RESUMO
The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of Hydroxyethyl Urea, which is reported to function as a humectant and a hair and skin conditioning agent. The Panel reviewed the available data to determine the safety of this ingredient. The Panel concluded that Hydroxyethyl Urea is safe in cosmetics in the present practices of use and concentration described in the safety assessment when formulated to be non-irritating.
Assuntos
Qualidade de Produtos para o Consumidor , Cosméticos , Ureia , Animais , Humanos , Cosméticos/toxicidade , Cosméticos/química , Cosméticos/farmacocinética , Medição de Risco , Testes de Toxicidade , Ureia/análogos & derivados , Ureia/toxicidadeRESUMO
Carbon-encapsulated magnetic nanoparticles are promising candidate materials for drug-delivery applications. However, due to their hydrophobic and aggregation properties, which indicate lower biocompatibility, proper surface modification of the carbon-based material is required. In the present study, we present the facile route to producing biocompatible magnetic nanocomposite iron oxide/carbon using the liquid medium arc-discharge method. The medium used was ethanol 50% with urea added in various concentrations. Using x-ray diffraction (XRD), the nanocomposite produced was confirmed to have a crystalline structure with distinctive peaks representing iron oxide, graphite, and urea. Fourier transform infrared spectroscopy (FTIR) analysis of the nanocomposite produced in ethanol/acetic acid or ethanol/urea medium shows several vibrations, including Fe-O, C-H, C-O, C=C, C-H, O-H, and C-N, which are intended to be the attached aromatic oxygen- and amine-containing functional groups. The nanocomposite particle was observed to have a core-shell structure that had an iron-compound core coated in a carbon shell possibly modified by polymeric urea groups. The presence of these groups suggested that the nanocomposite would be biocompatible with biological entities in the living body. Lastly, the prepared nanocomposite Fe3O4/C-urea underwent an in-vivo acute toxicity assay to confirm its toxicity. The highest dose of 2000 mg kg-1 BW in this study caused no deaths in the test animals even though cell damages were observed, especially in the liver. This highest dose is considered a maximum tolerable dose and is defined as practically non-toxic.
Assuntos
Nanocompostos , Animais , Materiais Biocompatíveis/toxicidade , Carbono , Etanol , Compostos Férricos , Humanos , Fenômenos Magnéticos , Nanocompostos/toxicidade , Alta do Paciente , Ureia/toxicidadeRESUMO
PURPOSE OF REVIEW: Urea has been utilized as a reductant in diesel fuels to lower emission of nitrogen oxides, igniting interest in probable human health hazards associated with exposure to exogenous urea. Here, we summarize and update key findings on potential health effects of exogenous urea, including carcinogenicity. RECENT FINDINGS: No definitive target organs for oral exposure were identified; however, results in animal studies suggest that the liver and kidney could be potential target organs of urea toxicity. The available human-subject literature suggests that the impact on lung function is minimal. Based on the literature on exogenous urea, we concluded that there was inadequate information to assess the carcinogenic potential of urea, or perform a quantitative assessment to derive reference values. Given the limited information on exogenous urea, additional research to address gaps for exogenous urea should include long-term cancer bioassays, two-generation reproductive toxicity studies, and mode-of-action investigations.
Assuntos
Exposição Ambiental/efeitos adversos , Ureia/toxicidade , Animais , Carcinógenos/toxicidade , Humanos , Neoplasias/induzido quimicamenteRESUMO
A recent hypothesis suggesting that the pharmacological target TRPV1 (transient receptor potential vanilloid subfamily, member 1) may function as a tumour suppressor, which potentially impacts the development of TRPV1 antagonist therapeutics for a range of conditions. However, little is known about the long-term physiologic effects of TRPV1 blockade in the skin. In vitro and in vivo studies suggested that the potent TRPV1 competitive antagonist AMG-9810 promoted proliferation in N/TERT1 cells (telomerase-immortalised primary human keratinocytes 1) and tumour development in mouse skin that was mediated through EGFR/Akt/mTOR signalling. We attempted to reproduce the reported in vitro and in vivo findings to further explore this hypothesis to understand the underlying mechanism and the risk associated with TRPV1 antagonism in the skin. In vitro proliferation studies using multiple methods and topical application with AMG-9810 and structurally similar TRPV1 antagonists such as SB-705498 and PAC-14028 were performed. Although we confirmed expression of TRPV1 in primary human epidermal keratinocytes (HEKn) and spontaneously immortalised human keratinocytes (HaCaT), we were unable to demonstrate cell proliferation in either cell type or any clear evidence of increased expression of proteins in the EGFR/Akt/mTOR signalling pathway with these molecules. We were also unable to demonstrate skin tumour promotion or underlying molecular mechanisms involved in the EGFR/Akt/mTOR signalling pathway in a single-dose and two-stage carcinogenesis mouse study treated with TRPV1 antagonists. In conclusion, our data suggest that inhibiting the pharmacological function of TRPV1 in skin by specific antagonists has not been considered to be indicative of skin tumour development.
Assuntos
Proliferação de Células/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Neoplasias Cutâneas/metabolismo , Canais de Cátion TRPV/antagonistas & inibidores , Acrilamidas/toxicidade , Animais , Antracenos/toxicidade , Compostos Bicíclicos Heterocíclicos com Pontes/toxicidade , Capsaicina/análogos & derivados , Capsaicina/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cocarcinogênese , Feminino , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologia , Camundongos , Camundongos Pelados , Piperidinas/toxicidade , Cultura Primária de Células , Piridinas/toxicidade , Pirrolidinas/toxicidade , Risco , Neoplasias Cutâneas/patologia , Canais de Cátion TRPV/genética , Ureia/análogos & derivados , Ureia/toxicidadeRESUMO
BACKGROUND: Cosmetic preservatives are used to protect cosmetic formulations and improve its shelf-life. However, these substances may exert phototoxic effects when used under sunlight. OBJECTIVE: To assess safety, efficacy and putative phototoxic effects of a sunscreen formulation SPF 30 and its excipients. MATERIALS/METHODS: Irradiation was performed with solar simulated light (SSL) and the sunscreen from the School of Pharmacy/UFRJ/Brazil. We used albino hairless mice in different groups (control (G1), only irradiated (G2), sunscreen plus irradiation (G3) and vehicle plus irradiation (G4) for morphological assessment and immunefluorescence detection to OKL38. In vitro analyses were with a Saccharomyces cerevisiae (SC) strain plus SSL in the presence of methylparaben, propylparaben, imidazolidinyl urea, aminomethyl propanol and their association. RESULTS: G3 and G4 displayed photosensitization leading to thickening of the epidermis and increased dermal cellularity. G4 displayed strong OKL38 labeling when compared with other groups. Aminomethyl propanol, methylparaben and propylparaben are endowed with phototoxic activity against SC. Propylparaben displayed the highest phototoxic effect, followed by excipients association. CONCLUSIONS: The sunscreen's vehicle is endowed with phototoxic activity. Propylparaben was the most phototoxic agent, increasing the overall phototoxicity of excipient association, pointing to a critical concern regarding vehicle associations intended to cosmetic purposes.
Assuntos
Pele/efeitos dos fármacos , Protetores Solares/farmacologia , Animais , Cosméticos , Composição de Medicamentos , Camundongos , Camundongos Pelados , Microscopia de Fluorescência , Parabenos/toxicidade , Propanolaminas/toxicidade , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos da radiação , Pele/patologia , Pele/efeitos da radiação , Luz Solar , Ureia/análogos & derivados , Ureia/toxicidadeRESUMO
Non-peptidomimetic drug-like protease inhibitors have potential for circumventing drug resistance. We developed a much-improved synthetic route to our previously reported inhibitor candidate displaying an unusual quaternized hemi-aminal. This functional group forms from a linear precursor upon passage into physiological media. Seven variants were prepared and tested in cellulo with our HIV-1 fusion-protein technology that result in an eGFP-based fluorescent readout. Three candidates showed inhibition potency above 20µM and toxicity at higher concentrations, making them attractive targets for further refinement. Importantly, our class of original inhibitor candidates is not recognized by two major multidrug resistance pumps, quite in contrast to most clinically applied HIV-1 protease inhibitors.
Assuntos
Inibidores da Protease de HIV/química , Protease de HIV/química , HIV-1/enzimologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células HEK293 , Protease de HIV/metabolismo , Inibidores da Protease de HIV/síntese química , Inibidores da Protease de HIV/toxicidade , Humanos , Camundongos , Células NIH 3T3 , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Ureia/síntese química , Ureia/química , Ureia/toxicidadeRESUMO
BACKGROUND: For blood purification systems using a semipermeable membrane, the convective mass transfer by ultrafiltration plays an important role in toxin removal. The increase in the ultrafiltration rate can improve the toxin removal efficiency of the device, ultimately reducing treatment time and cost. In this study, we assessed the effects of pulsatile flow on the efficiency of the convective toxin removal in blood purification systems using theoretical methods. METHODS: We devised a new mathematical lumped model to assess the toxin removal efficiency of blood purification systems in patients, integrating the mass transfer model for a human body with a dialyser. The human body model consists of a three-compartment model of body fluid dynamics and a two-compartment model of body solute kinetics. We simulated three types of blood purification therapy with the model, hemofiltration, hemodiafiltration, and high-flux dialysis, and compared the simulation results in terms of toxin (urea and beta-2 microglobulin) clearance and the treatment dose delivered under conditions of pulsatile and non-pulsatile pumping. In vivo experiments were also performed to verify the model results. RESULTS: Simulation results revealed that pulsatile flow improved the convective clearance of the dialyser and delivered treatment dose for all three types of therapy. Compared with the non-pulsatile pumping method, the increases in the clearance of urea and beta-2 microglobulin with pulsatile pumping were highest with hemofiltration treatment (122.7% and 122.7%, respectively), followed by hemodiafiltration (3.6% and 8.3%, respectively), and high-flux dialysis (1.9% and 4.7%, respectively). EKRc and std Kt/V averaged 28% and 23% higher, respectively, in the pulsatile group than in the non-pulsatile group with hemofiltration treatment. CONCLUSIONS: The pulsatile effect was highly advantageous for all of the toxins in the hemofiltration treatment and for beta2-microglobulin in the hemodiafiltration and high-flux dialysis treatments.
Assuntos
Simulação por Computador , Fluxo Pulsátil , Terapia de Substituição Renal/métodos , Humanos , Modelos Biológicos , Reprodutibilidade dos Testes , Fatores de Tempo , Ureia/isolamento & purificação , Ureia/toxicidade , Microglobulina beta-2/isolamento & purificação , Microglobulina beta-2/toxicidadeRESUMO
Hydrogen sulfide emission in sewers is associated with toxicity, corrosion, odor nuisance and a lot of costs. The possibility to inhibit sulfide generation by formaldehyde and its derivatives (paraformaldehyde and urea formaldehyde) has been evaluated under anaerobic conditions. The impact of formaldehyde on an activated sludge system and an appraisal of the economic aspects are also presented. The optimum dosage to inhibit sulfide generation in sewage was 12-19 mg L(-1) formaldehyde. The dosages of 32 mg L(-1) paraformaldehyde or 100 mg L(-1) urea formaldehyde were not capable of inhibiting sulfide generation in sewage. The impact of 19 mg L(-1) formaldehyde on activated sludge system was negligible in terms of COD removal, nitrification rate and oxygen uptake rate.
Assuntos
Formaldeído/química , Sulfeto de Hidrogênio/química , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Anaerobiose , Formaldeído/toxicidade , Sulfeto de Hidrogênio/metabolismo , Polímeros/toxicidade , Esgotos/microbiologia , Bactérias Redutoras de Enxofre/efeitos dos fármacos , Bactérias Redutoras de Enxofre/crescimento & desenvolvimento , Bactérias Redutoras de Enxofre/metabolismo , Ureia/toxicidade , Eliminação de Resíduos Líquidos/economiaRESUMO
A tiered testing strategy has been employed to evaluate the potential for new ingredients, tobacco processes, and technological developments to alter the mainstream smoke or biological activity that results from burning cigarette tobacco. The foundation of this evaluation strategy is comparative testing, typically including chemical and biological assessments. In the manufacture of cigarettes, diammonium phosphate (DAP) and urea have been historically used as ingredients added to tobacco, to reconstituted tobacco sheet, and to other processed tobaccos. As part of ongoing stewardship efforts, a toxicological assessment of cigarettes with and without DAP and urea was conducted. Chemical and biological analyses were conducted for test cigarettes added 0.5% DAP and 0.2% urea in the final blend and also for those added 1.0% DAP and 0.41% urea in the final blend compared to reference cigarettes without added DAP or urea. Principal components of this evaluation included a determination of selected mainstream smoke constituent yields, an Ames assay in Salmonella typhimurium strains TA98 and TA100, a sister chromatid exchange assay in Chinese hamster ovary cells, a 13-week inhalation study of mainstream cigarette smoke in Sprague-Dawley rats, and a 30-week dermal tumor-promotion evaluation of mainstream cigarette smoke condensate in SENCAR mice. Comparative evaluations demonstrated that the addition of DAP and urea to cigarettes at up to 1% and 0.41%, respectively, does not alter the biological activity compared to reference cigarettes without DAP or urea.
Assuntos
Carcinógenos/toxicidade , Qualidade de Produtos para o Consumidor , Mutagênicos/toxicidade , Nicotiana/química , Fosfatos/toxicidade , Ureia/toxicidade , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Células CHO , Cocarcinogênese , Cricetinae , Cricetulus , Feminino , Exposição por Inalação , Masculino , Tamanho do Órgão/efeitos dos fármacos , Especificidade de Órgãos , Ratos , Ratos Sprague-Dawley , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Troca de Cromátide Irmã/efeitos dos fármacos , Neoplasias Cutâneas/induzido quimicamente , Alcatrões/química , Alcatrões/toxicidade , Indústria do Tabaco/normas , Testes de ToxicidadeRESUMO
Around 75% of European ammonia (NH(3)) emissions come from livestock production. Emissions occur at all stages of manure management: from buildings housing livestock; during manure storage; following manure application to land; and from urine deposited by livestock on pastures during grazing. Ammoniacal nitrogen (total ammoniacal-nitrogen, TAN) in livestock excreta is the main source of NH(3). At each stage of manure management TAN may be lost, mainly as NH(3), and the remainder passed to the next stage. Hence, measures to reduce NH(3) emissions at the various stages of manure management are interdependent, and the accumulative reduction achieved by combinations of measures is not simply additive. This TAN-flow concept enables rapid and easy estimation of the consequences of NH(3) abatement at one stage of manure management (upstream) on NH(3) emissions at later stages (downstream), and gives unbiased assessment of the most cost-effective measures. We conclude that rapid incorporation of manures into arable land is one of the most cost-effective measures to reduce NH(3) emissions, while covering manure stores and applying slurry by band spreader or injection are more cost-effective than measures to reduce emissions from buildings. These measures are likely to rank highly in most European countries.
Assuntos
Poluentes Atmosféricos/análise , Amônia/análise , Criação de Animais Domésticos , Esterco/análise , Agricultura/economia , Agricultura/métodos , Criação de Animais Domésticos/instrumentação , Animais , Bovinos , Análise Custo-Benefício , Monitoramento Ambiental/métodos , Europa (Continente) , Fertilizantes/toxicidade , Suínos , Ureia/toxicidade , UrinaRESUMO
Although Urea is officially described as a buffering agent, humectant, and skin-conditioning agent-humectant for use in cosmetic products, there is a report stating that Urea also is used in cosmetics for its desquamating and antimicrobial action. In 2001, the Food and Drug Administration (FDA) reported that Urea was used in 239 formulations. Concentrations of use for Urea ranged from 0.01% to 10%. Urea is generally recognized as safe by FDA for the following uses: side-seam cements for food contact; an inhibitor or stabilizer in pesticide formulations and formulations applied to animals; internal sizing for paper and paperboard and surface sizing and coating of paper and paper board that contact water-in-oil dairy emulsions, low-moisture fats and oils, moist bakery products, dry solids with surface containing no free fats or oil, and dry solids with the surface of fat or oil; and to facilitate fermentation of wine. Urea is the end product of mammalian protein metabolism and the chief nitrogenous compound of urine. Urea concentrations in muscle, liver, and fetuses of rats increased after a subcutaneous injection of Urea. Urea diffused readily through the placenta and into other maternal and fetal organs. The half-life of Urea injected into rabbits was on the order of several hours, and the reutilization rate was 32.2% to 88.8%. Urea given to rats by a bolus injection or continuous infusion resulted in distribution to the following brain regions: frontal lobe, caudate nucleus, hippocampus, thalamus plus hypothalamus, pons and white matter (corpus callosum). The permeability constant after treatment with Urea of whole skin and the dermis of rabbits was 2.37 +/- 0.13 (x 10(6)) and 1.20 +/- 0.09 (x10(3)) cm/min, respectively. The absorption of Urea across normal and abraded human skin was 9.5% +/- 2.3% and 67.9% +/- 5.6%, respectively. Urea increased the skin penetration of other compounds, including hydrocortisone. No toxicity was observed for Urea at levels as high as 2000 mg/kg in acute oral studies using female rats or mice. No signs of toxicity were observed in male piglets dosed orally with up to 4 g/kg Urea for 5 days. Dogs dosed orally with 5 to 30 g/L Urea for 4 to 10 days had signs of toxicity, including weakness, anorexia, vomiting and retching, diarrhea and a decreased body temperature, which led to a deep torpor or coma. No significant microscopic changes were observed in the skin of male nude mice dermally exposed to 100% Urea for 24 h. No observable effect on fetal development was seen in rats and mice dosed orally with an aqueous solution of Urea (2000 mg/kg) on days 10 and 12 of gestation. The mean number of implants, live fetuses, percent fetal resorptions, mean fetal weight, and percent fetuses malformed were comparable to control group. A detergent containing 15% Urea was injected into pregnant ICR-JCl mice and dams and fetuses had no significant differences when compared to control animals. Urea given orally did not enhance the developmental toxicity of N-nitrosomethylurea. Female Sprague-Dawley rats injected in the uterine horn with 0.05 ml Urea on day 3 (preimplantation) or on day 7 (post implantation) exhibited no maternal mortality or morbidity; a dose-dependent reduction in embryo survival was seen with preimplantation treatment. Urea injected intra-amniotically induces mid-trimester abortions in humans. Urea was not genotoxic in several bacterial and mammalian assays; although in assays where Urea was used at a high concentration, genotoxicity was found, many in in vitro assays. Urea is commonly used in studies of DNA because it causes uncoiling of DNA molecules. Urea was not carcinogenic in Fisher 344 rats or C57B1/6 mice fed diets containing up to 4.5% Urea. Exposure of normal human skin to 60% Urea produced no significant irritation in one study, but 5% Urea was slightly irritating and 20% Urea was irritating in other reports. Burning sensations are the most frequently reported effect of Urea used alone or with other agents in treatment of diseased skin. Overall, there are few reports of sensitization among the many clinical studies that report use of Urea in treatment of diseased skin. The Cosmetic Ingredient Review (CIR) Expert Panel determined the data provided in this report to be sufficient to assess the safety of Urea. The Panel did note that Urea can cause uncoiling of DNA, a property used in many DNA studies, but concluded that this in vitro activity is not linked to any in vivo genotoxic activity. Although noting that formulators should be aware that Urea can increase the percutaneous absorption of other chemicals, the CIR Expert Panel concluded that Urea is safe as used in cosmetic products.
Assuntos
Qualidade de Produtos para o Consumidor , Cosméticos/toxicidade , Ureia/toxicidade , Animais , Cosméticos/efeitos adversos , Prova Pericial , Feminino , Humanos , Masculino , Coelhos , Ratos , Medição de Risco , Testes de Toxicidade , Ureia/efeitos adversosRESUMO
The legislative application of regulatory toxicology in Canada is reviewed, together with the sources of experimental evidence used for action. Examples are given of the critical toxicological information that led to a regulatory decision. Risk numbers have only been used to a limited extent in Canada. Some possibilities for future research are offered.