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1.
Arch Toxicol ; 95(8): 2659-2665, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34152453

RESUMO

Methylisothiazolinone (MI) as well as the mixture of chloromethylisothiazolinone/methylisothiazolinone [MCI/MI (3:1)] are biocides that are used in a variety of products of every-day life. Due to the skin sensitizing properties of these biocides, their use has come under scrutiny. We have previously examined the human metabolism of MI and MCI after oral dosage of isotope-labelled analogues in human volunteers and confirmed N-methylmalonamic acid to be a major, but presumably unspecific human urinary metabolite. In the present study, we have investigated the urinary kinetics of a mercapturic acid metabolite of MI and MCI using the same set of samples. Four human volunteers received 2 mg of isotopically labelled MI and MCI separately and at least 2 weeks apart. Consecutive urine samples were collected over 48 h and were examined for the content of the (labelled) 3-mercapturic acid conjugate of 3-thiomethyl-N-methyl-propionamide ("M-12"), a known metabolite in rats. On a molar basis, M-12 represented 7.1% (3.0-10.1%) of the dose excreted in urine after dosage of MI. Excretion of this mercapturate was fast with a mean half-life of 3.6 h. Surprisingly, for MCI the mercapturate M-12 represented only 0.13% of the dose excreted in urine. Thus, this biomarker is highly specific for exposures to MI and might be used to distinguish between different exposure patterns of these biocides [use of MI or MCI/MI (3:1)] in the general population.


Assuntos
Acetilcisteína/urina , Desinfetantes/farmacocinética , Tiazóis/farmacocinética , Acetilcisteína/química , Administração Oral , Adulto , Feminino , Meia-Vida , Humanos , Masculino , Tiazóis/administração & dosagem , Adulto Jovem
2.
Arch Oral Biol ; 110: 104623, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31830639

RESUMO

OBJECTIVE: The aim of this study was to determine chlorhexidine retention in different oral sites after a one-time 30 s mouth rinsing. DESIGN: Five volunteers were asked to rinse their mouth with 10 ml of 0.2 % chlorhexidine digluconate for 30 s. After rinsing, samples were collected from the interdental area, buccal dental pellicle, anterior labial and posterior buccal mucosa, and saliva with a microbrush at five-time points within 24 h. Retention of chlorhexidine was measured using matrix-assisted laser desorption/ionization-time of flight mass spectrometry with a quantification limit of 15 ng/ml. RESULTS: Chlorhexidine remained in the oral cavity at micrograms per milliliter levels for 11 h after mouth rinsing and was even detected 24 h after application. The results showed a distinct decline of intraoral chlorhexidine levels during the first 6 h after rinsing and it was then retained at low concentrations for at least 24 h. CONCLUSIONS: The dental pellicle and oral mucosa were favorable sites for chlorhexidine retention. The novel method used for chlorhexidine determination offered excellent quantification limits and readily permitted quantification of chlorhexidine.


Assuntos
Clorexidina , Desinfetantes , Boca , Antissépticos Bucais , Clorexidina/farmacocinética , Desinfetantes/farmacocinética , Humanos , Boca/química , Mucosa Bucal/química , Antissépticos Bucais/farmacocinética , Saliva/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
3.
J Endod ; 45(11): 1371-1377, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31542283

RESUMO

INTRODUCTION: Curcumin incorporation into polymeric fibers was tested for its antimicrobial properties and potential use in root canal disinfection. METHODS: Curcumin-modified fibers were processed via electrospinning and tested against a 7-day old established Actinomyces naeslundii biofilm. The medicaments tested were as follows: curcumin-modified fibers at 2.5 and 5.0 mg/mL, curcumin-based irrigant at 2.5 and 5.0 mg/mL, saline solution (negative control), and the following positive controls: 2% chlorhexidine, 1% sodium hypochlorite, and triple antibiotic paste (TAP, 1 mg/mL). All medicaments, except for the positive controls, were allocated according to the light exposure protocol (ie, photoactivation with a light-emitting diode every 30 seconds for 4 minutes or without photoactivation). After treatment, the medicaments were removed, and 1 mL saline solution was added; the biofilm was scraped from the well and used to prepare a 1:2000 dilution. Spiral plating was performed using anaerobic blood agar plates. After 24 hours, colony-forming units (colony-forming units/mL, n = 11/group) were counted to determine the antimicrobial effects. RESULTS: Data exhibited significant antimicrobial effects on the positive control groups followed by the curcumin irrigants and, lastly, the photoactivated curcumin-modified fibers. There was a significant reduction of viable bacteria in curcumin-based irrigants, which was greater than the TAP-treated group. Curcumin-free fibers, saline, and the nonphotoactivated curcumin-modified fibers did not display antimicrobial activity. CONCLUSIONS: Curcumin seems to be a potential alternative to TAP when controlling infection, but it requires a minimal concentration (2.5 mg/mL) to be effective. Photoactivation of curcumin-based medicaments seems to be essential to obtain greater antibiofilm activity.


Assuntos
Curcumina , Desinfetantes , Tratamento do Canal Radicular , Actinomyces/efeitos dos fármacos , Biofilmes , Curcumina/farmacocinética , Curcumina/farmacologia , Cavidade Pulpar , Desinfetantes/farmacocinética , Desinfetantes/farmacologia , Desinfecção , Liberação Controlada de Fármacos , Enterococcus faecalis , Irrigantes do Canal Radicular , Hipoclorito de Sódio
4.
Artigo em Inglês | MEDLINE | ID: mdl-31038002

RESUMO

Raw water (RW) from the Bangkok and Sing Buri water treatment plants located on the Chao Phraya River, river water, domestic wastewater (WW), and treated wastewater (TWW) from two wastewater treatment plants in Thailand were collected three times to investigate disinfection by-products' (DBPs) formation potential (FP) including trihalomethane FP (THMFP), iodo-THMFP (I-THMFP), haloacetonitriles FP (HANFP), and trichloronitromethane FP (TCNMFP). High THMFP levels were observed in river water, WW, and TWW. Considering average value, the THMFP of TWW was about two times higher than that of RW. Relatively high levels of I-THMFP were found in WW and TWW. The I-THMFP of TWW was three to seven times higher than that of RW. The HANFP of TWW was one to three times higher than that of RW. High levels of TCNMFP were found in WW and TWW. TCNMFP of TWW was six to thirteen times higher than that of RW. The discharge of TWW to RW must be prevented and controlled. The moderately positive linear relationship was obtained between dissolved organic carbon and TCNMFP in TWW. Considering measured weight concentration, THMFP was found as the highest DBPs. The highest lethal concentration 50-weighted and lowest cytotoxicity-weighted concentrations of DBPs were determined for HANFP.


Assuntos
Desinfecção , Águas Residuárias/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Desinfetantes/análise , Desinfetantes/química , Desinfetantes/farmacocinética , Água Doce/análise , Humanos , Rios/química , Tailândia , Trialometanos/análise , Água/química , Abastecimento de Água
5.
CMAJ ; 190(37): E1097-E1107, 2018 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-30224442

RESUMO

BACKGROUND: Emerging links between household cleaning products and childhood overweight may involve the gut microbiome. We determined mediating effects of infant gut microbiota on associations between home use of cleaning products and future overweight. METHODS: From the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort, we tested associations between maternal report of cleaning product use and overweight at age 3, and whether associations were mediated by microbial profiles of fecal samples in 3- to 4-month-old infants. RESULTS: Among 757 infants, the abundance of specific gut microbiota was associated with household cleaning with disinfectants and eco-friendly products in a dose-dependent manner. With more frequent use of disinfectants, Lachnospiraceae increasingly became more abundant (highest v. lowest quintile of use: adjusted odds ratio [AOR] 1.93, 95% confidence interval [CI] 1.08 to 3.45) while genus Haemophilus declined in abundance (highest v. lowest quintile of use: AOR 0.36, 95% CI 0.20 to 0.65). Enterobacteriaceae were successively depleted with greater use of eco-friendly products (AOR 0.45, 95% CI 0.27 to 0.74). Lachnospiraceae abundance significantly mediated associations of the top 30th centile of household disinfectant use with higher body mass index (BMI) z score (p = 0.02) and with increased odds of overweight or obesity (p = 0.04) at age 3. Use of eco-friendly products was associated with decreased odds of overweight or obesity independently of Enterobacteriaceae abundance (AOR 0.44, 95% CI 0.22 to 0.86), with no significant mediation (p = 0.2). INTERPRETATION: Exposure to household disinfectants was associated with higher BMI at age 3, mediated by gut microbial composition at age 3-4 months. Although child overweight was less common in households that cleaned with eco-friendly products, the lack of mediation by infant gut microbiota suggests another pathway for this association.


Assuntos
Desinfetantes , Exposição Ambiental/efeitos adversos , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Zeladoria , Obesidade Infantil/induzido quimicamente , Canadá/epidemiologia , Desenvolvimento Infantil , Pré-Escolar , Desinfetantes/efeitos adversos , Desinfetantes/farmacocinética , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Razão de Chances , Obesidade Infantil/microbiologia
6.
Biomacromolecules ; 19(6): 1888-1917, 2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29718664

RESUMO

Global health is increasingly being threatened by the rapid emergence of drug-resistant microbes. The ability of these microbes to form biofilms has further exacerbated the scenario leading to notorious infections that are almost impossible to treat. For addressing this clinical threat, various antimicrobial polymers, polymer-based antimicrobial hydrogels and polymer-coated antimicrobial surfaces have been developed in the recent past. This review aims to discuss such polymer-based antimicrobial strategies with a focus on their current advancement in the field. Antimicrobial polymers, whose designs are inspired from antimicrobial peptides (AMPs), are described with an emphasis on structure-activity analysis. Additionally, antibiofilm activity and in vivo efficacy are delineated to elucidate the real potential of these antimicrobial polymers as possible therapeutics. Antimicrobial hydrogels, prepared from either inherently antimicrobial polymers or biocide-loaded into polymer-derived hydrogel matrix, are elaborated followed by various strategies to engineer polymer-coated antimicrobial surfaces. In the end, the current challenges are accentuated along with future directions for further expansion of the field toward tackling infections and antimicrobial resistance.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Polímeros/química , Polímeros/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Desinfetantes/farmacocinética , Desenho de Fármacos , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Infecções/tratamento farmacológico , Infecções/microbiologia , Relação Estrutura-Atividade
7.
J Appl Toxicol ; 37(4): 508-512, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27593710

RESUMO

Workers in the USA are exposed to industrial formulations, which may be toxic. These formulations often contain preservatives or biocides such as ortho-phenylphenol (OPP). There are limited data describing OPP following intravenous administration to assess truly the clearance of this chemical in humans and other species. In vivo experiments were conducted in pigs to determine related pharmacokinetic parameters. 14 C-OPP was administered as an intravenous bolus dose. Blood, feces, urine and tissue samples were collected for analysis by liquid scintillation. Data were analyzed using non-compartmental and compartmental pharmacokinetic model approaches. These data fitted a three-compartment model and showed that the half-life of 14 C-OPP following the intravenous bolus in pigs was 46.26 ± 10.01 h. The kidneys play a crucial role in clearance of 14 C-OPP with a large percentage of the dose being found in the urine (70.3 ± 6.9% dose). Comparisons with other species suggest that 14 C-OPP clearance in pigs (2.48 ml h-1 kg-1 ) is less than that in humans (18.87 ml h-1 kg-1 ) and rats (35.51 ml h-1 kg-1 ). Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Compostos de Bifenilo/farmacocinética , Desinfetantes/farmacocinética , Administração Intravenosa , Animais , Área Sob a Curva , Compostos de Bifenilo/administração & dosagem , Fezes/química , Meia-Vida , Masculino , Sus scrofa , Suínos , Distribuição Tecidual
8.
Biointerphases ; 11(2): 011012, 2016 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-26964530

RESUMO

Fast and efficient osseointegration of implants into bone is of crucial importance for their clinical success; a process that can be enhanced by coating the implant surface with hydroxyapatite (HA) using the vacuum plasma spray technology (VPS). However, bacterial infections, especially the biofilm formation on implant surfaces after a surgery, represent a serious complication. With ever-increasing numbers of antibiotic-resistant bacteria, there is great interest in silver (Ag) as an alternative to classical antibiotics due to its broad activity against Gram-positive and Gram-negative bacterial strains. In the present study, silver ions were introduced into HA spray powder by ion exchange and the HA-Ag powder was applied onto titanium samples by VPS. The Ag-containing surfaces were evaluated for the kinetics of the silver release, its antibacterial effect against Staphylococcus aureus as well as Escherichia coli, and possible cytotoxicity against human bone cells. The HA-Ag coatings with different concentrations of Ag displayed mechanical and compositional properties that fulfill the regulatory requirements. Evaluation of the Ag release kinetic showed a high release rate in the first 24 h followed by a decreasing release rate over the four subsequent days. The HA-Ag coatings showed no cytotoxicity to primary human bone cells while exhibiting antibacterial activity to E. coli and S. aureus.


Assuntos
Materiais Revestidos Biocompatíveis , Desinfetantes/metabolismo , Desinfecção/métodos , Próteses e Implantes , Prata/metabolismo , Desinfetantes/química , Desinfetantes/farmacocinética , Durapatita , Escherichia coli/efeitos dos fármacos , Humanos , Gases em Plasma , Pós , Prata/química , Prata/farmacocinética , Staphylococcus aureus/efeitos dos fármacos , Vácuo
9.
J Appl Toxicol ; 35(5): 520-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25186650

RESUMO

Every year, 10 million workers are exposed to metalworking fluids (MWFs) that may be toxic. There are four types of MWFs: neat oils and three water-based MWFs (soluble oil, semisynthetic and synthetic), which are diluted with water and whose composition varies according to the mineral oils ratio. MWFs also contain various additives. To determine the absorption of six amines used as corrosion inhibitors and biocides in MWFs, porcine skin flow-through diffusion cell experiments were conducted with hydrophilic ethanolamines (mono-, di- and triethanolamine, MEA, DEA and TEA respectively) and a mixture of lipophilic amines (dibutylethanolamine, dicyclohexylamine and diphenylamine). The six amines were dosed in four vehicles (water and three generic water-based MWF formulations) and analyzed using a scintillation counter or gas chromatography/mass spectrometry. These 24 h studies showed that dermal absorption significantly (P < 0.05) increased from water for the six amines (e.g. 1.15 ± 0.29% dose; DEA in water) compared to other formulations (e.g. 0.13 ± 0.01% dose; DEA in semisynthetic MWF) and absorption was greatest for dibutylethanolamine in all the formulations. The soluble oil formulation tended to increase the dermal absorption of the hydrophilic amines. The permeability coefficient was significantly higher (P < 0.05) with TEA relative to the other hydrophilic amines (e.g. 4.22 × 10(-4) ± 0.53 × 10(-4) cm h(-1) [TEA in synthetic MWF] vs. 1.23 × 10(-4) ± 0.10 × 10(-4) cm h(-1) [MEA in synthetic MWF]), except for MEA in soluble oil formulation. Future research will confirm these findings in an in vivo pig model along with dermatotoxicity studies. These results should help MWF industries choose safer additives for their formulations to protect the health of metalworkers.


Assuntos
Aminas/farmacocinética , Metalurgia , Absorção Cutânea/efeitos dos fármacos , Animais , Cicloexilaminas/farmacocinética , Difenilamina/farmacocinética , Desinfetantes/farmacocinética , Etanolamina/farmacocinética , Etanolaminas/farmacocinética , Cromatografia Gasosa-Espectrometria de Massas , Modelos Lineares , Permeabilidade , Suínos
10.
J Toxicol Sci ; 39(3): 475-85, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24849682

RESUMO

Advances in the synthesis and utilization of new chemical compounds have led to improvements in our daily lives. However, new chemicals may be both beneficial and toxic. Thus, exposure to these new compounds should be restricted in an attempt to limit their potential toxicities. We predicted the safety of three biocides (p-cresol, diazinon and resmethrin) by comparing their skin permeability coefficients and desquamation rate (the counter flux of permeability coefficient for chemical compounds induced by skin turnover) following skin exposure. In vitro skin permeation experiments revealed that the permeability coefficients of diazinon and resmethrin were smaller than the desquamation rate; therefore, these biocides could not permeate the skin, which resulted in very low skin concentrations of these compounds. On the other hand, the skin concentration of p-cresol was high because of its higher permeability coefficient than the desquamation rate. Furthermore, low in vitro cell viability was reported for skin exposed to p-cresol. These results in the present study indicate that the method described herein is useful for predicting the toxicities of chemicals following their topical exposure.


Assuntos
Cresóis/farmacocinética , Cresóis/toxicidade , Diazinon/farmacocinética , Diazinon/toxicidade , Desinfetantes/farmacocinética , Desinfetantes/toxicidade , Permeabilidade/efeitos dos fármacos , Piretrinas/farmacocinética , Piretrinas/toxicidade , Pele/metabolismo , Administração Tópica , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cresóis/administração & dosagem , Diazinon/administração & dosagem , Desinfetantes/administração & dosagem , Relação Dose-Resposta a Droga , Humanos , Masculino , Piretrinas/administração & dosagem , Coelhos , Ratos , Ratos Wistar , Pele/citologia
11.
Hum Exp Toxicol ; 33(1): 81-91, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23800997

RESUMO

Methyl bromide (MeBr) is a chemically reactive compound that has found use as a fire retardant and fumigant used for wood, soil, fruits and grains. Its use is banned in many countries because of its ozone-depleting properties. Despite this ban, the use of MeBr persists in some parts of the world (e.g. New Zealand) due to its important role in maintaining strict biosecurity of exported and imported products. Its high chemical reactivity leads to a broad toxicological profile ranging from acute respiratory toxicity following inhalation exposure, through carcinogenicity to neurotoxicty. In this article, we discuss the chemistry of MeBr in the context of its mechanisms of toxicity. The chemical reactivity of MeBr clearly underlies its toxicity. Bromine (Br) is electronegative and a good leaving group; the δ+ carbon thus facilitates electrophilic methylation of biological molecules including glutathione (GSH) via its δ- sulphur atom, leading to downstream effects due to GSH depletion. DNA alkylation, either directly by MeBr or indirectly due to reduction in GSH-mediated detoxification of reactive alkylating chemical species, might explain the carcinogenicity of MeBr. The neurotoxicity of MeBr is much more difficult to understand, but we speculate that methyl phosphates formed in cells might contribute to its neurone-specific toxicity via cholinesterase inhibition. Finally, evidence reviewed shows that it is unlikely for Br⁻ liberated by the metabolism of MeBr to have any toxicological effect because the Br⁻ dose is very low.


Assuntos
Desinfetantes/toxicidade , Retardadores de Chama/toxicidade , Hidrocarbonetos Bromados/toxicidade , Mutagênicos/toxicidade , Animais , Transporte Biológico , Biotransformação , Desinfetantes/análise , Desinfetantes/química , Desinfetantes/farmacocinética , Retardadores de Chama/análise , Retardadores de Chama/farmacocinética , Fumigação , Meia-Vida , Humanos , Hidrocarbonetos Bromados/análise , Hidrocarbonetos Bromados/química , Hidrocarbonetos Bromados/farmacocinética , Mutagênicos/análise , Mutagênicos/química , Mutagênicos/farmacocinética , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/fisiopatologia , Perda de Ozônio , Distribuição Tecidual
12.
Sud Med Ekspert ; 57(4): 44-8, 2014.
Artigo em Russo | MEDLINE | ID: mdl-25764865

RESUMO

This study was designed to elucidate the specific features of the distribution of 2,4- and 2,6-dimethyl derivatives of hydroxybenzene in the body of the warm-blooded animals (rats) after the intragastric administration of these poisonous substances. It was shown that large amounts of these compounds are present in the unmetabolized form in the blood and internal organs of the experimental animals. Their largest quantities were found in the stomach contents, spleen, and small intestines.


Assuntos
Conteúdo Gastrointestinal/química , Fenol , Baço , Animais , Desinfetantes/química , Desinfetantes/isolamento & purificação , Desinfetantes/farmacocinética , Desinfetantes/toxicidade , Toxicologia Forense/métodos , Humanos , Intestino Delgado/química , Intestino Delgado/patologia , Espectrometria de Massas/métodos , Fenol/química , Fenol/isolamento & purificação , Fenol/farmacocinética , Fenol/toxicidade , Ratos , Baço/química , Baço/patologia , Estômago/química , Estômago/patologia , Distribuição Tecidual
13.
PLoS One ; 8(11): e79157, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24223899

RESUMO

BACKGROUND / AIMS: ClO2, the so-called "ideal biocide", could also be applied as an antiseptic if it was understood why the solution killing microbes rapidly does not cause any harm to humans or to animals. Our aim was to find the source of that selectivity by studying its reaction-diffusion mechanism both theoretically and experimentally. METHODS: ClO2 permeation measurements through protein membranes were performed and the time delay of ClO2 transport due to reaction and diffusion was determined. To calculate ClO2 penetration depths and estimate bacterial killing times, approximate solutions of the reaction-diffusion equation were derived. In these calculations evaporation rates of ClO2 were also measured and taken into account. RESULTS: The rate law of the reaction-diffusion model predicts that the killing time is proportional to the square of the characteristic size (e.g. diameter) of a body, thus, small ones will be killed extremely fast. For example, the killing time for a bacterium is on the order of milliseconds in a 300 ppm ClO2 solution. Thus, a few minutes of contact time (limited by the volatility of ClO2) is quite enough to kill all bacteria, but short enough to keep ClO2 penetration into the living tissues of a greater organism safely below 0.1 mm, minimizing cytotoxic effects when applying it as an antiseptic. Additional properties of ClO2, advantageous for an antiseptic, are also discussed. Most importantly, that bacteria are not able to develop resistance against ClO2 as it reacts with biological thiols which play a vital role in all living organisms. CONCLUSION: Selectivity of ClO2 between humans and bacteria is based not on their different biochemistry, but on their different size. We hope initiating clinical applications of this promising local antiseptic.


Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Compostos Clorados/farmacologia , Desinfetantes/farmacologia , Óxidos/farmacologia , Algoritmos , Animais , Anti-Infecciosos/farmacocinética , Bactérias/citologia , Bactérias/metabolismo , Permeabilidade da Membrana Celular , Compostos Clorados/farmacocinética , Difusão , Desinfetantes/farmacocinética , Relação Dose-Resposta a Droga , Humanos , Membranas Artificiais , Viabilidade Microbiana/efeitos dos fármacos , Modelos Biológicos , Óxidos/farmacocinética , Permeabilidade , Suínos , Fatores de Tempo , Bexiga Urinária/metabolismo , Urotélio/metabolismo
14.
Environ Mol Mutagen ; 54(9): 705-18, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24136419

RESUMO

Formaldehyde (FA), a major industrial chemical and ubiquitous environmental pollutant, has been classified as a leukemogen. The causal relationship remains unclear, however, due to limited evidence that FA induces toxicity in bone marrow, the site of leukemia induction, and in other distal organs. Although induction of DNA-protein crosslinks (DPC), a hallmark of FA toxicity, was not previously detected in the bone marrow of FA-exposed rats and monkeys in studies published in the 1980s, our recent studies showed increased DPC in the bone marrow, liver, kidney, and testes of exposed Kunming mice. To confirm these preliminary results, in the current study we exposed BALB/c mice to 0, 0.5, 1.0, and 3.0 mg m(-3) FA (8 hr per day, for 7 consecutive days) by nose-only inhalation and measured DPC levels in bone marrow and other organs of exposed mice. As oxidative stress is a potential mechanism of FA toxicity, we also measured glutathione (GSH), reactive oxygen species (ROS), and malondialdehyde (MDA), in the bone marrow, peripheral blood mononuclear cells, lung, liver, spleen, and testes of exposed mice. Significant dose-dependent increases in DPC, decreases in GSH, and increases in ROS and MDA were observed in all organs examined (except for DPC in lung). Bone marrow was among the organs with the strongest effects for DPC, GSH, and ROS. In conclusion, exposure of mice to FA by inhalation induced genotoxicity and oxidative stress in bone marrow and other organs. These findings strengthen the biological plausibility of FA-induced leukemogenesis and systemic toxicity.


Assuntos
Medula Óssea/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , DNA/metabolismo , Formaldeído/toxicidade , Leucócitos Mononucleares/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteínas/metabolismo , Administração por Inalação , Animais , Medula Óssea/metabolismo , DNA/genética , Desinfetantes/farmacocinética , Desinfetantes/toxicidade , Formaldeído/administração & dosagem , Formaldeído/farmacocinética , Glutationa/metabolismo , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Tecidual
15.
Arch Toxicol ; 87(9): 1709-23, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23943240

RESUMO

In vitro assays are often used for the hazard characterisation of compounds, but their application for quantitative risk assessment purposes is limited. This is because in vitro assays cannot provide a complete in vivo dose-response curve from which a point of departure (PoD) for risk assessment can be derived, like the no observed adverse effect level (NOAEL) or the 95 % lower confidence limit of the benchmark dose (BMDL). To overcome this constraint, the present study combined in vitro data with a physiologically based kinetic (PBK) model applying reverse dosimetry. To this end, embryotoxicity of phenol was evaluated in vitro using the embryonic stem cell test (EST), revealing a concentration-dependent inhibition of differentiation into beating cardiomyocytes. In addition, a PBK model was developed on the basis of in vitro and in silico data and data available from the literature only. After evaluating the PBK model performance, effective concentrations (ECx) obtained with the EST served as an input for in vivo plasma concentrations in the PBK model. Applying PBK-based reverse dosimetry provided in vivo external effective dose levels (EDx) from which an in vivo dose-response curve and a PoD for risk assessment were derived. The predicted PoD lies within the variation of the NOAELs obtained from in vivo developmental toxicity data from the literature. In conclusion, the present study showed that it was possible to accurately predict a PoD for the risk assessment of phenol using in vitro toxicity data combined with reverse PBK modelling.


Assuntos
Alternativas ao Uso de Animais , Desinfetantes/toxicidade , Células-Tronco Embrionárias/efeitos dos fármacos , Modelos Biológicos , Fenol/toxicidade , Teratogênicos/toxicidade , Animais , Biotransformação , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Citosol/enzimologia , Citosol/metabolismo , Desinfetantes/metabolismo , Desinfetantes/farmacocinética , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Feminino , Humanos , Cinética , Fígado/enzimologia , Fígado/metabolismo , Masculino , Camundongos , Microssomos Hepáticos/enzimologia , Microssomos Hepáticos/metabolismo , Especificidade de Órgãos , Fenol/metabolismo , Fenol/farmacocinética , Ratos , Medição de Risco/métodos , Especificidade da Espécie , Teratogênicos/metabolismo , Teratogênicos/farmacocinética
17.
Endodoncia (Madr.) ; 31(1): 7-12, ene.-mar. 2013. graf, ilus
Artigo em Espanhol | IBECS | ID: ibc-129963

RESUMO

Objetivo. El objetivo del estudio fue evaluar la actividad antimicrobiana de la solución de nanopartículas de plata en cultivo de Enterococcus faecalis (ATCC 29212) comparándola con diversas soluciones de hipoclorito de sodio (NaOCl). Material y Métodos. Cinco placas de Petri en agar fueron inoculadas con E. faecalis y sobre cada una de ellas se colocó un disco de celulosa saturado de solución de nanopartículas de plata, así como en cada una de las soluciones de hipoclorito de sodio evaluadas (Viarzon, Cloralex, Clorox). El digluconato de clorhexidina al 2% y solución salina estéril fueron utilizados como control. Transcurridas 24 horas de incubación a 37°C, en condiciones de aerobiosis, las zonas de inhibición de crecimiento bacteriano fueron medidas y los resultados sometidos a la prueba “t” entre los grupos experimentales (= 5%). Resultados. El Cloralex presentó la mayor media de inhibición en comparación con las demás substancias (p < 0,05), excepto con digluconato de clorhexidina al 2% (p > 0,05). La solución de nanopartículas de plata proporcionó mayor zona de inhibición que Clorox y Viarzon (p <0,05). El Clorox y el Viarzon no proporcionaron zonas de inhibición y fueron semejantes entre sí (p > 0,05). Conclusiones. La solución de nanopartículas de plata presenta actividad antimicrobiana en cultivo de E. faecalis, incluso mayor que las formas comerciales de hipoclorito de sodio. Futuros estudios deben ser realizados para comprobar su viabilidad como solución de irrigación en endodoncia (AU)


Objective. The objective of this study was to evaluate the antimicrobial activity of the silver nanoparticles solution in enterococcus faecallis cultures (ATCC 29212), compared with various solutions of sodium hypoclorithe (NaOCl). Material and methods. Five Agar Petri plates were inoculated with E. faecallis and each of them was placed a cellulose dish embedded with silver nanoparticles solution, or a solution of sodium hypochlorite evaluated (Viarzon, Cloralex, Clorox). Chlorhexidine digluconate 2% was used as positive control and sterile saline solution was used as negative control. After 24 hours of incubation at 37ºc, under aerobic conditions, the zones of inhibition of bacterial growth were measured and the results subjected to the statistical t test among the experimental groups (= 5%). Results. The Cloralex showed to be the most effective reflected in the extent of inhibition in relation to other substances (p< 0.05), except that the chlorhexidine digluconate 2% (p> 0.05). The solution of silver nanoparticles provided a greater zone of inhibition than the sodium hypochlorite solution (Clorox) and Viarzon (p< 0.05). Clorox and Viarzon didn’t provide zones of inhibition and were similar to each other (p> 0.05). Conclusions. The solution of silver nanoparticles presents antimicrobial activity in cultured E. faecallis, even higher than other commercial forms of sodium hypochlorite. Further studies should be carried out to determine its viability as irrigating solution in endodontics (AU)


Assuntos
Humanos , Enterococcus faecalis/patogenicidade , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Nanopartículas Metálicas/uso terapêutico , Compostos de Prata/farmacocinética , Irrigantes do Canal Radicular/farmacocinética , Tratamento do Canal Radicular/métodos , Desinfetantes/farmacocinética
18.
Am J Forensic Med Pathol ; 34(1): 29-33, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23361077

RESUMO

In this report, a unique and bizarre case of complicated suicide is presented. The decedent was found dead in the basin of a porta-potty, wearing women's pantyhose, jewelry, and makeup. The initial investigation was suspect for homicide. Although an autoerotic accidental death cannot be excluded, the patient's medical history and autopsy results provided evidence for suicide, including several substances positive in his serum. Tramadol was quantified to be 140 mg/L, approximately 470 times the therapeutic range. Moreover, formaldehyde was also present, presumably absorbed from the contents of the chemical toilet. An exhaustive search could not reveal similar circumstances of suicide in a porta-potty or with the levels of tramadol found in the decedent.


Assuntos
Suicídio , Banheiros , Travestilidade , Adulto , Anfetamina/análise , Analgésicos Opioides/análise , Analgésicos Opioides/intoxicação , Asfixia/etiologia , Estimulantes do Sistema Nervoso Central/análise , Desinfetantes/análise , Desinfetantes/farmacocinética , Overdose de Drogas , Febre/etiologia , Toxicologia Forense , Formaldeído/análise , Formaldeído/farmacocinética , Humanos , Masculino , Absorção Cutânea , Tramadol/análise , Tramadol/intoxicação
19.
Eye Contact Lens ; 39(1): 29-36, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23271476

RESUMO

Contact lens solutions are highly complex mixtures of biocides (preservatives), surfactants, and other agents designed to disinfect, clean, and wet contact lenses. The commercialization of silicone hydrogel (SiHy) lenses has resulted in unique challenges to the manufacturers of contact lens solutions, because the properties of these materials differ markedly from those seen previously with poly-hydroxyethyl methacrylate-based hydrogels. Historically, hydrogel lens uptake and release of low-molecular weight preservatives such as chlorhexidine and thimerosal were known to result in allergic reactions, resulting in corneal irritation, stinging, conjunctival hyperemia, development of corneal infiltrates, palpebral lid changes, and corneal staining. However, little is known about the interaction of modern care systems with modern soft lens materials. Factors to be considered when evaluating the uptake and release of care components include the water content, charge, relative hydrophobicity, surface treatment, and porosity of the lens material, in conjunction with the concentration, charge/molecule, ionicity in the product matrix, molecular weight, and hydrophobicity of the care component in question. These factors control the sorption of the solution components by lenses, resulting in a variety of differences in the amount of the component taken up into the lens material and the amount and rate of subsequent release onto the ocular surface. Because both natural (ocular) and environmental biota become part of the solution-lens system during regimen use of any lens care product, these extraneously introduced substances should also be considered regarding their potential for uptake and either subsequent release onto the ocular surface or functioning as a scaffold for the adhesion of microbes. This article will review current knowledge concerning these interactions and investigate what clinically observable complications may arise from these interactions. It also reviews whether current methods to determine these interactions could be improved on.


Assuntos
Lentes de Contato Hidrofílicas , Sistemas de Liberação de Medicamentos/métodos , Hidrogéis/química , Preparações Farmacêuticas/administração & dosagem , Silicones/química , Desinfetantes/farmacocinética , Humanos , Conservantes Farmacêuticos/farmacocinética
20.
Am J Infect Control ; 40(3): 250-7, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21741120

RESUMO

BACKGROUND: It has been shown that nontoxic concentrations of ethanol are absorbed after hand hygiene using ethanol-based hand rubs. This study investigated whether absorption of propan-1-ol and propan-2-ol from commercially available hand rubs results in measurable concentrations after use. METHODS: The pulmonary and dermal absorption of propanol during hand rubs was investigated. Rubs contained 70% (w/w) propan-1-ol, 63.14% (w/w) propan-2-ol, or 45% (w/w) propan-2-ol in combination with 30% (w/w) propan-1-ol. RESULTS: Peak median blood levels were 9.15 mg/L for propan-1-ol and 5.3 mg/L for propan-2-ol after hygienic hand rubs and 18.0 mg/L and 10.0 mg/L, respectively, after surgical hand rubs. Under actual surgical conditions, the highest median blood levels were 4.08 mg/L for propan-1-ol and 2.56 mg/L for propan-2-ol. The same procedure performed with prevention of pulmonary exposure through the use of a gas-tight mask resulted in peak median blood levels of 1.16 mg/L of propan-1-ol and 1.74 mg/L of propan-2-ol. CONCLUSION: Only minimal amounts of propanols are absorbed through the use of hand rubs. Based on our experimental data, the risk of chronic systemic toxic effects caused by hand rubs is likely negligible. However, our study did not evaluate the consequences of long-term daily and frequent use of hygienic hand rubs.


Assuntos
1-Propanol/farmacocinética , 2-Propanol/farmacocinética , Desinfetantes/farmacocinética , Desinfecção das Mãos/métodos , Absorção , Análise Química do Sangue , Desinfetantes/efeitos adversos , Feminino , Humanos , Masculino
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