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SEMICARBAZIDE HYDROCHLORIDE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Semicarbazide hydrochloride is a hydrazine derivative used as a reagent for making crystalline compounds having characteristic melting points (EPA, 1985). It is used as a chemical reagent for the qualitative determination of aldehydes and ketones, and also in the laboratory isolation of hormones and certain essential oil fractions (IARC, 1976).

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) C-H5-N3-O.Cl-H

Available Forms Sources

    A) FORMS
    1) Semicarbazide hydrochloride is produced in the United Kingdom for research purposes and is available in America in technical and chemically pure grades (IARC, 1976; Lewis, 1993).
    2) The hydrochloride dissociates in water to form the free base (Budavari, 1996). The free base appears to have a similar spectrum of toxicity as the hydrochloride.
    B) SOURCES
    1) Semicarbazide hydrochloride can be produced by reaction of benzylidenesemicarbazide with hydrochloric acid, or by an electrochemical reduction of nitrourea in aqueous hydrochloric acid (IARC, 1976; Budavari, 1996). It may also be synthesized from hydrazine sulfate, potassium or sodium cyanate, and sodium carbonate (Lewis, 1992).
    C) USES
    1) Semicarbazide hydrochloride is a reagent used for making crystalline compounds having characteristic melting points (EPA, 1985; Budavari, 1996). It is used as a chemical reagent for the qualitative determination of aldehydes and ketones, and also in the laboratory isolation of hormones and certain essential oil fractions (IARC, 1976; Lewis, 1992).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) NO CASES of HUMAN TOXICITY from SEMICARBAZIDE HYDROCHLORIDE exposure HAVE BEEN REPORTED.
    B) Experimental animals have developed tremors, ataxia, equilibrium difficulties, and generalized tonic-clonic convulsions after ingestion. Semicarbazide hydrochloride is a mutagen and an animal carcinogen and teratogen.
    0.2.7) NEUROLOGIC
    A) Exposed experimental animals have developed tremors and generalized tonic-clonic seizures.
    0.2.20) REPRODUCTIVE
    A) Semicarbazide hydrochloride is teratogenic in experimental animals.

Laboratory Monitoring

    A) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) No cases of human toxicity from exposure to semicarbazide hydrochloride have been reported. Pyridoxine has been effective in preventing seizures and tremors in experimental animals and should be considered for significantly exposed humans. Standard anticonvulsant therapy might also be beneficial.
    B) Emesis should not be induced.
    C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    D) GASTRIC LAVAGE: Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in the head down left lateral decubitus position or by endotracheal intubation. Control any seizures first.
    1) CONTRAINDICATIONS: Loss of airway protective reflexes or decreased level of consciousness in unintubated patients; following ingestion of corrosives; hydrocarbons (high aspiration potential); patients at risk of hemorrhage or gastrointestinal perforation; and trivial or non-toxic ingestion.
    E) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    F) PYRIDOXINE - No pyridoxine doses have been recommended to treat seizures from poisoning with this agent. The following suggested doses are extrapolated from those recommended for hydrazine poisoning.
    1) DOSE - 25 mg/kg, one-third administered IM and the other two-thirds given IV over 3 hours.
    a) CONTINUING SEIZURES - For continuing seizures, increase the dose by 25 mg/kg IV every 5 to 10 minutes to a maximum of 300 mg/kg. Administer no more pyridoxine than necessary to stop seizures. Other symptoms cannot be expected to respond to pyridoxine administration.
    2) CAUTIONS
    a) The maximum nontoxic pyridoxine dose is not known.
    b) A single 10 gram intravenous dose caused peripheral neuropathy in one reported case.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) Minimum lethal human exposure is unknown.

Clinical Effects

Summary Of Exposure

    A) NO CASES of HUMAN TOXICITY from SEMICARBAZIDE HYDROCHLORIDE exposure HAVE BEEN REPORTED.
    B) Experimental animals have developed tremors, ataxia, equilibrium difficulties, and generalized tonic-clonic convulsions after ingestion. Semicarbazide hydrochloride is a mutagen and an animal carcinogen and teratogen.

Neurologic

    3.7.1) SUMMARY
    A) Exposed experimental animals have developed tremors and generalized tonic-clonic seizures.
    3.7.2) CLINICAL EFFECTS
    A) SEIZURE
    1) Tremors and generalized tonic-clonic convulsions have occurred in exposed experimental animals (IARC, 1976; Sax, 1986). These effects have not been reported in exposed humans.
    B) NEUROPATHY
    1) NERVE DEGENERATION - In experimental animals, semicarbazide hydrochloride may cause degeneration of motor neurons in the spinal cord anterior horn (Spencer et al, 1985). This effect has not been reported in exposed humans.

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) DISORDER OF BONE
    1) OSTEOLATHYRISM - Rats chronically fed semicarbazide hydrochloride developed osteolathyrism with rough coats, protrusion of the sternum, bowing of the legs, stiffening of the joints, and bony growths (Weisburger et al, 1981). Osteoporosis was also noted in the long bones in these rats (Weisburger et al, 1981). Similar effects were observed in frog embryos (Schultz et al, 1985). These effects have not been reported in exposed humans.

Reproductive

    3.20.1) SUMMARY
    A) Semicarbazide hydrochloride is teratogenic in experimental animals.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) Semicarbazide hydrochloride is teratogenic in rats, when injected as a single dose on day 5, 7, 10, 13, or 15 of gestation. Abnormalities were produced in the brain, kidney, intestines, liver, skull, sternum and ribs (de la Fuente del Rey, 1986).
    a) Pregnant rats treated with semicarbazide hydrochloride had offspring with facial abnormalities including cleft palate and micrognathia (IARC, 1976). An oral dose on day 4 of gestation produced 100% cleft palates (Schardein, 1993; Steffek et al, 1972).
    b) Pregnant rats administered 50 or 100 milligrams per day of semicarbazide hydrochloride had a high incidence of fetal resorption. There was also a high incidence of cleft palate in the offspring (IARC, 1976).
    c) Pregnant rats administered 50 to 150 milligrams per kilogram of semicarbazide hydrochloride as a single dose on either days 5, 7, 10, 13, or 15 of gestation delivered offspring with brain, kidney, intestine, liver, and skeletal (skull, sternum, and rib) defects (de la Fuente et al, 1983) de al Fuente del Rey, 1986).
    d) In rat studies, a change in litter size and fetotoxicity was observed (RTECS. 1996).
    2) In hamster studies, fetotoxicity and specific developmental abnormalities in the musculoskeletal system were observed (RTECS, 1996).
    3) Micromelia has been produced in chick embryos by injection of semicarbazide hydrochloride into the yolk sac (Roth, 1974).
    4) Semicarbazide produced minor neural tube lesions in hamsters when given as a single oral dose of 100 mg/kg on day 7 of gestation (Wiley & Joneja, 1978).
    3.20.3) EFFECTS IN PREGNANCY
    A) ANIMAL STUDIES
    1) In rat studies, pre-implantation mortality was observed (RTECS, 1996).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS563-41-7 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) IARC Classification
    a) Listed as: Semicarbazide hydrochloride
    b) Carcinogen Rating: 3
    1) The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    3.21.4) ANIMAL STUDIES
    A) CARCINOMA
    1) ANIMAL STUDIES
    a) Semicarbazide hydrochloride produced angiomas, angiosarcomas, and lung tumors following oral administration to mice (IARC, 1976).
    b) Semicarbazide hydrochloride was found to be neoplastic by RTECS criteria in the mouse with vascular tumors and tumors of the lungs, thorax, or respiratory tract (RTECS, 1996).
    c) However, in one chronic feeding study with rats, semicarbazide hydrochloride was not carcinogenic under the conditions of the test (Weisburger et al, 1981).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count and liver and kidney function tests is suggested for patients with significant exposure.
    4.1.3) URINE
    A) URINALYSIS
    1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring urinalysis is suggested for patients with significant exposure.

Methods

    A) OTHER
    1) A potentiometric method for measurement of semicarbazide hydrochloride has been described that is sensitive to 0.3 milligrams (IARC, 1976).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.

Monitoring

    A) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) EMESIS/NOT RECOMMENDED
    1) Because of the potential for the development of seizures, EMESIS SHOULD NOT BE INDUCED.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    C) GASTRIC LAVAGE
    1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
    a) Consider lavage more than 60 minutes after ingestion of sustained-release formulations and substances known to form bezoars or concretions.
    2) PRECAUTIONS:
    a) SEIZURE CONTROL: Is mandatory prior to gastric lavage.
    b) AIRWAY PROTECTION: Place patients in the head down left lateral decubitus position, with suction available. Patients with depressed mental status should be intubated with a cuffed endotracheal tube prior to lavage.
    3) LAVAGE FLUID:
    a) Use small aliquots of liquid. Lavage with 200 to 300 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash (in older children or adults) and 10 milliliters/kilogram body weight of normal saline in young children(Vale et al, 2004) and repeat until lavage return is clear.
    b) The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance.
    c) CAUTION: Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.
    4) COMPLICATIONS:
    a) Complications of gastric lavage have included: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach, fluid and electrolyte imbalance (Vale, 1997). Combative patients may be at greater risk for complications (Caravati et al, 2001).
    b) Gastric lavage can cause significant morbidity; it should NOT be performed routinely in all poisoned patients (Vale, 1997).
    5) CONTRAINDICATIONS:
    a) Loss of airway protective reflexes or decreased level of consciousness if patient is not intubated, following ingestion of corrosive substances, hydrocarbons (high aspiration potential), patients at risk of hemorrhage or gastrointestinal perforation, or trivial or non-toxic ingestion.
    6.5.3) TREATMENT
    A) SEIZURE
    1) Standard anticonvulsant therapy might be beneficial.
    2) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    3) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    4) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    5) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2010; Chin et al, 2008).
    6) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    7) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    B) PYRIDOXINE
    1) Pyridoxine was efficacious in preventing seizures and tremors in experimental animals (Sax, 1986). Its use should be considered if exposed humans develop convulsions.
    2) No dosing recommendations for pyridoxine treatment of poisoning with semicarbazide hydrochloride were found at the time of this review. The following suggested doses are extrapolated from those recommended for seizure therapy in hydrazine poisoning.
    a) DOSE - 25 milligrams per kilogram, one-third administered intramuscularly and the remaining two-thirds given intravenously over 3 hours (Kirklin et al, 1976; Frierson, 1965).
    b) CONTINUING SEIZURES - For continuing seizures, increase the dose by 25 mg/kg intravenously every 5 to 10 minutes to a maximum of 300 mg/kg. Administer no more pyridoxine than necessary to stop seizures. Other symptoms cannot be expected to respond to pyridoxine administration.
    3) CAUTIONS - Pyridoxine doses of 0.2 to 5 grams daily for 2 to 40 months have caused ataxia and severe sensory nervous system dysfunction (Schaumburg et al, 1983; Parry & Bredesen, 1985; Berger & Schaumburg, 1984; Dalton, 1985).
    a) A mixed sensorimotor peripheral neuropathy has been described in one patient with hydrazine poisoning who received 10 grams of pyridoxine intravenously (Harati & Niakan, 1986). The maximum nontoxic pyridoxine dose is not known.
    C) HOSPITAL ADMISSION
    1) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

    A) EFFICACY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Range Of Toxicity

Summary

    A) Minimum lethal human exposure is unknown.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The maximum tolerated human exposure to this agent has not been delineated.

Workplace Standards

    A) ACGIH TLV Values for CAS563-41-7 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS563-41-7 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS563-41-7 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 3 ; Listed as: Semicarbazide hydrochloride
    a) 3 : The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals. Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental animals may be placed in this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans. Agents, mixtures and exposure circumstances that do not fall into any other group are also placed in this category.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS563-41-7 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) Rferences: RTECS, 1996; Lewis, 1992; IARC, 1976
    1) LD50- (ORAL)MOUSE:
    a) 145 mg/kg
    2) LD50- (SUBCUTANEOUS)MOUSE:
    a) 167 mg/kg

Pharmacology Toxicology

Toxicologic Mechanism

    A) Semicarbazide hydrochloride is a convulsant in experimental animals (Sax, 1986). It may cause degeneration of motor neurons in the spinal cord anterior horn (Spencer et al, 1985).
    1) Experimental animals fed a vitamin B6 deficient diet were more susceptible to the convulsant effects of semicarbazide hydrochloride (Sax, 1986). Concomitant administration of pyridoxine prevented the development of convulsions and tremors in experimental animals (Sax, 1986).
    2) Semicarbazide may produce its convulsant effects by depleting gamma-aminobutyric acid (GABA) (Sax, 1986). This GABA inhibition can be reversed in experimental animals by administration of pyridoxine (Sax, 1986).
    a) Semicarbazide caused inhibition of glutamic acid decarboxylase and gamma-aminobutyric acid transaminase activities in the mesencephalon and diencephalon in experimental animals (Sax, 1986).
    B) Serum zinc and pyridoxal phosphate levels are decreased in the blood of experimental animals fed 50 milligrams per kilogram of semicarbazide hydrochloride daily for 10 days (Slavik et al, 1985).
    C) Semicarbazide hydrochloride is mutagenic in Drosophila melanogaster (Sax, 1986). It is an animal teratogen and carcinogen (Lewis, 1992; (Sax, 1986) RTECS, 1996; (IARC, 1976).
    D) Semicarbazide and other lathrogens inhibit collagen cross-linking (Wiley & Joneja, 1978).

Physicochemical

Physical Characteristics

    A) Semicarbazide hydrochloride is a snow-white, prism-like crystalline solid (HSDB, 2005; EPA, 1985; IARC, 1976).

Molecular Weight

    A) 111.5 (IARC, 1976)

References

General Bibliography

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