Incubation of the (14)C-toluene-2,5-diamine sulfate with the human hepatocytes yielded an acetylated metabolite but no sulfated, glucuronidated, or monohydroxylated metabolites.
Three major metabolites were observed in the urine /of female Wistar Kyoto rats/ after oral dosing /of (14)C-toluene-2,5-diamine sulfate/, with the main metabolite identified as N,N-diacetyl-toluene-2,5-diamine. No parent compound was identified in the urine. Radioactivity in the urine of the dermal dose group was too low for separation and detection of metabolites.
Classification of carcinogenicity: 1) evidence in humans: No data; 2) evidence in animals: insufficient. Overall summary evaluation of carcinogenic risk to humans is Group 3: The agent is not classifiable as to its carcinogenicity to humans. /2,5-Diaminotoluene/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
暴露途径
这种物质可以通过皮肤接触和摄入被身体吸收。
The substance can be absorbed into the body through the skin and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
毒理性
皮肤症状
Redness.
Redness.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
毒理性
眼睛症状
红色。
Redness.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.
Methemoglobinemia - The presence of increased methemoglobin in the blood; the compound is classified as secondary toxic effect
Skin Sensitizer - An agent that can induce an allergic reaction in the skin.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
2,5-Diaminotoluene sulfate is absorbed through the skin of dogs and excreted in the urine. About 40 mg of the compound were absorbed from 50 mL of a lauryl sulfate-based gel containing 1.4 g 2,5-diaminotoluene within 3 hr. When 6% hydrogen peroxide was added to the gel immediately before use, the amount of 2,5-diaminotoluene sulfate absorbed was less than 3 mg
Ten milligrams of 2,5-diaminotoluene sulfate (equivalent to 5.54 mg 2,5- diamino-toluene) injected subcutaneously into six adult volunteers were excreted in the urine as the N,N'-diacetyl derivative, which accounted for approximately half of the injected dose, over 48 hr. During the process of hair dyeing with a dye formulation in which a total of 2.5 g 2,5-diaminotoluene sulfate were applied in conjunction with 6% hydrogen peroxide added just before application, it was estimated that 4.6 mg 2,5-diaminotoluene sulfate had been absorbed through the skin of five volunteers.
The absorption and elimination of toluene-2,5-diamine were studied in 5 male human subjects. A test formulation was prepared with [Me-(14)C]-toluene-2,5-diamine plus unlabeled toluene-2,5-diamine sulfate in a hair dye cream formulation containing 0.825% resorcinol. The final concentration of toluene-2,5-diamine sulfate was 1.65%. This formulation was then mixed with either 100 g of water (1:1) or 100 g of 6% hydrogen peroxide to produce formulation 1 and formulation 2, respectively. The subjects received 1 of the 2 formulations (45 g, containing a total of 371 mg of toluene-2,5-diamine) on a 250-sq cm area of the scalp. The formulation was thoroughly rinsed off after 30 minutes and the hair was shampooed. The mean total elimination rate of radioactivity of the applied dose in the urine and the feces was 4.81% +/-0.62% for formulation 1 and 1.31% +/- 0.14% in formulation 2. The amounts of toluene-2,5-diamine sulfate were 71 +/- 9.26 mgeq/ sq cm for formulation 1 and 20 +/- 2.02 mgeq/sq cm for formulation 2. The area under the curve (AUC) for whole blood recovery was 41.6 +/- 1.7 ngeq.hr/L and 9.2 +/- 3.1 ngeq.hr/L for formulations 1 and 2, respectively. The total recovery for formulation 1 was 91.2% +/- 1.73%, whereas the total recovery for formulation 2 was 47.64% +/- 3.43%. The authors concluded that the lower recovery for formulation 2 was due to higher retention of radiolabel in the hair as a result of the oxidative hair coloring process.
Percutaneous absorption of toluene-2,5-diamine sulfate in human skin samples was studied... Radiolabeled (97.2% pure) and non-radiolabeled (99.7% pure) toluene-2,5-diamine sulfate was added to a final concentration of 9% to 2 hair dye bases, one of which contained an equimolar amount of m-aminophenol as a coupler. The formulation containing the coupler was mixed with hydrogen peroxide (50:50) to yield a test substance with a final toluene-2,5-diamine sulfate concentration of 4.5%. The formulation base without the coupler was mixed with water or hydrogen peroxide, in both cases 50:50, to yield 2 other test substances with final concentrations of toluene-2,5-diamine sulfate of 4.5%. The formulations were then applied over an area of 2-sq cm to 350-mm-thick human skin (20 mg/sq cm) or samples of isolated epidermis mounted in perfusion cells. After an application period of 30 minutes, the test substance was rinsed off with water and a solution of sodium lauryl sulfate. Most of the test substance (93.5% of the applied dose) was recovered during rinsing at 30 minutes post application. Cumulative penetration (based on radioactivity in the receptor fluid) neared a plateau at approximately 5 hours. The total absorption in the formulation without coupler mixed with water was 4.17% +/- 2.54% (40.31 +/- 23.77 mgeq/sq cm). In the formulations mixed with peroxide, the total absorption was 3.41% +/- 1.32% (31.26 +/- 11.64 mgeq/sq cm) with the coupler and 3.44% +/- 2.84% (32.03 +/- 26.58 mgeq/sq cm) without the coupler.
The absorption, distribution, metabolism, and excretion of (14)C-toluene-2,5-diamine sulfate were investigated in rats in a series of studies... Groups of female Wistar Kyoto rats (4 per group in the mass balance portion of the study and 6 per group in the toxicokinetics portion of the study) received the test substance at either 2.5 or 25.0 mg/kg of body weight in a single oral gavage dose or at 33.3 mg/kg of body weight as a dermal application. Vehicle for the oral groups was water, whereas in the dermal group it was water/acetone (1:1). In the urine of the oral dose groups after 96 hours, the mean cumulative recovery of the applied dose was 62.2% in the 2.5-mg/kg dose group and 72.9% in the 25-mg/kg dose group, whereas in the feces, the recovery was 31.4% and 22.0%, respectively. The mean mass balance for both oral doses was about 98%. In the dermal application groups, 10.9% and 2.7% of the applied dose were recovered in the urine and feces, respectively. The mean mass balance for the dermal dose was nearly 100%. ...In plasma kinetics results, the time to peak concentration (Tmax) was 0.5 hours and 0.25 hours for the low- and high-dose oral groups, respectively, indicating rapid absorption. The AUC values for the 2 oral dose groups were 17.59 and 174 mgeq.hr/L, respectively, and for the dermal dose group 4.39 mgeq.hr/L.
[EN] NEW CATIONIC DYES, KITS AND COMPOSITIONS THEREOF, AND PROCESS FOR DYEING KERATIN FIBERS<br/>[FR] NOUVEAUX COLORANTS CATIONIQUES, KITS ET COMPOSITIONS LES CONTENANT, ET PROCÉDÉ DE TEINTURE DE FIBRES KÉRATINIQUES
申请人：ALFA PARF GROUP S P A
公开号：WO2014202150A1
公开（公告）日：2014-12-24
The present invention relates to new cationic dyes of general formula (I) and (II): The invention also relates to kits and compositions for dyeing keratin fibers, which contain at least one of these dyes as well as to a process for dyeing keratin fibers using at least one of these dyes.
BITTER TASTE MODIFIERS INCLUDING SUBSTITUTED 1-BENZYL-3-(1-(ISOXAZOL-4-YLMETHYL)-1H-PYRAZOL-4-YL)IMIDAZOLIDINE-2,4-DIONES AND COMPOSITIONS THEREOF
申请人：SENOMYX, INC.
公开号：US20160376263A1
公开（公告）日：2016-12-29
The present invention includes compounds and compositions known to modify the perception of bitter taste, and combinations of said compositions and compounds with additional compositions, compounds, and products. Exemplary compositions comprise one or more of the following: cooling agents; inactive drug ingredients; active pharmaceutical ingredients; food additives or foodstuffs; flavorants, or flavor enhancers; food or beverage products; bitter compounds; sweeteners; bitterants; sour flavorants; salty flavorants; umami flavorants; plant or animal products; compounds known to be used in pet care products; compounds known to be used in personal care products; compounds known to be used in home products; pharmaceutical preparations; topical preparations; cannabis-derived or cannabis-related products; compounds known to be used in oral care products; beverages; scents, perfumes, or odorants; compounds known to be used in consumer products; silicone compounds; abrasives; surfactants; warming agents; smoking articles; fats, oils, or emulsions; and/or probiotic bacteria or supplements.
Discovery of Pyridazinone and Pyrazolo[1,5-<i>a</i>]pyridine Inhibitors of C-Terminal Src Kinase
作者：Daniel P. O’Malley、Vijay Ahuja、Brian Fink、Carolyn Cao、Cindy Wang、Jesse Swanson、Susan Wee、Ashvinikumar V. Gavai、John Tokarski、David Critton、Anthony A. Paiva、Benjamin M. Johnson、Nicolas Szapiel、Dianlin Xie
DOI：10.1021/acsmedchemlett.9b00354
日期：2019.10.10
C-terminal Src kinase (CSK) functions as a negative regulator of T cell activation through inhibitory phosphorylation of LCK, so inhibitors of CSK are of interest as potential immuno-oncology agents. Screening of an internal kinase inhibitor collection identified pyridazinone lead 1, and a series of modifications led to optimized compound 13. Compound 13 showed potent activity in biochemical and cellular
[EN] CATIONIC DIRECT DYES<br/>[FR] COLORANTS DIRECTS CATIONIQUES
申请人：CIBA SC HOLDING AG
公开号：WO2005012437A1
公开（公告）日：2005-02-10
The present invention relates to novel the cationic dyes of formula (1) wherein R1 is an unsubstituted or substituted C1-C14 alkyl or an aryl radical; X<-> is an anion; R3 is an unsubstituted or substituted C1-C14 alkyl, aryl radical, C1-C6 alkoxy, cyanid, nitro or halide; n is 1 or 2; and if n is 1, then R2 is hydrogen, unsubstituted or substituted C1-C14 alkyl; or if n is 2, then R2 is an unsubstituted or substituted C1-C14 alkylen. Further, the present invention relates to compositions thereof, especially comprising other dyes, to processes for the preparation thereof and to the use thereof in the dyeing of organic material, such as keratin, wool, leather, silk, paper, cellulose or polyamides, and preferably human hair.
The present application relates to a preparation for dyeing keratin fibers which, before use, is mixed with an oxidizing agent and wherein a combination of
at least one 4,5-diaminopyrazole derivative of the general formula (II) or its physiologically compatible salts and
1
at least one phenylurea derivative of the general formula (I) or its physiologically compatible salts
2
is contained in a suitable cosmetic carrier, as well as a method for dyeing hair using this preparation.
