| GHS-Einstufung | This chemical does not meet GHS hazard criteria for 40% (2 of 5) of reports.DangerH225 (40%): Highly Flammable liquid and vapor [Danger Flammable liquids]P210, P233, P240, P241, P242, P243, P260, P261, P262, P264, P264+P265, P270, P271, P280, P301+P316, P301+P317, P301+P330+P331, P302+P352, P302+P361+P354, P303+P361+P353, P304+P340, P305+P351+P338, P305+P354+P338, P308+P316, P316, P317, P321, P330, P332+P317, P337+P317, P361+P364, P362+P364, P363, P370+P378, P403+P233, P403+P235, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 5 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
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| Regulatorische Informationen | Status: Active Update: 14-07-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/17100 |
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| Gefahrenübersicht | The chloride salt is highly irritating to the skin and eyes of rabbits and is not a skin sensitizer in guinea pigsSymptoms of severe oral intoxication include muscle tremors and convulsive contractions, salivation, vomiting, hypoglycemia, and circulatory disturbances[HSDB] |
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| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl guanidine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Guanidine Hydrochloride/ |
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| Special Reports | European Chemicals BureauIUCLID Dataset, Guanidine chloride (CAS # 50-01-1) (2000 CD-ROM edition). Available from the Database Query page at: http://ecb.jrc.it/esis/esis.php as of March 4, 2008. |
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| Hazard Classes and Categories | Flam. Liq. 2 (40%)Acute toxicity (Oral) - Category 4 |
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| Lagerbedingungen | Store at 25 °C (77 °F)excursions permitted to 15-30 °C (59-86 °F). /Guanidine hydrochloride/ |
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| Entsorgungsverfahren | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
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| Treatment | Kidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored. |
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| Wechselwirkungen | The characteristics of guanidine uptake in brush-border membrane vesicles isolated from rabbit renal cortex were investigated ... Guanidine uptake was only minimally inhibited by organic cations such as tetraethylammonium, N1-methylnicotinamide, and choline, but many other organic cations such as amiloride, clonidine, imipramine, and harmaline caused considerable inhibition. Uptake of radiolabeled guanidine was inhibited more effectively by guanidine than by tetraethylammonium, whereas uptake of radiolabeled tetraethylammonium was inhibited more effectively by tetraethylammonium than by guanidine. beta-Lactam antibiotics did not inhibit guanidine uptake but did inhibit tetraethylammonium uptake. Kinetic analysis showed that there were at least two kinetically distinct carrier systems for guanidine uptake, whereas tetraethylammonium uptake occurred via a single carrier system ...Concurrent therapy with other drugs that may cause bone-marrow suppression should be avoided. /Guanidine hydrochloride/ |
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| Gesundheitliche Auswirkungen | Chronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. |
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| Ökotoxizitätswerte | LC50Species: Cloeon dipterum (Mayfly, nymphs, length 9.3 mm, weight 5.6 mg)Conditions: freshwater, 25 °CConcentration: 22000 ug/L for 3 hr /Conditions of bioassay not specified in source examined/Concentration: 15000 ug/L for 6 hr /Conditions of bioassay not specified in source examined/Concentration: 7200 ug/L for 24 hr /Conditions of bioassay not specified in source examined/Concentration: 2000 ug/L for 48 hr /Conditions of bioassay not specified in source examined/LC50 Leuciscus idus (ide) 1758 mg/L/48 hr /Conditions of bioassay not specified in source examined/ /Guanidine chloride/ |
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| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 20(SRC), determined from a structure estimation method(2), indicates that guanidine is expected to have very high mobility in soil(SRC). However, guanidine has a pKa of 12.5(3) and should exist almost entirely as a cation under environmental conditions (pH 5-9)(SRC). As a result, guanidine may have greater adsorption and less mobility than its estimated Koc value indicates since cations generally adsorb more strongly to soils containing organic carbon and clay than neutral species(4). Volatilization from moist soil surfaces is not an important environmental fate process since cations do not volatilize(SRC). The potential to volatilize from dry soil surfaces exists based upon an estimated vapor pressure of 2.2 mm Hg(SRC), determined from a fragment constant method(5). Guanidine was degraded in soil samples incubated under aerobic conditions at varying rates as a function of the initial starting concentration(6). At an initial concentration of 10 mg/kg, guanidine was 78% biodegraded after 10 dayshowever, at an initial concentration of 400 mg/kg, guanidine was 62% biodegraded after 25 days(6).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 20(SRC), determined from a structure estimation method(2), indicates that guanidine is not expected to adsorb to suspended solids and sediment(SRC). However, guanidine has a pKa of 12.5(3) and should exist almost entirely as a cation under environmental conditions (pH 5-9)(SRC). As a result, guanidine may have greater adsorption to suspended solids and sediment than its estimated Koc value indicates(SRC). Volatilization of guanidine from water surfaces will not be an important fate process, since cations do not volatilize(SRC). According to a classification scheme(4), BCF values in the range of <0.1 to 0.1 measured in fish(5), suggest bioconcentration in aquatic organisms is low(SRC). Complete guanidine degradation in stream water samples obtained near a nitroguanidine production facility was observed in 20 days after an initial lag period 11 days and 68 days following a lag period 52 days(5).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), guanidine, which has an estimated vapor pressure of 2.2 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase guanidine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC)the half-life for this reaction in air is estimated to be 9 hours(SRC), calculated from its rate constant of 4.2X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Guanidine does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(4). |
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| Unerwünschte Wirkungen | Neurotoxin - Other CNS neurotoxin |
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| Expositionspfade | Rapidly absorbed and distributed |
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| Toxizitätsübersicht | Uremic toxins such as guaniidine are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (A7868). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (A7869). |
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| Signs and Symptoms | As a uremic toxin, this compound can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present. |
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| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of guanidine can be estimated to be 20(SRC). According to a classification scheme(2), this estimated Koc value suggests that guanidine is expected to have very high mobility in soil(SRC). The pKa of guanidine is 12.5(3), indicating that this compound will exist almost entirely as a cation in the environment(SRC). As a result, guanidine may have greater adsorption and less mobility than its estimated Koc value indicates since cations generally adsorb more strongly to soils containing organic carbon and clay than neutral species(4). |
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| Human Toxicity Excerpts | /SIGNS AND SYMPTOMS/ Severe guanidine intoxication is characterized by nervous hyperirritability, fibrillary tremors and convulsive contractions of muscle, salivation, vomiting, diarrhea, hypoglycemia, and circulatory disturbances. Administration of intravenous calcium gluconate may control the neuromuscular and convulsive symptoms and provide some relief of other toxic manifestations. /Guanidine hydrochloride//CASE REPORTS/ A 43-year-old man with Eaton-Lambert syndrome developed chronic interstitial nephritis after 4 years of guanidine hydrochloride therapy. The diagnosis of Eaton-Lambert syndrome was confirmed by clinical neurophysiologic studies and by intracellular electrode studies of end-plate potentials from an intercostal muscle biopsy. Because guanidine had toxic effects in this patient, an alternative form of therapy was tried. /Guanidine hydrochloride//ALTERNATIVE and IN VITRO TESTS/ Plasma proteins in hemodialysis patients display a significant increase in deamidated/isomerized Asx (asparagine and aspartic acid) content, a marker of protein fatigue damage ... The deamidated/isomerized Asx content of normal plasma incubated with several uremic toxins for 24 hr, 72 hr, and 7 days was measured, identifying a group of toxins that were able to elicit this kind of damage. Uremic toxins were also incubated with purified human albumin, and dose-response experiments with the two most toxic agents in terms of protein damage (guanidine and guanidinopropionic acid) were carried out ... Among the uremic toxins that are able to elicit protein damage, guanidine produced a dose-dependent increase in protein damage. No difference was found after a hemodialysis session./ALTERNATIVE and IN VITRO TESTS/ Plasma levels of endogenous guanidine compounds are increased in various pathologic conditions, including chronic renal failure. In the present study ... the effects of some of these compounds on basal and stimulated nitric oxide activity in human renal arteries /were tested/ ... Rings from human renal arteries were obtained from 22 patients undergoing nephrectomy ... The effects of N(G)-monomethyl-L-arginine (L-NMMA), N(G),N(G)-dimethyl-L-arginine (asymmetrical dimethylarginine (ADMA)), aminoguanidine (AG), and methylguanidine (MG) on artery rings under basal and stimulated conditions /were studied/ ... In precontracted arteries, L-NMMA (1 umol/L to 1 mmol/L) and ADMA (1 umol/L to 3 mmol/L) caused concentration- and endothelium-dependent contractions (median effective concentrations (EC50) = 13.3 umol/L and 17.5 umol/L, respectivelyEmax = 15 + or - 4% and 17 + or - 4% of the response to 100 mmol/L KCl, respectively). Aminoguanidine (0.01 to 3 mmol/L) and MG (0.01 to 3 mmol/L) produced endothelium-independent contractions (Emax = 9 + or -3% and 16 + or - 2% of the response to 100 mmol/L KCl, respectively). L-arginine (1 mmol/L) but not D-arginine (1 mmol/L) prevented the contractions by L-NMMA and ADMA, but did not change contractions induced by AG and MG. In precontracted arteries, the relaxation to acetylcholine was decreased but not abolished by L-NMMA and ADMA. The remaining relaxation was reduced by charybdotoxin (0.1 mol/L) and tetraethylammonium (1 mmol/L) ... The results demonstrate that L-NMMA and ADMA reduce basal and stimulated nitric oxide activity in human renal arteries. An increase in the plasma concentrations of methylarginines associated with renal disease should be considered as a risk factor for endothelial dysfunction and abnormal vasomotor tone in human renal arteries. /Endogenous guanidine compounds//OTHER TOXICITY INFORMATION/ Guanidino compounds are known as uremic toxins which increase in the blood of patients with renal failure. Guanidino succinic acid (GSA) and methyl guanidine (MG) ... reflect the pathological stage of nephritis. GSA correlates well with blood urea nitrogen and therefore indicates the reduction of renal function. MG does not appear in the early stage of renal failure and abruptly increases at the stage of serious uremia. /Guanidino compounds/ |
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| Artificial Pollution Sources | Guanidine's production and use as a starting material for munitions, polymeric resins, flame retardants, and pharmaceuticals(1) may result in its release to the environment through various waste streams(SRC). |
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