Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 75
Filtrar
1.
Bioresour Technol ; 400: 130673, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38583676

RESUMO

The ubiquitous use of volatile siloxanes in a myriad of product formulations has led to a widespread distribution of these persistent contaminants in both natural ecosystems and wastewater treatment plants. Microbial degradation under microaerobic conditions is a promising approach to mitigate D4 and D5 siloxanes while recovering energy in wastewater treatment plants. This study examined D4/D5 siloxanes biodegradation under both anaerobic and microaerobic conditions ( [Formula: see text]  = 0, 1, 3 %) using wastewater sludge. Results show that the use of microaeration in an otherwise strictly anaerobic environment significantly enhances siloxane conversion to methane. 16S rRNA gene sequencing identified potential degraders, including Clostridium lituseburense, Clostridium bifermentans and Synergistales species. Furthermore, chemical analysis suggested a stepwise siloxane conversion preceding methanogenesis under microaerobic conditions. This study demonstrates the feasibility of microaerobic siloxane biodegradation, laying groundwork for scalable removal technologies in wastewater treatment plants, ultimately highlighting the importance of using bio-based approaches in tackling persistent pollutants.


Assuntos
Biodegradação Ambiental , Metano , Siloxanas , Siloxanas/metabolismo , Metano/metabolismo , Esgotos/microbiologia , RNA Ribossômico 16S/genética , Aerobiose , Águas Residuárias/química , Volatilização
2.
Environ Toxicol Chem ; 43(1): 42-51, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37818875

RESUMO

The bioaccumulation behavior, including the uptake, internal distribution, depuration, and biotransformation rates, of three widely used linear methyl-siloxanes was investigated in rainbow trout. Dietary uptake efficiencies of octamethyltrisiloxane (L3), decamethyltetrasiloxane (L4), and dodecamethylpentasiloxane (L5) were 15% (3.3% standard error [SE]), 8.6% (1.4% SE), and 15% (1.8% SE), respectively, and for L3 and L4 were well below those of nonmetabolizable reference chemicals with similar octanol-water partition coefficients, suggesting significant intestinal biotransformation of L3 and L4. Somatic biotransformation rate constants were 0.024 (0.003 SE) day-1 for L3 and 0.0045 (0.0053 SE) day-1 for L4 and could not be determined for L5. Lipid-normalized biomagnification factors for L3, L4, and L5 were 0.24 (0.02 SE), 0.24 (0.01 SE), and 0.62 (0.05 SE) kg-lipid kg-lipid-1 , respectively. Bioconcentration factors standardized to a 5% lipid content fish for water in Canadian oligotrophic lakes with a dissolved organic carbon content of 7.1 mg L-1 were 2787 (354 SE) for L3, 2689 (312 SE) for L4, and 1705 (418 SE) L kg-wet weight-1 , respectively, and 3085 (392 SE) for L3, 4227 (490 SE) for L4, and 3831 (938 SE) L kg-wet weight-1 in water with a dissolved organic carbon content of 2.0 mg L-1 . A comparison of 238 bioaccumulation profiles for 166 different chemicals shows that the bioaccumulation profiles for L3, L4, and L5 are vastly different from those of other very hydrophobic compounds found in the environment. Environ Toxicol Chem 2024;43:42-51. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


Assuntos
Oncorhynchus mykiss , Poluentes Químicos da Água , Animais , Bioacumulação , Siloxanas/análise , Siloxanas/metabolismo , Matéria Orgânica Dissolvida , Canadá , Oncorhynchus mykiss/metabolismo , Poluentes Químicos da Água/análise , Água/metabolismo , Octanóis/metabolismo
3.
Viruses ; 15(12)2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-38140601

RESUMO

Molluscum contagiosum (MC) is characterized by skin lesions containing the highly contagious molluscum contagiosum poxvirus (MCV). MCV primarily infects children, with one US Food and Drug Administration (FDA)-approved drug-device treatment in use but no approved medications. Assessing antivirals is hindered by the inability of MCV to replicate in vitro. Here, we use vaccinia virus as a surrogate to provide evidence of the anti-poxvirus properties of berdazimer sodium, a new chemical entity, and the active substance in berdazimer gel, 10.3%, a nitric oxide-releasing topical in phase 3 development for the treatment of MC. We show that berdazimer sodium reduced poxvirus replication and, through a novel methodology, demonstrate that cells infected with drug-treated MCV virions have reduced early gene expression. Specifically, this is accomplished by studying the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB)-blocking protein MC160 as an example of an early gene. The results provide a plausible unique antiviral mechanism of action supporting increased MCV resolution observed in patients treated with berdazimer gel, 10.3% and describe a novel methodology that overcomes limitations in investigating MCV response in vitro to a potential new MC topical medication.


Assuntos
Molusco Contagioso , Vírus do Molusco Contagioso , Estados Unidos , Criança , Humanos , Vírus do Molusco Contagioso/genética , Molusco Contagioso/tratamento farmacológico , Siloxanas/metabolismo , Antivirais/farmacologia , Antivirais/metabolismo
4.
Toxicol In Vitro ; 82: 105379, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35561954

RESUMO

Literature shows contradictory information regarding the effect of freezing the excise skin ex vivo on the diffusion of substances into the skin. Few studies indicate that storing the human or animal skin in a frozen state decreases the barrier properties after thawing. Therefore, to understand the properties of frozen skin, we evaluated the effect of storage of ex vivo human skin (2 weeks at -20 °C) on the penetration of stratum corneum and permeation into deeper skin layers (epidermis, and dermis) as well as to the receptor fluid by octamethylcyclotetrasiloxane (D4) a representative test compound of cyclic siloxanes. The main research were preceded by checking the integrity of nonfrozen ex vivo human skin in comparison to the frozen-thawed one by using the Electrical Resistance technique (ER) and the fluorescence microscopy. Samples collected in the skin absorption experiment were analyzed by gas chromatography equipped with a flame ionization detector (GC-FID). The results of this study demonstrated that freezing of excised ex vivo human skin at -20 °C for up to 14 days does not alter the permeability of D4 in a statistically significant manner. Thus, our results confirmed the validity of using skin storage conditions for testing the penetration and permeation of xenobiotics recommended by the OECD, EMA, and WHO guidelines.


Assuntos
Siloxanas , Pele , Animais , Bioacumulação , Congelamento , Humanos , Permeabilidade , Siloxanas/metabolismo , Pele/metabolismo , Absorção Cutânea
5.
Ecotoxicol Environ Saf ; 213: 111983, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33582413

RESUMO

Methyl siloxanes are identified as emerging persistent toxic compounds and the ecological environment risks of these compounds have been caused of great concern worldwide. In this study, the concentrations of methyl siloxanes were reported in dissolved water and crucian carp around a methyl siloxane production factory located in Liaoning Province, Northeast China. D4, D5, D6, D7, L4, L5 and L6 were detectable both in dissolved water and crucian carp. The total concentrations of 7 methyl siloxanes (Σ7MS) were 14 ± 6.3 ng/L in dissolved water and 43 ± 22 ng/g ww in crucian carp, respectively. D5 has the highest concentration both in dissolved water (5.5 ± 3.5 ng/L) and crucian carp (17 ± 11 ng/g ww). Based on the monitoring values, bioaccumulation factor (BAF) of these compounds were calculated. Significant bioaccumulation potential was observed for D4 (BAF = 5900 ± 3500 L/kg) based on the bioaccumulation criteria suggested by USEPA and EU (BAF > 5000 L/kg). To our understanding, this is the first report of BAF values of methyl siloxane in field study, which will provide important support for further assessment of bioaccumulation of these compounds.


Assuntos
Carpas/metabolismo , Siloxanas/análise , Siloxanas/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Bioacumulação , China , Monitoramento Ambiental , Carpa Dourada/metabolismo , Poluentes Químicos da Água/análise
6.
J Hazard Mater ; 413: 125354, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-33609872

RESUMO

Available information on the bioaccumulation and trophodynamics of cyclic methylsiloxanes in aquatic food webs is insufficient for a reliable understanding of their toxicity and potential ecological harm. The concentrations of four cyclic methylsiloxanes in aquatic species collected from Lake Chaohu (China) were measured and the total concentration was in range of 2.01-36.1 ng/g dry weight. Dodecamethylcyclohexasiloxane (D6) represented 57.7% of the total measured methylsiloxane concentration. The distribution of these methylsiloxanes constitute the first tissue-specific record. The hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) tended to accumulate preferentially in fish muscles, while D6 was preferentially accumulated in fish liver and gills. In Lake Chaohu, significant trophic magnification of D3 (p < 0.01) and dilution of D6 (p < 0.05) were observed, and the trophic magnification factors (TMFs) were estimated at 4.94 and 0.68, respectively. No significant trends in D4 and D5 (p > 0.05) were observed within the food web. This study further confirmed the complexity of trophic transfer of the methylsiloxanes in the aquatic food web. The findings suggest that tissue-specific methylsiloxane distribution in aquatic species might also affect the observed TMFs. More research is required to investigate methylsiloxanes in additional species and their trophodynamics in different food webs.


Assuntos
Cadeia Alimentar , Poluentes Químicos da Água , Animais , Bioacumulação , China , Monitoramento Ambiental , Peixes/metabolismo , Lagos , Siloxanas/análise , Siloxanas/metabolismo , Poluentes Químicos da Água/análise
7.
Molecules ; 25(23)2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33271846

RESUMO

The trisiloxane polyether surfactant (3-[3-(hydroxy)(polyethoxy)propyl]-1,1,1,3,5,5,5 -heptamethyltrisiloxane) (TS-EO12) was successfully synthesized by a hydrosilylation reaction in the presence of Karstedt catalyst. The structural analysis of the surfactant was done by 1H-NMR, 13C-NMR, 29Si-NMR and FT-IR analysis. In addition the thermal stability of TS-EO12 was studied by the thermogravimetric measurements. On the one hand the surface properties of TS-EO12 at the water-air interface were investigated by surfactant aqueous solutions surface tension measurements carried out at 293 K, 303 K and 313 K, and on the other the aggregation properties were analyzed based on the solubilization properties of TS-EO12 aggregates at different temperatures. On the basis of the obtained thermodynamic parameters of adsorption and micellization of studied surfactant the temperature impact on its surface and volume properties were deduced. It was proved that the tendency of the studied surfactant molecules to adsorb at the water-air interface and to form micelles weakens with decreasing temperature. It was also concluded that the structure of the adsorption layer changes with temperature. Optical microscopy measurements were used for the TS-EO12 micelle morphology determination.


Assuntos
Siloxanas/química , Siloxanas/metabolismo , Tensoativos/química , Tensoativos/metabolismo , Temperatura , Termodinâmica , Adsorção , Propriedades de Superfície , Tensão Superficial
8.
J Invest Dermatol ; 140(12): 2531-2535.e2, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32428543
9.
J Hazard Mater ; 391: 122187, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32062547

RESUMO

The feasibility of simultaneous removal of siloxane and H2S from biogas was investigated using an aerobic biotrickling filter (BTF). The biodegradation of H2S in the BTF followed a first-order kinetic model and more than 95 % H2S was eliminated within a residence time of 0.3 min. The removal of decamethylcyclopentasiloxane (D5) increased with longer empty bed residence time (EBRT). The partition test and microbial community analysis further reveals that up to 52 % removal of D5 was reached mainly by the chemical-absorption in acid recycling liquid. Finally, D5 was converted into mixtures of dimethylsilanediol (DMSD) and hexamethyldisiloxane (L2) via ring-opening hydrolysis in acid liquid and ring-shrinking polyreaction using CH4 derived from biogas. These operational characteristics demonstrate that the abiotic removal of D5, in addition to biological removal of H2S in an aerobic BTF can significantly decrease the siloxane loading to the downstream siloxane removing units.


Assuntos
Poluentes Atmosféricos/metabolismo , Sulfeto de Hidrogênio/metabolismo , Siloxanas/metabolismo , Eliminação de Resíduos Líquidos , Aerobiose , Biocombustíveis , Filtração
10.
Sci Total Environ ; 650(Pt 2): 2364-2373, 2019 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-30292992

RESUMO

Volatile methylsiloxanes (VMSs) are massively produced chemicals that comprise a wide range of industrial and household applications. The presence of cyclic and linear VMSs in several environmental matrices and ecosystems indicates persistence associated with a potential of (bio)accumulation and food web transfer with possible toxicological effects. Due to the high anthropogenic pressure in its vicinities particularly in summer, coastal areas in Southern European countries are potential hotspots for the presence of VMSs. The massive afflux of tourists and consequent increase of the use of personal care products (PCPs) with VMSs in their formulations highlight the importance of VMSs assessment in such areas. In this study, different species of marine vegetation (algae and seaweed) were collected in three different geographical areas, covering the Atlantic Ocean (North coast of Portugal), as well as the Mediterranean Sea (coasts of the Region of Murcia, Spain and of the city of Marseille, France). Samples were analysed for the determination of 4 cyclic (D3, D4, D5, D6) and 3 linear (L3, L4, L5) VMSs employing a QuEChERS extraction methodology, followed by gas chromatography/mass spectrometry (GC/MS) quantification. VMSs were detected in 92% of the 74 samples analysed, with the sum of the concentrations per sample ranging from below the limit of detection (LOD) to 458 ±â€¯26 ng·g-1dw (dry weight). A strong predominance of cyclic VMSs over linear ones was verified in almost all samples studied, with D5 and D6 found at higher concentrations. Seasonal variation was also assessed and despite higher levels of VMSs being identified mostly in summer months, clear seasonal trends were not perceived. It was also noted that generally the higher incidence of VMSs occurred in samples from urban and industrialized areas or in the vicinities of WWTPs, suggesting a direct input from these sources in the levels of siloxanes observed.


Assuntos
Alismatales/metabolismo , Exposição Ambiental , Alga Marinha/metabolismo , Siloxanas/metabolismo , Compostos Orgânicos Voláteis/metabolismo , Poluentes Químicos da Água/metabolismo , Oceano Atlântico , Monitoramento Ambiental , França , Fucus/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Mar Mediterrâneo , Porphyra/metabolismo , Portugal , Espanha , Ulva/metabolismo
11.
Arch Environ Contam Toxicol ; 76(3): 496-507, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30259079

RESUMO

Despite the high production volume and widespread use of methyl siloxanes, limited studies have been conducted to investigate the bioconcentration, biomagnification, and trophic magnification potentials of these substances. In the present study, bioconcentration factors (BCFs) of methyl siloxanes were determined with common carp exposed at environmental relevant levels for 32 days. BCF of octamethylcyclotetrasiloxane (D4) was estimated as 6197 L/Kg, indicating strong bioconcentration potential in the common carp. To assess the food chain transfer of methyl siloxanes, 12 aquatic invertebrates and vertebrates species were collected from a food web in Shuangtaizi estuary in northeastern China and concentrations of methyl siloxanes in these species were determined with gas chromatography mass spectrometry. Trophic magnification factors (TMFs) of decamethylcyclopentasiloxane (D5), dodecamethylcyclohexasiloxane (D6), and linear siloxanes (L7-10) were significantly greater than 1 in one food chain selected, which suggest trophic magnification potentials of these methyl siloxanes. Biomagnification factors of D4-D6 and L7-L10 from planktons to Japanese snapping shrimp were greater than 1, indicating biomagnification potentials of these methyl siloxanes from the prey to predator. This is the first study to investigate the bioaccumulation behaviors of methyl siloxanes by coupling BCF and BMF with TMF.


Assuntos
Carpas/metabolismo , Monitoramento Ambiental/métodos , Siloxanas/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , China , Estuários , Cadeia Alimentar
12.
Biointerphases ; 13(4): 041009, 2018 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-30096984

RESUMO

Polysiloxanes have shown exquisite properties for fabrication of microstructures for various biomedical and biotechnological applications. Nevertheless, their biocompatibility in terms of cell adhesion and survival ability is controversial. A simple polysiloxane modifying procedure that reproducibly enhances cell adhesion was proposed. Sonication of the hybrid organic-inorganic polymer of polysiloxane type, Ormocomp, in potassium hydroxide (KOH)/ethanol solution enhanced adhesion and subsequent survival of a panel of four cell lines. Characterization of surface properties of untreated and KOH-treated Ormocomp coatings has revealed considerable negative charge of Ormocomp substrates based on measurements of zeta potentials. KOH treatment did not modify surface morphology as visualized by scanning electron microscopy, but it resulted in alteration in both chemical composition according to SIMS analysis and hydrophilicity evaluated by static water contact angles. The results suggest that the failure of the adherent cells to survive on Ormocomp coatings is related to cell adhesion. The negative surface charge of Ormocomp substrates may be one of the influencing factors; however, the modification of surface chemistry mediated by KOH and the resulting increase in hydrophilicity accompanied by modification of protein adsorption are more likely responsible for enhanced cell adhesion and survival on Ormocomp coatings. KOH treatment thus may serve as a simple, cost-effective procedure modifying polysiloxane-type polymers that leads to reproducible enhancement of cell adhesion.


Assuntos
Materiais Biocompatíveis/metabolismo , Adesão Celular , Hidróxidos/metabolismo , Compostos de Potássio/metabolismo , Siloxanas/metabolismo , Raios Ultravioleta , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/efeitos da radiação , Linhagem Celular , Sobrevivência Celular , Materiais Revestidos Biocompatíveis , Humanos , Interações Hidrofóbicas e Hidrofílicas , Teste de Materiais , Microscopia Eletrônica de Varredura , Siloxanas/química , Siloxanas/efeitos da radiação , Sonicação , Espectrometria de Massa de Íon Secundário , Propriedades de Superfície
14.
Toxicol Lett ; 279 Suppl 1: 75-97, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-28676441

RESUMO

Octamethylcyclotetrasiloxane (D4) is a cyclic volatile methylsiloxane primarily used in the synthesis of silicon-based materials used in a variety of consumer products. This paper details the chronic toxicity and oncogenicity evaluation of D4 in the Fischer 344 rat. Animals were exposed to 0, 10, 30, 150, or 700ppm D4 vapor for 6h/day, 5days/week for up to 104 weeks in whole-body inhalation chambers. Effects of two year chronic exposure included increased liver, kidney, testes, and uterine weight with correlating microscopic findings of hepatocellular hypertrophy (males only), chronic nephropathy (both sexes), interstitial cell hyperplasia, and cystic endometrial hyperplasia and endometrial adenoma, respectively. Upper respiratory tract irritation and lymphocytic leukocytosis were evident in both sexes. Increased neoplasia was demonstrated only in the uterus. Uterine endometrial adenomas were present in four of sixty animals exposed to 700ppm D4 for 24 months. None were present in the other treatment groups. In contrast, in 700ppm D4 group males the incidence of pituitary and pancreatic neoplasia was reduced as was thyroid c-cell adenoma/carcinoma in 700ppm females. This study has identified that D4 is a mild respiratory irritant and increases liver and kidney weight without inducing neoplasia in these tissues. The increased incidence of uterine adenoma was the only treatment-related neoplastic finding associated with chronic exposure to D4.


Assuntos
Adenoma/induzido quimicamente , Doença Hepática Induzida por Substâncias e Drogas/patologia , Neoplasias do Endométrio/induzido quimicamente , Nefropatias/induzido quimicamente , Siloxanas/toxicidade , Tecido Adiposo Marrom/química , Tecido Adiposo Marrom/metabolismo , Administração por Inalação , Animais , Relação Dose-Resposta a Droga , Poluentes Ambientais/administração & dosagem , Poluentes Ambientais/química , Poluentes Ambientais/metabolismo , Poluentes Ambientais/toxicidade , Feminino , Nefropatias/patologia , Masculino , Estrutura Molecular , Distribuição Aleatória , Ratos , Ratos Endogâmicos F344 , Siloxanas/administração & dosagem , Siloxanas/química , Siloxanas/metabolismo
15.
Toxicol Lett ; 279 Suppl 1: 98-114, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-28511864

RESUMO

Octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) are low molecular weight cyclic volatile methyl siloxanes (cVMSs) primarily used as intermediates or monomers in the production of high molecular weight silicone polymers. The use of D4 as a direct ingredient in personal care products has declined significantly over the past 20 years, although it may be present as a residual impurity in a variety of consumer products. D5 is still used as an intentional ingredient in cosmetics, consumer products and in dry cleaning. Persons who may be exposed include occupational exposure for workers, and potential inhalation or dermal exposure for consumers and the general public. Because of the diverse use, especially of D5, and the potential for human exposure, a comprehensive program was undertaken to understand the kinetics, metabolism, enzyme induction and toxicity of D4 and D5 in rats following relevant routes of exposure. Physiologically based pharmacokinetic (PBPK) models utilizing these studies have been reported for D4 and D5 in the rat and human following dermal and inhalation exposures, with the oral uptake component of the model being limited in its description. Data from high dose oral studies in corn oil and simethicone vehicles and neat were used in the D4/D5 harmonized PBPK model development. It was uncertain if the inability to adequately describe the oral uptake was due to unrealistic high doses or unique aspects of the chemistry of D4/D5. Low dose studies were used to provide data to refine the description of oral uptake in the model by exploring the dose dependency and the impact of a more realistic food-like vehicle. Absorption, distribution, metabolism and elimination (ADME) of D4 and D5 was determined following a single low oral gavage dose of 14C-D4 and 14C-D5 at 30 and 100mg/kg body weight (bw), respectively, in a rodent liquid diet. Comparison of the low vs. high dose oral gavage administration of D4 and D5 demonstrated dose-dependent kinetic behavior. Data and modeling results suggest differences in metabolism between low and high dose administration indicating high dose administration results in or approaches non-linear saturated metabolism. These low dose data sets were used to refine the D4/D5 multi-route harmonized PBPK model to allow for a better description of the disposition and toxicokinetics of D4/D5 following oral exposure. With a refined oral uptake description, the model could be used in risk assessment to better define the internal dose of D4 and D5 following exposure to D4 and D5 via multiple routes.


Assuntos
Poluentes Ambientais/metabolismo , Siloxanas/metabolismo , Tecido Adiposo/química , Administração por Inalação , Glândulas Suprarrenais/química , Animais , Área Sob a Curva , Isótopos de Carbono , Poluentes Ambientais/sangue , Poluentes Ambientais/química , Poluentes Ambientais/farmacocinética , Feminino , Trato Gastrointestinal/química , Fígado/química , Pulmão/química , Masculino , Ovário/química , Ratos , Ratos Endogâmicos F344 , Siloxanas/química , Siloxanas/farmacocinética , Baço/química , Testículo/química , Distribuição Tecidual , Útero/química
16.
Toxicol Lett ; 279 Suppl 1: 115-124, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-28438492

RESUMO

Critical factors (uptake, distribution, metabolism and elimination) for understanding the bioaccumulation/biomagnification potential of Octamethylcyclotetrasiloxane (D4) and Decamethylcyclopentasiloxane (D5) siloxanes in fish were investigated to address whether these chemicals meet the "B" criteria of the Persistent, Bioaccumulative, and Toxic (PBT) classification. A metabolism study was conducted in rainbow trout whereby a 15mg [14C]D4/kg bw or [14C]D5/kg bw as a single bolus oral dose was administered via gavage. Of the administered dose, 79% (D4) and 78% (D5) was recovered by the end of the study (96-h). Eighty-two percent and 25% of the recovered dose was absorbed based on the percentage of recovered dose in carcass (69% and 17%), tissues, bile and blood (12% and 8%) and urine (1%) for D4 and D5, respectively. A significant portion of the recovered dose (i.e. 18% for D4 and 75% for D5) was eliminated in feces. Maximum blood concentrations were 1.6 and 1.4µg D4 or D5/g blood at 24h post-dosing, with elimination half-lives of 39h (D4) and 70h (D5). Modeling of parent and metabolite blood concentrations resulted in estimated metabolism rate constants (km(blood)) of 0.15 (D4) and 0.17day-1(D5). Metabolites in tissues, bile, blood, and urine totaled a minimum of 2% (D4) and 14% (D5) of the absorbed dose. The highest concentration of 14C-activity in the fish following D4 administration was in mesenteric fat followed by bile, but the opposite was true for D5. Metabolites were not detected in fat, only parent chemical. In bile, 94% (D4) and 99% (D5) of the 14C-activity was due to metabolites. Metabolites were also detected in the digestive tract, liver and gonads. Approximately 40% of the 14C-activity detected in the liver was due to the presence of metabolites. Urinary elimination represented a minor pathway, but all the 14C-activity in the urine was associated with metabolites. Clearance may occur via enterohepatic circulation of metabolic products in bile with excretion via the digestive tract and urinary clearance of polar metabolites.


Assuntos
Poluentes Ambientais/metabolismo , Siloxanas/metabolismo , Administração Oral , Animais , Isótopos de Carbono , Poluentes Ambientais/sangue , Poluentes Ambientais/farmacocinética , Poluentes Ambientais/urina , Oncorhynchus mykiss , Prednisolona/análogos & derivados , Siloxanas/farmacocinética
17.
Toxicol Lett ; 279 Suppl 1: 125-135, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-28408153

RESUMO

The multi-compound, and multi-dose (MC-MD) route physiologically based pharmacokinetic (PBPK) model for cyclic siloxanes reported by McMullin et al. (2016) brought together the series of models for octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) in rat and human into a unified code structure that would allow simulation of both compounds following the inhalation and dermal routes of exposure. The refined MC-MD PBPK model presented here expands upon this effort to include representation of rat kinetic data in plasma, tissues and exhaled breath for the parent compounds after oral bolus administration. Additional refinements were made with regards to hepatic induction of metabolism in the liver and allometric scaling of rate constants for the deep tissue compartments which will allow the MC-MD model to be used in uncertainty analysis. Overall, the refined MC-MD model was able to reproduce both parent D4 and D5 kinetic data in rat and human after inhalation exposure (rat and human) or dermal exposure (human). The inclusion of sequestered (i.e., lipid associated) oral absorption into plasma after oral bolus dosing successfully described the lack of exhalation as well as the initial distribution of siloxane to the liver which was higher than simple partitioning from plasma would allow. The refined MC-MD PBPK model presented here can be incorporated into uncertainty and variability analysis and cross-species dosimetry for both D4 and D5.


Assuntos
Exposição Ambiental , Siloxanas/metabolismo , Administração Oral , Adulto , Animais , Relação Dose-Resposta a Droga , Feminino , Humanos , Exposição por Inalação , Masculino , Modelos Biológicos , Ratos , Siloxanas/toxicidade
18.
Chembiochem ; 18(4): 358-362, 2017 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-27905160

RESUMO

Chemical inducers that can control target-protein localization in living cells are powerful tools to investigate dynamic biological systems. We recently reported the retention using selective hook or "RUSH" system for reversible localization change of proteins of interest by addition/washout of small-molecule artificial ligands of streptavidin (ALiS). However, the utility of previously developed ALiS was restricted by limited solubility in water. Here, we overcame this problem by X-ray crystal structure-guided design of a more soluble ALiS derivative (ALiS-3), which retains sufficient streptavidin-binding affinity for use in the RUSH system. The ALiS-3-streptavidin interaction was characterized in detail. ALiS-3 is a convenient and effective tool for dynamic control of α-mannosidase II localization between ER and Golgi in living cells.


Assuntos
Ligantes , Modelos Moleculares , Ácidos Ftálicos/química , Transporte Proteico/fisiologia , Proteínas/metabolismo , Piridonas/química , Estreptavidina/química , Sulfonamidas/química , Sítios de Ligação , Cristalização , Humanos , Morfolinas/química , Morfolinas/metabolismo , Ácidos Ftálicos/farmacologia , Ligação Proteica , Proteínas/química , Piridonas/metabolismo , Piridonas/farmacologia , Siloxanas/química , Siloxanas/metabolismo , Solubilidade , Estreptavidina/metabolismo , Sulfonamidas/metabolismo
19.
Huan Jing Ke Xue ; 37(10): 4054-4061, 2016 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-29964443

RESUMO

Volatile methyl siloxanes (VMSs) are of great concern in the past few years due to their high production volume, ubiquitousness in the environment and toxicities. The bioaccumulation of VMSs is reported to be sensitive to their metabolism rates, however, little is known about their metabolic rates in aquatic organisms. The present study measured intrinsic clearance rates of 16 common VMSs (D3-D6 and L3-L14) incubated in liver microsomes of weever and quail. The intrinsic clearance rates of VMSs in weever microsomes were 0-0.031 mL·(h·mg)-1. The fact that D5 exhibited no significant decline trend in the incubations with liver microsomes of weever corresponded with its trophic magnification behaviour in aquatic food webs. L4-L14, similar to D5, were also persistent in microsomes, suggesting the high bioaccumulation potentials of the chemicals. The intrinsic clearance rates of VMSs incubated in quail microsomes [0.25-1.7 mL·(h·mg)-1] were significantly higher than those incubated in weever microsomes. The relatively high biotransformation rates of D3-D6 and L3-L14 suggested that these compounds may not exhibit high biomagnification potentials in birds. B[a]P was used as a benchmark chemical to normalize variations in determining the metabolism rates among batches, and the structure-activity relationships were explored for the normalized intrinsic clearance rates of quail microsomes. Hydrophobicity and electric properties were found to be major factors influencing the bird microsomal intrinsic clearance rates of VMSs.


Assuntos
Aves/metabolismo , Cadeia Alimentar , Siloxanas/metabolismo , Compostos Orgânicos Voláteis/metabolismo , Animais , Monitoramento Ambiental , Microssomos Hepáticos/metabolismo , Codorniz/metabolismo , Poluentes Químicos da Água
20.
J Mol Recognit ; 29(3): 115-22, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25726930

RESUMO

Calcium silicate particle containing mesoporous SiO2 (CaSiO3@SiO2) was grafted on the surface of non-woven polypropylene. The PP non-woven grafted calcium silicate containing mesoporous SiO2 (PP-g-CaSiO3@SiO2) was used as the matrix to prepare bovine serum albumin (BSA) molecularly imprinted polysiloxane (MIP) by using silanes as the functional monomers and BSA as the template. PP non-woven grafted BSA-imprinted polysiloxane (PP-g-CaSiO3@SiO2 MIP) was characterized by scanning electron microscope (SEM), Fourier transform infrared spectometry (FTIR) and drilling string compensator (DSC). Influence factors on the rebinding capacity of the MIP were investigated, such as grafting degree, the pH in treating CaSiO3 and the type and proportion of silanes. The rebinding properties of BSA on PP-g-CaSiO3@SiO2 and MIP were investigated under different conditions. The results indicated that the rebinding capacity of MIP for BSA reached 56.32 mg/g, which was 2.65 times of NIP. The non-woven polypropylene grafted BSA-imprinted polysiloxane could recognize the template protein and the selectivity factor (ß) was above 2.4 when using ovalbumin, hemoglobin and γ-globulin as control proteins. The PP-g-CaSiO3@SiO2 MIP has favorable reusability.


Assuntos
Compostos de Cálcio/química , Polipropilenos/química , Proteínas/metabolismo , Silicatos/química , Siloxanas/química , Animais , Microscopia Eletrônica de Varredura , Impressão Molecular , Estrutura Molecular , Siloxanas/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA