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1.
J Mater Chem B ; 8(13): 2719-2725, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32149293

RESUMO

The cross-linked small-molecule micelles (cSMs) have found applications in many fields but their low loading capacity and non-fluorescence property hindered their further development. Herein, water-soluble organic nanoparticles were applied as templates to "stretch" the hydrophobic core of cSMs and photo-cross-linking was employed to supply photoluminescence. The resulting cross-linked small-molecule capsules (cSCs) not only reserve the superior properties of cSMs of accurate monomer, easy functionalization and robust stability, but also achieve high drug loading capacity and excitation wavelength-dependent fluorescence, where the drug loading contents (DLCs) for various hydrophobic drugs were more than 30-fold higher than that of cSMs, and the maximum quantum yield could be as high as 12.0%. Featuring these superiorities, the cSCs hold promising potential in many fields and an example of doxorubicin-loaded cSCs (DOX@cSCs) for multichannel imaging-guided drug delivery is shown in this work.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Reagentes de Ligações Cruzadas/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Medições Luminescentes , Imagem Óptica , Bibliotecas de Moléculas Pequenas/química , Antibióticos Antineoplásicos/química , Cápsulas/síntese química , Cápsulas/química , Sobrevivência Celular/efeitos dos fármacos , Reagentes de Ligações Cruzadas/síntese química , Dimetilformamida/análise , Relação Dose-Resposta a Droga , Doxorrubicina/química , Desenho de Fármacos , Liberação Controlada de Fármacos , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Tamanho da Partícula , Processos Fotoquímicos , Bibliotecas de Moléculas Pequenas/síntese química , Propriedades de Superfície
2.
Scand J Work Environ Health ; 45(4): 396-401, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30904927

RESUMO

Objective There is limited epidemiological evidence of carcinogenicity on exposure of N,N-dimethylformamide (DMF). This study aimed to identify the possible association between cancer mortality and DMF exposure. Methods A cohort of 11 953 workers exposed to DMF between 1 January 2000 and 31 December 2004 was studied. A urinary metabolite of DMF, N-methylformamide level (UNMFL), was used for exposure assessment. This cohort was matched with the mortality data of the Korean National Statistical Office and followed up for cancer mortality between 2000 and 2011. Standardized mortality ratios (SMR) of the DMF-exposed workers with reference to Korean men were calculated. Adjusted hazard ratios (HRadj; also controlling for age, other carcinogen exposure including hepatitis B and C) were calculated for the workers categorized in three exposure groups with reference to workers with no exposure. Results The HRadj of overall cancer mortality were significantly increased in workers with 7.5-<15 mg/L [HRadj 2.72, 95% confidence interval (CI) 1.09-6.81] and ≥15 mg/L (HRadj 2.41, 95% CI 1.03-5.66) compared with non-exposed workers. Hepatocellular carcinoma mortality (HRadj 3.73, 95% CI 1.05-13.24) of workers with ≥15 mg/L and lung cancer mortality (HRadj 14.36, 95% CI 1.41-146.86) in workers with 7.5-<15 mg/L were significantly increased. Conclusions Workers with high DMF exposure showed increased mortalities for overall, liver, and lung cancer. Our results suggest that DMF causes cancer, especially hepatocellular carcinoma, which is in agreement with earlier studies on liver cancer in animal experiments.


Assuntos
Dimetilformamida/análise , Neoplasias/mortalidade , Exposição Ocupacional/análise , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Saúde Ocupacional , República da Coreia/epidemiologia , Adulto Jovem
3.
Arch Toxicol ; 92(7): 2183-2193, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29748790

RESUMO

This study was performed to assess the relation between occupational exposure to N,N-dimethylformamide after an 8 h work shift in the acrylic fibre industry and its three biological markers N-methylformamide (NMFtotal), N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC), and N-methylcarbamoyl adduct at haemoglobin (MCVal). External DMF exposure of 220 workers was determined during the whole shift. A standardised questionnaire was used to obtain information about the worker's general health status, medical treatment, smoking habits, protective measures, and possible symptoms caused by DMF exposure. NMF and AMCC were analysed in post-shift urine samples and MCVal in blood. For longitudinal assessment the average AMCC concentration was determined over a period of 4 weeks (weekly sampling) in a sub-collective of 89 workers. The median of DMF concentration in air was 3.19 mg/m3 (range < 0.15-46.9 mg/m3). The biological markers showed a median of 4.80 mg/L (range 0.20-50.6 mg/L) for NMFtotal, 4.75 mg/g creatinine (range 0.06-49.6 mg/g creatinine) for AMCC, and 57.5 nmol/g globin (range 0.5-414 nmol/g) for MCVal. A significant linear relationship was observed between DMF in air and NMF as well as between DMF in air and AMCC in post-shift urine samples. The mean AMCC values measured weekly over a period of 4 weeks correlated significantly with MCVal adducts too. Excluding workers who had been using breathing masks on the day of the study led to even tighter correlations. The results of the present study demonstrate the applicability of the DMF biomonitoring parameters NMFtotal in post-shift urine for the present-day exposure assessment, AMCC in the post-shift urine after several shifts for assessment of the cumulative exposure of the previous working days, and MCVal for assessment of long-term exposure during previous weeks and months. The data of the present study enable now the estimation of valid equivalents of these biomonitoring parameters to the external DMF exposure. From the risk assessment point of view, the exposure limit values for AMCC and MCVal, which are directly linked to the presumed toxic intermediate MIC, exhibit a significant advance.


Assuntos
Poluentes Ocupacionais do Ar , Dimetilformamida/análise , Monitoramento Ambiental/métodos , Exposição Ocupacional/análise , Adulto , Poluentes Ocupacionais do Ar/sangue , Poluentes Ocupacionais do Ar/urina , Biomarcadores/sangue , Biomarcadores/urina , Estudos Transversais , Alemanha , Humanos , Masculino , Jornada de Trabalho em Turnos , Inquéritos e Questionários
4.
Artigo em Inglês | MEDLINE | ID: mdl-29533984

RESUMO

The purpose of this study was to classify hazards at an industrial level and evaluate the exposure risks of workers exposed to dimethylformamide (DMF) used as a solvent in the workplace and to determine industries that need priority measures in managing DMF exposure. We calculated hazard quotients at an industrial level. The exposure data of DMF in the workplace were obtained from the work environment monitoring program provided by the Korea Occupational Safety and Health Agency. The evaluation was conducted on textile manufacturing, leather manufacturing, chemical manufacturing, pharmaceutical manufacturing, and rubber manufacturing industries, which have many unit work sites handling DMF. The highest central tendency exposure and reasonable maximum exposure were 2.13 and 18.66 mg/m³ for the rubber product manufacturing industry, respectively. A total of 63.8% of workplaces in the textile manufacturing sector had a hazard quotient higher than 1. The highest risk for exposure to DMF is in the rubber and plastic manufacturing industry, and the lowest risk was in the medical materials and pharmaceutical manufacturing sector. Based on this study, effective management of DMF exposure could be achieved by establishing priority management measures for the textile and rubber and plastic product industries.


Assuntos
Dimetilformamida/análise , Indústria Manufatureira/estatística & dados numéricos , Exposição Ocupacional/análise , Local de Trabalho/estatística & dados numéricos , Humanos , Indústrias , Saúde Ocupacional , República da Coreia , Medição de Risco , Borracha , Solventes
5.
Food Chem ; 221: 809-814, 2017 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-27979277

RESUMO

Among the different food categories, the oils and fats are important sources of exposure to polycyclic aromatic hydrocarbons (PAHs), a group of organic chemical contaminants. The use of a validated method is essential to obtain reliable analytical results since the legislation establishes maximum limits in different foods. The objective of this study was to optimize and validate a method for the quantification of four PAHs [benzo(a)anthracene, chrysene, benzo(b)fluoranthene, benzo(a)pyrene] in vegetable oils. The samples were submitted to liquid-liquid extraction, followed by solid-phase extraction, and analyzed by ultra-high performance liquid chromatography. Under the optimized conditions, the validation parameters were evaluated according to the INMETRO Guidelines: linearity (r2 >0.99), selectivity (no matrix interference), limits of detection (0.08-0.30µgkg-1) and quantification (0.25-1.00µgkg-1), recovery (80.13-100.04%), repeatability and intermediate precision (<10% RSD). The method was found to be adequate for routine analysis of PAHs in the vegetable oils evaluated.


Assuntos
Cromatografia Líquida de Alta Pressão , Óleos de Plantas/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Antracenos/análise , Benzo(a)pireno/análise , Crisenos/análise , Dimetilformamida/análise , Fluorenos/análise , Contaminação de Alimentos/análise , Extração Líquido-Líquido , Extração em Fase Sólida
6.
Int Arch Occup Environ Health ; 89(8): 1309-1320, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27587219

RESUMO

PURPOSE: There are still concerns regarding occupational exposure to hepatotoxic DMF. This study was designed to evaluate possible liver damaging effects of DMF under current workplace conditions in synthetic fibres industries. METHODS: Among other laboratory parameters, liver function parameters (alkaline phosphatase (ALP), aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase), the mean corpuscular erythrocyte volume (MCV) and carbohydrate-deficient transferrin (CDT) of the workforce of two companies present at the days of study were investigated. Internal exposure to DMF was assessed via three different biomarkers [sum of N-methylformamide and N-hydroxymethyl-N-methylformamide, N-acetyl-S-(N-carbamoyl)cysteine (AMCC) and 3-methyl-5-isopropylhydantoin (MIH)]. Alcohol consumption was assessed by means of direct ethanol metabolites (ethylglucuronide and ethylsulfate). RESULTS: None of the tested liver enzyme activities showed a positive association with any of the three exposure markers, nor did CDT and MCV. CDT was negatively associated with AMCC and the ALP activity negatively with all three exposure markers. Changes in liver function are seen mainly in conjunction with ethanol consumption but also with increasing body weight and age. MCV was associated with smoking. Almost half of the workers stated to experience alcohol flush reaction. CONCLUSION: The present study indicates that long-term exposure to DMF, which was specified by median urinary AMCC levels of 4.84 mg/g creatinine and DMF haemoglobin adduct levels of 60.5 nmol/MIH/g globin, respectively, does not result in any adverse liver effects. In contrast, these DMF exposure levels still elicit certain alcohol intolerance reactions.


Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Transtornos Induzidos por Álcool/etiologia , Dimetilformamida/análise , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/análise , Acetilcisteína/análogos & derivados , Acetilcisteína/urina , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Transtornos Induzidos por Álcool/fisiopatologia , Biomarcadores/urina , Creatinina/urina , Estudos Transversais , Dimetilformamida/efeitos adversos , Dimetilformamida/análogos & derivados , Monitoramento Ambiental/métodos , Índices de Eritrócitos , Formamidas/análise , Humanos , Hidantoínas/sangue , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/fisiopatologia , Exposição Ocupacional/efeitos adversos , Transferrina/análogos & derivados , Transferrina/análise
7.
Environ Technol ; 37(16): 2048-57, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26914341

RESUMO

The influence of different target pollutants and operation modes in sequencing batch bioreactors (SBRs) on sludge toxicity was compared in this study. Sludge toxicity was characterized by the inhibiting luminosity through using luminescent bacterium Photobacterium phosphoreum (P. phosphoreum) during either gradual acclimation or impaction processes with synthetic wastewater containing high-strength bisphenol A (BPA) or N, N-dimethylformamide (DMF). When the activated sludge was first acclimated with either 120 mg/L DMF or 20 mg/L BPA, and then respectively increased to 200 mg/L DMF and 40 mg/L BPA it was defined as gradual acclimation process, whereas when the activated sludge was, respectively, injected with 200 mg/L DMF and 40 mg/L BPA directly it was defined as impaction process. Results showed that the toxicity of the impacted sludge was greater than that of the gradual acclimated sludge, especially in the initial stage before 10 d. Activated sludge treating BPA synthetic wastewater exhibited higher toxicity due to the more inhibition of BPA to sludge activity compared to that of DMF. The proteomics analysis indicated that the stress responses of activated sludge to DMF and BPA stimulation were both significant. In turn, the secretions from two kinds of sludge under stress conditions contributed to sludge toxicity.


Assuntos
Compostos Benzidrílicos/análise , Reatores Biológicos , Dimetilformamida/análise , Fenóis/análise , Esgotos/química , Poluentes Químicos da Água/análise , Compostos Benzidrílicos/química , Dimetilformamida/química , Eletroforese em Gel Bidimensional , Fenóis/química , Esgotos/análise , Poluentes Químicos da Água/química
8.
Talanta ; 143: 64-70, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26078129

RESUMO

A single-step procedure for trace elements analysis of milk samples is presented. Solubilization with small amounts of dymethylformamide (DMF) was assayed prior to inductively coupled plasma mass spectrometry (ICPMS) detection with a high efficiency sample introduction system. All main instrumental conditions were optimized in order to readily introduce the samples without matrix elimination. In order to assess and mitigate matrix effects in the determination of As, Cd, Co, Cu, Eu, Ga, Gd, Ge, Mn, Mo, Nb, Nd, Ni, Pb, Pr, Rb, Sm, S, Sr, Ta, Tb, V, Zn, and Zr, matrix matching calibration with (103)Rh as internal standard (IS) was performed. The obtained limits of detection were between 0.68 (Tb) and 30 (Zn) µg L(-1). For accuracy verification, certified Skim milk powder reference material (BCR 063R) was employed. The developed method was applied to trace elements analysis of commercially available milks. Principal components analysis was used to correlate the content of trace metals with the kind of milk, obtaining a classification according to adults, baby or baby fortified milks. The outcomes highlight a simple and fast approach that could be trustworthy for routine analysis, quality control and traceability of milks.


Assuntos
Dimetilformamida/análise , Dimetilformamida/química , Espectrometria de Massas/métodos , Leite/química , Gases em Plasma/química , Adulto , Animais , Calibragem , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Análise de Componente Principal , Solubilidade
9.
Ecotoxicol Environ Saf ; 114: 350-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25064375

RESUMO

The emission rates of N,N-dimethylformamide (DMF), formamide (FAd), and certain hazardous volatile organic compounds (VOCs) were measured from seventeen mattress textile samples with four different raw material types: polyurethane (PU: n=3), polyester/polyethylene (PE: n=7), ethylene vinyl acetate (EV: n=3), and polyvinyl chloride (PC: n=4). To simulate the emissions in a heated room during winter season, measurements were made under temperature-controlled conditions, i.e., 50°C by using a mini-chamber system made of a midget impinger. Comparison of the data indicates that the patterns were greatly distinguished between DMF and FAd. PU products yielded the highest mean emission rates of DMF (2940 µg m(-2)h(-1): n=3) followed by PE (325 µg m(-2)h(-1): n=7), although its emission was not seen from other materials (EV and PC). In contrast, the pattern of FAd emission was moderately reversed from that of DMF: EV>PC>PE>PU. The results of our analysis confirm that most materials used for mattress production have the strong potential to emit either DMF or FAd in relatively large quantities while in use in children׳s care facilities, especially in winter months. Moreover, it was also observed that an increase in temperature (25°C to 50°C) had a significant impact on the emission rate of FAd and other hazardous VOCs. In addition to the aforementioned amides, the study revealed significant emissions of a number of hazardous VOCs, such as aromatic and carbonyl compounds.


Assuntos
Dimetilformamida/análise , Formamidas/análise , Substâncias Perigosas/análise , Têxteis/análise , Compostos Orgânicos Voláteis/análise , Decoração de Interiores e Mobiliário , Temperatura
10.
Ind Health ; 52(6): 512-20, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25224331

RESUMO

We evaluated total body burden of N,N-dimethylformamide (DMF) taken through the lung and skin by personal exposure of workers to DMF and urinalysis of N-methylformamide (NMF) and N-acetyl-S(N-methylcarbamoyl)-cysteine (AMCC). A total of 270 workers were engaged in four different jobs in a workplace distant from main production lines emanating high levels of DMF. They were not required to wear any personal protective equipment including respirators or gloves. We found that log-transformed urinary levels of NMF and AMCC increased with an increase in log-transformed concentrations of exposure to DMF. Urinary levels of NMF and AMCC were significantly higher in the summer than the winter, although there was no significant seasonal difference in the concentrations of exposure to DMF. Our findings suggested that the increased urinary levels of NMF and AMCC in the summer resulted in increased skin absorption of DMF due to an increased amount of DMF absorbed by the moisturized skin under humid and hot conditions. Seasonal changes in the relative internal exposure index confirmed the present finding of enhanced summertime skin absorption of DMF. AMCC is thought to be a useful biomarker for assessments of cumulative exposure to DMF over a workweek and for evaluations of workers' health effects.


Assuntos
Dimetilformamida/análise , Exposição por Inalação/efeitos adversos , Indústria Manufatureira , Exposição Ocupacional/análise , Estações do Ano , Absorção Cutânea , Acetilcisteína/análogos & derivados , Acetilcisteína/urina , Adulto , Feminino , Formamidas/análise , Temperatura Alta , Humanos , Umidade , Masculino , Pessoa de Meia-Idade
11.
Artigo em Chinês | MEDLINE | ID: mdl-25169092

RESUMO

OBJECTIVE: To assess the value of blood N-methylcarbamoylated haemoglobin (NMHb) as a biomarker of N, N-dimethylformamide (DMF) exposure. METHODS: Seventy-two DMF processing workers in a synthetic leather factory were included in the DMF exposure group, and 12 workers in a food factory without exposure to DMF were included in the control group. Long-time individual sampling in workplace was performed among 45 workers in the exposure group, accompanied by a questionnaire survey. Blood and urine were collected for the determination of urinary N-methylformamide (NMF), urinary creatinine, and blood NMHb. Air DMF and urinary NMF were determined by gas chromatography. NMHb in blood was degraded to 3-methyl-5-isopropylhydantoin by Edman degradation before it could be determined by gas chromatography/mass spectrometry. RESULTS: Air DMF in workplace and NMF in post-shift urine were both correlated with NMHb in blood, and the respective regression equations were LgNMHb (nmol/g globin) = 0.32×LgDMF (mg/m(3))+1.8 (r = 0.60, P < 0.005), and LgNMHb (nmol/g globin) = 0.47×LgNMF (mg/g Cr) + 1.4 (r = 0.56, P < 0.005). CONCLUSION: NMHb can be used as a biomarker of long-term exposure to DMF.


Assuntos
Biomarcadores/sangue , Dimetilformamida/análise , Exposição Ocupacional , Adulto , Hemoglobinas/análise , Humanos , Pessoa de Meia-Idade , Local de Trabalho , Adulto Jovem
12.
Chem Commun (Camb) ; 50(36): 4674-6, 2014 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-24623153

RESUMO

We performed the reaction of vitamin B12 with N,N-dimethylformamide dimethyl acetal for primary amide activation, and added MeOH as a nucleophile, to afford cobalester, the first amphiphilic cobalamin derivative. The unique combination of redox properties and solubility represents an asset for its use as a catalyst in C-C bond forming reactions.


Assuntos
Tensoativos/química , Vitamina B 12/química , Catálise , Cobamidas/análise , Cobamidas/química , Cobamidas/metabolismo , Dimetilformamida/análogos & derivados , Dimetilformamida/análise , Dimetilformamida/química , Dimetilformamida/metabolismo , Oxirredução , Tensoativos/análise , Tensoativos/metabolismo , Vitamina B 12/análise , Vitamina B 12/metabolismo , Difração de Raios X
13.
Huan Jing Ke Xue ; 34(4): 1363-8, 2013 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-23798115

RESUMO

The aerobic sequencing batch activated sludge system (SBR) was used to remove the toxic and refractory organic pollutant, N,N-dimethylformamide (DMF). The formation property and spatial distribution of the organic toxicity in sludge were studied. The operation parameters were controlled as follows: influent COD was about 300 mg x L(-1), every DMF concentration phase lasted 30 d(40 mg x L(-1), 80 mg x L(-1), 120 mg x L(-1)), the SBR cycle lasted 12 h, and DO was 2.0-3.0 mg x L(-1). The results showed that the sludge toxicity increased in the beginning and then decreased to a steady range at each DMF concentration phase; there was a positive correlation between the sludge toxicity and the initial DMF concentration; most of the sludge organic toxicity was caused by DMF biodegradation and existed in the inner extracellular polymeric substances (EPS) and intracellular section of sludge flocs.


Assuntos
Reatores Biológicos/microbiologia , Dimetilformamida/toxicidade , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Aerobiose , Biodegradação Ambiental , Dimetilformamida/análise , Dimetilformamida/metabolismo , Análise Espacial
14.
Magn Reson Chem ; 50(8): 525-8, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22730256

RESUMO

Quimi-Hib is a conjugate vaccine against Haemophilus influenza type b (Hib) where the Hib antigen is the only one produced by chemical synthesis. NMR has become the alternative of choice for the identity of intermediates during the chemical synthesis of Hib antigen. We explore a rapid quantitative proton magnetic resonance (qHNMR) assay for the determination of N,N-dimethylformamide (DMF) as a residual in one of the critical intermediates. The proposed assay has been shown to be accurate, precise for intermediate precision conditions (relative standard deviation <3% for spectrometer-to-spectrometer variations), specific (no detected interferences), and rugged (percentage difference <3% for day-to-day and spectrometer-to-spectrometer variations). The quantitative NMR assay can replace the common chromatographic methods for monitoring the DMF contents in one crucial step of the synthetic scheme.


Assuntos
Dimetilformamida/análise , Vacinas Anti-Haemophilus/química , Espectroscopia de Ressonância Magnética , Conformação Molecular , Prótons , Vacinas Conjugadas/química
15.
Artigo em Chinês | MEDLINE | ID: mdl-21033156

RESUMO

OBJECTIVE: To establish a method for the determination of dimethylformamide (DMF) and investigate dermal contamination and absorption among workers occupationally exposed to DMF. METHOD: 37 workers exposed to DMF were divided randomly into two groups. DMF was washed down by isopropyl alcohol in A group (16 workers) and water in B group(21 workers).Gas chromatography was used for the quantification of dermal contamination and N-methylformamide(NMF) in urine, correlative study was done between them. RESULTS: DMF could be detected in all samples in A group, but could not be detected in B group. The miscellaneous peaks could be completely separated from the DMF peak in the sample spectrum, without manual inference. The highest degree of total dermal contamination was observed in wet spinning workshop [(2.84 +/- 1.31) mg], postprocessing workshop [(2.50 +/- 0.95) mg] and dry spinning workshop [(1.95 +/- 0.61) mg] were lower. The respiratory cumulative exposure dosages were 351.3, 201.3 and 135.2 mg respectively. The average DMP concentration in air of the third printing processing workshop, the dry spinning workshop and the wet spinning workshop was 60.2, 89.6, 156.4 mg/m3 respectively, and the respiratory tract contamination in the workers of the three workshops were 135.2, 201.3 and 351.3 mg respectively. There was statistical independence between the quantification of total dermal contamination and NMF in urine (r = 0.176, P > 0.05). CONCLUSION: Isopropyl alcohol is the effective washing solvent.When the concentration of DMF in workplace air is above the occupational exposure limit, respiratory tract absorption is the principal pathway of DMF absorption,but dermal contamination of DMF should not be ignored.


Assuntos
Dimetilformamida/análise , Exposição Ocupacional/análise , Pele , 2-Propanol , Adolescente , Adulto , Monitoramento Ambiental/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Solventes , Água , Adulto Jovem
16.
J Pharm Biomed Anal ; 52(2): 311-5, 2010 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-20122810

RESUMO

The pressure to reduce cycle times of sample analysis has made it increasingly important to improve sample throughput during pharmaceutical process development. For ICP-based analyses, sample preparation is often the bottleneck of the entire analytical scheme due to the tedious digestion procedure and lacking a universal diluent for organic compounds. In this work, N,N-dimethylformamide (DMF) was used as a "universal" organic diluent so that the sample preparation can be simplified as a "dilute-and-shoot" procedure. An optimized interface with a commercial membrane desolvation unit was implemented, which enabled the introduction of organic solvents into an ICP-AES without organic loading. Mixed standard solutions of 15 elements (Al, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pd, Pt, Rh, Ru, W, Zn, and Zr), which covered the majority of processing metals routinely monitored in pharmaceutical development, were prepared for the study and stability of each element in a multi-element DMF solution was investigated. It was found that the addition of a stabilizing agent (EDTA) was necessary to ensure that all the elements at concentrations of 0.10-0.50 microg/mL remained physically stable in solution (recovery better than 95%) for 2 weeks. It was also important to use an internal standard (yttrium) in order to compensate for signal drift and matrix effects from different sample matrices. A 2-10-fold increase of sensitivity (due to enhanced analyte transport efficiency) and acceptable levels of precision (RSD<3%) and recoveries (91-111%) were achieved. The LOQs of all 15 elements were less than 10 microg/L in the solution, which translates to less than 5 microg/g or microg/mL in pharmaceutical samples tested. This technique would minimize the effort required for sample preparation, thus reducing the cycle time by approximately 60-90% in the entire analytical scheme for samples that are difficult to be dissolved in nitric acid. This will provide opportunities for a new level of sample handling and automation for metal analysis in pharmaceutical process development.


Assuntos
Dimetilformamida/análise , Metais/análise , Preparações Farmacêuticas/análise , Espectrofotometria Atômica/métodos , Calibragem , Limite de Detecção , Padrões de Referência , Sensibilidade e Especificidade , Solubilidade , Espectrofotometria Atômica/instrumentação
17.
Rapid Commun Mass Spectrom ; 22(17): 2629-38, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18666198

RESUMO

Mercapturic acids are highly important and specific biomarkers of exposure to carcinogenic substances in occupational and environmental medicine. We have developed and validated a reliable, specific and very sensitive method for the simultaneous determination of five mercapturic acids derived from several high-production chemicals used in industry, namely ethylene oxide, propylene oxide, acrylamide, acrolein and N,N-dimethylformamide. Analytes are enriched and cleaned up from urinary matrix by offline solid-phase extraction. The mercapturic acids are subsequently separated by means of high-performance liquid chromatography on a Luna C8 (2) column and specifically quantified by tandem mass spectrometric detection using isotopically labelled analytes as internal standards. The limits of detection (LODs) for N-acetyl-S-2-carbamoylethylcysteine (AAMA) and N-acetyl-S-2-hydroxyethylcysteine (HEMA) were 2.5 microg/L and 0.5 microg/L urine, while for N-acetyl-S-3-hydroxypropylcysteine (3-HPMA), N-acetyl-S-2-hydroxypropylcysteine (2-HPMA) and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) it was 5 microg/L. These LODs were sufficient to detect the background exposure of the general population. We applied the method on spot urine samples of 28 subjects of the general population with no known occupational exposure to these substances. Median levels for AAMA, HEMA, 3-HPMA, 2-HPMA and AMCC in non-smokers (n = 14) were 52.6, 2.0, 155, 7.1 and 113.6 microg/L, respectively. In smokers (n = 14), median levels for AAMA, HEMA, 3-HPMA, 2-HPMA and AMCC were 243, 5.3, 1681, 41.7 and 822 microg/L, respectively. Due to the simultaneous quantification of these mercapturic acids, our method is well suited for the screening of workers with multiple chemical exposures as well as the determination of the background excretion of the general population.


Assuntos
Acetilcisteína/urina , Biomarcadores/urina , Monitoramento Ambiental/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Acroleína/química , Acroleína/urina , Acrilamida/química , Acrilamida/urina , Adulto , Cromatografia Líquida de Alta Pressão , Dimetilformamida/análise , Dimetilformamida/química , Compostos de Epóxi/química , Compostos de Epóxi/urina , Óxido de Etileno/química , Óxido de Etileno/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/análise
18.
J Pharm Biomed Anal ; 48(1): 113-9, 2008 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-18584990

RESUMO

Residual solvents (RS) are volatile organic chemicals that are used or produced during the manufacturing process of drug substances or excipients. The European Pharmacopoeia (Ph. Eur.) limits the amount of RS in pharmaceuticals, considering the International Conference on Harmonization (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines for RS. According to the Ph. Eur. general method, water insoluble samples may be analyzed using DMF as dilution solvent at high equilibration temperatures such as 105 degrees C. This could be problematic in the case of antibiotics, many of which are water insoluble and temperature sensitive. Moreover, antibiotics are complex in nature and beside RS, one can expect several other volatile impurity peaks in the chromatogram. In this study, the Ph. Eur. method for RS analysis was evaluated for selected groups of antibiotics. An alternative dilution medium was proposed (DMSO-water), which offers optimum sensitivity while working at lower equilibration temperatures such as 80 degrees C. The optimized method was investigated for precision, accuracy, linearity and detection limits.


Assuntos
Antibacterianos/análise , Contaminação de Medicamentos/prevenção & controle , Elétrons , Compostos Orgânicos/análise , Preparações Farmacêuticas/química , Solventes/análise , Acetamidas/análise , Dimetil Sulfóxido/análise , Dimetilformamida/análise , Europa (Continente) , Excipientes/química , Guias como Assunto , Humanos , Imidazóis/análise , Imidazolidinas/análise , Imidazolidinas/química , Espectrometria de Massas/métodos , Solubilidade , Volatilização
19.
Sci Total Environ ; 388(1-3): 398-404, 2007 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-17854864

RESUMO

N,N-dimethylformamide (DMF) could be readily absorbed via skin and inhalation routes. It is difficult, however, to separate the internal dose contribution from skin vapor and inhalation exposure. This study attempts to quantitatively determine the separate skin vapor and inhalation exposure contributions using a semi-actual exposure approach. Six volunteers were tailgated by DMF-exposed employees completely for two exposure scenarios: with and without wearing a respirator. Individual airborne DMF (A-DMF) exposure was evaluated by integrating real-time DMF monitoring and time-activity log. Urinary N-methylformamide (U-NMF) concentrations in 4-h and 8-h one urine sample plus 24-h consecutive urine sample were determined to evaluate the internal DMF exposure dose. The average A-DMF concentrations for all participants were 8.10 (2.75) and 9.52 (3.47) ppm, respectively, for with respirator and without respirator scenarios. Area under the curve of U-NMF throughout 24-h showed 71% and 29% contribution from skin and inhalation exposure, respectively, indicates that the absorbed dose of DMF via skin vapor exposure was much greater than inhalation. In conclusion, the semi-actual approach provides a novel measure to accurately determine the relative skin vapor and inhalation exposure contributions to the internal dose. The skin vapor exposure deserves more attention in the prevention of chemical hazards in the exposed environment.


Assuntos
Poluentes Ocupacionais do Ar/farmacocinética , Dimetilformamida/farmacocinética , Exposição por Inalação , Pulmão/metabolismo , Exposição Ocupacional , Pele/metabolismo , Adulto , Poluentes Ocupacionais do Ar/análise , Dimetilformamida/análise , Monitoramento Ambiental , Formamidas/metabolismo , Humanos , Exposição por Inalação/análise , Cinética , Masculino , Respiração
20.
Sangyo Eiseigaku Zasshi ; 48(6): 214-20, 2006 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-17170515

RESUMO

Analysis by gas chromatograph after collection of personal samples is the most common method of evaluating individuals' exposures to organic solvents. This method provides us time-weighted averages (TWA) only, and does not measure fluctuating concentrations of organic solvents. A portable VOC monitor is widely used as a rapid screening instrument for volatile organic compounds (VOCs) in houses, schools, etc. The VOC monitor equipped with a photoionization detector can measure real-time concentrations of VOCs. In this study, the author investigated whether the VOC monitor can evaluate individuals' exposures to organic solvents. First, standard organic solvent gases were prepared and the gas concentrations were measured by a passive air sampler and the VOC monitor. Correction factors (CF) were obtained for the response of the isobutylene calibrated VOC monitor to equal concentrations of the organic solvents. Methyl ethyl ketone's CF was 0.5952, toluene's CF was 0.4418, and N,N-dimethylformamide's CF was 0.9017. Then, a mixed standard organic solvents gas was prepared and the gas concentration was measured by both methods. A significant correlation between both methods was obtained (p < 0.001). Subsequently, 37 male workers in a synthetic-leather factory were examined for solvent exposure using both the VOC and a passive sampler, Similar results were obtained by both methods (p < 0.001). Real-time data can be obtained using the VOC monitor and high exposure tasks can be identified. The VOC monitor will be useful for reducing occupational exposure. Since the VOC monitor provides detailed data of individuals' exposures to organic solvents.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental/instrumentação , Exposição Ocupacional/análise , Solventes/análise , Adulto , Butanonas/análise , Dimetilformamida/análise , Monitoramento Ambiental/métodos , Gases , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/prevenção & controle , Fatores de Tempo , Tolueno/análise , Volatilização
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