ACGIH: TWA 0.0002 mg/m3; STEL 0.0005 mg/m3 (Skin)OSHA: Ceiling 0.1 mg/m3NIOSH: IDLH 15 mg/m3; TWA 0.0002 mg/m3
物理描述：
Potassium chromate is a yellow crystalline solid. It is soluble in water. The primary hazard is the threat to the environment. Immediate steps should be taken to limit its spread to the environment. It is used in chemical analysis, in making pigments for paints and inks, as a fungicide, and to make other chromium compounds.
Chromium is absorbed from oral, inhalation, or dermal exposure and distributes to nearly all tissues, with the highest concentrations found in kidney and liver. Bone is also a major storage site and may contribute to long-term retention. Hexavalent chromium's similarity to sulfate and chromate allow it to be transported into cells via sulfate transport mechanisms. Inside the cell, hexavalent chromium is reduced first to pentavalent chromium, then to trivalent chromium by many substances including ascorbate, glutathione, and nicotinamide adenine dinucleotide. Chromium is almost entirely excreted with the urine. (A12, L16)
IDENTIFICATION AND USE: Potassium chromate forms lemon-yellow crystals. It has a limited application in enamels, finishing leather, and rustproofing of metals. Oxidizing agent in analytical chemistry. HUMAN EXPOSURE AND TOXICITY: If ingested, violent gastroenteritis, severe circulatory collapse and toxic nephritis may ensue, or peripheral vascular shock. Eye contact can cause severe damage with possible loss of vision. Evaluation of genotoxic effects of potassium chromate (K2CrO4) and was carried out in human blood lymphocytes in vitro as measured by the electron microscopy in situ end-labeling (EM-ISEL). EM-ISEL was used to assess DNA single-strand breaks (SSBs) expressed as number of immunogold particles per sq um of chromatin at both chromosomal and nuclear DNA levels. Quantification of SSBs by EM-ISEL showed that potassium chromate is genotoxic agent at non-cytotoxic concentrations. Potassium chromate quadrupled frequency of sister-chromatid exchanges in cultured human fibroblasts. Potassium chromate induced DNA damage and unscheduled DNA synthesis in cultured human fibroblasts. ANIMAL STUDIES: The embryotoxic and teratogenic potential of potassium chromate was evaluated by the teratological analysis of mouse fetuses. The test chemical was administered intraperitoneally to mice of both sexes for 30 days. Teratological scanning of the fetuses born to treated animals revealed a reduction in the number of live implants and litter size. Higher incidence of resorption and dead litter indicated the embryotoxic effect of the test chemical. Malformations, both skeletal and morphological, suggest the possibility of potassium chromate being fetotoxic. Potassium chromate induced significant and dose-related increase in micronucleated polychromatic erythrocytes (micronuclei) in bone marrow of mice following 2 ip injections of doses ranging from 12-48 mg/kg body wt. Potassium chromate was tested for its potential to induce forward mutations at the thymidine kinase locus in L5178Y mouse lymphoma cells. Strong positive responses at survivals greater than 10% were observed. ECOTOXICITY STUDIES: 90 Days after hatching, young carp were reared for 75 wk in test waters of pH 7 & 5 containing 0.1 ppm potassium chromate. This pollutant caused deformation in the bone by chronic leaching of calcium, and the low pH hastened the leaching.
Hexavalent chromium's carcinogenic effects are caused by its metabolites, pentavalent and trivalent chromium. The DNA damage may be caused by hydroxyl radicals produced during reoxidation of pentavalent chromium by hydrogen peroxide molecules present in the cell. Trivalent chromium may also form complexes with peptides, proteins, and DNA, resulting in DNA-protein crosslinks, DNA strand breaks, DNA-DNA interstrand crosslinks, chromium-DNA adducts, chromosomal aberrations and alterations in cellular signaling pathways. It has been shown to induce carcinogenesis by overstimulating cellular regulatory pathways and increasing peroxide levels by activating certain mitogen-activated protein kinases. It can also cause transcriptional repression by cross-linking histone deacetylase 1-DNA methyltransferase 1 complexes to CYP1A1 promoter chromatin, inhibiting histone modification. Chromium may increase its own toxicity by modifying metal regulatory transcription factor 1, causing the inhibition of zinc-induced metallothionein transcription. (A12, L16, A34, A35, A36)
WEIGHT OF EVIDENCE CHARACTERIZATION: Under the current guidelines (1986), Cr(VI) is classified as Group A - known human carcinogen by the inhalation route of exposure. Carcinogenicity by the oral route of exposure cannot be determined and is classified as Group D. Under the proposed guidelines (1996), Cr(VI) would be characterized as a known human carcinogen by the inhalation route of exposure on the following basis. Hexavalent chromium is known to be carcinogenic in humans by the inhalation route of exposure. Results of occupational epidemiological studies of chromium-exposed workers are consistent across investigators and study populations. Dose-response relationships have been established for chromium exposure and lung cancer. Chromium-exposed workers are exposed to both Cr(III) and Cr(VI) compounds. Because only Cr(VI) has been found to be carcinogenic in animal studies, however, it was concluded that only Cr(VI) should be classified as a human carcinogen. Animal data are consistent with the human carcinogenicity data on hexavalent chromium. Hexavalent chromium compounds are carcinogenic in animal bioassays, producing the following tumor types: intramuscular injection site tumors in rats and mice, intrapleural implant site tumors for various Cr(VI) compounds in rats, intrabronchial implantation site tumors for various Cr(VI) compounds in rats and subcutaneous injection site sarcomas in rats. In vitro data are suggestive of a potential mode of action for hexavalent chromium carcinogenesis. Hexavalent chromium carcinogenesis may result from the formation of mutagenic oxidatitive DNA lesions following intracellular reduction to the trivalent form. Cr(VI) readily passes through cell membranes and is rapidly reduced intracellularly to generate reactive Cr(V) and Cr(IV) intermediates and reactive oxygen species. A number of potentially mutagenic DNA lesions are formed during the reduction of Cr(VI). Hexavalent chromium is mutagenic in bacterial assays, yeasts and V79 cells, and Cr(VI) compounds decrease the fidelity of DNA synthesis in vitro and produce unscheduled DNA synthesis as a consequence of DNA damage. Chromate has been shown to transform both primary cells and cell lines. HUMAN CARCINOGENICITY DATA: Occupational exposure to chromium compounds has been studied in the chromate production, chromeplating and chrome pigment, ferrochromium production, gold mining, leather tanning and chrome alloy production industries. Workers in the chromate industry are exposed to both trivalent and hexavalent compounds of chromium. Epidemiological studies of chromate production plants in Japan, Great Britain, West Germany, and the United States have revealed a correlation between occupational exposure to chromium and lung cancer, but the specific form of chromium responsible for the induction of cancer was not identified ... Studies of chrome pigment workers have consistently demonstrated an association between occupational chromium exposure (primarily Cr(VI)) and lung cancer. Several studies of the chromeplating industry have demonstrated a positive relationship between cancer and exposure to chromium compounds. ANIMAL CARCINOGENICITY DATA: Animal data are consistent with the findings of human epidemiological studies of hexavalent chromium ... /Chromium (VI)/
Evaluation: There is sufficient evidence in humans for the carcinogenicity of chromium(VI) compounds. Chromium(VI) compounds cause cancer of the lung. Also positive associations have been observed between exposure to Chromium(IV) compounds and cancer of the nose and nasal sinuses. There is sufficient evidence in experimental animals for the carcinogenicity of chromium(VI) compounds. Chromium(VI) compounds are carcinogenic to humans (Group 1). /Chromium(VI) compounds/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
铬 hexavalent 化合物：已知是人类致癌物。/铬 hexavalent 化合物/
Chromium Hexavalent Compounds: known to be human carcinogens. /Chromium hexavalent compound/
Chromium compounds are known to be associated with cytotoxicity and carcinogenicity when applied via a skin route. The aim of this study was to evaluate the skin permeability and toxicological profiles of four chromium species. Chromium permeation across the skin, as determined by an in vitro Franz cell, decreased in the order of sodium chromate>potassium chromate>potassium dichromate>chromium nitrate. The uptake of chromium species within the skin generally showed a contrary trend to the results of permeation, although differences among the various compounds were not large. Levels of in vivo skin deposition of the four compounds showed no statistically significant differences. Potassium chromate produced the greatest disruption of the skin structure as determined by HE staining, followed in order by sodium chromate, potassium dichromate, and chromium nitrate. This indicates that hexavalent chromium elicited greater toxicity to the skin compared to trivalent chromium. A similar result was observed for the viability of skin fibroblasts. To improve our understanding of the molecular mechanisms leading to functional changes in proteins, proteomic tools, including 2-DE and MS techniques combined with sequence database correlations, were applied to identify target proteins altered by pathologic states. Eight protein spots, corresponding to cutaneous enzymes involved in energy metabolism and chaperon proteins, which were identified and discussed in this study, were associated with skin cytotoxicity, immunity, and carcinogenesis. In addition, functional proteomics of skin tissues may provide a promising tool for developing therapeutic strategies and can serve as the basis for further research.
After exposure of growing chicks to different concentrations of dietary chromium (Cr) as potassium chromate (K2CrO4) for a period of 3 wk, the Cr uptake by different internal organs was determined. More Cr was accumulated in the kidney, liver, pancreas and spleen than in the blood, muscle, heart and lung. A very small amount was found in the brains of the birds given different concentrations of Cr.
Asymmetric ring-closing metathesis reactions involving achiral and meso substrates
申请人：Massachusetts Institute of Technology
公开号：US06346652B1
公开（公告）日：2002-02-12
A composition and method for the catalytic conversion of a racemic mixture of dienes to a cyclic olefin by a ring-closing metathesis (RCM) reaction are disclosed. The composition, a transition metal complex with an M═C reaction site, contains a bidentate dialkoxide of at least 80% optical purity. Because the M═C reaction site is of a sufficient shape specificity, conferred in part by the dialkoxide of sufficient rigidity and a M═N—R1 site, reacting the composition with a mixture of two enantiomeric dienes results in an olefin metathesis product that has at least a 50% enantiomeric excess of one enantiomer in the mixture. A method is also provided for reacting a composition with a racemic diene mixture to generate a metathesis product that has an enantiomeric excess of at least 50%. Methods are also provided for catalytic enantioselective desymmetrization. One method involves an olefin metathesis reaction with a molecular substrate having a plane of symmetry to form a product free of a plane of symmetry. Another method provides a desymmetrization reaction to occur in the absence of solvent. A method for producing quaternary carbon centers through a desymmetrization reaction is also described.
DEUTERATED BENZYLBENZENE DERIVATIVES AND METHODS OF USE
申请人：Seed Brian
公开号：US20100063141A1
公开（公告）日：2010-03-11
Provided are compounds having an inhibitory effect on sodium-dependent glucose cotransporter SGLT. The invention also provides pharmaceutical compositions, methods of preparing the compounds, synthetic intermediates, and methods of using the compounds, independently or in combination with other therapeutic agents, for treating diseases and conditions that are affected by SGLT inhibition.
Deuterated benzylbenzene derivatives and methods of use
申请人：Seed Brian
公开号：US09061060B2
公开（公告）日：2015-06-23
Provided are compounds having an inhibitory effect on sodium-dependent glucose cotransporter SGLT. The invention also provides pharmaceutical compositions, methods of preparing the compounds, synthetic intermediates, and methods of using the compounds, independently or in combination with other therapeutic agents, for treating diseases and conditions that are affected by SGLT inhibition.
