... In the intravenous injection tests, approx 12% was absorbed in the rat and approx 33% in the rabbit ... The principal metabolite in both species was CO2 with other metabolites not identified. /It was/ proposed that the metabolism probably involved initial oxidation to corresponding carboxylic acids by aldehyde dehydrogenase, and then further oxidation to CO2.
... The probable major metabolic pathway /is considered to be/ initial oxidation to the corresponding mono- or dicarboxylic acid by aldehyde dehydrogenase and then further oxidation of the acidic intermediate to carbon dioxide.
IDENTIFICATION AND USE: Glutaraldehyde is a colorless liquid. It is registered for pesticide use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. It is used as algaecide, bacteriocide and fungicide. Glutaraldehyde is used as a tissue fixative in histology and electron and light microscopy, generally as a 1.5-6% aqueous solution. Glutaraldehyde is used, generally in conjunction with wetting agents, to control viruses and other micro-organisms in fish farming. Glutaraldehyde is allowed as a preservative in cosmetics in Europe at concentrations up to 0.1%. It is not allowed in aerosols and sprays. Glutaraldehyde is a biocide commonly used in a 2% concentration for cold sterilization of surgical and dental equipment. Biocides, such as glutaraldehyde, are added to eliminate bacterial growth in fracturing fluids. HUMAN EXPOSURE AND TOXICITY: Exposure to concentrations < 1 ppm by inhalation or skin contact may cause irritation of the skin and/or mucous membranes. The critical effects of glutaraldehyde exposure are eye, skin, and respiratory irritation, skin sensitization and occupational asthma. Nose and throat irritation has been observed in humans at vapor concentrations below 0.2 ppm. Occupational asthma has also been reported in workers exposed to dilute solutions of glutaraldehyde. Contact dermatitis and eye irritation have been reported in workers using glutaraldehyde solutions, usually 2% or higher. Skin sensitization has been confirmed in workers using dilute solutions. Other symptoms that may be brought on by glutaraldehyde exposure include heart palpitations and tachycardia. The incidence of death and incidence of cancer deaths in 186 male employees at a glutaraldehyde production unit were compared to those of US white males and to 29,000 other chemical workers during the period 1959 - 1978. All subjects were observed for 10 yr. The number of deaths was less than expected, as was the incidence of cancer deaths. ANIMAL STUDIES: Glutaraldehyde was corrosive to the skin and eyes of rabbits at high concentrations, with signs of skin irritation evident at 2%, and eye irritation at 0.2%. In an inhalation study where mice were exposed to glutaraldehyde at concentrations of 33 or 133 ppb for 24 hours, the animals exhibited panting and increased grooming, mice that inhaled the highest concentration developed toxic hepatitis. Following a single whole-body inhalation exposure at 1 ppm for 1 day, rats and mice developed coagulation pathology of the upper respiratory tract squamous epithelium. After 4 days of such exposures, inflammatory granulocytic infiltrate into the squamous epithelium and lamina propria with thickened epithelium of the nasal lumen ensued. In those animals inhaling 0.5 or 1 ppm glutaraldehyde for four days, the nasal passages became obstructed with intraluminal debris; degenerative/hyperplastic erosions with epithelial abscesses extended as far as the nasopharyngeal meatus in the 1-ppm exposure group. A study of male and female rats given glutaraldehyde in drinking water at concentrations of 0, 50, 250, or 100 ppm through two generations indicated a dose-related decrease in parental water consumption and body weight (attributed to adverse taste) and decrease in offspring (1000-ppm group) body weights. No adverse reproductive effects were observed. In other study there was a significant dose-dependent reduction in the average of maternal body weight gain and a significant increase in the number of stunted (body weight) and malformed fetuses at the 5 mL/mg/day dose level. Early mutagenicity studies were negative, but more recent studies have indicated that glutaraldehyde is mutagenic in vitro in bacterial assays and tests in mammalian cells. In vivo genotoxicity tests to date have proven negative. Groups of 50 male and 50 female rats and mice were exposed to glutaraldehyde vapor at concentrations of 0, 0.25, 0.50, or 0.75 (rats) and 0, 0.062, 0.12, or 0.25 ppm (mice) 6 hr/day, 5 days /week. The incidences of non-neoplastic lesions of the nose were reported to be significantly increased in the 0.50 and 0.75-ppm exposed rats and in the 0.12 and 0.25-ppm exposed male and female mice. ECOTOXICITY STUDIES: Available chronic toxicity data for glutaraldehyde indicate that continuous exposure results in measurable effects on coldwater fish at a concentration of 5.1 mg a.i./L. A second study on coldwater fish resulted in measurable effects at 2.5 mg a.i./L. Measurable effects on freshwater invertebrates were noted at concentrations of 8.5 mg/L product and 4.9 mg a.i./L.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A4;不能分类为人类致癌物。/戊二醛/
A4; Not classifiable as a human carcinogen. /Glutaraldehyde/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
对人类无致癌性(未列入国际癌症研究机构IARC清单)。
No indication of carcinogenicity to humans (not listed by IARC).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
暴露途径
该物质可以通过吸入其蒸汽、透过皮肤和通过摄入被身体吸收。
The substance can be absorbed into the body by inhalation of its vapour, through the skin and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
Dermal and intravenous studies in the rat with dilute aqueous glutaraldehyde solutions (0.075-7.5%) showed that, in dermal tests, approx 5% was absorbed in the rat, and 30-50% in the rabbit. In the intravenous injection tests, approx 12% was absorbed in the rat and approx 33% in the rabbit. There were no significant differences between males and females in the study. The dermal absorption rate constant was low (0.2-2 hr) in each species. The elimination times were long for both intravenous injection (t0.5 for the rat 10 hr, rabbit 15-30 hr) and dermal application (t0.5 for the rat 40-110 hr, rabbit 20-100 hr), possibly due to the binding of glutaraldehyde to protein and the slow excretion of metabolites. The principal metabolite in both species was CO2 with other metabolites not identified. /It was/ proposed that the metabolism probably involved initial oxidation to corresponding carboxylic acids by aldehyde dehydrogenase, and then further oxidation to CO2.
In vitro studies using human skin tissue showed that glutaraldehyde did not penetrate the thick skin of the sole, but 3-14% penetrated the stratum corneum of the chest and abdomen and 3-4% penetrated the epidermis.
Material balance and pharmacokinetic studies were conducted with rats & rabbits including iv or topical dosing with [14C]glutaraldehyde. Intravenous dosing resulted in radiochemical recovery from 86% to 101%. Principal route of recovery was as CO2 at 22% to 80% of the administered dose (7%-28% urinary, 0.2%-5% feces). Epicutaneous dosing resutled in radiochemical recovery primarily in the skin at the site of application (31%-61%) with no consistent accumulation in any other tissue. Rabbits absorbed 33% to 53% of the epicutaneously administered dose & rats absorbed 4.1% to 8.7%. Pharmacokinetic studies indicated percutaneous radiochemical absorption of 0.3% to 2.1% for rats & 2.5% to 15.6% for rabbits under conservative study conditions that are likely to overestimate potential human exposure conditions.
1.周国泰,化学危险品安全技术全书,化学工业出版社,1997 2.国家环保局有毒化学品管理办公室、北京化工研究院合编,化学品毒性法规环境数据手册,中国环境科学出版社.1992 3.Canadian Centre for Occupational Health and Safety,CHEMINFO Database.1998 4.Canadian Centre for Occupational Health and Safety, RTECS Database, 1989
Pd(II)-catalyzed deprotection of acetals and ketals containing acid sensitive functional groups
摘要:
The pincer complex [Pd(C-1,O-1,N-1-L)(NCMe)]ClO4 (L = monoanionic ligand resulting from deprotonation of the acetyl group of the dimethyl monoketal of 2,6-diacetylpyridine) is used for the high-yield and selective catalytic hydrolysis of aliphatic, aromatic, cyclic, and acyclic dimethyl-acetals, -ketals, and dioxolanes, even in the presence of large substituents. Other protecting groups, such as THP or TBDMS, or very acid-sensitive alcohols were not affected. The catalyst is easily prepared in high yield from Pd(AcO)(2) and 2,6-diacetylpyridinium perchlorate stable to air and moisture, easily and fully recoverable and reusable. (C) 2013 Elsevier Ltd. All rights reserved.
trifluoromethylation of N,N‐disubstituted hydrazones using the Togni reagent is demonstrated to proceed efficiently for aliphatic aldehyde‐derived substrates. The success of the reactions relied on the choice of the N,N‐diphenylamino group as the terminal hydrazone amino group where N,N‐dialkylamino groups were preferred for (hetero)aromatic aldehyde‐derived substrates. In addition, the trifluoromethylated N‐arylhydrazones
[EN] PYRIMIDINE JAK INHIBITORS FOR THE TREATMENT OF SKIN DISEASES<br/>[FR] INHIBITEURS DE JAK À BASE DE PYRIMIDINE POUR LE TRAITEMENT DE MALADIES DE LA PEAU
申请人:THERAVANCE BIOPHARMA R&D IP LLC
公开号:WO2020219640A1
公开(公告)日:2020-10-29
The invention provides compounds of formula (I): or pharmaceutically-acceptable salts thereof, that are inhibitors of Janus kinases. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat inflammatory and autoimmune skin diseases.
Phthalimide-Oxy Derivatives for 3′- or 5′-Conjugation of Oligonucleotides by Oxime Ligation and Circularization of DNA by “Bis- or Tris-Click” Oxime Ligation
phosphoramidites exhibiting a phthalimide-oxy group were synthesized. First, after treatment with hydrazine, the resulting 5- and 3-oxyamine oligonucleotides were conjugated with aldehyde derivatives by oximeligation. Second, oligonucleotides exhibiting an oxyamine at each end were circularized by means of different dialdehydes. Cyclic oligonucleotides of different lengths (9 to 31-mer) were rapidly obtained
A highly active organocatalyst for alcoholoxidation has been developed. 9-Azanoradamantane N-oxyl (Nor-AZADO 4), constituting an unhindered, stable nitroxyl radical, exhibits superior catalytic activity to 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and AZADOs in the oxidation of alcohols to their corresponding carbonyl compounds.