethanol (EtOH) had a superior performance to less volatile simulants when evaluating recovery rates of representative model substances in different volatility categories. To monitor possible interference of the FCM matrix with Ames MPF results, migrates were spiked with reference substances and recovery rates were established. Out of 30 samples tested, two caused significant inhibition of revertant formation in the presence of the spiking control. Overall detection limits of the applied test method were estimated by determination of the lowest effective concentrations (LEC) for 10 Ames-positive substances. Even though the current limits of detection are not sufficient to entirely fulfil regulatory and safety requirements, three out of 30 FCMs showed evidence of dose-dependent effects in the Ames MPF assay. Overall, the data obtained supported the relevance of testing FCM migrates for DNA reactive contaminants and showed the value of the Ames MPF assay for the safety assessment of FCMs.


Assuntos
Análise de Alimentos , Contaminação de Alimentos/análise , Testes de Mutagenicidade , Mutagênicos/análise , Embalagem de Alimentos , Humanos
11.
Food Chem Toxicol ; 132: 110677, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31310796

RESUMO

In the current investigation, five most potential HAs (MeIQx, 4,8-DiMeIQx, IQ, MeIQ and PhIP) were analyzed in traditional Saudi chicken dishes (shawaya, Ala Al-Faham, kebab, saleeg, mandi, kabsa and madhbi) prepared from local restaurants. The aims of the present study were to identify the presence of HAs in cooked chicken dishes, and to conclude how the levels and types of HAs could be affected by cooking methods and food ingredients. In control samples, HAs were found at higher levels ranged from not quantified to 33.72 ng/g. Nonetheless, in chicken dishes, the HAs (MeIQx, 4,8-DiMeIQx and PhIP) amounts are varied at higher range and relatively detected at lower levels from not quantified to 16.35 ng/g, IQ and MeIQ were not identified in any of the studied chicken dishes except shawaya where found to be not quantified. The HAs reduction rates were obtained at higher values in all of the studied samples, among them mandi sample demonstrates the reduction rates higher than 70%, whereas saleeg sample shows the reduction rates almost 100% except PhIP (~95%). The obtained outcomes have markedly showed that HAs occurrence in thermally processed chicken dishes is extremely affected from both cooking methods and addition of food ingredients.


Assuntos
Aminas/análise , Compostos Heterocíclicos/análise , Mutagênicos/análise , Produtos Avícolas , Aminas/efeitos adversos , Aminas/isolamento & purificação , Animais , Galinhas , Compostos Heterocíclicos/efeitos adversos , Compostos Heterocíclicos/isolamento & purificação , Limite de Detecção , Restaurantes , Arábia Saudita
12.
G Ital Med Lav Ergon ; 41(3): 193-201, 2019 07.
Artigo em Italiano | MEDLINE | ID: mdl-31242348

RESUMO

SUMMARY: The new EU directive on the protection of workers from the risks related to exposure to carcinogens and mutagens at work, issued on December 2017, will be integrated inside the Member States' national laws not later than 17th January 2020. The new directive brings in force new binding occupational exposure limit values (BOELVs) for several agents, some of great importance such as hard wood dusts, a set of hexavalent chromium compounds and crystalline silica dust; for some cases, the entry into force of the new limits is delayed in time. The new directive clarifies that the limit values are established considering factors distinct from health necessities too. The Member States are bound to adopt national limit values not avexceeding the corresponding EU ones, but are empowered to lower them. It is essential that the control of the actual respect of the limit values results not only from the application of theoretic previsional models, but is entrusted mainly to high quality exposure measurements and to estimates directly derived from measurements, on the base of publicly available JEMs. The specific health surveillance to be provided to any person both exposed and previously exposed to carcinogens at work should not be limited to proper oncological screening actions, but should include programs for biological monitoring of both exposures and related pre-neoplastic effects, every time any of these is possible and useful. A fair mapping of the exposures to carcinogens and mutagens at work and a systematical registration of cases of cancers attributable to occupational exposures will be placed side to side.


Assuntos
Carcinógenos/análise , Neoplasias/prevenção & controle , Exposição Ocupacional/prevenção & controle , Saúde do Trabalhador/legislação & jurisprudência , União Europeia , Humanos , Itália , Mutagênicos/análise , Exposição Ocupacional/legislação & jurisprudência
13.
Sci Total Environ ; 685: 911-922, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31247438

RESUMO

The present work investigated the autoxidation reaction of p-toluenediamine (PTD) - a precursor - widely used in permanent hair dyeing formulation, under experimental conditions close to the hair dyeing process (oxygen and/or peroxide in ammoniacal medium), by chromatographic and spectroscopic techniques. In additional, evaluated the mutagenicity of the PTD oxidation products and the presence of PTD and this products in wastewater from beauty salon, as well as in surface water and drinking water using HPLC coupled to a diode array detector and linear scan voltammetry. Through this study, it was possible the identification of semi-quinonediimine, quinonediimine, dimers (derived from toluenediamine), and trimer radical identified as Bandrowski's Base derivative (BBD) formed during autoxidation of PTD. Salmonella Typhimurium YG1041 assay with and without metabolic activation induced rat-liver (S9) indicated mutagenic activity for BBD. Levels of PTD were determined by the standard addition method in samples collected from the wastewater of a beauty salon, as well as from the water before and after treatment in a drinking water treatment plant (DWTP) reached concentrations of 2.08 ±â€¯0.21, 2.36 ±â€¯0.10 × 10-3, and 1.77 ±â€¯0.13 × 10-3 mg L-1, respectively. In addition, linear sweep voltammetry was used to monitor the BBD found at the concentration of 1.59 ±â€¯0.35 mg L-1 in wastewater collected from the beauty salon.


Assuntos
Mutagênicos/toxicidade , Fenilenodiaminas/química , Poluentes Químicos da Água/química , Barbearia , Peróxido de Hidrogênio , Testes de Mutagenicidade , Mutagênicos/análise , Mutagênicos/química , Oxirredução , Fenilenodiaminas/toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
14.
Environ Sci Pollut Res Int ; 26(19): 19445-19452, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31077041

RESUMO

Genotoxicity of three toxic elements (chromium, cadmium, nickel) and a metalloid (arsenic) has been studied in a freshwater fish, Channa punctatus using micronuclei (MN) test, comet assay, and erythrocyte nuclear alterations (ENAs) as fingerprints of genotoxicity. These tests yielded different results suggesting involvement of different mechanisms for their genotoxicity. While highest frequency of blebbed nuclei was observed in chromium-treated fish (6.5 ± 0.76), lowest was observed in cadmium-treated fish (4.0 ± 1.0). Maximum number of notched nuclei was recorded in arsenic-treated fish (5.5 ± 1.15) whereas highest numbers of lobed nuclei were found in cadmium-treated fish (4.5 ± 0.13). These differences might be attributed to selective bioaccumulation and chemodynamics of each element. Other parameters used to determine genotoxicity viz.: lipid peroxidation and DNA damage also suggested different mechanisms of their genotoxicity. It is suggested that an integrative approach, using a battery of tests for determining genotoxicity, should be made while making environmental health risk assessment and ecotoxicological studies of these toxic elements.


Assuntos
Dano ao DNA , Peixes/genética , Água Doce/química , Metais Pesados/toxicidade , Mutagênicos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Ensaio Cometa , Eritrócitos/efeitos dos fármacos , Eritrócitos/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Metais Pesados/análise , Testes para Micronúcleos , Mutagênicos/análise , Poluentes Químicos da Água/análise
15.
AAPS PharmSciTech ; 20(5): 166, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30989447

RESUMO

The presence of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) impurities in angiotensin II receptor blocker (ARB) drugs containing tetrazole ring has triggered worldwide product recalls. The purpose of this article is to identify the potential gap area in current pharmaceutical industry practice that might have led to the NMDA and NDEA impurities escaping the drug manufacturer's and FDA's attention. The impact of process change was not adequately assessed by the manufacturer of contaminated APIs (active pharmaceutical ingredients), and potential for generation of mutagenic or other toxic impurities was not considered. The safety and risk associated with a chemical synthetic process was also not evaluated. This is primarily due to current industry practice which focuses on controlling the impurities above reporting threshold. ICH Q3A and FDA guidance on genotoxic and carcinogenic impurities in drug substances and products need to be integrated so that the ICH Q3A decision tree (attachment 3) begins by checking whether the synthetic process has been evaluated for the potential to generate toxic impurities. The compliance with ICH Q3A limits should be carried out only after the process has been determined to be safe without the risk of generating mutagenic and carcinogenic impurities.


Assuntos
Contaminação de Medicamentos , Recall de Medicamento , Valsartana/química , Bloqueadores do Receptor Tipo 1 de Angiotensina II/análise , Bloqueadores do Receptor Tipo 1 de Angiotensina II/toxicidade , Dietilnitrosamina/análise , Dimetilnitrosamina/análise , Composição de Medicamentos , Indústria Farmacêutica , Humanos , Mutagênicos/análise , Mutagênicos/toxicidade , Segurança do Paciente , Estados Unidos , United States Food and Drug Administration
16.
Food Chem ; 290: 114-124, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31000027

RESUMO

This study was undertaken to estimate the concentrations of the formed polycyclic aromatic hydrocarbons (PAHs) in heat-treated (boiled, pan-fried and grilled) meats collected from Egypt. Dietary intakes and cancer risks of PAHs among Egyptian adults were calculated. Benzo[a]pyrene (B[a]P)-induced mutagenicity and oxidative stress in human colon (CaCo-2) cell line and mechanisms behind such effects were also investigated. Finally, protection trials using rosmarinic (RMA) and ascorbic acids (ASA) were carried out. The results indicated formation of PAHs at high levels in the heat-treated meats. Calculated incremental life time cancer risk among Egyptian adults were 7.05179E-07, 7.00604 E-06 and 1.86069 E-05 due to ingestion of boiled, pan-fried and grilled meats, respectively. B[a]P-exposed CaCo-2 cells had high abilities for mutagenicity (490.05 ±â€¯21.37 His + revertants) and production of reactive oxygen species. RMA and ASA protected CaCo-2 cells via reduction of B[a]P-induced mutagenicity and oxidative stress and upregulation of phase II detoxification enzymes and xenobiotic transporters.


Assuntos
Ácido Ascórbico/farmacologia , Benzo(a)pireno/análise , Benzo(a)pireno/toxicidade , Cinamatos/farmacologia , Depsídeos/farmacologia , Temperatura Alta , Carne/análise , Estresse Oxidativo/efeitos dos fármacos , Adulto , Células CACO-2 , Colo/patologia , Citoproteção/efeitos dos fármacos , Egito , Humanos , Mutagênicos/análise , Mutagênicos/toxicidade , Medição de Risco
17.
Artigo em Inglês | MEDLINE | ID: mdl-30806168

RESUMO

Heterocyclic amines (HCAs) are foodborne carcinogens for which their formation is highly dependent on cooking conditions. HCAs have been commonly quantified in food items prepared with simple procedures. This approach is suitable for elucidating HCAs' formation, but it only partially reflects the contamination in consumed food. In the current investigation, the generation of HCAs has been investigated in fried beef items prepared with elaborated cooking recipes, and their occurrence has been compared with control beef fried without the addition of ingredients other than oil. The food recipes that included a variety of food ingredients had lower yields of mutagenic HCAs (≥47% reduction, with individual HCA levels ranging between 0.01 and 2.22 ng/g) with respect to the control beef. In contrast, the co-mutagens norharman and harman were formed generally at greater levels (up to three times the contamination in the control fried beef) in the items prepared including a greater variety of ingredients.


Assuntos
Aminas/análise , Culinária , Compostos Heterocíclicos/análise , Mutagênicos/análise , Aminas/química , Animais , Carbolinas/análise , Bovinos , Contaminação de Alimentos/análise , Harmina/análogos & derivados , Harmina/análise , Compostos Heterocíclicos/química , Mutagênicos/química , Carne Vermelha/análise
18.
J Pharm Biomed Anal ; 168: 23-29, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30784886

RESUMO

Alkyl sulfonate esters have been widely concerned as genotoxic impurities (GTIs). A gas chromatography triple-quadrupole mass spectrometry (GC-MS/MS) method has been developed for trace determination of 9 commonly encountered sulfonate esters in drug substances. Three different solvents of acetonitrile (ACN), dichloromethane (DCM) and ethyl acetate (EtOAc) were evaluated as diluents to accommodate different solubilities of test articles and multiple reactions monitoring (MRM) mode was applied for quantitation of these 9 GTIs. The method was validated in terms of linearity, sensitivity, injection precision, accuracy and solution stability. The limit of quantitation (LOQ) for the 9 commonly encountered sulfonate esters in drug substances was within 0.10-1.05 ng mL-1, which was much lower than the reported LOQs in other methods (2.5-1500 ng mL-1). It is indicated that the method gave extremely high sensitivity for all the target analytes. The correlation coefficient (r) values of 9 GTIs were no less than 0.9993 in the range of 2.0-100 ng mL-1. Recoveries of all the target analytes at 10, 20, 50 ng mL-1 (equivalent to 2, 4, 10 ppm relative to 5 mg mL-1 API samples) in two different drug substance (capecitabine and imatinib methanesulfonate) were within 75%˜120%. All alkyl sulfonates were stable in these three solvents up to 36 h. This method has been successfully used for determination of these alkyl sulfonates in capecitabine and imatinib methanesulfonate and can be further applied to other drug substances.


Assuntos
Alcanossulfonatos/análise , Capecitabina/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Mesilato de Imatinib/análise , Contaminação de Medicamentos , Limite de Detecção , Mutagênicos/análise , Reprodutibilidade dos Testes , Solubilidade , Solventes/química , Espectrometria de Massas em Tandem/métodos
19.
Environ Sci Pollut Res Int ; 26(9): 8885-8894, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30719671

RESUMO

Polycyclic aromatic hydrocarbons (PAHs), some of which are classified as possible carcinogens (WHO), have been detected in cooking fumes in considerable amounts. Distribution of 24 PAHs on varying particle sizes was analyzed in cooking emission. Analysis of cooking fumes from vegetarian and non-vegetarian food was carried out separately in the kitchen of a hostel mess in IIT Kanpur during November 2012 and February 2013. Respirable suspended particulate matter (RSPM) and particle-bound polycyclic aromatic hydrocarbons (PPAHs) showed a similar sequence regarding concentration observed in vegetarian and non-vegetarian food. PAHs with carcinogenic potential was detected and quantified mostly in the fine particles. Total PAH concentrations in the fine and ultrafine ranges together accounted for > 90% of the total carcinogenic PAHs, highlighting them as primary carriers of PAHs rather than coarser particles. Benzo [a] pyrene (B [a]P) levels contribute > 70% to total carcinogenic potential and > 60%, to mutagenic potential, respectively. The total toxicity impact on the workers due to the PAHs emitted from cooking fumes was 3.374 × 10-10 DALYs, with B [a] P contributing the most (> 70%) despite its low concentration. Exposure to cooking fumes especially for people involved in this activity on a daily basis (chefs, hostel mess workers, among others) raises health concerns. An extensive examination of impacts due to exposure to emissions in both particle and gas phase on a long-term basis is required.


Assuntos
Poluentes Atmosféricos/análise , Culinária , Exposição Ocupacional , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluição do Ar em Ambientes Fechados , Benzo(a)pireno/análise , Carcinógenos/análise , Gases/análise , Avaliação do Impacto na Saúde , Humanos , Exposição por Inalação/análise , Mutagênicos/análise , Tamanho da Partícula
20.
Environ Pollut ; 246: 678-687, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30616058

RESUMO

Oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) are a group of environmental pollutants found in complex mixtures together with PAHs. In contrast to the extensively studied PAHs, which have been established to have mutagenic and carcinogenic properties, much less is known about the effects of oxy-PAHs. The present work aimed to investigate the genotoxic potency of a set of environmentally relevant oxy-PAHs along with environmental soil samples in human bronchial epithelial cells (HBEC). We found that all oxy-PAHs tested induced DNA strand breaks in a dose-dependent manner and some of the oxy-PAHs further induced micronuclei formation. Our results showed weak effects in response to the oxy-PAH containing subfraction of the soil sample. The genotoxic potency was confirmed in both HBEC and HepG2 cells following exposure to oxy-PAHs by an increased level of phospho-Chk1, a biomarker used to estimate the carcinogenic potency of PAHs in vitro. We further exposed zebrafish embryos to single oxy-PAHs or a binary mixture with PAH benzo[a]pyrene (B[a]P) and found the mixture to induce comparable or greater effects on the induction of DNA strand breaks compared to the sum of that induced by B[a]P and oxy-PAHs alone. In conclusion, oxy-PAHs were found to elicit genotoxic effects at similar or higher levels to that of B[a]P which indicates that oxy-PAHs may contribute significantly to the total carcinogenic potency of environmental PAH mixtures. This emphasizes further investigations of these compounds as well as the need to include oxy-PAHs in environmental monitoring programs in order to improve health risk assessment.


Assuntos
Dano ao DNA , Monitoramento Ambiental/métodos , Mutagênicos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Animais , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Ensaio Cometa , Desenvolvimento Embrionário/efeitos dos fármacos , Desenvolvimento Embrionário/genética , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Células Hep G2 , Humanos , Mutagênicos/análise , Oxigênio/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Peixe-Zebra/embriologia
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