Assuntos
Acetaldeído , Odorantes , Perfumes , Humanos , Perfumes/toxicidade , Perfumes/química , Animais , Medição de Risco , Acetaldeído/toxicidade , Acetaldeído/química , Acetaldeído/análogos & derivados , Acetais/toxicidade , Acetais/química , Determinação de Ponto Final , Qualidade de Produtos para o Consumidor , Testes de Toxicidade , Nível de Efeito Adverso não Observado , Bases de Dados de Compostos QuímicosAssuntos
Acetais , Aldeídos , Perfumes , Testes de Toxicidade , Acetais/química , Acetais/toxicidade , Aldeídos/química , Aldeídos/toxicidade , Animais , Células Cultivadas , Bases de Dados de Compostos Químicos , Humanos , Camundongos , Testes para Micronúcleos , Perfumes/química , Perfumes/toxicidade , Reprodução/efeitos dos fármacos , Absorção Cutânea , Testes CutâneosAssuntos
Acetais , Aldeídos , Perfumes , Acetais/química , Acetais/toxicidade , Aldeídos/química , Aldeídos/toxicidade , Animais , Células Cultivadas , Bases de Dados de Compostos Químicos , Humanos , Perfumes/química , Perfumes/toxicidade , Sistema de Registros , Pele/metabolismo , Absorção Cutânea , Testes de ToxicidadeRESUMO
Hydroxycitronellal dimethyl acetal was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog hydroxycitronellal diethyl acetal (CAS # 7779-94-4) show that hydroxycitronellal dimethyl acetal is not expected to be genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the TTC for a Cramer Class I material and the exposure to hydroxycitronellal dimethyl acetal is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). Data from hydroxycitronellal dimethyl acetal and from read-across material hydroxycitronellal diethyl acetal (CAS # 7779-94-4) show that there are no safety concerns for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; hydroxycitronellal dimethyl acetal is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; hydroxycitronellal dimethyl acetal was found not to be PBT as per the IFRA Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., PEC/PNEC), are <1.
Assuntos
Acetais/toxicidade , Octanóis/toxicidade , Odorantes , Acetais/química , Animais , Qualidade de Produtos para o Consumidor , Avaliação Pré-Clínica de Medicamentos , Determinação de Ponto Final , Escherichia coli/efeitos dos fármacos , Humanos , Testes de Mutagenicidade , Nível de Efeito Adverso não Observado , Octanóis/química , Medição de Risco , Salmonella typhimurium/efeitos dos fármacosAssuntos
Acetais/toxicidade , Aerossóis/toxicidade , Sistemas Eletrônicos de Liberação de Nicotina/normas , Aromatizantes/química , Mentol/química , Acetais/química , Acetais/normas , Aerossóis/química , Aerossóis/normas , Aldeídos/química , Aldeídos/normas , Aromatizantes/normas , Humanos , Mentol/normas , Solventes/química , Solventes/normas , Estados Unidos , United States Food and Drug Administration/normasRESUMO
Vanillin propylene glycol acetal (VPGA) has been used as a flavoring agent. Here, we performed a 13-week subchronic toxicity study of VPGA in F344 rats with oral administration by gavage at doses of 0, 100, 300, and 1000â¯mg/kg body weight (BW)/day. In the 1000â¯mg/kg BW group, loss of vigorous activity and listlessness immediately after administration were observed for both sexes throughout the experimental period. Reduction of body weight gain was noted in both sexes at 1000â¯mg/kg BW. Serum biochemistry demonstrated significant increases in total protein, albumin, total cholesterol, calcium, inorganic phosphorus, and γ-glutamyl transpeptidase in both sexes at 1000â¯mg/kg BW and increases in the albumin/globulin ratio and urea nitrogen in the male 1000â¯mg/kg BW group. A significant increase in relative liver weight was detected in both sexes at 1000â¯mg/kg BW. Histopathologically, centrilobular hepatocellular hypertrophy in the liver was observed in both sexes at 1000â¯mg/kg BW. In addition, the incidence of fatty changes in hepatocytes in the male 1000â¯mg/kg BW group was decreased compared with that in the control. Based on these results, the no-observed-adverse-effect level for VPGA was evaluated to be 300â¯mg/kg BW/day for both sexes in the current study.
Assuntos
Acetais/toxicidade , Aromatizantes/toxicidade , Propilenoglicóis/toxicidade , Acetais/administração & dosagem , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Aromatizantes/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Nível de Efeito Adverso não Observado , Tamanho do Órgão/efeitos dos fármacos , Propilenoglicóis/administração & dosagem , Ratos Endogâmicos F344RESUMO
Tumor hypoxia is a significant factor leading to the resistance of tumors to treatment, especially for photodynamic therapy and radiotherapy where oxygen is needed to kill cancer cells. Oxygen delivery agents such as oxygen-saturated perfluorocarbon nanoemulsions and lipid oxygen microbubbles have been employed to supply oxygen to hypoxic tumors with ultrasound activation. Such oxygen delivery systems are still associated with several drawbacks, including premature oxygen release and the dependence of external stimuli. To address these limitations, we developed oxygen nanobubbles that were enclosed by the acetalated dextran polymer shells for spontaneous oxygeneration in response to a minor pH drop in the tumor microenvironment. The acetalated dextran polymer shell serves as a robust barrier against gas dissolution in the circulating blood to retain the majority of the oxygen payload, and its pH-responsive property enables an abrupt burst release of oxygen in the mild acidic tumor microenvironment. The acetalated dextran oxygen nanobubbles exhibited excellent stability and biocompatibility. In vitro and in vivo experiments were conducted to investigate the pH-responsive oxygen release. The external stimuli-free supply of oxygen by the acetalated dextran oxygen nanobubbles was evaluated on CNE2 tumor-bearing mice, and the intratumoral oxygen level increased by 6-fold after the administration of the oxygen nanobubbles, manifesting that our pH-responsive oxygen nanobubbles hold great potential as a potent oxygen delivery agent to overcome the hypoxia-induced resistance.
Assuntos
Portadores de Fármacos/química , Nanoestruturas/química , Oxigênio/farmacologia , Hipóxia Tumoral/efeitos dos fármacos , Acetais/química , Acetais/toxicidade , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Meios de Contraste/toxicidade , Dextranos/química , Dextranos/toxicidade , Portadores de Fármacos/toxicidade , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Nanoestruturas/toxicidade , Ultrassonografia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
E-cigarette aerosol emission studies typically focus on benchmarking toxicant levels versus those of cigarettes. However, such studies do not fully account for the distinct chemical makeup of e-liquids and their unique properties. These approaches often conclude that there are fewer and lower levels of toxins produced by e-cigarettes than by cigarettes. In 2015, we reported the discovery of new hemiacetals derived from the reaction of formaldehyde and the e-liquid solvents. The main finding was that they constituted a significant proportion of potentially undetected formaldehyde. Moreover, unlike gaseous formaldehyde, the hemiacetals reside in the aerosol particulate phase, and thus are capable of delivering formaldehyde more deeply into the lungs. However, the findings were criticized by those claiming that some of the results were obtained under conditions that are averse to vapers. A "reinvestigation" of our study was recently published addressing this latter issue. However, this reinvestigation ignored major details, including no mention of the formaldehyde hemiacetals. Herein, we isolated both gaseous formaldehyde and formaldehyde hemiacetals at an intermediate power level claimed, in the "reinvestigation", to be relevant to "non-averse," "normal" usage. The results were that both gaseous formaldehyde and formaldehyde from hemiacetals were produced at levels above OSHA workplace limits.
Assuntos
Acetais/isolamento & purificação , Aerossóis/isolamento & purificação , Formaldeído/isolamento & purificação , Acetais/toxicidade , Aerossóis/toxicidade , Cromatografia Líquida de Alta Pressão , Sistemas Eletrônicos de Liberação de Nicotina , Formaldeído/toxicidade , Espectroscopia de Ressonância MagnéticaAssuntos
Acetais/química , Acetais/toxicidade , Aldeídos/química , Aldeídos/toxicidade , Bases de Dados de Compostos Químicos , Perfumes/química , Perfumes/toxicidade , Acetais/administração & dosagem , Aldeídos/administração & dosagem , Animais , Qualidade de Produtos para o Consumidor , Vias de Administração de Medicamentos , Determinação de Ponto Final , Humanos , Nível de Efeito Adverso não Observado , Perfumes/administração & dosagem , Medição de Risco , Testes de ToxicidadeAssuntos
Acetais/química , Acetais/toxicidade , Aldeídos/química , Aldeídos/toxicidade , Bases de Dados de Compostos Químicos , Perfumes/química , Perfumes/toxicidade , Acetais/administração & dosagem , Aldeídos/administração & dosagem , Animais , Qualidade de Produtos para o Consumidor , Vias de Administração de Medicamentos , Determinação de Ponto Final , Humanos , Nível de Efeito Adverso não Observado , Perfumes/administração & dosagem , Medição de Risco , Testes de ToxicidadeAssuntos
Acetais/química , Acetais/toxicidade , Bases de Dados de Compostos Químicos , Perfumes/química , Perfumes/toxicidade , Acetais/administração & dosagem , Animais , Qualidade de Produtos para o Consumidor , Vias de Administração de Medicamentos , Determinação de Ponto Final , Humanos , Nível de Efeito Adverso não Observado , Perfumes/administração & dosagem , Medição de Risco , Testes de ToxicidadeAssuntos
Acetais/química , Acetais/toxicidade , Aldeídos/química , Aldeídos/toxicidade , Bases de Dados de Compostos Químicos , Perfumes/química , Perfumes/toxicidade , Acetais/administração & dosagem , Aldeídos/administração & dosagem , Animais , Qualidade de Produtos para o Consumidor , Vias de Administração de Medicamentos , Determinação de Ponto Final , Humanos , Nível de Efeito Adverso não Observado , Perfumes/administração & dosagem , Medição de Risco , Testes de ToxicidadeAssuntos
Acetais/química , Acetais/toxicidade , Bases de Dados de Compostos Químicos , Perfumes/química , Perfumes/toxicidade , Acetais/administração & dosagem , Animais , Qualidade de Produtos para o Consumidor , Vias de Administração de Medicamentos , Determinação de Ponto Final , Humanos , Nível de Efeito Adverso não Observado , Perfumes/administração & dosagem , Medição de Risco , Testes de ToxicidadeRESUMO
Grundmann's ketone is converted to a spiroacetal containing a 5-hydroxymethyl-5-nitro-1,3-dioxane moiety whose hydroxymethyl group can be esterified or directly substituted with primary and secondary amines. Among the resulting aminomethyl spiroacetals, several ones bearing diamino residues were found to be inhibitors of the enzyme Δ8,7-isomerase in cholesterol biosynthesis. The complex bicyclic building block derived from Grundmann's ketone could be replaced by a properly substituted tetraline scaffold, without noteworthy loss in activity. This opens the opportunity to perform further structural modifications for the design of new steroidomimetic inhibitors of human Δ8,7-isomerase.
Assuntos
Acetais/síntese química , Acetais/farmacologia , Anticolesterolemiantes/síntese química , Anticolesterolemiantes/farmacologia , Colesterol/biossíntese , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Esteroide Isomerases/antagonistas & inibidores , Acetais/toxicidade , Anticolesterolemiantes/toxicidade , Sobrevivência Celular , Relação Dose-Resposta a Droga , Desenho de Fármacos , Inibidores Enzimáticos/toxicidade , Células HL-60 , Humanos , Concentração Inibidora 50 , Mimetismo Molecular , Estrutura Molecular , Esteroide Isomerases/metabolismo , Relação Estrutura-AtividadeRESUMO
Pectenotoxin-2 (PTX2) is a shellfish toxin and has a non-anomeric spiroacetal, which is not stabilized by an anomeric effect. The selective construction of the non-anomeric spiroacetal has been a major problem in the synthesis of PTX2. Described herein is the stereoselective total synthesis of PTX2 via the isomerization of anomeric spiroacetal pectenotoxin-2b (PTX2b). The synthesis of PTX2b was achieved by a simple process including sulfone-mediated assembly of spirocyclic and bicyclic acetals and subsequent macrocyclization by ring-closing olefin metathesis. Finally, the selective construction of PTX2 was accomplished by the early termination of a dynamic transition process to equilibrium in the acid-catalyzed isomerization of anomeric PTX2b. [6,6]-Spiroacetal pectenotoxin-2c (PTX2c) was also synthesized from PTX2b. The cytotoxicity assay of the synthetic compounds against HepG2 and Caco2 cancer cells showed a potency of the order: PTX2â«PTX2b>PTX2c.