Sodium dithionite is not stable under physiological conditions, with the rate of decomposition increasing with increasing acidity. Upon contact with moisture, it is oxidized to hydrogen sulfite, sulfite and hydrogen sulfate, and under strongly acidic conditions it may liberate sulfur dioxide. Under anaerobic conditions (such as in the lower gastrointestinal tract), hydrogen sulfite and thiosulfate may be formed. Hydrogen sulfite can be absorbed after ingestion. It is efficiently metabolized, and the major part rapidly excreted as sulfate into the urine.
As sodium dithionite is chemically unstable in the presence of water and oxygen, in particular under acidic conditions, rapid conversion of sodium dithionite into various related sulfite species is expected to occur under physiological conditions. Therefore, it is justified to take account of toxicological data of sodium sulfite, sodium hydrogen sulfite, and disodium disulfite (= sodium metabisulfite) in the human health assessment of dithionite ... In this context, sodium sulfite and sodium hydrogen sulfite are considered to be the predominant chemicals that are systemically available to the body.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
毒性总结
人体健康：在生理条件下，亚硫酸钠不稳定，分解速率随酸度增加而增加。接触水分后，它会氧化成亚硫酸氢钠、亚硫酸钠和硫酸氢钠，在强酸性条件下可能会释放二氧化硫。在无氧条件下（如在下消化道），可能会形成亚硫酸氢钠和硫代硫酸钠。亚硫酸氢钠在摄入后可被吸收。它能有效代谢，大部分迅速作为硫酸盐随尿液排出体外。大鼠口服亚硫酸钠的急性LD50约为2500毫克/千克体重，在接近或超过LD50剂量的情况下，主要临床和病理体征包括肌肉无力、胃肠道刺激、腹泻和呼吸困难。没有急性皮肤和急性吸入的研究数据。亚硫酸钠对兔子的皮肤有轻微刺激性，对眼睛有强烈刺激性。在酸性条件下，亚硫酸钠可能会释放二氧化硫，已知二氧化硫会在人类中引起呼吸道刺激。关于致敏性的动物数据不可用。在人类中，由于接触亚硫酸盐导致的过敏性皮炎是罕见的，因此亚硫酸钠被认为不具有显著的皮肤致敏潜力。尽管没有关于亚硫酸钠的具体报告，但敏感个体在口服或吸入暴露后应假定有过敏样反应（"亚硫酸盐哮喘"）的可能。亚硫酸钠未进行重复剂量的毒性测试。由于在体内条件下迅速降解，因此使用了其分解产物的毒性数据来评估这一终点。包括亚硫酸盐、亚硫酸氢钠、硫酸盐和硫代硫酸盐在内的转化产物被认为具有非常低的系统性毒性。需要注意的是，一般来说，亚硫酸盐会减少食物中的硫胺素含量。对于二硫酸钠，大鼠系统毒性和局部胃肠道毒性的口服NOAEL（30周和104周）分别为942毫克/千克体重/天和217毫克/千克体重/天。这些结果似乎也足够代表亚硫酸钠的评估。使用皮肤或呼吸道途径进行的动物重复剂量研究不可用。在标准细菌测试中，亚硫酸钠在有无代谢激活的情况下均不具有诱变性（OECD TG 471, 472）。关于亚硫酸钠在体外诱导染色体畸变的潜在性的实验数据不可用。在给小鼠腹腔注射高剂量（2 x 500或2 x 750毫克/千克体重）的亚硫酸氢钠和亚硫酸钠混合物（亚硫酸钠在生理条件下的分解产物）后，发现骨髋细胞中的微核频率增加。关于亚硫酸钠的致癌潜力的实验数据不可用。1992年，IARC得出结论，亚硫酸钠的分解产物，即二氧化硫、亚硫酸盐、亚硫酸氢钠和焦亚硫酸盐“在人类的致癌性上不可分类（第3组）”。亚硫酸钠尚未对其对生殖和发育的影响进行测试。基于其理化行为和在体内的迅速转化，预计完整分子不会到达生殖器官，或对生殖和发育产生直接影响。关于亚硫酸钠分解产物的数据也未表明有任何不利影响。然而，在高膳食剂量下，可导致母体营养不良和破坏硫胺素，观察到胎儿生长迟缓。在一项大鼠膳食研究中，使用亚硫酸钠（类似于OECD TG 414），发育毒性的NOAEL为5%（约1450毫克/千克体重/天；最高测试剂量）。在这一剂量下，观察到明显的母体毒性（LOAEL，母体毒性：5%的饲料=约1450毫克/千克体重/天）。母体毒性的NOAEL为饲料中的2.5%（约850毫克/千克体重/天）。环境：对鱼类（Leuciscus idus）的急性毒性测试中，96小时LC50为62.3毫克/升。对于藻类（Scenedesmus subspicatus），72小时ErC50为206毫克/升，72小时NOErC为62.5毫克/升（相应的生物量值为135和62.5毫克/升；名义浓度）。对于水蚤（Daphnia magna），急性毒性值48小时EC50为98.3毫克/升，慢性值21天NOEC大于10毫克/升。由于在鱼类和急性水蚤测试的高测试浓度下，测试开始时的氧气浓度小于1毫克/升，因此不能排除这些研究中发现的效果值至少部分是由缺氧引起的。使用评估因子100，从慢性值（水蚤的NOEC大于10毫克/升）计算出对水生生物的PNEC为0.1毫克/升。
Human Health: Sodium dithionite is not stable under physiological conditions, with the rate of decomposition increasing with increasing acidity. Upon contact with moisture, it is oxidized to hydrogen sulfite, sulfite and hydrogen sulfate, and under strongly acidic conditions it may liberate sulfur dioxide. Under anaerobic conditions (such as in the lower gastrointestinal tract), hydrogen sulfite and thiosulfate may be formed. Hydrogen sulfite can be absorbed after ingestion. It is efficiently metabolized, and the major part rapidly excreted as sulfate into the urine. The acute oral LD50 of sodium dithionite in rats was about 2500 mg/kg bw, with atony, gastro-intestinal irritation, diarrhea and dyspnea as the main clinical and pathological signs at doses near to or exceeding the LD50. There were no acute dermal and no valid acute inhalation studies available. Sodium dithionite was slightly irritating to the skin, and strongly irritating to the eyes of rabbits. Under acidic conditions, sodium dithionite may liberate sulfur dioxide, which is known to induce respiratory irritation in humans. There was no animal data available regarding sensitization. In humans, allergic dermatitis from exposure to sulfites is rare and, consequently, sodium dithionite is not considered to possess a significant skin sensitization potential. Although there were no specific reports with regard to sodium dithionite available, the potential for allergoid reactions ("sulfite-asthma") should be assumed in sensitive individuals following oral or inhalation exposure. Sodium dithionite was not tested for its toxicity after repeated dosing. Due to its rapid degradation under in vivo conditions, the toxicity data on its decomposition products were used for the evaluation of this endpoint. The conversion products, including sulfite, hydrogen sulfite, sulfate and thiosulfate, are considered as substances of very low order systemic toxicity. It should be noted that sulfites, in general, reduce the thiamine content in food. For disodium disulfite, oral NOAELs (30 and 104 weeks) of 942 mg/kg bw/day and 217 mg/kg bw/day were obtained for systemic toxicity and local gastrointestinal toxicity in rats, respectively. These results appear to be sufficiently representative also for the assessment of sodium dithionite. Repeated dose studies in animals using the dermal or respiratory routes were not available. Sodium dithionite was not mutagenic in standard bacterial tests with and without metabolic activation (OECD TG 471, 472). No experimental data was available on the potential of sodium dithionite to induce chromosomal aberrations in vitro. An increase in the frequency of micronuclei in bone marrow cells of mice was found after intraperitoneal injection of high doses (2 x 500 or 2 x 750 mg/kg bw) of a mixture of sodium hydrogen sulfite and sodium sulfite, the degradation products of sodium dithionite under physiological conditions. No experimental data were available on the carcinogenic potential of sodium dithionite. In 1992, IARC concluded that degradation products of dithionite, i.e. sulfur dioxide, sulfites, hydrogen sulfites and metabisulfites "are not classifiable as to their carcinogenicity to humans (Group 3)". Sodium dithionite has not been tested for its effects on reproduction and development. Based on its physicochemical behavior and its rapid conversion in the body, it is not expected that the intact molecule reaches the reproductive organs, or has any direct effect on reproduction and development. Data relating to the degradation products of sodium dithionite do also not indicate any adverse effects. At high dietary doses, which can cause maternal malnutrition and destruction of thiamine, fetal growth retardation was however observed. In a rat dietary study with sodium sulfite (similar to OECD TG 414), the NOAEL for developmental toxicity was at 5 % (about 1450 mg/kg bw/day; highest tested dose). At this dose clear signs of maternal toxicity were observed (LOAEL, maternal toxicity: 5 % in diet = about 1450 mg/kg bw/day). The NOAEL for maternal toxicity was at 2.5 % in feed (about 850 mg/kg bw/day). Environment: From acute toxicity test to fish (Leuciscus idus), 96-hr LC50 was 62.3 mg/L. For algae (Scenedesmus subspicatus), 72-hr ErC50 was 206 mg/L and 72-hr NOErC was 62.5 mg/L (corresponding values for biomass are 135 and 62.5 mg/L respectively; nominal concentration). For Daphnia magna, the acute toxicity value of 48-hr EC50 was 98.3 mg/L, and the chronic value of 21-day NOEC was > 10 mg/L. Due to oxygen concentrations < 1 mg/L at test start in high test concentrations in the fish and acute daphnia test, it cannot be excluded that the effect values found in these studies are at least partly caused by oxygen deficiency. A PNEC of 0.1 mg/L for the aquatic organisms was calculated from the chronic value (NOEC for daphnia > 10 mg/L) using an assessment factor of 100.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
暴露途径
这种物质可以通过摄入被身体吸收。
The substance can be absorbed into the body by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
毒理性
吸入症状
咳嗽。喉咙痛。
Cough. Sore throat.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
毒理性
眼睛症状
红斑。疼痛。
Redness. Pain.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
毒理性
摄入症状
恶心。腹痛。呕吐。腹泻。
Nausea. Abdominal pain. Vomiting. Diarrhoea.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
Method of wound healing using A2B adenosine receptor antagonists
申请人：Zeng Dewan
公开号：US20060058322A1
公开（公告）日：2006-03-16
The present invention relates to methods of wound healing using A
2B
adenosine receptor antagonists. The invention also relates to methods for the preparation of such compounds, and to pharmaceutical compositions containing them.
The present invention relates to compounds of phosphonic acid-containing T3 mimetics and monoesters thereof, stereoisomers, pharmaceutically acceptable salts, co-crystals, and prodrugs thereof and pharmaceutically acceptable salts and co-crystals of the prodrugs, as well as their preparation and uses for preventing and/or treating metabolic diseases such as obesity, NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, metabolic syndrome x and diabetes.
Process for the preparation of aniline-derived thyroid receptor ligands
申请人：——
公开号：US20030157671A1
公开（公告）日：2003-08-21
Provided are processes for the synthesis of aniline derivatives, specifically certain aniline derivatives which have activity as thyroid receptor ligands.
The present invention provides processes useful for preparing 5-lipoxygenase activating protein (FLAP) inhibitors and their intermediates. In particular, processes for preparing 3-[3-(tert-butylsulfanyl)-1-[4-(6-ethoxy-pyridin-3-yl)benzyl]-5-(5-methyl-pyridin-2-yl-methoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid, the anhydrous Form C polymorph of sodium 3-[3-(tert-butylsulfanyl)-1-[4-(6-ethoxy-pyridin-3-yl)benzyl]-5-(5-methyl-pyridin-2-yl-methoxy)-1H-indol-2-yl]-2,2-dimethyl-propionate, and intermediates useful in said processes are provided.
