RESUMO
Veverimer is a polymer being developed as a potential treatment of metabolic acidosis in patients with chronic kidney disease. Veverimer selectively binds and removes hydrochloric acid from the gastrointestinal tract, resulting in an increase in serum bicarbonate. Veverimer is not systemically absorbed, so potential drug-drug interactions (DDIs) are limited to effects on the absorption of other oral drugs through binding to veverimer in the gastrointestinal tract or increases in gastric pH caused by veverimer binding to hydrochloric acid. In in vitro binding experiments using a panel of 16 test drugs, no positively charged, neutral, or zwitterionic drugs bound to veverimer. Three negatively charged drugs (furosemide, aspirin, ethacrynic acid) bound to veverimer; however, this binding was reduced or eliminated in the presence of normal physiologic concentrations (100-170 mM) of chloride. Veverimer increased gastric pH in vivo by 1.5-3 pH units. This pH elevation peaked within 1 hour and had returned to baseline after 1.5-3 hours. Omeprazole did not alter the effect of veverimer on gastric pH. The clinical relevance of in vitro binding and the transient increase in gastric pH was evaluated in human DDI studies using two drugs with the most binding to veverimer (furosemide, aspirin) and two additional drugs with pH-dependent solubility effecting absorption (dabigatran, warfarin). None of the four drugs showed clinically meaningful DDI with veverimer in human studies. Based on the physicochemical characteristics of veverimer and results from in vitro and human studies, veverimer is unlikely to have significant DDIs. SIGNIFICANCE STATEMENT: Patients with chronic kidney disease, who are usually on many drugs, are vulnerable to drug-drug interactions (DDIs). The potential for DDIs with veverimer was evaluated based on the known site of action and physicochemical structure of the polymer, which restricts the compound to the gastrointestinal tract. Based on the findings from in vitro and human studies, we conclude that veverimer is unlikely to have clinically significant DDIs.
Assuntos
Acidose/tratamento farmacológico , Polímeros/farmacocinética , Insuficiência Renal Crônica/tratamento farmacológico , Absorção Fisico-Química , Acidose/etiologia , Administração Oral , Adolescente , Adulto , Aspirina/administração & dosagem , Aspirina/química , Aspirina/farmacocinética , Estudos Cross-Over , Dabigatrana/administração & dosagem , Dabigatrana/química , Dabigatrana/farmacocinética , Interações Medicamentosas , Ácido Etacrínico/administração & dosagem , Ácido Etacrínico/química , Ácido Etacrínico/farmacocinética , Feminino , Furosemida/administração & dosagem , Furosemida/química , Furosemida/farmacocinética , Absorção Gastrointestinal , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Polímeros/administração & dosagem , Polímeros/química , Polimedicação , Insuficiência Renal Crônica/complicações , Solubilidade , Varfarina/administração & dosagem , Varfarina/química , Varfarina/farmacocinética , Adulto JovemRESUMO
Polyquaternium-22 and polyquaternium-39 are polymers that function as antistatic agents, film formers, and hair fixatives in cosmetic products. These ingredients are being used at concentrations up to 2% (polyquaternium-22, in a rinse-off product) and up to 3% (polyquaternium-39, in rinse-off and leave-on products). The unreacted monomer content of these ingredients was considered low and of no toxicological concern. Limited data showed no skin irritation/sensitization. Although these ingredients were nongenotoxic in bacterial assays, mammalian genotoxicity, carcinogenicity, and reproductive and developmental toxicity data were not available. These polymers, however, are large, highly polar molecules that would likely not be absorbed, and neither local effects in the respiratory tract nor systemic toxicity are expected following product application/exposure. The Expert Panel concluded that polyquaternium-22 and polyquaternium-39 are safe in the present practices of use and concentration in cosmetic formulations.
Assuntos
Qualidade de Produtos para o Consumidor , Cosméticos/normas , Polímeros/toxicidade , Compostos de Amônio Quaternário/toxicidade , Animais , Qualidade de Produtos para o Consumidor/legislação & jurisprudência , Cosméticos/química , Humanos , Estrutura Molecular , Polímeros/química , Polímeros/farmacocinética , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacocinética , Relação Estrutura-Atividade , Testes de Toxicidade/métodos , Toxicocinética , Estados Unidos , United States Food and Drug AdministrationRESUMO
Despite major advances in the treatment of rheumatoid arthritis (RA) led by the success of biologic therapies, the lack of response to therapy in a proportion of patients, as well as therapy discontinuation owing to systemic toxicity, are still unsolved issues. Unchecked RA might develop into progressive structural joint damage, loss of function and long-term disability, disorders which are associated with a considerable health-economic burden. Therefore, new strategies are required to actively target and deliver therapeutic agents to disease sites in order to promote in situ activity and decrease systemic toxicity. Polymer-drug conjugates can improve the pharmacokinetics of therapeutic agents, conferring desirable properties such as increased solubility and tissue penetration at sites of active disease. Additionally, nanotechnology is an exciting modality in which drugs are encapsulated to protect them from degradation or early activation in the circulation, as well as to reduce systemic toxicity. Together with the targeting capacity of antibodies and site-specific peptides, these approaches will facilitate selective accumulation of therapeutic agents in the inflamed synovium, potentially improving drug efficacy at disease sites without affecting healthy tissues. This Review aims to summarize key developments in the past 5 years in polymer conjugation, nanoparticulate drug delivery and antibody or peptide-based targeting--strategies that might constitute the platform for the next generation of RA therapeutics.
Assuntos
Antirreumáticos/administração & dosagem , Antirreumáticos/farmacocinética , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Animais , Artrite Reumatoide/economia , Sistemas de Liberação de Medicamentos , Desenho de Fármacos , Humanos , Terapia de Alvo Molecular , Nanoestruturas/administração & dosagem , Polímeros/administração & dosagem , Polímeros/farmacocinéticaRESUMO
The poly[La-(Glc-Leu)] copolymer was applied in the present investigation as polymeric carrier to fabricate naltrexone (NTX)-loaded poly[La-(Glc-Leu)] microspheres in the single emulsion solvent evaporation technique for the long-term treatment of alcohol dependence. Newly synthesized poly[La-(Glc-Leu)] copolymer exhibited diminished crystallanity, good biocompatibility and favorable biodegradability to be explored for drug delivery application. Scanning Electron Microscopy study revealed smooth and spherical-shaped NTX-loaded polymeric microspheres with a mean size of 10-90 µm. Influence of various decisive formulation variables such as amount of polymer, stabilizer concentration, homogenization speed, homogenization time, drug loading and organic-to-aqueous phase ratio on particle size, and entrapment efficiency was studied. Differential scanning calorimeter and X-ray diffractometry study confirmed the drug entrapment within polymer matrix into the microsphere environment. In vitro drug release showed the sustained drug release of formulation for the period of 28 d giving biphasic release pattern. Histological examination of NTX-loaded poly[La-(Glc-Leu)] microspheres injected intramuscularly into the thigh muscle of Wistar rats showed minimal inflammatory reaction, demonstrating that NTX-loaded microspheres were biocompatible. Insignificant increase in the serum creatine phosphokinase level (p < 0.05) as compared with the normal value revealed good muscle compatibility of the poly[La-(Glc-Leu)] microsphere system. Biocompatible nature and sustained drug-release action of poly[La-(Glc-Leu)] microspheres may have potential application in depot therapy.
Assuntos
Alcoolismo/tratamento farmacológico , Ácido Láctico/química , Leucina/química , Naltrexona/química , Naltrexona/farmacologia , Ácido Poliglicólico/química , Polímeros/química , Animais , Química Farmacêutica , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Emulsões/química , Emulsões/farmacocinética , Emulsões/farmacologia , Microesferas , Naltrexona/farmacocinética , Tamanho da Partícula , Polímeros/farmacocinética , Polímeros/farmacologia , Ratos , Ratos Wistar , Solventes/química , Solventes/farmacocinética , Solventes/farmacologiaRESUMO
Propylene glycol is an aliphatic alcohol that functions as a skin conditioning agent, viscosity decreasing agent, solvent, and fragrance ingredient in cosmetics. Tripropylene glycol functions as a humectant, antioxidant, and emulsion stabilizer. Polypropylene glycols (PPGs), including PPG-3, PPG-7, PPG-9, PPG-12, PPG-13, PPG-15, PPG-16, PPG-17, PPG-20, PPG-26, PPG-30, PPG-33, PPG-34, PPG-51, PPG-52, and PPG-69, function primarily as skin conditioning agents, with some solvent use. The majority of the safety and toxicity information presented is for propylene glycol (PG). Propylene glycol is generally nontoxic and is noncarcinogenic. Clinical studies demonstrated an absence of dermal sensitization at use concentrations, although concerns about irritation remained. The CIR Expert Panel determined that the available information support the safety of tripropylene glycol as well as all the PPGs. The Expert Panel concluded that PG, tripropylene glycol, and PPGs ≥3 are safe as used in cosmetic formulations when formulated to be nonirritating.
Assuntos
Qualidade de Produtos para o Consumidor , Cosméticos/química , Fármacos Dermatológicos/toxicidade , Polímeros/toxicidade , Propilenoglicol/toxicidade , Propilenoglicóis/toxicidade , Administração Cutânea , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/toxicidade , Cosméticos/toxicidade , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/química , Fármacos Dermatológicos/farmacocinética , Humanos , Polímeros/administração & dosagem , Polímeros/química , Polímeros/farmacocinética , Propilenoglicol/administração & dosagem , Propilenoglicol/química , Propilenoglicol/farmacocinética , Propilenoglicóis/administração & dosagem , Propilenoglicóis/química , Propilenoglicóis/farmacocinética , Higiene da Pele/efeitos adversos , Testes de Toxicidade , ViscosidadeRESUMO
PURPOSE: To investigate the potential of magnetic resonance imaging (MRI) for accurate assessment of the three-dimensional (166)Ho activity distribution to estimate radiation-absorbed dose distributions in (166)Ho-loaded poly (L-lactic acid) microsphere ((166)Ho-PLLA-MS) liver radioembolization. METHODS AND MATERIALS: MRI, computed tomography (CT), and single photon emission CT (SPECT) experiments were conducted on an anthropomorphic gel phantom with tumor-simulating gel samples and on an excised human tumor-bearing liver, both containing known amounts of (166)Ho-PLLA-MS. Three-dimensional radiation-absorbed dose distributions were estimated at the voxel level by convolving the (166)Ho activity distribution, derived from quantitative MRI data, with a (166)Ho dose point-kernel generated by MCNP (Monte Carlo N-Particle transport code) and from Medical Internal Radiation Dose Pamphlet 17. MRI-based radiation-absorbed dose distributions were qualitatively compared with CT and autoradiography images and quantitatively compared with SPECT-based dose distributions. Both MRI- and SPECT-based activity estimations were validated against dose calibrator measurements. RESULTS: Evaluation on an anthropomorphic phantom showed that MRI enables accurate assessment of local (166)Ho-PLLA-MS mass and activity distributions, as supported by a regression coefficient of 1.05 and a correlation coefficient of 0.99, relating local MRI-based mass and activity calculations to reference values obtained with a dose calibrator. Estimated MRI-based radiation-absorbed dose distributions of (166)Ho-PLLA-MS in an ex vivo human liver visually showed high correspondence to SPECT-based radiation-absorbed dose distributions. Quantitative analysis revealed that the differences in local and total amounts of (166)Ho-PLLA-MS estimated by MRI, SPECT, and the dose calibrator were within 10%. Excellent agreement was observed between MRI- and SPECT-based dose-volume histograms. CONCLUSIONS: Quantitative MRI was demonstrated to provide accurate three-dimensional (166)Ho-PLLA-MS activity distributions, enabling localized intrahepatic radiation-absorbed dose estimation by convolution with a (166)Ho dose point-kernel for liver radioembolization treatment optimization and evaluation.
Assuntos
Embolização Terapêutica/métodos , Hólmio/farmacocinética , Ácido Láctico/farmacocinética , Neoplasias Hepáticas/metabolismo , Imageamento por Ressonância Magnética/métodos , Microesferas , Polímeros/farmacocinética , Radioisótopos/farmacocinética , Algoritmos , Autorradiografia/métodos , Humanos , Fígado/diagnóstico por imagem , Fígado/metabolismo , Neoplasias Hepáticas/diagnóstico por imagem , Método de Monte Carlo , Imagens de Fantasmas , Poliésteres , Dosagem Radioterapêutica , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada por Raios XRESUMO
A laboratory experiment was conducted to study the influence of biochar on the residues of chlorobenzenes (CBs) in soil. Two treatments as the control and the addition of 1% wheat straw biochar were designed. Three chemical extractions as butanol, HPCD and Tenax extractions and earthworm accumulation were used to assess the changes of the bioavailability of CBs in soil. The results showed that the residues of HCB, PeCB and 1,2,4,5-TeCB in the control were 29.87%, 18.02% and 5.16% after 4 months incubation, however, the residues of HCB, PeCB and 1,2,4,5-TeCB in biochar amended soil were 68.25%, 61.32% and 58.02%, respectively, indicating that biochar amendment would inhibit the dissipation of CBs in soil. Butanol, HPCD and Tenax extraction as well as earthworm accumulation results demonstrated that the bioavailability of CBs in soil was significantly affected by biochar amendment (P < 0.05). With aging time increase, the biochar amendment significantly lowered the bioavailability of CBs. The extraction ratios differed among different chemical extraction methods. The extraction ratio was HCB > PeCB > 1,2,4,5-TeCB for butanol and Tenax extraction, while 1,2,4,5-TeCB > PeCB > HCB for HPCD extraction. The bioaccumulation factor of CBs by earthworm was significantly lower in biochar amended soil compared to the control (P < 0.05). This study showed that the biochar could reduce the bioavailability of organic pollutants, however, the high residues of the pollutants in soil showed potential environmental risk.
Assuntos
Carvão Vegetal/química , Clorobenzenos/isolamento & purificação , Poluentes do Solo/isolamento & purificação , Animais , Disponibilidade Biológica , Butanóis/isolamento & purificação , Butanóis/farmacocinética , Clorobenzenos/farmacocinética , Oligoquetos/metabolismo , Caules de Planta/química , Polímeros/isolamento & purificação , Polímeros/farmacocinética , Poluentes do Solo/farmacocinética , Triticum/químicaRESUMO
Fully bioresorbable vascular scaffolds (BVS) are attractive platforms for the treatment of ischemic artery disease owing to their intrinsic ability to uncage the treated vessel after the initial scaffolding phase, thereby allowing for the physiological conditioning that is essential to cellular function and vessel healing. Although scaffold erosion confers distinct advantages over permanent endovascular devices, high transient by-product concentrations within the arterial wall could induce inflammatory and immune responses. To better understand these risks, we developed in this study an integrated computational model that characterizes the bulk degradation and by-product fate for a representative BVS composed of poly(L-lactide) (PLLA). Parametric studies were conducted to evaluate the relative impact of PLLA degradation rate, arterial remodeling, and metabolic activity on the local lactic acid (LA) concentration within arterial tissue. The model predicts that both tissue remodeling and PLLA degradation kinetics jointly modulate LA fate and suggests that a synchrony of these processes could minimize transient concentrations within local tissue. Furthermore, simulations indicate that LA metabolism is a relatively poor tissue clearance mechanism compared to convective and diffusive transport processes. Mechanistic understanding of factors governing by-product fate may provide further insights on clinical outcome and facilitate development of future generation scaffolds.
Assuntos
Implantes Absorvíveis , Prótese Vascular , Ácido Láctico/farmacocinética , Modelos Cardiovasculares , Polímeros/farmacocinética , Animais , Humanos , Ácido Láctico/química , Poliésteres , Polímeros/químicaRESUMO
Myocardial contrast echocardiography is a rapidly evolving technique for the assessment of myocardial perfusion. Many studies have indicated their ability to detect flow-limiting coronary artery disease. Imagify (perflubutane polymer microspheres) injectable suspension, also known as AI-700, is a new ultrasound contrast agent that satisfies all the characteristics of an ideal agent for the assessment of myocardial perfusion. Preliminary studies with Imagify indicate that it is comparable with radionuclide perfusion techniques (presently the most widely used imaging technique to assess coronary artery disease) without the disadvantages of radiation and lack of availability at the bedside. This article provides an overview of Imagify, a new ultrasound contrast agent.
Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Fluorocarbonos , Polímeros , Ensaios Clínicos como Assunto , Fluorocarbonos/efeitos adversos , Fluorocarbonos/farmacocinética , Humanos , Microesferas , Polímeros/efeitos adversos , Polímeros/farmacocinética , UltrassonografiaRESUMO
Metoclopramide HCl showed controlled release behavior when embedded in a hydrophilic matrix of chitosan and sodium alginate. The in vitro release data was found to be first order according to the Higuchi mechanism. An in vivo evaluation of the metoclopramide controlled release matrix on six male volunteers was carried out. The plasma samples were analyzed using a high-performance liquid chromatography (HPLC) method using a mobile phase of acetonitrile:acetic acid (30:70), with the pH adjusted to 4.7, a reverse phase Hypersil BDS Phenyl column (4 microm, 250 x 4 mm) and the detection was performed at 305 nm. The controlled release formula was found to be effective in delaying absorption (t(max) 4.5h as compared to 1.2h), reducing the peak plasma concentrations (C(max) 63.4 ng/ml as compared to 95.9 ng/ml) and maintaining higher concentrations during the elimination phase when compared to the immediate release formula. This proves the suitability of the suggested system for further studies.
Assuntos
Metoclopramida/sangue , Metoclopramida/farmacocinética , Polímeros/farmacocinética , Adulto , Química Farmacêutica , Intervalos de Confiança , Estudos Cross-Over , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Humanos , Masculino , Metoclopramida/química , Polímeros/químicaRESUMO
The objective of our study was to compare the in vitro release kinetics of a sustained-release injectable microsphere formulation of the polypeptide drug, calcitonin (CT), to optimize the characteristics of drug release from poly-(lactide-co-glycolide) (PLGA) copolymer biodegradable microspheres. A modified solvent evaporation and double emulsion technique was used to prepare the microspheres. Release kinetic studies were carried out in silanized tubes and dialysis bags, whereby microspheres were suspended and incubated in phosphate buffered saline, sampled at fixed intervals, and analyzed for drug content using a modified Lowry protein assay procedure. An initial burst was observed whereby about 50% of the total dose of the drug was released from the microspheres within 24 hr and 75% within 3 days. This was followed by a period of slow release over a period of 3 weeks in which another 10-15% of drug was released. Drug release from the dialysis bags was more gradual, and 50% CT was released only after 4 days and 75% after 12 days of release. Scanning electron micrographs revealed spherical particles with channel-like structures and a porous surface after being suspended in an aqueous solution for 5 days. Differential scanning calorimetric studies revealed that CT was present as a mix of amorphous and crystalline forms within the microspheres. Overall, these studies demonstrated that sustained release of CT from PLGA microspheres over a 3-week period is feasible and that release of drug from dialysis bags was more predictable than from tubes.
Assuntos
Calcitonina/farmacocinética , Ácido Láctico/farmacocinética , Ácido Poliglicólico/farmacocinética , Polímeros/farmacocinética , Preparações de Ação Retardada/farmacocinética , Diálise/métodos , Microesferas , Copolímero de Ácido Poliláctico e Ácido PoliglicólicoRESUMO
Dioxins are highly toxic by-products of incineration processes and of production of chloro-organic chemicals. Accidental poisonings have occurred repeatedly. The main human exposure is via the dietary route. Species comparisons of toxic effects on the basis of ingested doses are not possible because of the highly differing toxicokinetics between humans and experimental animals. On the basis of internal doses or body burdens acute toxic and tumorigenic responses are observed at similar levels in humans and rats. PCB/PCDD/F contamination at levels which have been reported of marketed chicken meat and eggs in 1999 in Belgium may have increased body burdens by approximately 10%. However, it is estimated that a several hundred-fold higher uptake would be necessary to reach body burdens leading to overt toxicity in normal human subjects.
Assuntos
Dioxinas/toxicidade , Contaminação de Alimentos/análise , Dibenzodioxinas Policloradas/análogos & derivados , Animais , Benzofuranos/análise , Benzofuranos/farmacocinética , Benzofuranos/toxicidade , Carga Corporal (Radioterapia) , Galinhas , Dioxinas/análise , Dioxinas/farmacocinética , Ovos/análise , Exposição Ambiental , Humanos , Carne/análise , Bifenilos Policlorados/análise , Bifenilos Policlorados/farmacocinética , Bifenilos Policlorados/toxicidade , Dibenzodioxinas Policloradas/análise , Dibenzodioxinas Policloradas/farmacocinética , Dibenzodioxinas Policloradas/toxicidade , Polímeros/análise , Polímeros/farmacocinética , Polímeros/toxicidade , Medição de RiscoRESUMO
Using lysozyme as a model protein, this study investigated protein stability, protein--polymer interaction in different release media and their influence on protein release profile and in vitro--in vivo correlation. Lysozyme was microencapsulated into PLGA 50:50 by a double emulsion--solvent extraction/evaporation method. Protein stability, protein--PLGA adsorption and protein in vitro release were studied in various test media. Differential scanning calorimetry analysis showed lysozyme to be most conformationally stable in pH 4.0 acetate buffer with highest T(m) at 77.2 degree C and DeltaH(cal) 83.1 kcal/mol. Lysozyme exhibited good stability in pH 2.5 glycine buffer with T(m) at 63.8 degree C and DeltaH(cal) 69.9 kcal/mol. In pH 7.4 phosphate-buffered saline (PBS), lysozyme showed a trend toward aggregation when the temperature was elevated. When PLGA polymer was incubated with lysozyme in the various buffers, adsorption was found to occur in PBS only. The adsorption severely limited the amount of lysozyme available for release from microspheres, resulting in slow and incomplete release in PBS. In contrast, the release of the microspheres in acetate and glycine buffers was complete within 40 and 70 days, respectively. Radiolabeled lysozyme blood levels in rats from the microspheres correlated qualitatively well with in vitro release in glycine buffer as a release medium. This study suggests that protein stability and adsorption are critical factors controlling protein release kinetics and in vitro--in vivo correlation of PLGA microspheres.
Assuntos
Ácido Láctico/química , Ácido Láctico/farmacocinética , Muramidase/química , Muramidase/farmacocinética , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Polímeros/química , Polímeros/farmacocinética , Adsorção , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacocinética , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Avaliação Pré-Clínica de Medicamentos/métodos , Estabilidade Enzimática , Masculino , Microesferas , Muramidase/ultraestrutura , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Sprague-DawleyRESUMO
Inuit people living in the Arctic receive an unusually high dose of dioxin-like compounds through their traditional diet, which comprises large amounts of fatty tissues from various sea mammal species. During breast feeding, the mother transfers part of their body burden to its newborn. We estimated the impact of breast feeding on the body burden of Inuit from birth to age 75 years. Simulations performed with a toxicokinetic model revealed that breast feeding strongly influences body burden during childhood but not after age 20 years. Liver and adipose tissue concentrations expected in Inuit are well below those which induced severe adverse health effects in laboratory animals, e.g. cancer and reproduction. However, these concentrations approach levels generating subtle effects on reproductive systems.
Assuntos
Benzofuranos/toxicidade , Aleitamento Materno , Inuíte , Dibenzodioxinas Policloradas/análogos & derivados , Tecido Adiposo/metabolismo , Adolescente , Adulto , Idoso , Envelhecimento/metabolismo , Benzofuranos/farmacocinética , Carga Corporal (Radioterapia) , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Fígado/metabolismo , Pessoa de Meia-Idade , Dibenzodioxinas Policloradas/farmacocinética , Dibenzodioxinas Policloradas/toxicidade , Polímeros/farmacocinética , Polímeros/toxicidade , Fatores de RiscoRESUMO
A Japanese was estimated to ingest 3 and 11 pg/kg/day of TEQ from PCDD/PCDFs and coplanar PCBs respectively through foods. A Japanese baby was calculated to consume 100-530 pg/kg/day level of TEQ through breast milk feeding, more than 60% being attributed to TEQ of coplanar PCBs. These intakes of TEQ were compared to the average (154 ng/kg/day) and minimum (28 ng/kg/day) intakes of Yusho, a PCB posioning occurred in Japan in 1968. There are three or four orders of magnitude difference between the daily TEQ intakes of general population and Yusho patients. However, the TEQ intakes by breast milk-fed babies of general population are at least 53 times less than the minimum intake of Yusho patients.