Peringatan Keamanan

Oral LD50 for Cr (VI) is 135 - 175 mg/kg in mouse and 46 - 113 mg/kg in rat L1982. Oral LD50 for Cr (III) in rat is >2000 mg/kg L1982. LD50 of chromium (III) oxide in rats is reported to be > 5g/kg L1983. Other LD50 values reported for rats include: 3.5 g/kg (CI 3.19-3.79 g/kg) for chromium sulphate; 11.3 g/kg for chromium (III) acetate; 3.3 g/kg for chromium nitrate; and 1.5 g/kg for chromium nitrate nonahydrate L1983.

Acute overdose of chromium is rare and seriously detrimental effects of hexavalent chromium are primarily the result of chronic low-level exposure L1982. In case of overdose with minimal toxicity following acute ingestion, treatment should be symptomatic and supportive L1982. There is no known antidote for chromium toxicity.

Hexavalent chromium is a Class A carcinogen by the inhalation route of exposure and Class D by the oral route L1982. The oral lethal dose in humans has been estimated to be 1-3 g of Cr (VI); oral toxicity most likely involves gastrointestinal bleeding rather than systemic toxicity L1982. Chronic exposure may cause damage to the following organs: kidneys, lungs, liver, upper respiratory tract MSDS. Soluble chromium VI compounds are human carcinogens. Hexavalent chromium compounds were mutagenic in bacteria assays and caused chromosome aberrations in mammalian cells. There have been associations of increased frequencies of chromosome aberrations in lymphocytes from chromate production workers L1981. In human cells in vitro, Cr (VI) caused chromosomal aberrations, sister chromatid exchanges and oxidative DNA damage L1982.

Chromium

DB11136

small molecule approved

Deskripsi

Chromium is a transition element with the chemical symbol Cr and atomic number 24 that belongs to Group 6 of the periodic table. It is used in various chemical, industrial and manufacturing applications such as wood preservation and metallurgy. The uses of chromium compounds depend on the valency of chromium, where trivalent Cr (III) compounds are used for dietary Cr supplementation and hexavalent Cr (VI) compounds are used as corrosion inhibitors in commercial settings and are known to be human carcinogens L1982. Humans can be exposed to chromium via ingestion, inhalation, and dermal or ocular exposure L1983. Trivalent chromium (Cr(III)) ion is considered to be an essential dietary trace element as it is involved in metabolism of blood glucose, regulation of insulin resistance and metabolism of lipids. Clinical trials and other studies suggest the evidence of chromium intake improving glucose tolerance in patients with Type I and II diabetes, however its clinical application in the standard management of type II diabetes mellitus is not established. Chromium deficiency has been associated with a diabetic-like state, impaired growth, decreased fertility and increased risk of cardiovascular diseases A32343, A32351, L1982.

According to the National Institute of Health, the daily dietary reference intake (DRI) of chromium for adult male and non-pregnant female are 35 ?g and 25 ?g, respectively L1986. Chromium picolinate capsules may be used as nutritional adjuvant in patients with or at risk of type 2 diabetes mellitus (T2DM) to improve blood sugar metabolism and stabilize the levels of serum cholesterol. Chromium chloride is available as an intravenous injection for use as a supplement to intravenous solutions given for total parenteral nutrition (TPN) FDA Label.

Struktur Molekul 2D

Berat 51.9961
Wujud solid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The elimination half-life of hexavalent chromium is 15 to 41 hours [L1982].
Volume Distribusi Absorbed chromium is distributed to all tissues of the body and its distribution in the body depends on the species, age, and chemical form [L1990]. Circulating Cr (III) following oral or parenteral administration of different compounds can be taken up by tissues and accumulates in the liver, kidney, spleen, soft tissue, and bone [L1986].
Klirens (Clearance) Excretion of chromium is via the kidneys ranges from 3 to 50 ?g/day [FDA Label]. The 24-hour urinary excretion rates for normal human subjects are reported to be 0.22 ?g/day [L1990].

Absorpsi

Chromium compounds are both absorbed by the lung and the gastrointestinal tract. Oral absorption of chromium compounds in humans can range between 0.5% and 10%, with the hexavalent (VI) chromium more easily absorbed than the trivalent (III) form L1982. Absorption of chromium from the intestinal tract is low, ranging from less than 0.4% to 2.5% of the amount consumed L1986. Vitamin C and the vitamin B niacin is reported to enhance chromium absorption L1986. Most hexavalent Cr (VI) undergoes partial intragastric reduction to Cr (III) upon absorption, which is an action mainly mediated by sulfhydryl groups of amino acids L1982. Cr (VI) readily penetrates cell membranes and chromium can be found in both erythrocytes and plasma after gastrointestinal absorption of Cr (IV). In comparison, the presence of chromium is limited to the plasma as Cr (III) displays poor cell membrane penetration L1982. Once transported through the cell membrane, Cr (VI) is rapidly reduced to Cr (III), which subsequently binds to macromolecules or conjugate with proteins. Cr (III) may be bound to transferrin or other plasma proteins, or as complexes, such as glucose tolerance factor (GTF).

Metabolisme

The metabolism of Cr (VI) involves reduction by small molecules and enzyme systems to generate Cr (III) and reactive intermediates. During this process, free radicals can be generated, which is thought to induce damage of cellular components and cause toxicity of chromium L1983. The metabolites bind to cellular constituents L1982.

Rute Eliminasi

Absorbed chromium is excreted mainly in the urine, accounting for 80% of total excretion of chromium; small amounts are lost in hair, perspiration and bile L1982. Chromium is excreted primarily in the urine by glomerular filtration or bound to a low molecular-weight organic transporter L1990.

Interaksi Makanan

2 Data
  • 1. Administer vitamin supplements. Niacin (from food or supplements) may increase the absorption of chromium.
  • 2. Take with foods containing vitamin C. Vitamin C may increase the absorption of chromium.

Interaksi Obat

713 Data
Cyclosporine Cyclosporine may decrease the excretion rate of Chromium which could result in a higher serum level.
Icosapent Icosapent may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefotiam Cefotiam may decrease the excretion rate of Chromium which could result in a higher serum level.
Mesalazine Mesalazine may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefmenoxime Cefmenoxime may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefmetazole Cefmetazole may decrease the excretion rate of Chromium which could result in a higher serum level.
Pamidronic acid Pamidronic acid may decrease the excretion rate of Chromium which could result in a higher serum level.
Tenofovir disoproxil Tenofovir disoproxil may decrease the excretion rate of Chromium which could result in a higher serum level.
Indomethacin Indomethacin may decrease the excretion rate of Chromium which could result in a higher serum level.
Cidofovir Cidofovir may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefpiramide Cefpiramide may decrease the excretion rate of Chromium which could result in a higher serum level.
Ceftazidime Ceftazidime may decrease the excretion rate of Chromium which could result in a higher serum level.
Loracarbef Loracarbef may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefalotin Cefalotin may decrease the excretion rate of Chromium which could result in a higher serum level.
Nabumetone Nabumetone may decrease the excretion rate of Chromium which could result in a higher serum level.
Ketorolac Ketorolac may decrease the excretion rate of Chromium which could result in a higher serum level.
Tenoxicam Tenoxicam may decrease the excretion rate of Chromium which could result in a higher serum level.
Celecoxib Celecoxib may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefotaxime Cefotaxime may decrease the excretion rate of Chromium which could result in a higher serum level.
Tolmetin Tolmetin may decrease the excretion rate of Chromium which could result in a higher serum level.
Foscarnet Foscarnet may decrease the excretion rate of Chromium which could result in a higher serum level.
Rofecoxib Rofecoxib may decrease the excretion rate of Chromium which could result in a higher serum level.
Piroxicam Piroxicam may decrease the excretion rate of Chromium which could result in a higher serum level.
Methotrexate Methotrexate may decrease the excretion rate of Chromium which could result in a higher serum level.
Cephalexin Cephalexin may decrease the excretion rate of Chromium which could result in a higher serum level.
Fenoprofen Fenoprofen may decrease the excretion rate of Chromium which could result in a higher serum level.
Valaciclovir Valaciclovir may decrease the excretion rate of Chromium which could result in a higher serum level.
Valdecoxib Valdecoxib may decrease the excretion rate of Chromium which could result in a higher serum level.
Diclofenac Diclofenac may decrease the excretion rate of Chromium which could result in a higher serum level.
Sulindac Sulindac may decrease the excretion rate of Chromium which could result in a higher serum level.
Bacitracin Bacitracin may decrease the excretion rate of Chromium which could result in a higher serum level.
Amphotericin B Amphotericin B may decrease the excretion rate of Chromium which could result in a higher serum level.
Cephaloglycin Cephaloglycin may decrease the excretion rate of Chromium which could result in a higher serum level.
Flurbiprofen Flurbiprofen may decrease the excretion rate of Chromium which could result in a higher serum level.
Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Chromium which could result in a higher serum level.
Pentamidine Pentamidine may decrease the excretion rate of Chromium which could result in a higher serum level.
Etodolac Etodolac may decrease the excretion rate of Chromium which could result in a higher serum level.
Mefenamic acid Mefenamic acid may decrease the excretion rate of Chromium which could result in a higher serum level.
Acyclovir Acyclovir may decrease the excretion rate of Chromium which could result in a higher serum level.
Naproxen Naproxen may decrease the excretion rate of Chromium which could result in a higher serum level.
Sulfasalazine Sulfasalazine may decrease the excretion rate of Chromium which could result in a higher serum level.
Phenylbutazone Phenylbutazone may decrease the excretion rate of Chromium which could result in a higher serum level.
Meloxicam Meloxicam may decrease the excretion rate of Chromium which could result in a higher serum level.
Carprofen Carprofen may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefaclor Cefaclor may decrease the excretion rate of Chromium which could result in a higher serum level.
Diflunisal Diflunisal may decrease the excretion rate of Chromium which could result in a higher serum level.
Tacrolimus Tacrolimus may decrease the excretion rate of Chromium which could result in a higher serum level.
Ceforanide Ceforanide may decrease the excretion rate of Chromium which could result in a higher serum level.
Salicylic acid Salicylic acid may decrease the excretion rate of Chromium which could result in a higher serum level.
Meclofenamic acid Meclofenamic acid may decrease the excretion rate of Chromium which could result in a higher serum level.
Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Chromium which could result in a higher serum level.
Carboplatin Carboplatin may decrease the excretion rate of Chromium which could result in a higher serum level.
Oxaprozin Oxaprozin may decrease the excretion rate of Chromium which could result in a higher serum level.
Ketoprofen Ketoprofen may decrease the excretion rate of Chromium which could result in a higher serum level.
Balsalazide Balsalazide may decrease the excretion rate of Chromium which could result in a higher serum level.
Ibuprofen Ibuprofen may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefditoren Cefditoren may decrease the excretion rate of Chromium which could result in a higher serum level.
Atazanavir Atazanavir may decrease the excretion rate of Chromium which could result in a higher serum level.
Colistimethate Colistimethate may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefuroxime Cefuroxime may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefapirin Cefapirin may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefadroxil Cefadroxil may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefprozil Cefprozil may decrease the excretion rate of Chromium which could result in a higher serum level.
Ceftriaxone Ceftriaxone may decrease the excretion rate of Chromium which could result in a higher serum level.
Olsalazine Olsalazine may decrease the excretion rate of Chromium which could result in a higher serum level.
Lumiracoxib Lumiracoxib may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefamandole Cefamandole may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefazolin Cefazolin may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefonicid Cefonicid may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefoperazone Cefoperazone may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefotetan Cefotetan may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefoxitin Cefoxitin may decrease the excretion rate of Chromium which could result in a higher serum level.
Ceftizoxime Ceftizoxime may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefradine Cefradine may decrease the excretion rate of Chromium which could result in a higher serum level.
Magnesium salicylate Magnesium salicylate may decrease the excretion rate of Chromium which could result in a higher serum level.
Salsalate Salsalate may decrease the excretion rate of Chromium which could result in a higher serum level.
Choline magnesium trisalicylate Choline magnesium trisalicylate may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefepime Cefepime may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefacetrile Cefacetrile may decrease the excretion rate of Chromium which could result in a higher serum level.
Ceftibuten Ceftibuten may decrease the excretion rate of Chromium which could result in a higher serum level.
Cefpodoxime Cefpodoxime may decrease the excretion rate of Chromium which could result in a higher serum level.
Antrafenine Antrafenine may decrease the excretion rate of Chromium which could result in a higher serum level.
Aminophenazone Aminophenazone may decrease the excretion rate of Chromium which could result in a higher serum level.
Antipyrine Antipyrine may decrease the excretion rate of Chromium which could result in a higher serum level.
Tiaprofenic acid Tiaprofenic acid may decrease the excretion rate of Chromium which could result in a higher serum level.
Lopinavir Lopinavir may decrease the excretion rate of Chromium which could result in a higher serum level.
Etoricoxib Etoricoxib may decrease the excretion rate of Chromium which could result in a higher serum level.
Hydrolyzed Cephalothin Hydrolyzed Cephalothin may decrease the excretion rate of Chromium which could result in a higher serum level.
Cephalothin Group Cephalothin Group may decrease the excretion rate of Chromium which could result in a higher serum level.
Oxyphenbutazone Oxyphenbutazone may decrease the excretion rate of Chromium which could result in a higher serum level.
Latamoxef Latamoxef may decrease the excretion rate of Chromium which could result in a higher serum level.
Nimesulide Nimesulide may decrease the excretion rate of Chromium which could result in a higher serum level.
Benoxaprofen Benoxaprofen may decrease the excretion rate of Chromium which could result in a higher serum level.
Metamizole Metamizole may decrease the excretion rate of Chromium which could result in a higher serum level.
Zomepirac Zomepirac may decrease the excretion rate of Chromium which could result in a higher serum level.
Ceftobiprole Ceftobiprole may decrease the excretion rate of Chromium which could result in a higher serum level.
Cimicoxib Cimicoxib may decrease the excretion rate of Chromium which could result in a higher serum level.
Ceftaroline fosamil Ceftaroline fosamil may decrease the excretion rate of Chromium which could result in a higher serum level.
Lornoxicam Lornoxicam may decrease the excretion rate of Chromium which could result in a higher serum level.
Aceclofenac Aceclofenac may decrease the excretion rate of Chromium which could result in a higher serum level.

Target Protein

Cytochrome b5 CYB5A

Referensi & Sumber

Artikel (PubMed)
  • PMID: 3886757
    Wallach S: Clinical and biochemical aspects of chromium deficiency. J Am Coll Nutr. 1985;4(1):107-20.
  • PMID: 10705100
    Anderson RA: Chromium in the prevention and control of diabetes. Diabetes Metab. 2000 Feb;26(1):22-7.
  • PMID: 22423897
    Hua Y, Clark S, Ren J, Sreejayan N: Molecular mechanisms of chromium in alleviating insulin resistance. J Nutr Biochem. 2012 Apr;23(4):313-9. doi: 10.1016/j.jnutbio.2011.11.001.

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