Guanidine

59.072

59.07

204-021-8

JU58VJ6Y3B

DTXSID0023117

Deliquescent crystalline mass

75.9

-1.63 (est)

Solid

50 °C

829 mg/mL

Store at 25 deg C (77 deg F); excursions permitted to 15-30 deg C (59-86 deg F). /Guanidine hydrochloride/

2.2 mm Hg at 25 deg C (est)

12.5None

Henry's Law constant = 2.34X10-11 atm-cu m/mol at 25 °C (est)

12.5|pKa = 12.5

Hydroxyl radical reaction rate constant = 4.2X10-11 cu cm/molec-sec at 25 °C (est)

P260, P264, P270, P280, P301+P312, P301+P330+P331, P303+P361+P353, P304+P340, P305+P351+P338, P310, P321, P330, P363, P405, P501

H302

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.

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/

European Chemicals Bureau; IUCLID 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.

|Danger|H225 (100%): Highly Flammable liquid and vapor [Danger Flammable liquids]|P210, P233, P240, P241, P242, P243, P260, P261, P264, P270, P271, P280, P301+P310, P301+P312, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P307+P311, P310, P311, P312, P321, P322, P330, P361, P363, P370+P378, P403+P233, P403+P235, P405, and P501|Aggregated GHS information provided by 3 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P260, P264, P270, P280, P301+P312, P301+P330+P331, P303+P361+P353, P304+P340, P305+P351+P338, P310, P321, P330, P363, P405, and P501

LD50 = 475 mg/kg (oral, rat). Can cause severe gastrointestinal symptoms (nausea, vomiting and diarrhea), bone marrow suppression, renal insufficiency and other hematologic abnormalities (anemia, leucopenia). Severe guanidine intoxication is characterized by nervous hyperirritability, fibrillary tremors and convulsive contractions of muscle, salivation, vomiting, diarrhea, hypoglycemia, and circulatory disturbances.

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/

LD50 Rat (male) oral 557 mg/kg free guanidine base (908 mg/kg bw guanidine chloride)|LD50 Rat (female) oral 475 mg free guanidine base (774 mg/kg bw guanidine chloride)|LD50 Rat oral 1120 mg/kg /Guanidine chloride/|LD50 Mouse oral (male) 571 mg/kg /Guanidine chloride/|For more Non-Human Toxicity Values (Complete) data for GUANIDINE (8 total), please visit the HSDB record page.

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).

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 days; however, 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).

The rate constant for the vapor-phase reaction of guanidine with photochemically-produced hydroxyl radicals has been estimated as 4.2X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 9 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Guanidine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Guanidine does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(2).

BCF values of <0.1 to 0.1 were measured for carp exposed to 2 and 20 ug/L of guanidine over a 6 week incubation period(1). According to a classification scheme(2), these BCF values suggest bioconcentration in aquatic organisms is low(SRC).

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).

The pKa of guanidine is 12.5(1). This value indicates that guanidine will exist almost entirely as a cation at environmental pH (pH 5-9). Volatilization from moist soil and water 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(2).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 465 workers (78 of these were female) were potentially exposed to guanidine in the US(1). Occupational exposure to guanidine may occur through inhalation and dermal contact with this compound at workplaces where guanidine is produced or used(SRC).

For the reduction of the symptoms of muscle weakness and easy fatigability associated with the myasthenic syndrome of Eaton-Lambert. It is not indicated for treating myasthenia gravis.

Guanidine is indicated for the reduction of the symptoms of muscle weakness and easy fatigability associated with the myasthenic syndrome of Eaton-Lambert. It is not indicated for treating myasthenia gravis. The Eaton-Lambert syndrome is ordinarily differentiated from myasthenia gravis by the usual association of the syndrome with small cell carcinoma of the lung, but myography may be necessary to make the diagnosis. /Guanidine hydrochloride/|... Low-dose guanidine and pyridostigmine combination therapy /was used/ in 9 patients with LEMS /Lambert-Eaton myasthenic syndrome/ and ... its long-term safety and effectiveness /was analyzed/. In all patients, a liberal amount of pyridostigmine was used, while daily guanidine dose was kept below 1000 mg a day, and guanidine was given between pyridostigmine dosings. This combination therapy was used for 3 to 102 months (mean: 34.1 months) and improved clinical status in all patients. Although guanidine had to be discontinued due to severe gastrointestinal symptoms in 3 cases, no serious side reactions such as bone marrow suppressions or signs of renal insufficiency developed in any case ... /Guanidine hydrochloride/

Anemia, leukopenia, and thrombocytopenia resulting from bone-marrow suppression attributable to guanidine have been reported. Other adverse reactions that have been observed are: General: sore throat, rash, fever. Neurologic: paresthesia of lips, face, hands, feet; cold sensations in hands and feet; nervousness, lightheadedness, jitteriness, increased irritability; tremor, trembling sensation; ataxia; emotional lability; psychotic state; confusion; mood changes, and hallucinations. Gastrointestinal: dry mouth; gastric irritation; anorexia; nausea; diarrhea; abdominal cramping. Gastrointestinal side effects may preclude the use of guanidine as a desired form of therapy. Dermatologic: rash, flushing or pink complexion; folliculitis; petechiae, purpura, ecchymoses; sweating; skin eruptions; dryness and scaling of the skin. Renal: elevation of blood creatinine, uremia; chronic interstitial nephritis, acute interstitial nephritis, and renal tubular necrosis. Hepatic: abnormal liver function tests. Cardiac: palpitation, tachycardia, atrial fibrillation, hypotension. /Guanidine hydrochloride/|Mild gastrointestinal disorders, such as anorexia, increased peristalsis, or diarrhea are early warnings that tolerance is being exceeded. These symptoms may be relieved by atropine, but nevertheless note should be taken of these symptoms and dosage reductions considered. Slight numbness or tingling of the lips and fingertips shortly after taking a dose of guanidine has been reported. This per se is not an indication to discontinue treatment and/or reduce dosage. /Guanidine hydrochloride/|Physicians should be given adequate precautions pertaining to the gastrointestinal side effects and the possibility of induced behavior disorders. /Guanidine hydrochloride/|Renal function may be affected in some patients receiving guanidine. Patients should therefore have regular urine examinations and serum creatinine determinations while taking this drug. Physicians should be given adequate precautions pertaining to the gastrointestinal side effects and the possibility of induced behavior disorders. Treatment should not be continued longer than necessary. /Guanidine hydrochloride/|For more Drug Warnings (Complete) data for GUANIDINE (11 total), please visit the HSDB record page.

Guanidine apparently acts by enhancing the release of acetylcholine following a nerve impulse. It also appears to slow the rates of depolarization and repolarization of muscle cell membranes.

Rapidly absorbed and distributed|Accumulation of specific guanidine compounds (GCs) has been related to neurological, cardiovascular, hematological, and immunological complications of renal failure ... The obvious increases of urea, guanidinosuccinic acid, creatinine, guanidine, methylguanidine, and N(G)N(G)-dimethylarginine (symmetrical dimethylarginine) seen in blood of oldest heterozygous and younger homozygous polycystic kidney disease (PKD) rats were largely within the same range as those found in the studied human PKD population, especially in patients with a glomerular filtration rate below 60 mL/min/1.73 sq m. The decreased levels of plasma guanidinoacetic acid seen at end-stage renal disease in homozygous and oldest heterozygous PKD/Mhm rats were also observed in serum of patients with a glomerular filtration rate below 20 mL/min/1.73 sq m ... /Guanidino compounds/|Brush-border membrane vesicles were prepared from donor human kidneys ... Uptake of (14)C-guanidine ... in the vesicles, as determined by rapid filtration, was significantly greater in the presence of an outwardly-directed proton gradient, at all early time points, than in the absence of the gradient ... Evidence was obtained suggesting that the transporter for guanidine is distinct from the previously described organic cation proton antiporter for TEA. /Tetraethylammonium/|The characteristics of guanidine uptake in brush-border membrane vesicles isolated from rabbit renal cortex were investigated. Guanidine uptake was markedly stimulated by an outwardly directed H+ gradient, resulting in a transient uphill transport. This stimulation was not due to an inside-negative, H+-diffusion potential because an ionophore-induced H+-diffusion potential and a K+-diffusion potential (both inside-negative) failed to enhance guanidine uptake. The H+ gradient itself appeared to be the driving force for the uptake ...|... The plasma, erythrocyte, and urinary concentration of guanidino compounds in 30 hemodialysis patients and 15 patients with chronic renal failure who had not undergone hemodialysis /were determined/ ... Plasma levels of taurocyamine, guanidinosuccinic acid, alpha-N-acetyl-L-arginine, creatine, guanidinobutyric acid, guanidine, and methylguanidine were significantly increased in patients with chronic renal failure with or without hemodialysis. In contrast, plasma guanidinoacetic acid concentrations were significantly decreased. Erythrocyte concentrations of creatinine, guanidinosuccinic acid, guanidine and methylguanidine were also markedly elevated. No correlation was observed between plasma creatinine concentration and erythrocyte concentration of guanidinosuccinic acid or methylguanidine. However, there was a significant correlation between plasma and erythrocyte methylguanidine, and between plasma and erythrocyte guanidinosuccinic acid. /Guanidino compounds/|For more Absorption, Distribution and Excretion (Complete) data for GUANIDINE (7 total), please visit the HSDB record page.

Not metabolized.

7-8 hours

Guanidine apparently acts by enhancing the release of acetylcholine following a nerve impulse. It also appears to slow the rates of depolarization and repolarization of muscle cell membranes. /Guanidine hydrochloride/|Guanidine-induced alterations in substrate dependent kinetics of hepatic and renal succinate dehydrogenase (SDH) have been investigated under in vitro conditions. Guanidine hydrochloride (GuHCl) induced a mixed type of inhibition by decreasing the maximal velocity (Vmax) and increasing the Michaelis-Menten constant (Km). The competitive (Ki) and non-competitive (Ki) inhibitory constants ... showed that the inhibitory influence of GuHCl is more due to decreased enzyme substrate affinity rather than reduction in the active site density of the enzyme as revealed by low Ki values. /Guanidine hydrochloride/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/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, respectively; Emax = 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/

Chloride, Guanidinium

Oral: Tablets 125 mg guanidine hydrochloride (Schering Canada for Key Pharm) /Guanidine hydrochloride/

On heating to 160 °C it is converted to melamine and NH3

Environmental transformation -> Pesticide transformation products (metabolite, successor)

Guanidine is a known environmental transformation product of Dodine.