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1.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209778

RESUMO

We performed a taxonomic and comparative genomics analysis of 67 novel Paraburkholderia isolates from forest soil. Phylogenetic analysis of the recA gene revealed that these isolates formed a coherent lineage within the genus Paraburkholderia that also included Paraburkholderiaaspalathi, Paraburkholderiamadseniana, Paraburkholderiasediminicola, Paraburkholderiacaffeinilytica, Paraburkholderiasolitsugae and Paraburkholderiaelongata and four unidentified soil isolates from earlier studies. A phylogenomic analysis, along with orthoANIu and digital DNA-DNA hybridization calculations revealed that they represented four different species including three novel species and P. aspalathi. Functional genome annotation of the strains revealed several pathways for aromatic compound degradation and the presence of mono- and dioxygenases involved in the degradation of the lignin-derived compounds ferulic acid and p-coumaric acid. This co-occurrence of multiple Paraburkholderia strains and species with the capacity to degrade aromatic compounds in pristine forest soil is likely caused by the abundant presence of aromatic compounds in decomposing plant litter and may highlight a diversity in micro-habitats or be indicative of synergistic relationships. We propose to classify the isolates representing novel species as Paraburkholderia domus with LMG 31832T (=CECT 30334) as the type strain, Paraburkholderia nemoris with LMG 31836T (=CECT 30335) as the type strain and Paraburkholderia haematera with LMG 31837T (=CECT 30336) as the type strain and provide an emended description of Paraburkholderia sediminicola Lim et al. 2008.


Assuntos
Burkholderiaceae/classificação , Burkholderiaceae/genética , Hidrocarbonetos Aromáticos/metabolismo , Técnicas de Tipagem Bacteriana , Burkholderiaceae/isolamento & purificação , Burkholderiaceae/metabolismo , Ácidos Cumáricos/metabolismo , Ácidos Cumáricos/farmacocinética , DNA Bacteriano/análise , DNA Bacteriano/genética , Recuperação e Remediação Ambiental/métodos , Florestas , Genoma Bacteriano , Hidrocarbonetos Aromáticos/farmacocinética , Filogenia , RNA Ribossômico 16S/genética , Recombinases Rec A/análise , Recombinases Rec A/genética , Análise de Sequência de DNA , Microbiologia do Solo
2.
Arch Biochem Biophys ; 659: 85-92, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30367827

RESUMO

Human aldehyde oxidase 1 (AOX1) catalyzes the oxidation of various drugs and endogenous compounds. Recently, we found that AOX1 catalyzed the reduction of drugs such as nitrazepam and dantrolene. In this study, we aimed to clarify the substrate selectivity of human AOX1 for the reduction of nitroaromatic drugs to obtain helpful information for drug development. We investigated whether 11 nitroaromatic drugs were reduced by AOX1 using recombinant AOX1 and human liver cytosol (HLC) in the presence of N1-methylnicotinamide, an electron donor to AOX1. We found that clonazepam, flunitrazepam, flutamide, nilutamide, nimesulide, and nimetazepam were substantially reduced by recombinant AOX1 and HLC, whereas azelnidipine, nifedipine, and nimodipine were slightly reduced and metronidazole and tolcapone were not reduced. Via structural analysis, we observed that nitroaromatic drugs reduced by AOX1 possessed a relatively electron-deficient nitro group. Since the addition of NADPH to human liver microsomes (HLM) did not increase the reductase activities of the drugs that were reduced by recombinant AOX1, it was determined that NADPH-dependent enzymes in microsomes, such as cytochrome P450, were not involved in this process. Inhibition studies using known AOX1 inhibitors supported the role of AOX1 in the reduction of drugs in HLC. In conclusion, this provides new information related to the substrate selectivity of human AOX1 for the reduction of nitroaromatic drugs.


Assuntos
Aldeído Oxidase/metabolismo , Hidrocarbonetos Aromáticos/química , Hidrocarbonetos Aromáticos/metabolismo , Nitrogênio/química , Humanos , Hidrocarbonetos Aromáticos/farmacocinética , Hidrocarbonetos Aromáticos/toxicidade , Cinética , Oxirredução , Especificidade por Substrato
3.
Int Arch Occup Environ Health ; 86(2): 157-65, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22411213

RESUMO

PURPOSE: Few studies compare the variabilities that characterize environmental (EM) and biological monitoring (BM) data. Indeed, comparing their respective variabilities can help to identify the best strategy for evaluating occupational exposure. The objective of this study is to quantify the biological variability associated with 18 bio-indicators currently used in work environments. METHOD: Intra-individual (BV(intra)), inter-individual (BV(inter)), and total biological variability (BV(total)) were quantified using validated physiologically based toxicokinetic (PBTK) models coupled with Monte Carlo simulations. Two environmental exposure profiles with different levels of variability were considered (GSD of 1.5 and 2.0). RESULTS: PBTK models coupled with Monte Carlo simulations were successfully used to predict the biological variability of biological exposure indicators. The predicted values follow a lognormal distribution, characterized by GSD ranging from 1.1 to 2.3. Our results show that there is a link between biological variability and the half-life of bio-indicators, since BV(intra) and BV(total) both decrease as the biological indicator half-lives increase. BV(intra) is always lower than the variability in the air concentrations. On an individual basis, this means that the variability associated with the measurement of biological indicators is always lower than the variability characterizing airborne levels of contaminants. For a group of workers, BM is less variable than EM for bio-indicators with half-lives longer than 10-15 h. CONCLUSION: The variability data obtained in the present study can be useful in the development of BM strategies for exposure assessment and can be used to calculate the number of samples required for guiding industrial hygienists or medical doctors in decision-making.


Assuntos
Poluentes Ocupacionais do Ar/farmacocinética , Monitoramento Ambiental , Modelos Biológicos , Exposição Ocupacional/análise , Acetona/farmacocinética , Meia-Vida , Hexanos/farmacocinética , Humanos , Hidrocarbonetos Aromáticos/farmacocinética , Hidrocarbonetos Clorados/farmacocinética , Método de Monte Carlo , Estatísticas não Paramétricas
4.
J Occup Environ Hyg ; 9(11): 624-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22978813

RESUMO

Disposable filtering facepiece respirators (FFRs) used by health care workers are not designed to reduce the inhalation of volatile organic compounds (VOCs). Smoke-generating surgical procedures release VOCs and have been associated with the following complaints: foul smell, headaches, nausea, irritated throat and lungs, and asthma. Organic vapor FFRs that contain activated carbon are used by industrial workers to provide odor relief. These respirators remove irritating odors but are not marketed as respirators that provide respiratory protection against a gas or vapor. This study investigated the aromatic hydrocarbon adsorption capabilities of nuisance organic vapor (OV) FFRs. Three OV FFR models were tested to determine the 10% breakthrough time of three aromatic hydrocarbons at ambient room temperature and relative humidity. All respirator models were exposed to each vapor separately in three duplicate tests (n = 27). The respirator was sealed with silicone to an AVON-ISI headform that was placed in a chamber and exposed to VOC-laden air (20 ppm, 37 L/min). Periodically, gas samples were directed to an SRI gas chromatograph (Model 8610C) for analysis. All respirators performed similarly. The average 10% breakthrough values for all tests were at least 64 min, 96 min, and 110 min for benzene, toluene, and xylene, respectively. Respirators were tested with challenge concentrations at nuisance levels (20 ppm) and did not exceed 10% breakthrough values for at least 61 min. While the results of this pilot study hold promise, there is a need for further investigation and validation to determine the effectiveness of nuisance FFRs in mitigating organic vapors such as benzene, toluene, and xylene.


Assuntos
Hidrocarbonetos Aromáticos/farmacocinética , Exposição Ocupacional/prevenção & controle , Dispositivos de Proteção Respiratória/normas , Fumaça , Adsorção , Poluentes Ocupacionais do Ar , Benzeno/farmacocinética , Carbono , Filtração/normas , Humanos , Odorantes , Projetos Piloto , Procedimentos Cirúrgicos Operatórios , Tolueno/farmacocinética , Xilenos/farmacocinética
5.
Bioorg Med Chem Lett ; 20(12): 3545-9, 2010 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-20483599

RESUMO

Further optimization of the biaryl amide series via extensively exploring structure-activity relationships resulted in potent and subtype selective M(1) agonists exemplified by compounds 9a and 9j with good rat PK properties including CNS penetration. Synthesis, structure-activity relationships, subtype selectivity for M(1) over M(2-5), and DMPK properties of these novel compounds are described.


Assuntos
Amidas/síntese química , Amidas/farmacocinética , Hidrocarbonetos Aromáticos/síntese química , Hidrocarbonetos Aromáticos/farmacocinética , Receptor Muscarínico M1/agonistas , Amidas/farmacologia , Animais , Barreira Hematoencefálica/metabolismo , Sistema Nervoso Central/metabolismo , Descoberta de Drogas , Hidrocarbonetos Aromáticos/farmacologia , Estrutura Molecular , Ratos , Relação Estrutura-Atividade , Distribuição Tecidual
6.
J Appl Toxicol ; 30(6): 525-35, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20809541

RESUMO

Aromatic hydrocarbons, as well as aliphatic hydrocarbons, diffusing from interior materials in automotive cabins are the most common compounds contributing to interior air pollution. In this study, the amounts of seven selected aromatic hydrocarbons absorbed by a car driver were estimated by evaluating their inhalation toxicokinetics in rats. Measured amounts of these substances were injected into a closed chamber system containing a rat, and the concentration changes in the chamber were examined. The toxicokinetics of the substances were evaluated on the basis of the concentration-time course using a nonlinear compartment model. The amounts absorbed in humans at actual concentrations in automobile cabins without ventilation were extrapolated from the results obtained from rats. The absorbed amounts estimated for a driver during a 2 h drive were as follows (per 60 kg of human body weight): 30 microg for toluene (interior median concentration, 40 microg m(-3) in our previous study), 10 microg for ethylbenzene (12 microg m(-3)), 6 microg for o-xylene (10 microg m(-3)), 8 microg for m-xylene (11 microg m(-3)), 9 microg for p-xylene (11 microg m(-3)), 11 microg for styrene (11 microg m(-3)) and 27 microg for 1,2,4-trimethylbenzene (24 microg m(-3)). Similarly, in a cabin where air pollution was marked, the absorbed amount of styrene (654 microg for 2 h in a cabin with an interior maximum concentration of 675 microg m(-3)) was estimated to be much higher than those of other substances. This amount (654 microg) was approximately 1.5 times the tolerable daily intake of styrene (7.7 microg kg(-1) per day) recommended by the World Health Organization.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Automóveis/normas , Hidrocarbonetos Aromáticos , Exposição por Inalação/análise , Manufaturas/análise , Modelos Biológicos , Absorção , Poluição do Ar em Ambientes Fechados/efeitos adversos , Animais , Difusão , Cabelo/metabolismo , Hidrocarbonetos Aromáticos/farmacocinética , Hidrocarbonetos Aromáticos/toxicidade , Exposição por Inalação/efeitos adversos , Masculino , Manufaturas/normas , Ratos , Ratos Sprague-Dawley , Pele/metabolismo , Níveis Máximos Permitidos
7.
Int J Toxicol ; 29(3): 277-90, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20448260

RESUMO

This article reports the results of neurobehavioral tests on representative aromatic constituents, specifically C(9) to C(11) species. The testing evaluated effects in several domains including clinical effects, motor activity, functional observations, and visual discrimination performance. Exposures ranging from 600 to 5000 mg/m(3), depending on the molecular weights of the specific aromatic constituents, produced minor, reversible effects on the central nervous system (CNS), particularly in the domains of gait and visual discrimination. There was little evidence of effects at lower exposure levels. There was some evidence of respiratory effects at 5000 mg/m(3) in 1 study, and there were also minor changes in body weight and temperature. The CNS effects became less pronounced with repeated exposures, corresponding to lower concentrations in the brain of 1 representative substance, 1,2,4-trimethyl benzene (TMB). At high exposure levels, the alkyl benzenes apparently induced their own metabolism, increasing elimination rates.


Assuntos
Hidrocarbonetos Aromáticos/toxicidade , Exposição por Inalação/efeitos adversos , Solventes/toxicidade , Animais , Nível de Alerta/efeitos dos fármacos , Derivados de Benzeno/administração & dosagem , Derivados de Benzeno/metabolismo , Derivados de Benzeno/farmacocinética , Derivados de Benzeno/toxicidade , Regulação da Temperatura Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Sistema Nervoso Central/efeitos dos fármacos , Convulsivantes/administração & dosagem , Convulsivantes/metabolismo , Convulsivantes/farmacocinética , Convulsivantes/toxicidade , Relação Dose-Resposta a Droga , Marcha/efeitos dos fármacos , Hidrocarbonetos Aromáticos/administração & dosagem , Hidrocarbonetos Aromáticos/metabolismo , Hidrocarbonetos Aromáticos/farmacocinética , Masculino , Atividade Motora/efeitos dos fármacos , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/metabolismo , Fármacos Neuromusculares/farmacocinética , Fármacos Neuromusculares/toxicidade , Distribuição Aleatória , Ratos , Ratos Wistar , Sistema Respiratório/efeitos dos fármacos , Solventes/administração & dosagem , Solventes/metabolismo , Solventes/farmacocinética , Fatores de Tempo , Percepção Visual/efeitos dos fármacos
8.
Med Res Rev ; 29(1): 29-64, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18688784

RESUMO

Anticancer prodrugs designed to target specifically tumor cells should increase therapeutic effectiveness and decrease systemic side effects in the treatment of cancer. Over the last 20 years, significant advances have been made in the development of anticancer prodrugs through the incorporation of triggers for reductive activation. Reductively activated prodrugs have been designed to target hypoxic tumor tissues, which are known to overexpress several endogenous reductive enzymes. In addition, exogenous reductive enzymes can be delivered to tumor cells through fusion with tumor-specific antibodies or overexpressed in tumor cells through gene delivery approaches. Many anticancer prodrugs have been designed to use both the endogenous and exogenous reductive enzymes for target-specific activation and these prodrugs often contain functional groups such as quinones, nitroaromatics, N-oxides, and metal complexes. Although no new agents have been approved for clinical use, several reductively activated prodrugs are in various stages of clinical trial. This review mainly focuses on the medicinal chemistry aspects of various classes of reductively activated prodrugs including design principles, structure-activity relationships, and mechanisms of activation and release of active drug molecules.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Desenho de Fármacos , Pró-Fármacos/farmacologia , Animais , Antineoplásicos/farmacocinética , Hipóxia Celular , Óxidos N-Cíclicos/química , Óxidos N-Cíclicos/farmacocinética , Óxidos N-Cíclicos/farmacologia , Humanos , Hidrocarbonetos Aromáticos/química , Hidrocarbonetos Aromáticos/farmacocinética , Hidrocarbonetos Aromáticos/farmacologia , Compostos Organometálicos/química , Compostos Organometálicos/farmacocinética , Compostos Organometálicos/farmacologia , Oxirredução , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Quinonas/química , Quinonas/farmacocinética , Quinonas/farmacologia , Relação Estrutura-Atividade
9.
Bioorg Med Chem ; 17(11): 3995-8, 2009 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-19410467

RESUMO

N-alquil nitrones 1c and 3-6 were prepared from aromatic aldehydes and N-tert-butylhydroxylamine or N-methylhydroxylamine in good yields and soft conditions. Their protective effect against microvascular damages caused by ischemia/reperfusion in 'hamster cheek pouch' assay was investigated and compare with that observed for nitrones 1a,b and 2, previously studied. Nitrones 3b, 4b and 4c were the most active ones in inhibiting macromolecular permeability increase induced by ischemia/reperfusion when administered by gavage and intravenous, while 3a and 4a were active only after intravenous administration. N-tert-butylhydroxylamine and Nt-methylhydroxylamine, products of the hydrolysis of these nitrones, were weakly active when administered by gavage or intravenous. Nitrone (4a) was the most potent in inhibiting macromolecular permeability increase induced by histamine. In this case, N-tert-butylhydroxylamine was as active as 4a. The lypophylicity in nitrones, specially in N-methyl nitrones, play an important role on the protective action when compounds were administered by gavage.


Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Hidrocarbonetos Aromáticos/farmacologia , Isquemia , Óxidos de Nitrogênio/química , Reperfusão , Animais , Cricetinae , Hidrocarbonetos Aromáticos/química , Hidrocarbonetos Aromáticos/farmacocinética , Masculino , Camundongos , Estrutura Molecular , Óxidos de Nitrogênio/farmacologia
10.
J Toxicol Environ Health A ; 72(13): 832-41, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19557611

RESUMO

Metalworking fluids (MWF) are complex mixtures consisting of a variety of components and additives. A lack of scientific data exists regarding the dermal permeation of its components, particularly biocides. The aim of this study was to evaluate the dermal permeation of biocides and other aromatic chemicals in water and in three generic soluble oil, semi-synthetic, and synthetic MWF types in order to evaluate any differences in their permeation profiles. An in vitro flow-through diffusion cell study was performed to determine dermal permeation. An infinite dose of different groups of chemicals (6 biocides and 29 aromatic chemicals) was applied to porcine skin, with perfusate samples being collected over an 8-h period. Perfusate samples were analyzed by gas chromatography/mass spectrometry (GC-MS) and ultra-performance liquid chromatography/mass spectroscopy (UPLC-MS), and permeability was calculated from the analysis of the permeated chemical concentration-time profile. In general, the permeation of chemicals was highest in aqueous solution, followed by synthetic, semi-synthetic, and soluble oil MWF. The absorption profiles of most of the chemicals including six biocides were statistically different among the synthetic and soluble oil MWF formulations, with reduced permeation occurring in oily formulations. Permeation of almost all chemicals was statistically different between aqueous and three MWF formulation types. Data from this study show that permeation of chemicals is higher in a generic synthetic MWF when compared to a soluble oil MWF. This indicates that a soluble oil MWF may be safer than a synthetic MWF in regard to dermal permeation of chemicals to allow for an increased potential of systemic toxicity. Therefore, one may conclude that a synthetic type of formulation has more potential to produce contact dermatitis and induce systemic toxicological effects. The dilution of these MWF formulations with water may increase dermal permeability of biocides, allowing for an enhanced risk for systemic toxicological effects and dermatitis potential.


Assuntos
Misturas Complexas/química , Desinfetantes/farmacocinética , Hidrocarbonetos Aromáticos/farmacocinética , Absorção Cutânea/efeitos dos fármacos , Animais , Desinfetantes/química , Hidrocarbonetos Aromáticos/química , Metalurgia , Exposição Ocupacional , Permeabilidade , Suínos
11.
Biotechnol Bioeng ; 99(1): 86-98, 2008 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-17570716

RESUMO

The whole-cell bioluminescent biosensor Pseudomonas putida F1G4 (PpF1G4), which contains a chromosomally-based sep-lux transcriptional fusion, was used as a tool for direct measurement of the bioavailability of hydrophobic organic compounds (HOCs) partitioned into surfactant micelles. The increased bioluminescent response of PpF1G4 in micellar solutions (up to 10 times the critical micellar concentration) of Triton X-100 and Brij 35 indicated higher intracellular concentrations of the test compounds, toluene, naphthalene, and phenanthrene, compared to control systems with no surfactants present. In contrast, Brij 30 caused a decrease in the bioluminescent response to the test compounds in single-solute systems, without adversely affecting cell growth. The decrease in bioluminescent response in the presence of Brij 30 did not occur in the presence of multiple HOCs extracted into the surfactant solutions from crude oil and creosote. The effect of the micellar solutions on the toluene biodegradation rate was consistent with the bioluminescent response in single-solute systems. None of the surfactants were toxic to PpF1G4 at the doses employed in this study, and PpF1G4 did not produce a bioluminescent response to the surfactants nor utilize them as growth substrates. TEM images suggest that the surfactants did not rupture the cell membranes. The results demonstrate that for Pseudomonas putida F1, nonionic surfactants such as Triton X-100 and Brij 35, at doses between 2 and 10 CMC, may increase the bioavailability and direct uptake of micellar phase HOCs that are common pollutants at contaminated sites.


Assuntos
Bioensaio/métodos , Técnicas Biossensoriais/métodos , Hidrocarbonetos Aromáticos/farmacologia , Hidrocarbonetos Aromáticos/farmacocinética , Pseudomonas putida/efeitos dos fármacos , Pseudomonas putida/metabolismo , Tensoativos/química , Disponibilidade Biológica , Proliferação de Células/efeitos dos fármacos , Hidrocarbonetos Aromáticos/análise , Hidrocarbonetos Aromáticos/química , Íons
12.
Aquat Toxicol ; 87(1): 19-27, 2008 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-18294709

RESUMO

The aryl hydrocarbon receptor (AhR) is an ancient protein that is conserved in vertebrates and invertebrates, indicating its important function throughout evolution. AhR has been studied largely because of its role in toxicology-gene expression via AhR is induced by many aromatic hydrocarbons in mammals. Recently, however, it has become clear that AhR is involved in various aspects of development such as cell proliferation and differentiation, and cell motility and migration. The mechanisms by which AhR regulates these various functions remain poorly understood. Across-species comparative studies of AhR in invertebrates, non-mammalian vertebrates and mammals may help to reveal the multiple functions of AhR. Here, we have studied AhR during larval development of Baltic salmon (Salmon salar). Our results indicate that AhR protein is expressed in nervous system, liver and muscle tissues. We also present putative regulatory modules and module-matching genes, produced by chromatin immunoprecipitation (ChIP) cloning and in silico analysis, which may be associated with evolutionarily conserved functions of AhR during development. For example, the module NFKB-AHRR-CREB found from salmon ChIP sequences is present in human ULK3 (regulating formation of granule cell axons in mouse and axon outgrowth in Caernohabditis elegans) and SRGAP1 (GTPase-activating protein involved in the Slit/Robo pathway) promoters. We suggest that AhR may have an evolutionarily conserved role in neuronal development and nerve cell targeting, and in Wnt signaling pathway.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hidrocarbonetos Aromáticos/toxicidade , Neurônios/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico/metabolismo , Salmo salar , Poluentes Químicos da Água/toxicidade , Saco Vitelino/efeitos dos fármacos , Animais , Países Bálticos , Diferenciação Celular , Movimento Celular , Proliferação de Células , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Humanos , Hidrocarbonetos Aromáticos/farmacocinética , Camundongos , Neurônios/citologia , Neurônios/fisiologia , Receptores de Hidrocarboneto Arílico/genética , Salmo salar/embriologia , Salmo salar/crescimento & desenvolvimento , Distribuição Tecidual , Poluentes Químicos da Água/farmacocinética , Saco Vitelino/embriologia , Saco Vitelino/crescimento & desenvolvimento
13.
J Agric Food Chem ; 66(27): 6968-6974, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29953221

RESUMO

The evaluation of mineral oils by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) provided high acceptable daily intakes for classes largely falling into the mass range strongly accumulated by humans. Because they are roughly 2 orders of magnitude above the present exposure, they authorize strongly increased exposure. An approach based on accumulation seems more adequate. Increased organ weights might be more critical than granulomas. Aromatic hydrocarbons with 1-2 aromatic rings should be distinguished from those with at least 3 aromatic rings. If mineral oil saturated hydrocarbon limits were low, no limit might be needed for the 1-2 ring aromatics. It should be considered to phase out substantial use of mineral oils in food application.


Assuntos
Aditivos Alimentares/toxicidade , Alimentos , Hidrocarbonetos/química , Hidrocarbonetos/toxicidade , Óleo Mineral/toxicidade , Animais , Aditivos Alimentares/química , Humanos , Hidrocarbonetos Aromáticos/química , Hidrocarbonetos Aromáticos/farmacocinética , Hidrocarbonetos Aromáticos/toxicidade , Óleo Mineral/química , Testes de Toxicidade/métodos
14.
Environ Toxicol Chem ; 26(3): 491-6, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17373513

RESUMO

Through their diet, herbivores inhabiting contaminated sites may be chronically exposed to a variety of aryl hydrocarbons (e.g., dioxins and polycyclic aromatic hydrocarbons [PAHs]). However, little is known about how differences in morphology and physiology among plant species alter the environmental accumulation of aryl hydrocarbons or their release and subsequent activity in the gastrointestinal tract of herbivores after ingestion. In the present study, the activity of aryl hydrocarbons during digestion was examined using six Arctic plant species growing in impacted and reference sites near Inuvik, Northwest Territories, Canada. The plant species studied were black spruce (Picea mariana), labrador tea (Ledum groenlandicum), bog birch (Betula glandulosa), green alder (Alnus crispa), water sedge (Carex aquatilis), and little-tree willow (Salix arbusculoides). Plants were digested using a simulator of the upper digestive tract, and aryl hydrocarbon release was evaluated using an aryl hydrocarbon-receptor assay. Bioaccessible aryl hydrocarbon activity varied among the plant species tested. The species with the greatest activity was green alder, and the species with the least activity was black spruce. Further investigation revealed that digested plant extracts may antagonize the aryl hydrocarbon receptor and prevent bioactivation of the aryl compound benzo[a]pyrene. Thus, PAH risk from the ingestion of vegetation varies among plant species and may depend on antagonists present in the vegetation.


Assuntos
Hidrocarbonetos Aromáticos/análise , Hidrocarbonetos Aromáticos/farmacocinética , Plantas/metabolismo , Animais , Benzo(a)pireno/metabolismo , Digestão , Dioxinas , Cadeia Alimentar , Mamíferos , Modelos Biológicos , Extratos Vegetais , Hidrocarbonetos Policíclicos Aromáticos , Receptores de Hidrocarboneto Arílico/antagonistas & inibidores , Especificidade da Espécie
15.
Toxicol Sci ; 45(1): 26-32, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9848107

RESUMO

The role of kinetics in the acute inhalation toxicity of nonreactive, volatile organic compounds (VOCs), including lipophilic and hydrophilic compounds, was analyzed with a physiologically based pharmacokinetic (PB-PK) model for the rat. For 15 VOCs, a total of 23 LC50 values were retrieved from the literature. It was observed that the external exposure parameter (LC50.exposure length; in ppm.h), varied approximately 60-fold. Concentrations of compounds in the lipoid brain fraction were simulated using a kinetic model. This lead to a more than 10-fold reduction in the toxic range of the 15 VOCs. The average value for this simulated dose surrogate was 70 +/- 31 mM for all VOCs. These observations support the presumption that nonspecific, acute narcotic lethality is directly related to the extent of VOC distribution into lipoid brain constituents. The present results can be used for estimation of the acute lethality of nonreactive VOCs on the basis of kinetic simulations. In addition, the presently calculated dose surrogate for VOC lethality in rats is found to be very similar to the reported internal lethal concentrations of so-called "baseline toxicity compounds" in fish. This indicates a common mechanism of acute VOC toxicity among mammalian and aquatic species.


Assuntos
Alcanos/farmacocinética , Alcanos/toxicidade , Encéfalo/metabolismo , Hidrocarbonetos Aromáticos/farmacocinética , Hidrocarbonetos Aromáticos/toxicidade , Hidrocarbonetos Clorados/farmacocinética , Hidrocarbonetos Clorados/toxicidade , Animais , Biotransformação , Exposição por Inalação , Dose Letal Mediana , Modelos Biológicos , Ratos
16.
Anticancer Res ; 20(1B): 519-22, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10769717

RESUMO

Chemical carcinogens generally require metabolic activation in order to be able to bind to DNA and contribute to cancer causation. Most of the human metabolizing enzymes are genetically polymorphic, and these polymorphisms may affect the enzyme activity or inducibility. In our present study we investigated the connection between genetic polymorphism of cytochrome P450 1A1, 2E1 (phase I enzymes) and glutathione-S-transferase M1 (a phase II enzyme) and colorectal cancer occurrence in a Hungarian population. The CYP 2E1 c2 allele proved to be in significant association with colorectal cancer (OR: 1.91, 95% CI: 1.05-3.52), the CYP 1A1 Val allele was also overrepresented among colon cancer patients (OR: 1.57, 95% CI: 0.90-2.74), and the frequency of GSTM1 homozygous 0 genotype showed only minor difference (OR: 1.19, 95% CI: 0.75-1.35). Combined analysis of the polymorphisms showed that individuals carrying all the three "high-risk" alleles have a strikingly increased risk for sporadic colorectal cancer (OR: 4.62, 95% CI: 1.23-25.68).


Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP2E1/genética , Glutationa Transferase/genética , Isoenzimas/genética , Adenocarcinoma/enzimologia , Adenocarcinoma/epidemiologia , Idoso , Alelos , Biotransformação/genética , Carcinógenos Ambientais/farmacocinética , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/epidemiologia , Análise Mutacional de DNA , Feminino , Deleção de Genes , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Hungria , Hidrocarbonetos Aromáticos/farmacocinética , Masculino , Pessoa de Meia-Idade , Nitrosaminas/farmacocinética , Mutação Puntual , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Risco , População Branca/genética
17.
J Toxicol Environ Health A ; 55(7): 503-16, 1998 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-9860324

RESUMO

Pyrene was chosen as a noncarcinogen model of polycyclic aromatic hydrocarbons (PAHs). Groups of male Wistar rats were dosed with pyrene and with mixture of pyrene and fluoranthene, pyrene and benz[a]anthracene, or pyrene, fluoranthene, and benz[a]anthracene at 20 mg/kg by intravenous or oral routes. Blood samples were taken at 0.25, 0.5, 1, 2, 3, 4, and 5 h after administration. The concentration of pyrene was determined by gas chromatography. The toxicokinetic parameters for pyrene were determined from the time course of blood concentration. A significant increase in the bioavailability of pyrene after treatment with other PAHs was observed. Urinary 1-hydroxypyrene excretion was analyzed after pretreatment with acenaphthene, naphthalene, chrysene, phenanthrene, benz[a]anthracene, and benzo[a]pyrene. The urine from rats was collected for 3 d and the concentration of 1-hydroxypyrene was determined using high-performance liquid chromatography (HPLC). Most compounds examined caused a decrease in the urinary excretion of the metabolite of pyrene.


Assuntos
Hidrocarbonetos Aromáticos/farmacocinética , Hidrocarbonetos Cíclicos/farmacocinética , Mutagênicos/farmacocinética , Pirenos/farmacocinética , Administração Oral , Animais , Carga Corporal (Radioterapia) , Hidrocarbonetos Aromáticos/efeitos adversos , Hidrocarbonetos Aromáticos/farmacologia , Hidrocarbonetos Cíclicos/efeitos adversos , Hidrocarbonetos Cíclicos/farmacologia , Injeções Intravenosas , Cinética , Masculino , Mutagênicos/efeitos adversos , Pirenos/efeitos adversos , Ratos , Ratos Wistar
18.
Chemosphere ; 54(1): 61-70, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14559258

RESUMO

Uptake and depuration of toxic chlorinated compounds such as planar polychlorinated biphenyls (PCBs 77, 126, 169), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDF) were monitored during a 50-day field study where American oysters (Crassostrea virginica) were transplanted back and forth between a heavily polluted area (Houston Ship Channel, SC) and a relatively unimpacted area (Hanna's Reef, HR) within Galveston Bay, TX. In general, low molecular weight, less lipophilic compounds accumulated in the oysters to a larger extent than high molecular weight ones. Estimated half-lives for planar PCB congeners 77 and 126 were 28 and 51 days, respectively for depuration of newly contaminated oysters (HR-SC-HR) while longer half-lives (42 and 60 days, respectively) were observed for the same compounds as they were eliminated from chronically contaminated individuals (SC-HR). Estimated half-lives for 2,3,7,8-TCDD and 2,3,7,8-TCDF were 35 and 36 days, respectively and were similar to the tetrachlorinated biphenyls (PCBs 77 and 81). Compared with ortho-substituted PCB congeners of the same chlorination level, the more toxic PCBs take longer to depurate from the oysters. With few exceptions, elimination of all toxic compounds investigated proceeded at a slower rate from the chronically exposed population that from the newly contaminated one.


Assuntos
Hidrocarbonetos Aromáticos/farmacocinética , Hidrocarbonetos Halogenados/farmacocinética , Ostreidae/metabolismo , Animais , Cromatografia Gasosa-Espectrometria de Massas , Hidrocarbonetos Aromáticos/toxicidade , Hidrocarbonetos Halogenados/toxicidade , Texas
19.
Chemosphere ; 37(9-12): 1941-55, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9828321

RESUMO

Female Sprague Dawley rats were treated subcutaneously for 20 weeks with an environmentally relevant mixture of dioxin-like PHAHs with (PHAH+) or without (PHAH-) 2,2',4,4',5,5'-hexachlorobiphenyl. The hepatic retention (% of given dose) of the various PHAH congeners differed considerably and in the following order: 2,3,4,7,8-pentachlorodibenzofuran (30.5-43.1%), 3,3',4,4',5-pentachlorobiphenyl (12.8-17.6%), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (6.9-10.8%), 2,3,7,8-tetrachlorodibenzo-p-dioxin (3.2-4.5%), 2,3,3',4,4',5-hexachlorobiphenyl (1.0-1.7%), 2,2',4,4',5,5'-hexachlorobiphenyl (0.5-0.8%) and 2,3',4,4',5-pentachlorobiphenyl (0.2-0.4%). A decrease of the hepatic retention of 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD and 2,3,4,7,8-PeCDF was found at increasing doses of the PHAH+ mixture. 2,2',4,4',5,5'-Hexachlorobiphenyl increased the hepatic retention (1.3-2 times) of all congeners in the PHAH+ group, compared to the TEQ equivalent dosed PHAH- group. No interactions were observed on the ethoxyresorufin-O-deethylase activity.


Assuntos
Poluentes Ambientais/farmacocinética , Hidrocarbonetos Aromáticos/farmacocinética , Hidrocarbonetos Halogenados/farmacocinética , Bifenilos Policlorados/farmacocinética , Animais , Relação Dose-Resposta a Droga , Poluentes Ambientais/toxicidade , Feminino , Meia-Vida , Hidrocarbonetos Aromáticos/toxicidade , Hidrocarbonetos Halogenados/toxicidade , Fígado/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
20.
Environ Toxicol Chem ; 20(7): 1450-6, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11434284

RESUMO

This paper investigates the ability of the traditional organic matter partitioning (OMP) model to predict the solid-water distribution, and hence the dissolved exposures, of hydrophobic organic compounds (HOCs) in real field situations. Observed organic-carbon-normalized partitioning coefficients (Koc)obs) of polychlorinated biphenyls, polychlorinated benzenes, polychlorinated dibenzo-dioxins and -furans, and p,p'-dichlorodiphenyltrichlorethane (DDT) with metabolites were selected from the literature and compared with their respective OMP model estimates. For all compound classes and in a majority of the investigated cases, (Koc)obs values were significantly larger than predicted. This translated into factors of overestimated dissolved exposures ranging from 1 to 1,000. Various reasons are discussed for the discrepancies between predictions and actual observations, such as the effect of the diagenetic state and other properties of the particulate organic matter. The greater enhancement in (Koc)obs of planar over nonplanar compounds suggests in certain cases that efficient interactions with aromatic soot phases may be significant. For an improved predictability of (Koc)obs and dissolved exposures of HOCs in the real environment, the inclusion of soot and possibly other distinct subfractions of bulk organic carbon into an extended solid-water partitioning model may be considered.


Assuntos
Monitoramento Ambiental , Hidrocarbonetos Aromáticos/química , Modelos Teóricos , Poluentes do Solo/farmacocinética , Disponibilidade Biológica , Previsões , Sedimentos Geológicos/química , Hidrocarbonetos Aromáticos/farmacocinética , Solubilidade , Água
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