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PDFHYDRAZINE
Human Health Effects:
Evidence for Carcinogenicity:
Evaluation: There is inadequate evidence in humans for the carcinogenicity of
hydrazine. There is sufficient evidence
in experimental animals for the carcinogenicity of hydrazine. Overall evaluation: Hydrazine is possibly carcinogenic to humans
(Group 2B).
CLASSIFICATION: B2; probable human carcinogen. BASIS FOR CLASSIFICATION:
Tumors have been induced in mice, rats and hamsters following oral, inhalation
or intraperitoneal administration of hydrazine and hydrazine sulfate. Hydrazine is mutagenic in numerous assays.
HUMAN CARCINOGENICITY DATA: Inadequate. ANIMAL CARCINOGENICITY DATA: Sufficient.
A3. Confirmed animal carcinogen with unknon relevance to humans.
Human Toxicity Excerpts:
SKIN CONTACT WITH ANHYDROUS HYDRAZINE
LEADS TO CAUSTIC-LIKE BURNS & DISSOLVES HAIR ...
ONE PERSON ACCIDENTALLY DRANK "BETWEEN A MOUTHFUL & A CUPFUL." HE
IMMEDIATELY VOMITED & LOST CONSCIOUSNESS. HOSPITALIZED, HE WAS FLUSHED, BUT
AFEBRILE, UNCONSCIOUS, & VOMITING; PUPILS WERE DILATED BUT CENTRAL &
LIGHT REACTIVE. WITHIN 12 HR VOMITING CEASED ... & HE WAS SPORADICALLY
VIOLENT. LATER, HIS MEMORY & VOLUNTARY MOVEMENTS WERE NORMAL BUT HE WAS
ATAXIC & UNABLE TO WRITE. THERE WAS LATERAL NYSTAGMUS TO THE RIGHT & HIS
ABILITY TO SENSE VIBRATION WAS LOST.
... WORKER HANDLED HYDRAZINE HYDRATE
ONCE A WK FOR 6 MO. EARLY SIGNS WERE LETHARGY, CONJUNCTIVITIS, & TREMORS. ON
LAST DAY OF EXPOSURE HE DEVELOPED FEVER, VOMITING, & DIARRHEA. LATER HE
DEVELOPED ABDOMINAL PAINS ... & BECAME INCOHERENT. HIS ABDOMEN WAS ENLARGED
& LIVER WAS PALPABLE & TENDER. THERE WAS FLUID IN CHEST CAVITY &
LUNG SHADOWING. BILIRUBIN & CREATININE LEVELS WERE INCREASED. ... HE ...
DIED 20 DAYS AFTER THE LAST EXPOSURE TO HYDRAZINE. AUTOPSY REVEALED SEVERE TRACHEITIS,
BRONCHITIS, LUNGS FILLED WITH EXUDATE, ENLARGED KIDNEYS WITH ... NECROSIS &
GRANULAR CYTOPLASMIC DEGENERATION, & ENLARGED HEART WITH MUSCLE FIBER
DEGENERATION & HYPEREMIA. /HYDRAZINE
HYDRATE/
TWO REPORTS OF CANCER MORTALITY IN WORKERS EXPOSED TO HYDRAZINE HAVE APPEARED IN RECENT YEARS.
CHOROIDAL MELANOMA WAS OBSERVED IN ONE MAN WHO HAD BEEN EXPOSED TO HYDRAZINE FOR 6 YEARS. A PRELIMINARY REPORT OF
AN EPIDEMIOLOGICAL STUDY OF MEN ENGAGED IN HYDRAZINE MANUFACTURE REVEALED NO UNUSUAL
EXCESS OF CANCER. THIS STUDY COMPRISED 423 MEN, WITH A 64% VITAL STATUS
ASCERTAINMENT. NONE OF THE 5 CANCERS REPORTED (3 OF STOMACH, 1 PROSTATIC & 1
NEUROGENIC) OCCURRED IN THE GROUP WITH HIGHEST EXPOSURE. MORTALITY FROM ALL
CAUSES WAS NOT ELEVATED (49 OBSERVED, 61.5 EXPECTED), & THE ONLY EXCESS
ENTAILED 2 LUNG CANCER CASES WITHIN THE HIGHEST EXPOSURE CATEGORY, WITH A
RELATIVE RISK 1.2 (95% CONFIDENCE INTERVAL, 0.2-4.5).
The liquid is corrosive, producing penetrating burns & severe dermatitis.
In cases of acute human poisoning, vomiting, severe irritation of the
respiratory tract with the development of pulmonary edema, central nervous
system depression, and hepatic and renal damage have been reported.
After a laboratory technician had drunk 20-30 ml of a 6% aqueous solution of
hydrazine (free base), he immediately
vomited. Four hours later, weakness, somnolence, and arrhythmia were observed.
Laboratory findings showed a slight but persistent leukocytosis. The
serum-albumin fraction was decreased with an increase in the urine noted, while
the patient showed irregular breathing. Five days after exposure, the patient
had recovered.
The case of a 24-yr-old man who accidentally ingested a mouthful of hydrazine successfully treated with megadoses
of intravenous pyridoxine hydrochloride (vitamin B6) injection, 10 g over a few
hr, who subsequently developed sensory polyneuropathy, is reported. The
neuropathy spontaneously resolved over the next 6 months. It was concluded that
although part of the peripheral neuropathy could have been due to hydrazine toxicity, the predominantly sensory
neuropathy with axonal degeneration and spontaneous recovery is due to
pyridoxine hydrochloride (vitamin B6) induced peripheral neuropathy.
Contact dermatitis caused by hydrazine was reported in two patients who
worked in a gold plating factory. The workers wore gloves when carrying baskets
between the different plating baths, but they had frequent spills over their
hands and arms and were exposed to the vapor. The first case was a 54 year old
man who worked for 20 years in the plating industry. After three weeks in the
gold plating department the worker developed a recurrent hand eczema. It was
located on the dorsal side of the hands and spread to the forearms. The patient
recovered completely after changing his work responsibilities. The second case
was a 23 year old worker in the same gold plating department who developed
periorbital eczema four months after starting work in the gold plating
department. The worker recovered completely after changing the working
environment. The standard ICORG test procedures was used in performing the patch
testing. In both workers, 1% hydrazine
sulfate, and 1 and 10% gold plating stabilizer gave positive epicutaneous test
reactions and potassium dicyanoaurate gave a negative reaction. /Observations
indicated that/ there was evidence that hydrazine in the gold plating baths caused the
dermatitis.
Toxic effects of hydrazine /routes
not specified/ include conjunctivitis, pulmonary edema, anemia (hemolytic),
ataxia, convulsions, kidney toxicity, and liver toxicity. /from table/
Skin and eye irritation has occurred in humans, and allergic contact
dermatitis has been reported. No systemic responses were described in any of
these reported exposures. Several incidents of systemic poisoning have been
reported, mainly showing effects on the CNS, respiratory system, and stomach.
Vomiting, weakness, and irregular breathing, with recovery in 5 days, occurred
following ingestion of 20-30 ml of a 6% aq solution. A second ingestion incident
reported vomiting, unconsciousness, and sporadic, violent behavior with
paraesthesia; the outcome was not described.
An accidental swallowing of a mouthful of hydrazine led to confusion, lethargy, and
restlessness in a 24-yr old man. Clinical liver damage was detected, but other
signs of systemic toxicity appear to have been masked by the aggressive
management of the patient.
A male worker sustained severe chemical burns (involving 22% of the body
surface) following a hydrazine
explosion. After a comatose period and with biochemical indicators of liver
malfunction, recovery was seen in 5 weeks.
Inhalation of vapors has produced pulmonary edema which has been successfully
treated with pyridoxine.
An occupational exposure (conc unknown) over a 6-mo period produced
conjunctivitis, tremor, and lethargy. Lung and liver damage occurred, and the
individual died 21 days after the last exposure. Skin contact and inhalation
exposure occurred.
A significant incr in cases of myocardial infarction was reported in a plant
manufacturing hydrazine. The author
cautions that the conclusion is based on very small numbers, and no follow-up
info is available.
Exposure to the eyes can produce temporary blindness. Liquid splashes to the
eyes can produce corneal injury and burns. Liquid splashes to the skin can also
produce severe burns. Hydrazine can also
produce dermatitis and skin sensitization.
Nineteen workers (18 males, 1 female) of a garbage dump (mean age 39.9 years,
range 19-58 years) were admitted to our hospital because of inhalation of a
hydrazine-like gas of unknown origin.
They complained of an ammoniacal odor with sweet taste followed by burning of
the eyes, rawness in the throat and dyspnea, dizziness and nausea. Ten patients
(group A) arrived about 2 hr after they had experienced their first symptoms.
The nine other patients (group B) were admitted about 70 hr later. On the second
day the white cell counts were significantly elevated compared to those of the
days before and after (P < 0.02-0.005). The lung function showed in two
patients a moderate obstruction. The PO2 was significantly reduced within 1 to
12 hr after admission (P < 0.02-0.005) compared to the measurement before (P
< 0.005) and after 25 (P < 0.02) and 50 (P < 0.01) hr. A significantly
reduced PC02 was found after 25 hr compared to the time of admission (P <
0.03). These investigations show that workers of a garbage dump had an alarming
decrease of oxygen after inhalation of nitrogenous gases released by the trash.
Hydrazine was produced at a factory
in the East Midlands of the United Kingdom between 1945 and 1971. The cohort of
all 427 men who were employed there for at least six months with varying degrees
of occupational exposure to hydrazine
was followed up until the end of January 1992. By the end of July 1982 49 deaths
had occurred and the observed mortality was close to that expected at each level
of exposure. By the end of January 1992 a further 37 deaths had occurred. Again
the observed mortality was close to that expected for all causes and also for
lung cancer, cancers of the digestive system, other cancers, and all other
causes, respective of the level of exposure. The results weigh against there
having been any material hazard of occupational exposure to hydrazine. The small number of men studied
means, however, that a relative risk as high as 3.5 for lung cancer cannot
confidently be excluded.
A case of residual neurobehavioral impairment possibly related to
occupational exposure to hydrazine was
described. A 38 year old Israeli male was treated for repeated complaints of
sore throat and colds. His wife noticed that he had difficulties remembering
things that she had asked him to do. He became impotent. He had similar
difficulties at work in performing tasks that he had previously done
effortlessly. He had been employed as a water technician at a hospital for 7
years. His job activities involved monitoring water quality, adding hydrazine mixtures when necessary, and
overseeing the workings of the hospital pumping system. He had intense
intermittent inhalation and skin exposure to hydrazine while mixing and pouring hydrazine preparations, and almost constant
inhalation exposure to hydrazine vapors
in his workplace. He developed thrombocytopenia which was treated with steroids.
He returned briefly to work, but had to be discharged because of recurring
episodes of colds and malaise. His memory and concentration problems persisted
and he became unable to work or understand and remember material he had read.
Neuropsychological testing revealed deficits in specific task performance,
memory, concentration, learning, judgment, and abstraction and mood problems. A
computed tomographic examination showed no signs of brain damage. Over the next
4 years the patient showed a gradual improvement in his general well being, mood
status, and ability to carry out some tasks. He was unable to hold down jobs or
perform tasks commensurate with his previous level of technical and
organizational skills. He eventually found work as a part time gardener. /It
was/ concluded that exposure to hydrazine during his work as a water
technician is the most likely explanation for the neurobehavioral impairment.
The case illustrates the need to be aware that exposure to hydrazine can cause neurobehavioral problems
as sequelae.
Skin, Eye and Respiratory Irritations:
Vapors are very irritating to the mucous membranes, nose, throat, and upper
respiratory tract.
Medical Surveillance:
Based partly on exptl data, placement should incl a history of exposure to
other carcinogens, smoking, alcohol, medications, & family history. The
skin, eye, liver, kidney, blood & CNS should be evaluated. Sputum or urine
cytology may give useful information. Hydrazine may be detected in blood.
Probable Routes of Human Exposure:
... Route of human exposure to hydrazine is ingestion of trace residues in
processed foods. ...
THE SMOKE FROM A BLENDED US CIGARETTE CONTAINED 31.5 NG HYDRAZINE.
An industrial hygiene assessment of the extent of exposure to hydrazine compounds was carried out due to the
growing number of such compounds shown to be animal carcinogens in laboratory
studies. The report summarizes production and uses of hydrazine compounds, the toxic effects of such
compounds, relevant exposure standards, sampling and analytical methods relevant
to exposure assessment, and observations made during surveys conducted at eight
facilities in the United States where these compounds were either prepared or
used. The sites visited for the survey were of four basic types: those which
used hydrazine compounds as propellants,
those which manufactured the compounds, those which used hydrazine as an aircraft emergency power unit
fuel, or sites where hydrazine was used
in boiler water treatment. Personal exposures measured were generally within the
range from below the limit of detection to 1.0 ppm as an 8 hour time weighted
average. The OSHA permissible exposure limits for the hydrazine compounds of interest ranged from
0.5 to 5 ppm. The number of workers exposed was found to be low. Large scale
propellant and emergency jet power unit usage was relatively new, and the
manufacturing methods had not been used until recently. /Data indicated/ that
the accumulated person years of exposure are relatively low; it is unlikely that
suitable cohorts exist for retrospective expsoure studies.
NIOSH (NOES Survey 1981-1983) has statistically estimated that 59,147 workers
(2,840 of these are female) are potentially exposed to hydrazine in the US(1). About 2000 Finnish
employees were exposed to hydrazine
between the years 1980-1989(2). Occupational exposure may be through inhalation
and dermal contact with this compound at workplaces where hydrazine is produced or used(SRC). The
general population will be exposed to hydrazine via inhalation of ambient air and
cigarette smoke, ingestion of food, and dermal contact with vapors and other
products containing hydrazine(SRC).
Emergency Medical Treatment:
Emergency Medical Treatment:
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The following Overview, *** HYDRAZINE ***, is relevant for this HSDB record chemical. |
| Life Support: |
o This overview assumes that basic life support measures
have been instituted. |
| Clinical Effects: |
SUMMARY OF EXPOSURE
0.2.1.1 ACUTE EXPOSURE
o Hydrazine can be corrosive or irritating to the eyes,
skin, nose, mucous membranes, throat, and respiratory
system. Contact with the liquid can cause burns or
permanent damage to the eyes. It is a hemolytic agent
and can cause nausea, vomiting, anorexia, hypoglycemia,
CNS stimulation, seizures, and coma. Inhalation of
vapors has caused pulmonary edema.
o Liver and kidney damage can also occur. Hydrazine is
an animal carcinogen and a suspected human carcinogen,
but limited epidemiological studies have not indicated
that occupational exposure to hydrazine is a risk for
cancer.
VITAL SIGNS
0.2.3.1 ACUTE EXPOSURE
o Anoxia, cyanosis, irregular respiration, or fever may
occur.
HEENT
0.2.4.1 ACUTE EXPOSURE
o Hydrazine is irritating or corrosive to the eyes, nose,
mucous membranes, throat and respiratory tract. Vapors
may cause delayed eye irritation. Liquids may cause
severe eye damage. Facial edema, conjunctivitis,
salivation and headache have been reported from
exposure to hydrazines.
RESPIRATORY
0.2.6.1 ACUTE EXPOSURE
o Acute exposure to low concentrations of hydrazines may
cause delayed death (days) and produce bronchial mucous
destruction and pulmonary edema.
NEUROLOGIC
0.2.7.1 ACUTE EXPOSURE
o CNS stimulation, excitability, tremors, convulsions,
and coma have occurred.
GASTROINTESTINAL
0.2.8.1 ACUTE EXPOSURE
o Nausea, vomiting, diarrhea and anorexia are common
symptoms. The nausea may be refractory to medication.
HEPATIC
0.2.9.1 ACUTE EXPOSURE
o Fatty degeneration and occasional hepatic necrosis may
occur in human poisonings. Elevations in alkaline
phosphatase and bilirubin, hepatic cholestasis, and
hepatic hemosiderosis occurred in dogs.
GENITOURINARY
0.2.10.1 ACUTE EXPOSURE
o Severe renal damage, possibly secondary to hemolysis,
may occur. Kidney damage is usually less severe than
hepatic effects.
FLUID-ELECTROLYTE
0.2.12.2 CHRONIC EXPOSURE
o Electrolyte imbalance, possibly secondary to kidney
failure, was seen in one fatal case of chronic exposure
to hydrazine hydrate.
HEMATOLOGIC
0.2.13.1 ACUTE EXPOSURE
o Hydrazine is a moderate hemolytic agent.
DERMATOLOGIC
0.2.14.1 ACUTE EXPOSURE
o Hydrazine may cause corrosion or strong skin
irritation.
0.2.14.2 CHRONIC EXPOSURE
o Hydrazine is a sensitizer and may cross react with
other hydrazines.
MUSCULOSKELETAL
0.2.15.1 ACUTE EXPOSURE
o Hydrazine has produced arthralgias.
ENDOCRINE
0.2.16.1 ACUTE EXPOSURE
o Hypoglycemia or hyperglycemia may occur, depending on
the glycogen reserves in the liver.
PSYCHIATRIC
0.2.18.1 ACUTE EXPOSURE
o Violent behavior, restlessness, lethargy and confusion
have been seen in human poisonings.
0.2.18.2 CHRONIC EXPOSURE
o Lethargy and incoherence were seen in one human case.
IMMUNOLOGIC
0.2.19.2 CHRONIC EXPOSURE
o Some hydrazines are skin sensitizers. One case of a
lupus-like syndrome has been reported from occupational
exposure to hydrazine sulfate.
REPRODUCTIVE HAZARDS
o Hydrazine has been embryotoxic and fetotoxic in rats and
mice, but at doses which were also toxic to the mothers.
There is no evidence that hydrazine is a human
reproductive hazard, but data are lacking.
CARCINOGENICITY
0.2.21.1 IARC CATEGORY
o IARC (Hydrazine) (RTECS, 1991)
1. Animal: Sufficient evidence
2. Group 2B
0.2.21.2 HUMAN OVERVIEW
o Hydrazine has been carcinogenic in rats, mice, and
hamsters and is a suspected human carcinogen. Limited
epidemiological evidence suggests that occupational
exposure does not increase the risk of cancer, however.
GENOTOXICITY
o Hydrazine is genotoxic at the level of inducing DNA
repair, mutations, chromosome aberrations, and oncogenic
transformation in vitro.
OTHER
0.2.23.1 ACUTE EXPOSURE
o Hydrazine can be hazardous by any route of exposure.
Its toxicity appears to be due to generation of
pyridoxine deficiency. |
| Laboratory: |
o If respiratory tract irritation or respiratory depression
is evident, monitor arterial blood gases, chest x-ray, and
pulmonary function tests.
o 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.
o Monitor methemoglobin and blood sugar. |
| Treatment Overview: |
SUMMARY EXPOSURE
o FIRST AID (NIOSH, 1995) -
1. EYE EXPOSURE - Immediately wash the eyes with large
amounts of water, occasionally lifting the lower and
upper lids. Get medical attention immediately.
Contact lenses should not be worn when working with
this chemical.
2. DERMAL EXPOSURE - Immediately flush the contaminated
skin with water. If this chemical penetrates the
clothing, immediately remove the clothing and flush the
skin with water. Get medical attention promptly.
3. INHALATION EXPOSURE - Move the exposed person to fresh
air at once. If breathing has stopped, perform
mouth-to-mouth resuscitation. Keep the affected person
warm and at rest. Get medical attention as soon as
possible.
4. INGESTION EXPOSURE - If this chemical has been
swallowed, get medical attention immediately.
5. TARGET ORGANS - Eyes, skin, respiratory system, central
nervous system, liver, and kidneys. Cancer site: (in
animals: tumors of the lungs, liver, blood vessels &
intestine).
o GENERAL -
1. Move victims of inhalation exposure from the toxic
environment and administer 100% humidified supplemental
oxygen with assisted ventilation as required. Exposed
skin and eyes should be copiously flushed with water.
Because of the potential for rapid onset of CNS
depression or seizures with possible aspiration of
gastric contents, EMESIS SHOULD NOT BE INDUCED.
Cautious gastric lavage followed by administration of
activated charcoal may be of benefit if the patient is
seen soon after the exposure.
o INHALATION EXPOSURE -
1. 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 beta2 agonist and corticosteroid aerosols.
2. If bronchospasm and wheezing occur, consider treatment
with inhaled sympathomimetic agents.
3. ACUTE LUNG INJURY: Maintain ventilation and
oxygenation and evaluate with frequent arterial blood
gas or pulse oximetry monitoring. Early use of PEEP
and mechanical ventilation may be needed.
o DERMAL EXPOSURE -
1. DECONTAMINATION: Remove contaminated clothing and wash
exposed area thoroughly with soap and water. A
physician may need to examine the area if irritation
or pain persists.
2. Treat dermal irritation or burns with standard topical
therapy. Patients developing dermal hypersensitivity
reactions may require treatment with systemic or
topical corticosteroids or antihistamines.
o EYE EXPOSURE -
1. DECONTAMINATION: Irrigate exposed eyes with copious
amounts of tepid water for at least 15 minutes. If
irritation, pain, swelling, lacrimation, or photophobia
persist, the patient should be seen in a health care
facility.
o INGESTION EXPOSURE -
1. Because of the potential for gastrointestinal tract
irritation, do not induce emesis.
2. Significant esophageal or gastrointestinal tract
irritation or burns may occur following ingestion. The
possible benefit of early removal of some ingested
material by cautious gastric lavage must be weighed
against potential complications of bleeding or
perforation.
3. 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 Trendelenburg
and left lateral decubitus position or by endotracheal
intubation. Control any seizures first.
a. 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.
4. 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.
5. Observe patients with ingestion carefully for the
possible development of esophageal or gastrointestinal
tract irritation or burns. If signs or symptoms of
esophageal irritation or burns are present, consider
endoscopy to determine the extent of injury.
6. SEIZURES: Administer a benzodiazepine IV; DIAZEPAM
(ADULT: 5 to 10 mg, repeat every 10 to 15 min as
needed. CHILD: 0.2 to 0.5 mg/kg, repeat every 5 min
as needed) or LORAZEPAM (ADULT: 2 to 4 mg; CHILD:
0.05 to 0.1 mg/kg).
a. Consider phenobarbital if seizures recur after
diazepam 30 mg (adults) or 10 mg (children > 5
years).
b. Monitor for hypotension, dysrhythmias, respiratory
depression, and need for endotracheal intubation.
Evaluate for hypoglycemia, electrolyte disturbances,
hypoxia.
ORAL EXPOSURE
o Do NOT induce emesis.
o DILUTION: Immediately dilute with 4 to 8 ounces (120 to
240 mL) of milk or water (not to exceed 4 ounces/120 mL
in a child).
o 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 Trendelenburg and
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.
o 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.
o SEIZURES: Administer a benzodiazepine IV; DIAZEPAM
(ADULT: 5 to 10 mg, repeat every 10 to 15 min as
needed. CHILD: 0.2 to 0.5 mg/kg, repeat every 5 min
as needed) or LORAZEPAM (ADULT: 2 to 4 mg; CHILD: 0.05
to 0.1 mg/kg).
1. Consider phenobarbital if seizures recur after diazepam
30 mg (adults) or 10 mg (children > 5 years).
2. Monitor for hypotension, dysrhythmias, respiratory
depression, and need for endotracheal intubation.
Evaluate for hypoglycemia, electrolyte disturbances,
hypoxia.
o ACUTE LUNG INJURY: Maintain ventilation and oxygenation
and evaluate with frequent arterial blood gas or pulse
oximetry monitoring. Early use of PEEP and mechanical
ventilation may be needed.
o METHEMOGLOBINEMIA: Administer 1 to 2 mg/kg of 1%
methylene blue slowly IV in symptomatic patients.
Additional doses may be required.
o Pyridoxine may be antidotal. Dose of pyridoxine is 25
mg/kg, 1/3 given IM and 2/3 given IV over 3 hours.
Increase the dose by 25 mg/kg every 5 to 10 minutes to a
maximum of 300 mg/kg/dose for continuing symptoms.
INHALATION EXPOSURE
o Rescuers must not enter areas with potential high
airborne concentrations of this agent without
SELF-CONTAINED BREATHING APPARATUS (SCBA) to avoid
becoming secondary victims.
o 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
beta2 agonist and corticosteroid aerosols.
o SEIZURES: Administer a benzodiazepine IV; DIAZEPAM
(ADULT: 5 to 10 mg, repeat every 10 to 15 min as
needed. CHILD: 0.2 to 0.5 mg/kg, repeat every 5 min
as needed) or LORAZEPAM (ADULT: 2 to 4 mg; CHILD: 0.05
to 0.1 mg/kg).
1. Consider phenobarbital if seizures recur after diazepam
30 mg (adults) or 10 mg (children > 5 years).
2. Monitor for hypotension, dysrhythmias, respiratory
depression, and need for endotracheal intubation.
Evaluate for hypoglycemia, electrolyte disturbances,
hypoxia.
o ACUTE LUNG INJURY: Maintain ventilation and oxygenation
and evaluate with frequent arterial blood gas or pulse
oximetry monitoring. Early use of PEEP and mechanical
ventilation may be needed.
o METHEMOGLOBINEMIA: Administer 1 to 2 mg/kg of 1%
methylene blue slowly IV in symptomatic patients.
Additional doses may be required.
o Pyridoxine may be antidotal. Dose of pyridoxine is 25
mg/kg, 1/3 given IM and 2/3 given IV over 3 hours.
Increase the dose by 25 mg/kg every 5 to 10 minutes to a
maximum of 300 mg/kg/dose for continuing symptoms.
EYE EXPOSURE
o DECONTAMINATION: Irrigate exposed eyes with copious
amounts of tepid water for at least 15 minutes. If
irritation, pain, swelling, lacrimation, or photophobia
persist, the patient should be seen in a health care
facility.
o Patients symptomatic following exposure should be
observed in a controlled setting until all signs and
symptoms have fully resolved.
o SEIZURES: Administer a benzodiazepine IV; DIAZEPAM
(ADULT: 5 to 10 mg, repeat every 10 to 15 min as
needed. CHILD: 0.2 to 0.5 mg/kg, repeat every 5 min
as needed) or LORAZEPAM (ADULT: 2 to 4 mg; CHILD: 0.05
to 0.1 mg/kg).
1. Consider phenobarbital if seizures recur after diazepam
30 mg (adults) or 10 mg (children > 5 years).
2. Monitor for hypotension, dysrhythmias, respiratory
depression, and need for endotracheal intubation.
Evaluate for hypoglycemia, electrolyte disturbances,
hypoxia.
o ACUTE LUNG INJURY: Maintain ventilation and oxygenation
and evaluate with frequent arterial blood gas or pulse
oximetry monitoring. Early use of PEEP and mechanical
ventilation may be needed.
o METHEMOGLOBINEMIA: Administer 1 to 2 mg/kg of 1%
methylene blue slowly IV in symptomatic patients.
Additional doses may be required.
o Pyridoxine may be antidotal. Dose of pyridoxine is 25
mg/kg, 1/3 given IM and 2/3 given IV over 3 hours.
Increase the dose by 25 mg/kg every 5 to 10 minutes to a
maximum of 300 mg/kg/dose for continuing symptoms.
DERMAL EXPOSURE
o Hydrazine can SPONTANEOUSLY IGNITE upon contact with
cloth; clothing should be removed immediately.
o DECONTAMINATION: Remove contaminated clothing and wash
exposed area thoroughly with soap and water. A
physician may need to examine the area if irritation or
pain persists.
o Treat dermal irritation or burns with standard topical
therapy. Patients developing dermal hypersensitivity
reactions may require treatment with systemic or topical
corticosteroids or antihistamines.
o SEIZURES: Administer a benzodiazepine IV; DIAZEPAM
(ADULT: 5 to 10 mg, repeat every 10 to 15 min as
needed. CHILD: 0.2 to 0.5 mg/kg, repeat every 5 min
as needed) or LORAZEPAM (ADULT: 2 to 4 mg; CHILD: 0.05
to 0.1 mg/kg).
1. Consider phenobarbital if seizures recur after diazepam
30 mg (adults) or 10 mg (children > 5 years).
2. Monitor for hypotension, dysrhythmias, respiratory
depression, and need for endotracheal intubation.
Evaluate for hypoglycemia, electrolyte disturbances,
hypoxia.
o ACUTE LUNG INJURY: Maintain ventilation and oxygenation
and evaluate with frequent arterial blood gas or pulse
oximetry monitoring. Early use of PEEP and mechanical
ventilation may be needed.
o METHEMOGLOBINEMIA: Administer 1 to 2 mg/kg of 1%
methylene blue slowly IV in symptomatic patients.
Additional doses may be required.
o Pyridoxine may be antidotal. Dose of pyridoxine is 25
mg/kg, 1/3 given IM and 2/3 given IV over 3 hours.
Increase the dose by 25 mg/kg every 5 to 10 minutes to a
maximum of 300 mg/kg/dose for continuing symptoms. |
| Range of Toxicity: |
o Minimum lethal human exposure is unknown. |
Antidote and Emergency Treatment:
Inhalation of vapors has produced pulmonary edema which has been successfully
treated with pyridoxine.
Specific treatment for exposure consists of thorough washing of all exposed
skin areas with soap and water, copious irrigation of the eyes, and prompt
removal of the patient from the source of exposure. /Hydrazines/
After inhalation, observation for progressive respiratory distress is
necessary. Chest X-ray and arterial blood gases should be monitored.
Administration of oxygen, intubation, and assisted ventilation may become
necessary. Pneumonia and bronchitis need to be excluded. /Hydrazines/
If ingestion has occurred, gastric lavage or emesis should be followed by
administration of activated charcoal and catharsis. Emesis is most effective if
it is initiated within 30 minutes of ingestion. /Hydrazines/
Pyridoxine may be antidotal. The suggested dose is with half of this dose
given intramuscularly and two-thirds given IV over 3 hours. Seizures should be
controlled with diazepam, phenytoin, or phenobarbital. Blood sugar levels should
be monitored for severe hypoglycemia, which may appear with or without preceding
significant hyperglycemia. The patient should be observed for evidence of
intravascular hemolysis, methemoglobinemia, and consequent deterioration of
renal function. Patients who are symptomatic or who demonstrate a methemoglobin
level greater than 30 per cent should be treated with methylene blue slowly IV
every 4 hours as needed. Improvement is dramatic if diagnosis is correct. Liver
function should be monitored because hydrazines are known hepatotoxins.
/Hydrazines/
Elimination is enhanced by forced diuresis and acidification of the urine.
Hemodialysis and peritoneal dialysis should be effective, but insufficient human
data exist on the use of these modalities. Treatment is otherwise symptomatic
and supportive. /Hydrazines/
Animal Toxicity Studies:
Evidence for Carcinogenicity:
Evaluation: There is inadequate evidence in humans for the carcinogenicity of
hydrazine. There is sufficient evidence
in experimental animals for the carcinogenicity of hydrazine. Overall evaluation: Hydrazine is possibly carcinogenic to humans
(Group 2B).
CLASSIFICATION: B2; probable human carcinogen. BASIS FOR CLASSIFICATION:
Tumors have been induced in mice, rats and hamsters following oral, inhalation
or intraperitoneal administration of hydrazine and hydrazine sulfate. Hydrazine is mutagenic in numerous assays.
HUMAN CARCINOGENICITY DATA: Inadequate. ANIMAL CARCINOGENICITY DATA: Sufficient.
A3. Confirmed animal carcinogen with unknon relevance to humans.
Non-Human Toxicity Excerpts:
... 30 MALE & 30 FEMALE WHITE MICE /WERE INJECTED IP/ WITH 0.5 MG HYDRAZINE IN PHYSIOLOGICAL SALINE. A TOTAL
DOSE OF 400 MG/KG BODY WT WAS GIVEN IN 16 SEPARATE DOSES OVER 46 DAYS. OF 13/34
SURVIVORS, 4 MICE DEVELOPED RETICULUM CELL SARCOMAS OF MEDIASTINUM & 9
DEVELOPED MYELOID LEUKEMIAS WITHIN 100-313 DAYS. THYMIC LYMPHOMA WAS OBSERVED IN
1/60 CONTROL MICE. AN INCREASE IN THE NUMBER OF LUNG TUMORS WAS ALSO OBSERVED IN
OTHER STRAINS OF MICE NAMELY (BALB/C X DBA/2)F1 HYBRID, C57BL, SWR &
BALB/C/CB/SE (NEWBORN).
TWO DOGS EXPOSED TO 5 PPM FOR 6 MO DEVELOPED DECR APPETITE, WT LOSS, EASY
FATIGABILITY, & MUSCULAR TREMORS ... TWO OF FOUR DOGS SURVIVED 194 6-HR
EXPOSURES TO CONCN AVERAGING 14 PPM. ALL 4 ANIMALS DEVELOPED SIGNS OF SEVERE
INTOXICATION.
HYDRAZINE HEMOLYZES RED BLOOD CELLS
WHEN INJECTED IV OR ... GIVEN BY STOMACH TUBE, BUT BLOOD CELL DESTRUCTION &
ANEMIA ARE LESS CONSISTENT FINDINGS AFTER SC INJECTION OR INHALATION, USUALLY
OCCURRING ONLY AFTER CHRONIC EXPOSURE & SEVERE INTOXICATION.
THE EXTENT OF AFFECT ON BLOOD SYSTEM OF RATS BECAME MORE SEVERE WITH INCR
AGE.
USING MOUSE LIVER MICROSOMAL MUTAGENICITY ASSAY, HYDRAZINE WAS MUTAGENIC TO 5 STRAINS OF
SALMONELLA TYPHIMURIUM.
OF THE 10 CHEMICALS TESTED FOR THEIR ABILITIES TO PRODUCE
NOVOBIOCIN-RESISTANT MUTANTS IN HEMOPHILUS INFLUENZAE, HYDRAZINE WAS UNIQUE BECAUSE IT INDUCED A HIGH
INCIDENCE OF MUTATION WITHOUT KILLING SIGNIFICANT NUMBERS OF CELLS AT
CONCENTRATIONS TESTED. HYDRAZINE MAY BE
ACTING AS BOTH MUTAGEN & ANTIMUTAGEN IN THIS SYSTEM.
PREGNANT FISCHER 344 RATS WERE TREATED WITH 0 TO 10.0 MG/KG IP ON GESTATION
DAYS 6-15. DOSE-RELATED EMBRYOLETHALITY (PRINCIPLE TOXIC EFFECT) & MATERNAL
TOXICITY WERE OBSERVED @ 2 HIGHER DOSES.
CONCENTRATIONS GREATER THAN 10 MG/L ADMIN DURING NEURULATION WERE TERATOGENIC
TO XENOPUS LAEVIS, THE SOUTH AFRICAN CLAWED TOAD. LOWER CONCN PERMITTED SURVIVAL
& DEVELOPMENT INTO NORMAL LARVAE.
HYDRAZINE HAS BEEN SHOWN TO BE
MUTAGENIC IN ... HIGHER PLANTS & DROSOPHILA. ...
TWELVE DAY OLD EGGS OF RAINBOW TROUT SALMO GAIRDNERI WERE EXPOSED TO 0.01,
0.1, 1.0 & 5.0 MG/L. EGGS WERE EXPOSED FOR 48 HR & SUBSEQUENTLY
MAINTAINED IN RECIRCULATING-FLOW SYSTEM. EXPOSURE DID NOT RESULT IN MORTALITY OR
REDUCTION IN HATCHING. ABERRATIONS IN MORPHOGENESIS OF LARVAE INCL LOSS OF
MUSCULAR CONTROL, REDUCED GROWTH RATES & LOSS OF TACTILE SENSITIVITY AT 1.0
& 5.0 MG/L.
MEGAMITOCHONDRIA WERE INDUCED (REVERSIBLE PROCESS) IN MOUSE & RAT
HEPATOCYTES BY FEEDING DIET CONTAINING HYDRAZINE.
THE TOXICITY OF MONOMETHYLHYDRAZINE, HYDRAZINE & UNSYMMETRICAL
DIMETHYLHYDRAZINE WAS DETERMINED FOR MIXED & UNICULTURE CULTURES OF
NITRIFYING, DENITRIFYING, & ANAEROBIC METHANOGENIC BACTERIA.
MONOMETHYLHYDRAZINE WAS MORE TOXIC THAN HYDRAZINE, WHICH WAS MORE TOXIC THAN
DIMETHYLHYDRAZINE. THE TOXICITY LEVELS WERE LOW ENOUGH TO PRECLUDE BIOLOGICAL
WASTE TREATMENT OF THESE COMPOUNDS.
Hydrazine is carcinogenic to the
mouse and rat, but three ealier studies have reported no carcinogenicity of
hydrazine in the hamster. Administration
of hydrazine to mice, rats and hamsters
results in rapid methylation of liver DNA guanine for which endogenous
formaldehyde appears to be the source of the methyl moiety. Hamsters were given
hydrazine sulfate at 170, 340 and 510
mg/l in the drinking water for 2 years (average dose of 4.6, 8.3 and 10.3 mg
hydrazine (free base)/kg body wt over
the 2-year period), during which levels of methylation of DNA guanine in liver,
kidney and lung, and histopathologic examinations of these tissues were carried
out; dimethylnitrosamine, as a positive control, was administered at 10 mg/l in
the drinking water (average dose of 1.1 mg/kg body wt over the 4-month
measurement period). Both 7-methylguanine and O6-methylguanine were readily
detectable at 6 months exposure in hamsters given hydrazine or dimethylnitrosamine; in hydrazine-treated animals only trace amounts
of these bases could be detected after 12 months exposure; these bases were
again detected in liver DNA at exposure times of 18 and 24 months.
Hepatocellular carcinomas were observed in hamsters treated at the highest dose
of hydrazine sulfate after 78 weeks of
exposure; the incidence of liver cancer was dose-related over the course of the
experiment: 32% for hamsters exposed to 510 mg hydrazine sulfate/l, 12% for 340 mg/l and none
at 170 mg/l. Hamsters given dimethylnitrosamine developed high levels of
7-methylguanine and even higher levels of O6-methylguanine and both liver
cholangiocellular carcinomas (73% incidence), as reported before, and
hepatocellular carcinomas (27% incidence), a new finding. These results
demonstrate for the first time that hydrazine is a liver carcinogen in the hamster
and provide new information regarding the accumulation of DNA damage during the
entire induction period for the carcinomas.
Rabbit skin that was treated with 3 ml of anhydrous hydrazine for 1 min, followed by washing the
treated area, resulted in mortality between 60 and 90 min after application.
Acute toxicity is characterized by liver damage consisting of fatty
degeneration, red blood cell destruction and anemia, anorexia, weight loss,
weakness, vomiting, excitability, hypoglycemia, and convulsions. /Anhydrous
hydrazine/
In a 6-mo inhalation study, rats, mice, dogs, and monkeys were exposed
continuously to hydrazine at 0.2 ppm or
1 ppm, or the animals were exposed 6 hr/day, 5 days/wk at 1 or 5 ppm. At 0.2
ppm, body weights of rats were lower than the controls, hepatic degeneration was
sen in mice, anemia was seen in dogs, and a minimal incr in fat deposition in
the liver was seen in monkeys. In addition to these changes, at 1 ppm, there was
incr mortality with central nervous system (CNS) depression (primarily lethargy)
in mice, body weight reductions in dogs, and ocular irritation in monkeys. At 5
ppm (along with the above changes), tonic convulsions were seen in one dog.
Exposure of rats 6 hours/day, 5 days/wk for from 5-40 days at 20, 53, or 224
ppm, or for 6 mo at 4.5 ppm or 14 ppm resulted in incr mortality and decr body
weights in a dose-dependent fashion through all test groups. Lethargy was seen
during exposures, and lung and liver damage were detected in rats from all test
groups.
In a variety of studies, hydrazine
has been shown to cause benign and malignant tumors. Chronic, oral admin of
hydrazine to mice resulted in a wide
variety of neoplastic changes incl pulmonary adenomas and carcinomas,
hepatocarcinomas, myeloid leukemia, reticulum cell sarcoma of the mediastinum,
and lymphomas. In contrast, two studies in which hydrazine was given orally to mice failed to
produce an incr in the number of tumors. Chronic oral admin of hydrazine to rats also resulted in lung
adenomas, carcinomas, and liver tumors. By contrast, hamsters failed to show an
incr in tumors following oral admin of hydrazine.
Hydrazine produced tumors in the
mouse following ip injection but did not incr the tumor yield in rats following
either sc injection or intratracheal application.
Mice were exposed to hydrazine vapors
for 6 mo at 0.2, 1, or 5 ppm conc. In all groups, there was an incr incidence of
pulmonary tumors. Another inhalation study was conducted in which rats, mice,
dogs, or hamsters were exposed at vapor conc of 0.05 (rats and mice), 0.25, 1.0,
and 5.0 ppm (rats, mice (except 5 ppm), hamsters, and dogs) for 1 yr and
subsequently followed for their lifespan or 38 mo. Exposures were conducted 6
hr/day, 5 days/wk. An incr incidence of benign and malignant nasal tumors were
observed at 1 and 5 ppm in rats. At 0.05 ppm, the incidence of nasal tumors in
rats was slightly incr, but not significantly, above controls. An incr incidence
of benign nasal polyps was observed at 5 ppm in hamsters. In addition, hamsters
exposed at 0.25 ppm and higher conc showed pathological changes characteristic
of degenerative disease, incl amyloidosis. Thyroid tumors and colon tumors were
only slightly incr in hamsters exposed at 5 ppm. An incr incidence of pulmonary
adenomas was observed at 1 ppm in mice. No incr in tumors was observed in mice
exposed below 1 ppm. No compound-related neoplastic effects or non-neoplastic
effects were observed in dogs at any conc.
Hydrazine has proven to be
carcinogenic following lifetime admin in the majority of the rodent studies. The
main target tissues are the liver, the lungs, and following inhalation, the
epithelium of the nasal cavity...these effects occur generally under conditions
in which frank signs of toxicity (irritation, tissue damage) are occurring.
Groups of rats were exposed orally during gestation of 8 mg hydrazine (as monohydrochloride)/kg bw.
Maternal toxicity, incl mortality and bw loss, was seen, along with fetal
toxicity that incl reduced fetal weight and viability. Although some fetuses
were pale and edematous, no major congenital malformations occurred. /hydrazine monohydrochloride/
A ... developmental toxicity study was carried out in rats given oral doses
of 0, 2.5, 5, or 10 mg hydrazine (free
base)/kg from days 6-15 of gestation. The study also incl a group treated with
10 mg/kg on days 7-9. Maternal toxicity and fetal toxicity occurred at the 5-
and 10-mg dose levels with 2.5 mg/kg being an apparent NOEL. Developmental
delays, but no terata, were seen in the fetuses. Mice treated ip with 0, 4, 12,
20, 30, or 40 mg hydrazine (free
base)/kg bw from days 6-9 of gestation resulted in maternal mortality at 40
mg/kg, an incr in fetal deaths at 30 and 40 mg/kg, and reduced fetal weights and
incr numbers of litters with malformed young (exencephaly, hydronephrosis,
supernumerary ribs) at 12 and 20 mg/kg.
In a gavage study, no evidence of developmental toxicity was seen in rats
treated with 13 mg/kg daily for 30 days prior to mating. In a study where rats
were exposed to hydrazine in drinking
water (0.00016-0.16 mg/kg doses), no effects were seen in either maternal or
fetal animals.
Hydrazine is positive in most
standard assays for genotoxicity. It is positive in producing forward mutation
in Bacillus subtilis, in plants, and in mammalian cells. Hydrazine produced reverse mutation in B.
subtilis, fungi, and in the host-mediated assay in mice. It produced sex-linked
recessive lethals in Drosophila and chromosomal breaks or aberrations in plant
and animal cells. Although positive in one micronucleus test, hydrazine was inactive in two other assays for
clastogenesis, in the production of nuclear aberrations following oral exposure
to mice, or in incr the yield of dominant lethals following ip injection in
mice.
IN RATS, DOSE OF 20 MG/KG CAUSED ACCUM OF LIPID, SWELLING OF MITOCHONDRIA
& APPEARANCE OF MICROBODIES IN PERIPORTAL & MIDZONAL HEPATOCYTES &
IN PROXIMAL TUBULAR CELLS OF KIDNEY. PRETREATMENT WITH PHENOBARBITAL OR
PIPERONYL BUTOXIDE, RESPECTIVELY, REDUCED & INCREASED SEVERITY OF FATTY
LIVER.
The toxicities of hydrazine and
phenylhydrazine to embryos and larvae of zebrafish, Brachydanio rerio, were
studied under standardized conditions. Exposures to the chemicals started at the
blastula stage and the effect on hatching and survival were monitored for 15
days. The results showed that toxicities of phenylhydrazine to both embryos and
larvae were more than those of hydrazine. The Lowest Observed Effect
Concentration for hatching was 0.049 mg/l for hydrazine and 0.0078 mg/l for phenylhydrazine,
the Lowest Observed Effect Concentration for survival of larvae was 0.0035 mg/l
for hydrazine and 0.00098 mg/l for
phenylhydrazine, respectively. The No Observed Effect Concentration for hatching
was 0.0245 mg/l for hydrazine and 0.0039
mg/l for phenylhydrazine and the No Observed Effect Concentration for survival
of larvae was 0.00175 mg/l for hydrazine
and 0.00049 mg/l for phenylhydrazine, respectively. The safe concentration was
0.00175 mg/l for hydrazine and 0.00049
mg/l for phenylhydrazine.
Hydrazine hepatotoxicity in vivo, as
manifested by triglyceride accumulation, depletion of ATP and reduced
glutathione (GSH) was shown to be dose related. The effect of pretreatment of
rats with various inhibitors and inducers of cytochrome p450 on these
dose-response relationships was investigated. Pretreatment with the inhibitor
piperonyl butoxide increased triglyceride accumulation whereas pretreatment with
the inducers phenobarbital and beta-naphthoflavone resulted in reduced
triglyceride accumulation. Pretreatment with the inducers acetone and isoniazid
also enhanced triglyceride accumulation. Only phenobarbital pretreatment also
significantly reduced glutathione and ATP depletion. A linear correlation was
found between hepatic glutathione and ATP levels in non-pretreated animals given
various doses of hydrazine. However,
exponential relationships were found between hepatic triglycerides and both
hepatic ATP and glutathione. The results suggest that i) the hepatotoxicity of
hydrazine can be modulated by inducing
or inhibiting particular isoenzymes of cytochrome p450, ii) ATP and glutathione
depletion may not be directly involved in the development of fatty liver.
The metabolism and disposition of hydrazine and its effects on endogenous
metabolites has been studied in rats by the use of high resolution proton NMR
spectroscopy of urine. Several metabolites of hydrazine were detected, notably acetyl- and
diacetylhydrazine and a cyclised metabolite which results from a hydrazone
formed from 2-oxoglutarate and hydrazine. Effects of hydrazine on endogenous metabolites in urine
and plasma were also observed; notably a dose-related increase in urinary
taurine, a dose-related increase in urinary and plasma lactate, increases in
urinary alpha-alanine, beta-alanine, methylamine and a decrease in urinary
2-oxoglutarate. This study has indicated the utility of using high resolution
proton NMR spectroscopy to analyze urine for both metabolites and endogenous
compounds after exposure of animal to toxic substances.
The neonatal rat, because of its relatively rapid rate of liver DNA
replication without chemical or surgical induction, was used to assess the
genotoxicity of the carcinogen hydrazine. Hydrazine is a more potent acute toxicant in
the neonate than in the adult rat. Administration of hydrazine sc (1.5-50 mg/kg body wt) to newborn
rats during the period of rapid liver DNA synthesis, 72-96 hr after birth,
resulted in the formation of 7-methylguanine and 06-methylguanine in hepatic
DNA; 06-methylguanine was seen only in animals given near-lethal doses of the
carcinogen. Methylguanines were detectable in liver DNA only when the dose of
hydrazine was necrogenic, but lethal
doses of hydrazine to neonates produced
more methylguanines in liver DNA than in adult rats given equal doses. Southern
analyses were performed on liver DNA from neonates treated with 25 or 50 mg
hydrazine/kg, doses which were
necrogenic to the liver. The results indicated that one or more MspI restriction
sites (5'-C decreases CGG-3') were lost or blocked in liver DNA from hydrazine-treated animals and that these sites
were located at or near the genes for gamma-glutamyl transpeptidase and
cytochrome p450 IIBl. Restriction sites near albumin, H-ras, and cytochrome p450
IIEl genes cut by MspI, HpaII, or HhaI did not appear to be affected by hydrazine treatment. The results suggest that
hydrazine-induced damage is not random
in the DNA molecule. The neonate shows less DNA adduct formation at low doses of
hydrazine, but higher levels at high
doses.
Cultured rat hepatocytes were exposed to hydrazine for 4 hr, 17 hr or 4 hr followed by
a 13-hr post-exposure period. Hydrazine
was cytotoxic as measured by leakage of lactate dehydrogenase, caused depletion
of ATP and inhibited protein synthesis. The cytotoxicity and depletion of ATP in
cultures exposed to hydrazine for 4 hr
was less than that previously reported in hepatocyte suspensions exposed for 4
hr. The threshold cytotoxic concentration (20 mM) was also higher in cells in
culture than in cells in suspension (16 mM). Inhibition of protein synthesis was
detected at a much lower concentration of hydrazine (0.5 mM) than was required to
deplete ATP (16 mM) or cause cytotoxicity (20 mM). ATP depletion and inhibition
of protein synthesis were similar after a 4-hr exposure with or without a 13-hr
post-exposure period, but leakage of lactate dehydrogenase still occurred during
this period. After the 17-hr exposure, the leakage of lactate dehydrogenase, ATP
depletion and inhibition of protein synthesis were greater and the threshold
concentration of hydrazine required for
a significant effect on all three parameters was lower. This was so whether
compared with a 4-hr exposure, or a 4-hr exposure plus a 13-hr post-exposure
period. The results of this study indicate the following: (a) the sensitivity of
cultured hepatocytes to hydrazine is no
greater than that of hepatocytes in suspension; (b) the duration of exposure to
hydrazine is important but the effect
depends on the parameter measured; (c) hydrazine causes a dose-dependent inhibition
of protein synthesis at much lower concentrations than those causing lactate
dehydrogenase leakage; (d) maintenance of cytochrome p450 in cultured
hepatocytes by exposure to metyrapone did not alter the cytotoxicity of hydrazine.
A single dose of hydrazine (3 mg/kg
ip) caused hepatic accumulation of triglycerides and depletion of ATP in rats
after 9 hr. Repeated exposure of rats to hydrazine (approximately equal to 2.5
mg/kg/day) for 10 days resulted in depletion of hepatic reduced glutathione and
triglycerides. Repeated exposure to hydrazine also caused a significant (time
dependent) induction of p-nitrophenol hydroxylase activity together with changes
in other hepatic microsomal enzymes. These included 7-pentoxyresorufin
O-deethylase and 7-ethoxyresorufin O-deethylase activity, total cytochrome p450,
cytochrome b5 and cytochrome p450 reductase activity. Repeated exposure to lower
levels of hydrazine (approximately equal
to 0.250 mg/kg/day) caused no significant hepatic biochemical or microsomal
changes after 5 or 10 days except for an increase in p-nitrophenol hydroxylase
activity (17%) and liver ATP (15%) after 5 days.
A two phase study was conducted to assess the oncogenic potential of hydrazine in rats and hamsters exposed to
hydrazine for repeated short or lifetime
exposures and to investigate the acute and subchronic effects of hydrazine in relation to nasal tumorigenesis.
Groups of male and female Fischer-344-rats and male Syrian-Golden-hamsters were
exposed by inhalation to 750 ppm hydrazine for one (acute) or ten (subchronic)
1 hour weekly sessions, or to 75 ppm hydrazine in a lifetime exposure. The animals
were killed at the end of the designated exposure period for a complete
necropsy, histopathological evaluation, and morphological diagnosis of
apoptosis. The regions of the nasal passages most severely affected by acute and
subchronic hydrazine exposures included
the lateral aspects of the naso and maxilloturbinates and the lateral wall in
the anterior part of the nasal cavity. Degeneration and necrosis of the
transitional, respiratory, and olfactory epithelia in the anterior nose were
revealed by histopathologic examination after acute and subchronic exposures.
Morphological diagnosis showed apoptosis in the olfactory and squamous
metaplastic transitional epithelium. The squamous metaplastic transitional
epithelium reverted back to normal seeming transitional epithelium by the end of
24 months. Low incidences of hyperplasia (2.6%) and neoplasia (5.7%) were
detected after 24 months in rats exposed to 750 ppm hydrazine, and a similar trend was seen in
hamsters. Because the distribution and severity of the lesion observed in the
nasal mucosa of rats and hamsters in this study correlated well with reported
inspiratory air flow patterns in the rat nasal passages, the authors suggest
that hydrazine uptake as well as mucosal
injury in these regions of the anterior nose was most likely enhanced by airflow
patterns. The hyperplasias and polypoid adenomas seen in the hydrazine exposed groups appeared to be
derived from the transitional epithelium of both rats and hamsters. Site
specificity of these proliferative lesions correlated precisely with regions
most severely affected by hydrazine in
both acute and subchronic exposures.
The ability of hydrazine,
acetylphenylhydrazine, methylhydrazine, and phenylhydrazine to stimulate
proteolysis in red cells has been characterized. All four hydrazines effectively
stimulated proteolysis in red cells and in hemolysate as evidenced by a two to
threefold increase in the rate of tyrosine release. The rate of tyrosine release
varied linearly with time, increased with increasing concentration of hydrazine, and also increased as a function of
hematocrit. The rank order for stimulation of proteolysis in red cells was
phenylhydrazine greater than methylhydrazine greater than hydrazine approximately equal to
acetylphenylhydrazine. Inhibitors of glycolysis in red cells only minimally
(13-27%) decreased the rate of tyrosine release stimulated by the different
hydrazines. Agents which diminished electron transport decreased the rate of
tyrosine release. NADP inhibited the rate of tyrosine release stimulated by
hydrazine, methylhydrazine, and
acetylphenylhydrazine by approximately 36 to 41%; 2'-AMP was less effective. The
rate of tyrosine release resulting from insult by the hydrazines was increased
slightly by methylene blue, moderately inhibited (approximately 10 to 27%) by
the chelator o-phenanthroline and inhibited approximately 30 to 40% by
N-ethylmaleimide. Use of an oxygen-depleted atmosphere (nitrogen) increased
slightly the rate of tyrosine release stimulated by hydrazines, in contrast,
carbon monoxide decreased proteolysis stimulated by hydrazine, methylhydrazine, and
acetylphenylhydrazine by approximately 50%. Although the antioxidants
dimethylfuran, dimethylthiourea, and methylsulfoxide failed to diminish
proteolysis stimulated by the hydrazines, N-acetylcysteine exerted a protective
effect, decreasing hydrazine-stimulated
tyrosine release in red cells approximately 30 to 50%. Inclusion of
3-amino-1,2,4-triazole in the incubation failed to increase further the rate of
hydrazine-stimulated proteolysis. These
data suggest that more reactive free radicals generated from the hydrazine are responsible for protein damage,
that damaged protein (hemoglobin) is degraded via proteolysis, and that an
ATP-independent process primarily participates in the degradation of abnormal
proteins in the red cell. Thus, proteolytic enzymes present in the erythrocyte
appear to exert a protective effect against cellular damage through the removal
of abnormal proteins generated as a consequence of xenobiotic insult. The
ability of proteolytic enzymes to recognize and degrade abnormal proteins may be
of importance in using protein (hemoglobin)-xenobiotic adducts to assess
exposure to toxic agents (risk assessment).
Non-Human Toxicity Values:
LD50 Rat oral 60 mg/kg
LD50 Rabbit and guinea pig dermal 93-283 mg/kg
LC50 Rat inhalation 4 hr 570 ppm
Ecotoxicity Values:
STATIC 96-HR MEDIAN LETHAL CONCN FOR BLUEGILL WAS 1.08 MG/L & 96-HR
CONTINUOUS FLOW NO LETHAL EFFECT CONCN WAS 0.43 MG/L.
TSCA Test Submissions:
Hydrazine (CAS# 302-01-2) was
evaluated for acute inhalation toxicity. The test substance was administered as
saturated vapors to rats (strain, sex, and number not reported) for 30 minutes
resulting in 17% mortality. Clinical signs included restlessness, nasal
bleeding, salivation, and convulsions. Pathological findings included lesions of
the bronchiolar mucosa.
Hydrazine (CAS# 302-01-2) was
evaluated for acute intravenous toxicity. The test substance was administered as
an intravenous injection in rabbits (strain, sex, and number not reported). The
LD50 was reported to be 26 mg/kg. No further information was
submitted.
Hydrazine (CAS# 302-01-2) was
evaluated for acute dermal toxicity. The test substance was applied undiluted to
the clipped skin of rabbits (strain, sex, and number not reported). The test
substance produced a prompt local effect consisting of a purplish discoloration
appearing in 2-5 minutes and disappearing over the next 48-hours. The
discoloration was suspected to be a subcutaneous hemorrhage which in some
subjects would slough off the overlying skin and produce a scar. A delayed
systemic effect consisted of extensor rigidity of the forelegs and hind legs
followed by intermittent clonic convulsions. The LD50 was reported to be 91
mg/kg (mortality data not reported).
Hydrazine (CAS# 302-01-2) was
evaluated for eye irritation. The test substance was applied undiluted to the
corneas of rabbits (strain, sex, and number not reported). Doses as low as 0.3
mm3 produced moderately severe irritation, and doses at 5 mm3 produced an area
of hemorrhage in the nictitating membrane within minutes and persisted for 24-48
hours.
Hydrazine (CAS# 302-01-2) was
evaluated for carcinogenicity. The test substance was administered to rats (sex,
strain, and number not reported) at a concentration of 750 ppm for 1-hour/week
for 10 weeks. Non-malignant lesions in the nasal tissue was detected in the
treated animals indicating regenerative compensation. Also, a treatment-related
incidence of hyperplasia or adenomatous polyps in 15 or 16 animals out of 600
animals was observed.
Hydrazine (CAS# 302-01-2) was
evaluated for carcinogenicity. The test substance was administered to 100 male
hamsters at a concentration of 750 ppm or 75 ppm for 1 hour/week for 10 weeks.
Histopathological results included polypoid adenomas on the nasal turbinates in
3/94 hamsters in the 750 ppm group, and 1/93 hamsters in the 75 ppm
group.
Hydrazine (CAS# 302-01-2) was
evaluated for mutagenicity in the mammalian spot test. The test substance was
administered to C57B1/6J Han female inbred mice at a dose level of 40 mg/kg b.w.
as an intraperitoneal infection on the 9th day post-conception. The test
substance was highly toxic to the mother animals and embryos resulting in less
animals with litters and smaller litter size. Mortality at 40 mg/kg resulted in
8/173 mothers dying at delivery. Although the test substance produced a
statistically nonsignificant increase in the frequency of color spots of genetic
relevance (SGR), it was concluded that the test substance is a weak mutagen.
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
HYDRAZINE HAS BEEN FOUND TO BE A
PRIMARY PRODUCT OF NITROGEN FIXATION BY AZOTOBACTER AGILE.
HYDRAZINE ... IS ... ACETYLATED VERY
RAPIDLY IN MOST SPECIES. THE REACTION IS SO FAST THAT THE MONOACETYL METABOLITE
IS NOT DETECTED, & THE EXCRETED DIACETYL METABOLITE ACCOUNTS ALMOST ENTIRELY
FOR THE ADMIN DOSE.
HYDRAZINE IS POSSIBLY DEGRADED TO
AMMONIA, AS EVIDENCED BY ELEVATION OF BLOOD AMMONIA IN DOGS GIVEN HYDRAZINE; HOWEVER, DIACETYLHYDRAZINE IS NOT.
...
(15)N-LABELED HYDRAZINE &
CONVENTIONAL METHODS WERE USED TO ACCOUNT FOR APPROX 75% OF SINGLE DOSES OF
HYDRAZINE (1 MMOL/KG). IN 48 HR, ABOUT
30% APPEARED IN URINE AS HYDRAZINE &
ABOUT 20% EMERGED AS DERIV THAT IS ACID-HYDROLYZABLE TO HYDRAZINE. ABOUT 25% CONVERTED TO NITROGEN.
TOTAL & FREE HYDRAZINE WAS
DETECTED IN PLASMA & WHOLE BLOOD 1 HR AFTER 1ST DOSE OF ISONIAZID (300 MG,
ORALLY) & RIFAMPICIN (600 MG, ORALLY) IN SLOW & FAST ACETYLATORS. TOTAL
HYDRAZINE WAS DETECTED IN BOTH
ACETYLATORS 24 HR AFTER THE DRUGS ON DAYS 8 & 15. THIS DATA MAY HAVE
IMPORTANT TOXICOLOGICAL IMPLICATIONS IN PATIENTS WITH TUBERCULOSIS TREATED WITH
ISONIAZID.
STUDY OF RAT LIVER HOMOGENATE REVEALED THAT HYDRAZINE WAS FORMED PREFERENTIALLY FROM
ISONIAZID WHICH WAS CATALYZED BY HYDROLYTIC ENZYMES.
Administration of the hepatotoxin and carcinogen, inorganic hydrazine, to rodents results in the formation
of 7-methylguanine and O6-methylguanine in liver DNA; co-administration of
(methyl-(14)C)methionine or (14)C formate with the hydrazine labels the methylquanines,
suggesting involvement of the 1-carbon pool in the methylation process.
Formaldehyde levels were refractory to the pretreatments; hepatic acetaldehyde
levels were increased, but hydrazine
administration under such conditions did not result in the formation of
ethylated quanines in DNA. Hydrazine
incubated with liver S9 fracton and calf thymus DNA induced the formation of
7-methylquanine and O6-methylquanine when formaldehyde was present in the
incubation system.
The disposition and metabolism of hydrazine was studied in Sprague-Dawley-rats.
Rats were treated with 3, 9, 27, or 81 mg/kg hydrazine-hydrate in water. Livers were
removed for determination of toxicity and hydrazine levels after 4 days. Blood was
sampled 10, 30, 90, and 270 minutes after treatment and analyzed for hydrazine using gas chromatography and mass
spectroscopy. Urine samples were collected daily for determination of
metabolites. Another group of rats were dosed with 1.88 mmol/kg or 2.5 mmol/kg
labeled hydrazine-hydrate; plasma and
urine hydrazine levels measured 4 and 24
hours later. Hydrazine concentrations
were initially higher in the liver than in the plasma with hydrazine doses of 3 and 9 mg/kg, but this was
reversed with doses of 27 and 81 mg/kg. No relationship between hydrazine dose and liver or plasma
concentrations were seen. Twenty four hours after treatment with labeled hydrazine, the liver contained five times the
amount of hydrazine seen in the plasma.
Hydrazine and acetylhydrazine were
identified in the urine of rats O to 24 hours after treatment, and their
concentration increased with increasing doses. After 4 days, animals treated
with 81 mg/kg hydrazine lost more weight
and drank less water overall, than controls. Histological examination of livers
from animals treated with 27 and 811 mg/kg hydrazine demonstrated vacuolation, and
intracellular fat droplets were identified in animals treated with the higher
dose.
It has been demonstrated that hydrazine is metabolized by rat liver enzymes
located in the microsomal fraction. This metabolism was reduced in the absence
of oxygen or NADPH and was increased by NADH in the presence of NADPH. 2.
Microsomal enzyme inhibitors, piperonyl butoxide and metyrapone, significantly
inhibited hydrazine metabolism but
glutathione had no affect and was not depleted. 3. In addition to p450, flavin
monooxygenase may also be involved in catalysing the microsomal metabolism of
hydrazine. 4. Liver microsomes prepared
from either beta-naphthoflavone, acetone or the isoniazid-pretreated rat did not
show a significant increase in hydrazine
metabolism compared with microsomes from the control rat. However, although
phenobarbitone pretreatment increased overall microsomal hydrazine metabolism this was not increased
relative to p450 content. 5. Hydrazine
metabolism was 20-70% lower in human microsomes prepared from three individuals
compared with the control rat. 6. Hydrazine is also metabolized by rat liver
mitochondria but the monoamine oxidase inhibitors clorgyline and pargyline do
not significantly decrease this.
Previous work has demonstrated that hydrazine after formylation to its
corresponding hydrazone may be activated both in vivo and in vitro to a
methylating intermediate resulting in the formation of 06-methyl- and
N7-methylguanines in DNA. Incubation of calf thymus DNA with the hydrazine derivative, hydralazine, and
formaldehyde resulted in the production of N7-methylguanine and two aberrant
bases in DNA. These bases were separated by strong cation-exchange
high-performance liquid chromatographic fractionation of neutral thermal
hydrolysates. Administration of hydralazine to rats resulted in the formation of
N7-methylguanine in liver DNA, but the two unknown bases observed in the in
vitro experiment could not be demonstrated in vivo. In contrast to hydrazine, administration of hydralazine
resulted in the methylation of DNA only at doses approaching the LD50,
suggesting that formylation does not represent a significant mechanism for
hydralazine toxicity in the system described. Hydralazine in combination with
formaldehyde resulted in the formation of triazolophthalazine, a metabolite
which has been characterized in man. The ability of 17 other hydrazine derivatives to alkylate liver DNA
was determined after single administration to young adult male Sprague-Dawley
rats or C57BL6 mice. Quantifiable amounts of N7-methylguanine were measured in
liver DNA from animals treated with 10 of the 17 compounds. In 3 of the 10 cases
quantifiable amounts of 06-methylguanine were also measured. Methylation of
liver DNA guanine was obtained with hydrazine, hydralazine, procarbazine,
isoniazid, phenylhydrazine, nialamide, nitrofurazone, maleic hydrazide,
sulfomethoxypyridazine, and sulfamethiazole and two hydrazine-formaldehyde polymerization
products, formalazine and tetraformyltrisazine.
Absorption, Distribution & Excretion:
... ABSORBED FROM LUNGS, GI TRACT, PARENTERAL INJECTION SITES, & THROUGH
INTACT SKIN.
ABSORPTION OF HYDRAZINE THROUGH SKIN
IN DOGS IS RAPID, AND THE HYDRAZINE CAN
BE DETECTED IN FEMORAL /ARTERY/ BLOOD WITHIN 30 SECONDS.
HYDRAZINONITROGEN (ASSUMED TO BE LARGELY UNCHANGED HYDRAZINE) IS EXCRETED IN URINE AFTER IV OR SC
ADMIN OF HYDRAZINE IN DOGS. 5-11% OF
LARGE DOSES (50 MG/KG--TWICE THE LD50) EXCRETED WITHIN FIRST 4 HR & APPROX
50% OF 15 MG/KG DOSES IS EXCRETED WITHIN FIRST 2 DAYS AFTER INJECTION.
Hydrazine is rapidly and well
absorbed by the skin, GI tract, and lungs, although its vapors are not absorbed
significantly through the skin.
Biological Half-Life:
(DISAPPEARANCE OF HYDRAZINE FROM
BLOOD WAS BIPHASIC WITH HALF-LIVES OF 0.74 & 26.9 HR.
Mechanism of Action:
Injection of hydrazine (0.7 mmole/kg)
in male fasting rats caused an increase in phosphatidate phosphohydrolase
acitiviy in the soluble fraction of the liver. The increased phosphatidate
phosphohydrolase activity was parallel with a rise in hepatic triacylglycerol
(3.5-fold) and in the catecholamine concentration (3.4-fold) in adrenal glands.
Hydrazine also increased serum glucose.
The hydrazine-induced increased in
phosphatidate phosphohydrolase activity and triacylglycerol accumulation was
completely prevented by adrenalectomy. The data suggest that increased
phosphatidate phosphohydrolase activity is at least partly responsible for hydrazine-induced fatty liver and that adrenal
hormones may take part in the mechanism by which hydrazine exerts its effects on the liver.
Hydrazine is acutely neurotoxic,
hepatotoxic and nephrotoxic; it is also carcinogenic to liver and lung in
rodents. Administration of hydrazine
results in formation of 7-methylquanine and O6-methylguanine in target organ DNA
of rats, mice, hamsters and guinea pigs. It has been suggested that hydrazine reacts with endogenous formaldehyde
to form a condensation product which could be metabolized to a methylating
agent. Solutions of 0.50 mM hydrazine
and formaldehyde have, upon mixing, NMR spectra (300 mHz) consistent with the
formation of formaldehyde hydrazone but not other possible condensation products
such as tetraformyltriazine or formaldehyde azine. These same solutions
evidencing hydrazone formation, when incubated in an in vitro system containing
post-mitochondrial (S9), microsomal, cytosolic or mitochondrial cell fractions,
resulted in the methylation of DNA guanine; S9 was the most active fraction.
Neither the p450 monooxygenase nor flavin monooxygenase systems appeared to be
important in hydrazine/formaldehyde-induced methylation of
DNA. However, sodium azide, cyanamide and carbon monoxide all inhibited
S9-supported DNA methylation. Bovine liver catalase, a heme-containing
cytochrome, readily transformed hydrazine/formaldehyde to a methylating agent.
The data support formation of formaldehyde hydrazine as the condensation product of hydrazine and formaldehyde which is rapidly
transformed in various liver cell fractions, perhaps by catalase and/or
catalase-like enzyme, to a methylating agent.
The genotoxicity of a variety of hydrazine derivatives was examined in the DNA
repair test on rat or mouse hepatocytes. Out of 32 hydrazine derivatives, 6 chemicals, ie,
N'-acetyl-4-(hydroxymethyl)phenylhydrazine, 1,2-dimethylhydrazine
dihydrochloride, 1-hydrazinophthalazine hydrochloride, methylhydrazine.sulfate,
p,p-oxybisbenzene disulfonylhydrazide and phenylhydrazine hydrochloride,
elicited positive DNA repair responses in the test on rat hepatocytes. In the
test on mouse hepatocytes, 4 more hydrazine derivatives, ie,
1,1-dimethylhydrazine, hydrazine
hydrate, hydrazine sulfate and
2-methyl-4-chlorophenoxyacetic acid hydrazide hydrochloride also generated
positive responses, in addition to the 6 positive compounds in the rat assay.
These results suggest that mouse hepatocytes are more susceptible to the
genotoxicity of hydrazine derivatives,
and that the species differences in genotoxicity appear to be in agreement with
the in vivo carcinogenicity of these agents.
The induction of liver DNA adducts by hydrazine was investigated in two mouse
strains. Male Swiss Webster mice and B6C3F1 mice were administered single
intraperitoneal injections of 0, 5, 10, 20 or 40 mg/kg hydrazine and were sacfificed 24 hours later.
Isolated liver DNA was analyzed for chemical adducts involving purine bases,
using high performance liquid chromatography and fluorescence spectrophotometry.
Dose dependent formation of 7-methylguanine (7MG) and O6-methylguanine (06MG)
was observed in liver DNA of both strains of mice. The persistence of the
methylguanines in mouse liver DNA was determined in Swiss Webster mice and
B6C3F1 mice administered 20 mg/kg hydrazine and sacrificed at 24 hour intervals
for up to 96 hours. The rates of formation of 7-methylguanine and
O6-methylguanine and the rate of removal of 7-methylguanine were similar in the
two strains of mice. However, the rate of disappearance of O6-methylguanine was
considerably slower in B6C3F1 mice than in Swiss Webster mice, with estimated
half lifes of 200 hours and 17 hours in the two strains, respectively. The
results of this study were compared with those of a similar study in which
levels of O6-methylguanine and 7-methylguanine in liver DNA were followed in
Syrian golden hamsters administered hydrazine in their drinking water for a period
of 2 years. /Results indicate/ that hydrazine may be a hepatocarcinogen to which
B6C3F1 mice may be particularly susceptible due to the persistence of
O6-methylguanine in this mouse strain.
...The mechanism of action appears to be through indirect alkylation of DNA,
which itself is closely connected to the toxic action of hydrazine (i.e., through reacting with a
cellular intermediate in the initiation of neoplastic transformation).
Interactions:
COMBINED ACTION OF COMMERCIAL HYDRAZINE-BENZENE & BENZIDINE-SULFATE IN
RATS INCREASED THE INCIDENCE OF TUMORS & REDUCED THE MEAN LATENT PERIOD OF
NEOPLASM DEVELOPMENT.
Pretreatment of Vicia faba root-tip meristems with a nontoxic dose of either
hydrazine or N,N'-diformylhydrazine
prior to the administration of maleic hydrazide, separated by 2 hr, resulted in
a significant reduction of the yield of maleic hydrazide-induced chromatid
aberrations compared to control treatments (maleic hydrazide only). This
clastogenic adaptation was not observed when the alkylating agent triethylene
melamine was used instead of maleic hydrazide. Thus, pretreatment with the
hydrazines induces an error-free repair system which reduces maleic
hydrazide-induced damage and both hydrazines and maleic hydrazide appear able to
induce oxidative DNA lesions.
Administration of the hepatotoxin and carcinogen, inorganic hydrazine, to rodents results in the formation
of 7-methylguanine and O6-methylguanine in liver DNA; co-administration of
methyl-(14)C-methionine or (14)C-formate with the hydrazine lables the methylguanines,
suggesting involvement of the 1-carbon pool in the methylation process. The
present study investigates the proposal that the methylation mechanism involves
reaction of hydrazine with endogenous
formaldehyde to yield formaldehyde hydrazone, which could be metabolized to the
potent methylating agent diazomethane. Hamsters were pretreated with methanol,
ethanol or cyanamide to alter the endogenous hepatic aldehyde levels prior to
administration of hydrazine.
Formaldehyde levels were refractory to the pretreatment; hepatic acetaldehyde
levels were increased, but hydrazine
administration under such conditions did not result in the formation of
ethylated guanines in DNA. Methanol and ethanol inhibited hydrazine-induced methylaton of DNA. Hydrazine incubated with liver S9 fraction and
calf thymus DNA induced the formation of 7-methylguanine and O6-methylguanine
when formaldehyde was present in the incubation system; substitution of
formaldehyde with acetaldehyde in the incubation medium did not result in any
detectable alkylation of DNA. Both liver microsomal and cytosolic fractions
demonstrated heat-liable activity in supporting the hydrazine-induced methylation process.
Tetraformyltrisazine or a similar reaction product of hydrazine and formaldehyde, may be a more
important intermediate than formaldehyde hydrazone in the hydrazine-induced methylation of DNA.
Pharmacology:
Therapeutic Uses:
EXPTL USE: THE RESPONSE OF RED CELLS FROM PATIENTS WITH SICKLE CELL DISEASE
TO HYDRAZINE TREATMENT IN VITRO IS TO
INHIBIT THE SICKLED MORPHOLOGY, WHILE THE METABOLIC CHARACTERISTICS &
OSMOTIC FRAGILITY OF THE CELLS REMAIN UNALTERED. HOWEVER, THE OXYGEN AFFINITY OF
THE SICKLE CELL HEMOGLOBIN IS DECREASED.
Interactions:
COMBINED ACTION OF COMMERCIAL HYDRAZINE-BENZENE & BENZIDINE-SULFATE IN
RATS INCREASED THE INCIDENCE OF TUMORS & REDUCED THE MEAN LATENT PERIOD OF
NEOPLASM DEVELOPMENT.
Pretreatment of Vicia faba root-tip meristems with a nontoxic dose of either
hydrazine or N,N'-diformylhydrazine
prior to the administration of maleic hydrazide, separated by 2 hr, resulted in
a significant reduction of the yield of maleic hydrazide-induced chromatid
aberrations compared to control treatments (maleic hydrazide only). This
clastogenic adaptation was not observed when the alkylating agent triethylene
melamine was used instead of maleic hydrazide. Thus, pretreatment with the
hydrazines induces an error-free repair system which reduces maleic
hydrazide-induced damage and both hydrazines and maleic hydrazide appear able to
induce oxidative DNA lesions.
Administration of the hepatotoxin and carcinogen, inorganic hydrazine, to rodents results in the formation
of 7-methylguanine and O6-methylguanine in liver DNA; co-administration of
methyl-(14)C-methionine or (14)C-formate with the hydrazine lables the methylguanines,
suggesting involvement of the 1-carbon pool in the methylation process. The
present study investigates the proposal that the methylation mechanism involves
reaction of hydrazine with endogenous
formaldehyde to yield formaldehyde hydrazone, which could be metabolized to the
potent methylating agent diazomethane. Hamsters were pretreated with methanol,
ethanol or cyanamide to alter the endogenous hepatic aldehyde levels prior to
administration of hydrazine.
Formaldehyde levels were refractory to the pretreatment; hepatic acetaldehyde
levels were increased, but hydrazine
administration under such conditions did not result in the formation of
ethylated guanines in DNA. Methanol and ethanol inhibited hydrazine-induced methylaton of DNA. Hydrazine incubated with liver S9 fraction and
calf thymus DNA induced the formation of 7-methylguanine and O6-methylguanine
when formaldehyde was present in the incubation system; substitution of
formaldehyde with acetaldehyde in the incubation medium did not result in any
detectable alkylation of DNA. Both liver microsomal and cytosolic fractions
demonstrated heat-liable activity in supporting the hydrazine-induced methylation process.
Tetraformyltrisazine or a similar reaction product of hydrazine and formaldehyde, may be a more
important intermediate than formaldehyde hydrazone in the hydrazine-induced methylation of DNA.
Environmental Fate & Exposure:
Environmental Fate/Exposure Summary:
Hydrazine's production and use as a
chemical intermediate, reducing agent, as rocket fuel and as a boiler water
treatment agent may result in its release to the environment through various
waste streams. Hydrazine is also
naturally produced by Azotobacter agile during nitrogen fixation. If released to
the atmosphere, hydrazine will exist
solely in the vapor phase in the ambient atmosphere, based on a measured vapor
pressure of 14.4 mm Hg at 25 deg C. Vapor-phase hydrazine is degraded in the atmosphere by
reaction with photochemically-produced hydroxyl radicals and ozone with
estimated half-lives of about 6 and 9 hours, respectively. Release of hydrazine to soil is expected to result in
degradation in soils containing a high percentage of organic carbon and in
strong adsorption in soils containing high clay content. In other soils,
especially sandy soils, hydrazine may
have high mobility. Volatilization from moist soil surfaces is not expected
based on an estimated Henry's Law constant of 6.1X10-7 atm-cu m/mole. The
potential for volatilization of hydrazine from dry soil surfaces may exist
based on the vapor pressure of this compound. Biodegradation is not expected to
be an important environmental fate process in the presence of a large amount of
hydrazine due to its toxicity to
microorganisms; it may be important at low hydrazine concentrations. Release of hydrazine to water should result in rapid
degradation of hydrazine, especially in
water containing high concentrations of organic matter and dissolved oxygen. The
estimated half-life of hydrazine in pond
water is 8.3 days. Based on soil studies, hydrazine may bind to clay and organic matter
found in sediments and particulate material in water; it should not strongly
adsorb to other types of particulates. This compound should not volatilize from
water surfaces given its estimated Henry's Law constant. A measured BCF value of
316 suggests that bioconcentration in aquatic organisms may be high. Based on
the physical properties of this compound, low bioconcentration is predicted.
Occupational exposure may occur through inhalation or dermal contact at
workplaces where hydrazine is produced
or used. The general population may be exposed to hydrazine through inhalation of cigarette
smoke or the ingestion of trace residues in processed foods. (SRC)
Probable Routes of Human Exposure:
... Route of human exposure to hydrazine is ingestion of trace residues in
processed foods. ...
THE SMOKE FROM A BLENDED US CIGARETTE CONTAINED 31.5 NG HYDRAZINE.
An industrial hygiene assessment of the extent of exposure to hydrazine compounds was carried out due to the
growing number of such compounds shown to be animal carcinogens in laboratory
studies. The report summarizes production and uses of hydrazine compounds, the toxic effects of such
compounds, relevant exposure standards, sampling and analytical methods relevant
to exposure assessment, and observations made during surveys conducted at eight
facilities in the United States where these compounds were either prepared or
used. The sites visited for the survey were of four basic types: those which
used hydrazine compounds as propellants,
those which manufactured the compounds, those which used hydrazine as an aircraft emergency power unit
fuel, or sites where hydrazine was used
in boiler water treatment. Personal exposures measured were generally within the
range from below the limit of detection to 1.0 ppm as an 8 hour time weighted
average. The OSHA permissible exposure limits for the hydrazine compounds of interest ranged from
0.5 to 5 ppm. The number of workers exposed was found to be low. Large scale
propellant and emergency jet power unit usage was relatively new, and the
manufacturing methods had not been used until recently. /Data indicated/ that
the accumulated person years of exposure are relatively low; it is unlikely that
suitable cohorts exist for retrospective expsoure studies.
NIOSH (NOES Survey 1981-1983) has statistically estimated that 59,147 workers
(2,840 of these are female) are potentially exposed to hydrazine in the US(1). About 2000 Finnish
employees were exposed to hydrazine
between the years 1980-1989(2). Occupational exposure may be through inhalation
and dermal contact with this compound at workplaces where hydrazine is produced or used(SRC). The
general population will be exposed to hydrazine via inhalation of ambient air and
cigarette smoke, ingestion of food, and dermal contact with vapors and other
products containing hydrazine(SRC).
Natural Pollution Sources:
Hydrazine has been found to be a
primary product of nitrogen fixation by Azotobacter algae
Artificial Pollution Sources:
ONE SOURCE HAS REPORTED THAT THE BURNING OF ROCKET FUELS BASED ON HYDRAZINE & DIMETHYLHYDRAZINE PRODUCES
EXHAUST GASES WHICH CONTAIN ONLY TRACE QUANTITIES OF UNCHANGED FUEL.
Hydrazine's production and use as a
chemical intermediate, reducing agent, as rocket fuel(1) and as a boiler water
treatment agent(2) may result in its release to the environment through various
waste streams(SRC).
THE USE OF HYDRAZINE IN BOILER WATER
TREATMENT MIGHT RESULT IN ITS BRIEF APPEARANCE IN WASTE DISCHARGE, BUT IT WOULD
REACT WITH OXYGEN RAPIDLY.
Environmental Fate:
THE USE OF HYDRAZINE AS A CHEMICAL
INTERMEDIATE WOULD NOT BE LIKELY TO RESULT IN ITS APPEARANCE IN UNREACTED FORM
IN THE ENVIRONMENT.
TERRESTRIAL FATE: Of the initial concentration of hydrazine in cleaned sand (100% sand),
Vandenburg Air Force Base soil (99.1% sand, 0.4% clay, pH 6.1), organic soil
(96.1% sand, 1% clay, 1% carbon, pH 6.4), and clay (69.3% sand, 27.95% clay, pH
3.7), 0%, 14%, 28%, and 18% was degraded, respectively(1). Based on further
results from this study, hydrazine
should be mobile in most soils. Of the initial amount of hydrazine applied to the same four soil types
as above, cleaned sand, Vandenburg Air Force Base (VAFB) soil, organic soil, and
clay, 2%, 44%, 25%, and 59% was adsorbed, respectively(1). Therefore, leaching
of this compound may result upon release of hydrazine to sandy soil; however, hydrazine is expected to degrade in soil high
in organic carbon and to adsorb to soils high in clay content(1,SRC).
Biodegradation is not expected to be significant when large amounts of hydrazine are released due to the high
microbial toxicity of hydrazine(2); at
lower concentrations, however, hydrazine
biodegradation could be important(3,SRC). Volatilization of hydrazine should not be important from moist
soil surfaces(SRC) given an estimated Henry's Law constant of 6.1X10-7 atm-cu
m/mole(SRC), calculated from experimental values for vapor pressure(4) and water
solubility(5). The potential for volatilization of hydrazine from dry soil surfaces may
exist(SRC) based on a measured vapor pressure of 14.4 mm Hg(4).
AQUATIC FATE: The estimated half-life of hydrazine, initially present at 1.8 mM, in
pond water is 8.3 days(1). In river water, containing substantial amounts of
organic matter, 22.6%, 96%, and 100% of the added hydrazine, initially at 5 mg/l, was degraded
after about 1 hour, 1 day and 2 days, respectively. In pond water, 20%, 74%,
80%, and 81.6% of the added hydrazine,
initially at 5 mg/l, was degraded after about 1 hr, 1 day, 2 days and 3 days,
respectively(2). Hydrazine will react
with dissolved oxygen at a rate inversely proportional to the concentration of
hydrazine. After 4 days, 52%, 48%, 21.4%
and 7.4% of the added hydrazine had
degraded in hard water, moderately hard water, slightly hard water, and soft
water samples, respectively(2). The addition of organic matter increased the
amount of hydrazine degraded(2). Based
on soil studies(1), hydrazine may bind
to clay and organic matter found in sediments and particulate material in water;
it should not strongly adsorb to other types of particulates(SRC).
AQUATIC FATE: Based on limited data, biodegradation is not expected to be
significant upon the release of large amounts of hydrazine as it is microbially toxic(1); at
lower hydrazine concentrations
biodegradation may be important(2,SRC). Hydrazine is not expected to volatilize from
water surfaces(3,SRC) based on an estimated Henry's Law constant of 6.1X10-7
atm-cu m/mole(SRC), calculated from experimental values for vapor pressure(4)
and water solubility(5). According to a classification scheme(6), a BCF value of
316, measured in guppies(7), suggests that bioconcentration in aquatic organisms
may be high; however, based on the physical properties of this compound (an
estimated BCF value of 0.01(3,SRC), from a measured log Kow(8)), only low
bioconcentration is predicted(SRC).
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of
semivolatile organic compounds in the atmosphere(1), hydrazine, which has a measured vapor pressure
of 14.4 mm Hg at 25 deg C(2), will exist solely as a vapor in the ambient
atmosphere. Vapor-phase hydrazine 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 about 6
hours(3,SRC). Based on experimental data and assuming an ozone concentration of
7X10+11 molecules/cu cm, the half-life for the reaction between ozone and hydrazine is about 9 hr(4,SRC). It was
estimated that the half-life for the reaction of hydrazine with ozone would be < 10 min
during ozone pollution episodes and < 2 hr in the 'natural' troposphere(5).
Hydrazine will react rapidly with
nitrogen oxides in the light and in the dark with a half-life of about 2 hr(6).
Direct photolysis is not expected to be an important fate process(SRC).
Environmental Biodegradation:
Pure cultures of Azotobacter vinelandii are capable of metabolizing hydrazine to three carboxylic acids related to
3,4-dihydropyridazinone-5-carboxylic acid and ammonia and nitrogen gas(1) and
unidentified, acid-labile compounds(2). The degradation of hydrazine hydrate in river water follows 1st
order reaction kinetics(3). The degradation rate increases with increasing
temperature, dissolved oxygen, and the presence of microorganisms at pH values
of 6-8(3). Hydrazine at 500 mg/l,
present in a wastewater mixture of other hydrazine compounds, was incubated with an
inoculum prepared from a trickling filter plant; following a 24 hour lag period,
this mixture of compounds was readily biodegraded as measured by oxygen
uptake(4). No specific information on the fate of hydrazine alone was available in this
study(4).
Environmental Abiotic Degradation:
The absolute rate constant for the reaction of vapor phase hydrazine with hydroxyl radicals over the
temperature range 298-424 K determined by flash photolysis-resonance
fluorescence is 6.1X10-11 cu cm/molecule sec(1). This corresponds to an
atmospheric half-life of about 6 hours at an atmospheric concentration of 5X10+5
hydroxyl radicals per cu cm(1,SRC). The rate constant for the reaction of
vapor-phase hydrazine with ozone,
determined in a static system with an FT-IR detector, is 3X10-17 cu
cm/molecule/sec at 298 K(2). This corresponds to an atmospheric half-life of
about 9 hours at an atmospheric concentration of 7X10+11 ozone molecules per cu
cm(2,SRC). Apparent rate constants of about 0.2 ppm/min and about 0.3 ppm/min
for the reaction between ozone and hydrazine were estimated from decay rates for
the two species determined in the dark in an outdoor 30,000 l Teflon bag at
21-24 and 44 deg C(3). The major product of the reaction was hydrogen peroxide;
N20 and NH3 were minor products(3). It was estimated that the half-life for the
reaction of hydrazine with ozone would
be < 10 min during ozone pollution episodes and < 2 hr in the 'natural'
troposphere(3). In the absence of ozone, the hydrazine half-life at 15 deg C and 16%
relative humidity is 5 hr, and at 14 deg C and 85% relative humidity is 1.8
hr(3). Ammonia was detected but accounted for only 5-10% of the hydrazine which decayed(3).
When a mixture of 0.87 ppm NO and 0.12 ppm nitrogen dioxide and 1.3 ppm of
hydrazine in a 30,000 l Teflon chamber
was exposed to sunlight, nearly 100% of the hydrazine was degraded in 30 min(1). The level
of nitrous oxide increased throughout the experiment. In the dark under similar
conditions, 15% of the initial hydrazine
degraded in 26 min and the half-life was about 2 hr(1). Decomposition of the
hydrazine to nitrogen gas and water
predominated and no evidence of a reaction between hydrazine and nitrogen oxides was observed(1).
The half-life for the reaction between hydrazine in atmospheric aerosols with ozone
is about 100 min(2). Nitrogen and water are products of the aqueous ozone
oxidation of hydrazine(2). The relative
contributions to ozone oxidation of hydrazine via aqueous and gas phase routes
were estimated for both a moderately polluted and a remote environment; aqueous
and gas phase oxidation rates, based on the total amounts of hydrazines present
in all forms were slower in the polluted than in the remote environment(3).
Aqueous aerosol from a polluted environment would have a much lower pH where 99%
or more of the total particular hydrazine present is dissolved in the aerosol
as the protonated form; this form oxidizes slowly, if at all(3).
Hydrazine was added at 5.0 mg/l to
city, county and stored laboratory water which had been adjusted to the same
temperature and dissolved oxygen levels. After 4 days, 10%, 100% and 40% of the
added hydrazine had degraded in the
city, county and laboratory waters, respectively(1). This result was attributed
to the relatively high hardness of the county water(1). The contribution of
water hardness to hydrazine degradation
was confirmed in another experiment. Samples of hard water, moderately hard
water, slightly hard water, and soft water were mixed with 5 mg/l hydrazine. After 4 days, 52%, 48%, 21.4% and
7.4% of the added hydrazine had degraded
in the hard water, moderately hard water, lightly hard water, and soft water,
respectively(1). After 4 days in hard water with and without fish excreta, 100%
and 55% of the added hydrazine had
degraded. After 4 days in soft water with and without fish excreta, 70% and 10%
of the added hydrazine had degraded(1).
Polluting material, rich in organic matter, was the leading contributor to hydrazine degradation(1); it was shown that
dissolved organic matter in pond water reduces the effective concentration of
added copper, decreasing the rate of hydrazine autoxidation(2). In aqueous systems,
the primary mechanism of hydrazine
degradation seems to be a four-electron oxidation to N2 gas by oxygen. The
oxidation rate was very slow in distilled water but increased with the addition
of catalysts such as Cu(II) and phosphate ions. Ammonia as well as N2 gas
evolution was correlated with Cu(II) and phosphate ion concentration(3). Hydrazine solutions are inherently unstable in
the presence of oxygen under alkaline or neutral conditions (the autoxidation
rate was found to be higher at pH 7.0 than at pH 9.0); however, they are quite
stable under strongly acidic conditions or in the absence of oxygen(3). After
four hours, approximately 72%, 60%, 47%, and 39% of the hydrazine initially present at 0.047, 0.068,
0.158 and 0.195 ppm, respectively, reacted with oxygen in air-saturated
distilled water at 20 deg C and pH 9(4).
Environmental Bioconcentration:
Bioconcentration in guppies was studied using a hydrazine concentration in water of 0.5 ug/g.
After 96 hours, the concentration of hydrazine in guppies was about 144 ug/g(1).
These values give a bioconcentration factor of 316. An estimated BCF value of
0.01 was calculated for hydrazine(SRC),
using a measured log Kow of -2.07(2) and a recommended regression-derived
equation(3). According to a classification scheme(4), these BCF values suggest
that bioconcentration in aquatic organisms may be high, as for guppies; however,
based on this compound's values for log Kow(2) and water solubility(5), the
potential for bioconcentration in aquatic organisms is generally expected to be
low(SRC).
Soil Adsorption/Mobility:
Of the initial amount of hydrazine
applied to cleaned sand (100% sand), Vandenburg Air Force Base (VAFB) soil
(99.1% sand, 0.4% clay, pH 6.1), organic soil (96.1% sand, 1% clay, 1% carbon,
pH 6.4), and clay (69.3% sand, 27.95 clay, pH 3.7), 2%, 44%, 25%, and 59% was
adsorbed, respectively. Passage of water through columns containing cleaned
sand, VAFB soil, organic soil and clay (10% clay soil plus 90% pure sand)
treated with 10 ml of a 0.1 v/v solution of hydrazine resulted in 89.1%, 1.6%, 1.3% and
7.6% recovery of hydrazine,
respectively(1). The adsorption of hydrazine to montmorillonite follows an L-2
type isotherm with an initial slope that is nonlinear and concave with respect
to the abscissa(2). This indicates that hydrazine has a preferential sorption
initially compared to the solvent or other solutes, with sorption decreasing as
more hydrazine is sorbed(2).
Hydrazine is a weak base (pKa= 7.96);
at pH values well below the pKa, hydrazine exists primarily as the protonated
form and can take part in cation exchange reactions(1). The nature and extent of
hydrazine adsorption by clays and soils
is very dependent on suspension pH and on the types of surface functional groups
present on the solid matrix. Under acidic conditions, pH 4.0, 99.9% of the hydrazine is present as the protonated species
and should be able to readily replace Na+ from exchange sites(1). Under alkaline
conditions, pH 8.0, approximately 50% of the hydrazine is protonated and 50% is in neutral
form. The primary mechanism of hydrazine
adsorption in a montmorillonite clay suspension was cation exchange, both at pH
4 and 8; adsorption of hydrazine was
lower at the higher pH value(1). The main mechanism for hydrazine retention at pH 4 and at low hydrazine concentrations in the upper
Arrendondo soil horizon (fine sand) was also cation exchange. At higher
concentrations more than 60% of the hydrazine interacted with a different type of
binding site, possibly with organic-surface functional groups such as carbonyl
groups(1). Under alkaline conditions, using upper horizon Arrendondo soil, (at
pH 8.0) hydrazine was adsorbed more
readily than at pH 4(1).
Volatilization from Water/Soil:
With an air velocity at the liquid surface of 63.5 cm/sec, the volatilization
of hydrazine from petri dishes
containing 25%, 50% and 75% hydrazine-water mixtures was 0.5 g after 6.66
hr, about 1 g after 5 hr, and about 3 g after 5 hr, respectively(1). At each
concentration, the rate of volatilization decreased with time(1). The Henry's
Law constant for hydrazine is estimated
as 6.1X10-7 atm-cu m/mole(SRC) from its experimental values for vapor pressure,
14.4 mm Hg(2), and water solubility (miscible in water at 25 deg C)(3). This
value indicates that hydrazine will be
essentially nonvolatile from water surfaces(4,SRC). Hydrazine's Henry's Law constant(2,3,SRC)
indicates that volatilization from moist soil surfaces should not occur(SRC).
The potential for volatilization of hydrazine from dry soil surfaces may
exist(SRC) based on the vapor pressure of this compound(2,SRC).
Other Environmental Concentrations:
THE SMOKE FROM A BLENDED US CIGARETTE CONTAINED 31.5 NG HYDRAZINE.
Environmental Standards & Regulations:
TSCA Requirements:
Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety
Data Reporting Rule. The section 8(d) model rule requires manufacturers,
importers, and processors of listed chemical substances and mixtures to submit
to EPA copies and lists of unpublished health and safety studies. Hydrazine is included on this list.
CERCLA Reportable Quantities:
Persons in charge of vessels or facilities are required to notify the
National Response Center (NRC) immediately, when there is a release of this
designated hazardous substance, in an amount equal to or greater than its
reportable quantity of 1 lb or 0.454 kg. The toll free number of the NRC is
(800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The
rule for determining when notification is required is stated in 40 CFR 302.4
(section IV. D.3.b).
Releases of CERCLA hazardous substances are subject to the release reporting
requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to
the requirements of 40 CFR part 355. Hydrazine is an extremely hazardous substance
(EHS) subject to reporting requirements when stored in amounts in excess of its
threshold planning quantity (TPQ) of 1,000 lbs.
RCRA Requirements:
U133; As stipulated in 40 CFR 261.33, when hydrazine, as a commercial chemical product or
manufacturing chemical intermediate or an off-specification commercial chemical
product or a manufacturing chemical intermediate, becomes a waste, it must be
managed according to Federal and/or State hazardous waste regulations. Also
defined as a hazardous waste is any residue, contaminated soil, water, or other
debris resulting from the cleanup of a spill, into water or on dry land, of this
waste. Generators of small quantities of this waste may qualify for partial
exclusion from hazardous waste regulations (40 CFR 261.5).
Atmospheric Standards:
Listed as a hazardous air pollutant (HAP) generally known or suspected to
cause serious health problems. The Clean Air Act, as amended in 1990, directs
EPA to set standards requiring major sources to sharply reduce routine emissions
of toxic pollutants. EPA is required to establish and phase in specific
performance based standards for all air emission sources that emit one or more
of the listed pollutants. Hydrazine is
included on this list.
Chemical/Physical Properties:
Molecular Formula:
H4-N2
Molecular Weight:
32.05
Color/Form:
COLORLESS OILY LIQUID
WHITE CRYSTALS
Colorless fuming, oily liquid ... (Note: A solid below 36 degrees F).
Anhydrous hydrazine is a waxy solid.
Odor:
PENETRATING ODOR RESEMBLING AMMONIA
... Ammonia-like odor ...
Boiling Point:
113.5 deg C at 760 mm Hg
Melting Point:
2.0 DEG C
Critical Temperature & Pressure:
CRITICAL TEMPERATURE: 380 DEG C; CRITICAL PRESSURE: 14 ATM
Density/Specific Gravity:
1.011 at 15 deg C/4 deg C; 1.0036 at 25 deg C/4 deg C; 0.9955 at 35 deg C/4
deg C; 1.0253 at 0 deg C/4 deg C; 1.024 at 2 deg C/4 deg C; 1.146 at -5 deg C/4
deg C
Dissociation Constants:
pKa= 7.96
Heat of Combustion:
-8345 BTU/LB = -4636 CAL/G = -194.1X10+5 J/KG
Heat of Vaporization:
45.27 kJ/mol
Octanol/Water Partition Coefficient:
LogP= -2.07
pH:
Aqueous solutions of hydrazine are
highly alkaline. pH of a 64 wt% aqueous solution of hydrazine is 12.75.
Solubilities:
Miscible with water, methyl, ethyl, propyl, and isobutyl alcohols
SLIGHTLY MISCIBLE WITH HYDROCARBONS, HALOGENATED HYDROCARBONS
INSOL IN CHLOROFORM & ETHER
water solubility = 1X10+6 mg/l
Spectral Properties:
Index of Refraction: 1.46979 at 22.3 deg C/D; 1.46444 at 35 deg C/D
Surface Tension:
66.7 mN/m at 25 deg C
Vapor Pressure:
14.4 mm Hg at 25 deg C
Viscosity:
0.974 uPa-sec at 20 deg C
Other Chemical/Physical Properties:
FORMS SALTS WITH INORGANIC ACIDS; HIGHLY POLAR SOLVENT; POWERFUL REDUCING
AGENT
A GALLON OF COMMERCIAL PRODUCT WEIGHS 8.38 LB; DISSOLVES MANY INORGANIC
SUBSTANCES; FORMS AZEOTROPIC MIXT WITH WATER WITH BP OF 120.3 DEG C THAT
CONTAINS 55 MOLE-% N2H4; CONTRACTS ON FREEZING
Heat capacity: 92.9 J/mole deg K at 1 atm, 25 deg C
DIPOLE MOMENT 1.83-1.90; DIELECTRIC CONSTANT: 51.7 AT 25 DEG C; LATENT HEAT
OF FUSION AT MP: 3.025 KCAL/MOLE
Ionization potential: 8.36 eV
Fuming refractive liq, faint characteristic odor; Density 1.03 at 21 deg C;
MP: -51.7 deg C or below -65 deg C (two eutectics); BP: 118-19 deg C at 740 mm
Hg; Index of refraction: 1.42842 at 20 deg C/d /Hydrazine hydrate/
Strong base, very corrosive, attacks glass, rubber, cork; very powerful
reducing agent; miscible with water or alcohol; insol in chloroform & ether
/Hydrazine hydrate/
Surface tension 74.3 mN/m at 25 deg C, viscosity: 1.5 mPa.s at 25 deg C,
index of refraction: 1.4644 at 25 deg C/d, heat of formation -242.71 kJ/mol
/Hydrazine hydrate/
Colorless crystals; density 1.42; MP: 198 deg C (loses hydrogen chloride);
BP: 200 deg C (decomposes); slightly sol in alcohol /Hydrazine dihydrochloride/
White, crystalline flakes; MP: 81-87 deg C, decompose at approx 190 deg, sol
in lower alcohols, insol in most organic solvents /Hydrazine monohydrobromide/
Solubility: 282.0 g/100 g water at 25 deg C; Melting point= 86.5 deg C /Hydrazine monohydrobromide/
White crystalline flakes, mp: 87-92 deg C, decomposes at approx 240 deg C,
sol in water (37 g/100 g water at 20 deg C), somewhat sol in lower alcohols,
insol in most organic solvents /Hydrazine monohydrochloride/
Solid; density 1.939; MP: 137 deg C; BP: 145 deg C; decomp in water; sol in
alcohol, insol in ether, benzene, chloroform, & carbon disulfide /Hydrazine perchlorate, hemihydrate/
MP: 127 deg C; sol in water at 25 deg C /Hydrazine monohydroiodide/
MP: 70.71 deg C, alpha, 62.09, beta; solubility: 327.5 g/100 g water at 25
deg C /Hydrazine nitrate/
Diacidic base
Boiling point= 56 deg C at 71 mm Hg; 170 deg at 5 atm; 200 deg C at 10 atm;
236 deg C at 20 atm
Heat of formation= 50.63 kJ/mol; Anhydrous hydrazine is self-explosive.
hydroxyl radical rate constant = 6.50X10-11 cu-cm/molc sec @ 25 deg C
Chemical Safety & Handling:
Odor Threshold:
3-4 PPM
Skin, Eye and Respiratory Irritations:
Vapors are very irritating to the mucous membranes, nose, throat, and upper
respiratory tract.
Fire Potential:
HYDRAZINE VAPOR IS EXCEPTIONALLY
HAZARDOUS IN THAT ONCE IT IS IGNITED IT WILL CONTINUE TO BURN BY EXOTHERMIC
DECOMP IN COMPLETE ABSENCE OF AIR OR OTHER OXIDANT.
Flammable liquid. Flammable over a wide range including 100% pure material.
Air or oxygen is not required for decomposition. Closed containers may rupture
violently when heated. Thermally unstable. Ignites in air at room temperature on
metal oxide surfaces, & in a wide variety of porous materials, such as
cellulosic materials.
NFPA Hazard Classification:
Health: 3. 3= Materials that, on short exposure, could cause serious
temporary or residual injury, including those requiring protection from all
bodily contact. Fire fighters may enter the area only if they are protected from
all contact with the material. Full protective clothing, incl self-contained
breathing apparatus, coat, pants, gloves, boots and bands around legs, arms and
waist should be provided. No skin surface should be exposed.
Flammability: 3. 3= Includes Class IB and IC flammable liquids and materials
that can be easily ignited under almost all normal temp conditions. Water may be
ineffective in controlling or extinguishing fires in such materials.
Reactivity: 3. 3= This degree includes materials that, in themselves, are
capable of detonation, explosive decomposition, or explosive reaction, but
require a strong initiating source or heating under confinement. This includes
materials that are sensitive to thermal and mechanical shock at elevated
temperatures and pressures and materials that react explosively with water.
Fires involving these materials should be fought from a protected location.
Flammable Limits:
Lower flammable limit: 2.9% by volume; Upper flammable limit: 98% by volume
Flash Point:
100 deg F; 38 deg C (Closed cup)
Autoignition Temperature:
Ignition temperatures vary widely in contact with iron rust 74 deg F (23 deg
C); black iron 270 deg F (132 deg C); stainless steel 313 deg F (156 deg C);
glass 518 deg F (270 deg C).
Fire Fighting Procedures:
If material on fire or involved in fire: Do not extinguish fire unless flow
can be stopped or safely confined. Use water in flooding quantities as fog.
Solid streams of water may be ineffective. Cool all affected containers with
flooding quantities of water. Apply water from as far a distance as possible.
Use "alcohol" foam, dry chemical or carbon dioxide. /Hydrazine, anhydrous/
If material on fire or involved in fire: Do not extinguish fire unless flow
can be stopped. Use water in flooding quantities as fog. Cool all affected
containers with flooding quantities of water. Apply water from as far a distance
as possible. Solid streams of water may be ineffective. Use "alcohol" foam, dry
chemical or carbon dioxide. /Hydrazine,
aqueous solution/
Explosive Limits & Potential:
EXPLODES DURING DISTILLATION IF TRACES OF AIR ARE PRESENT, ALSO AFFECTED BY
UV & METAL ION CATALYSTS.
Vapors explosive.
Hazardous Reactivities & Incompatibilities:
RESIDUE FROM DEHYDRATING HYDRAZINE
WITH BARIUM OR CALCIUM OXIDE SLOWLY DECOMP EXOTHERMICALLY IN DAYLIGHT &
FINALLY EXPLODES.
EXPLOSIVE METAL HYDRAZIDES FORM WHEN HYDRAZINE & ALKALI METALS ARE MIXED IN
LIQUID AMMONIA.
While boiling a sample of a polyester fiber in hydrazine in a glass beaker, the technician
used a somewhat rusty pair of metal tweezers to handle the sample. When the
tweezers were put in the solution, the solution ignited. The ignition
temperature of hydrazine varies from 75
deg F in the presence of iron oxide to 518 deg F in a glass container.
During the measurement of shock sensitivity of a mixture containing hydrazine, a drop of the hydrazine mixture fell inadvertently on the
tetryl donor explosive. The tetryl immediately burst into flame.
Oxidizers, hydrogen peroxide, nitric acid, metallic oxides, acids (Note: Can
ignite SPONTANEOUSLY on contact with oxidizers or porous materials such as
earth, wood, & cloth).
Hydrazine ignites in contact wiht
chlorine.
Hydrazine is decomposed explosively
by chromates & chromic anhydride.
Hydrazine reacts vigorously with
cupric oxide.
Spontaneous ignition occurs when /fluorine & hydrazine/ are mixed.
The catalytic decomposition of hydrazine in the presence of Raney nickel may
be vigorous at room temp.
The blue precipitate formed from nickel perchlorate & hydrazine in water exploded violently when a
glass stirring rod was introduced into the suspension.
Spontaneous ignition occurs when nitrous oxide & lithium hydride or hydrazine are mixed.
Potassium dichromate or sodium dichromate reacts explosively with hydrazine.
The action of an ethereal soln of hydrazine on zinc diamide or diethyl zinc,
gives a product, zinc hydrazine, which
explodes at 70 deg C.
Prior History of Accidents:
A Southern Pacific train derailment on July 28, 1991 in Sea Cliff, CA
resulted in punctures to sixteen 55 gal drums of hydrazine hydrate. No serious injuries were
reported. However, 300 local residents were evacuated, and two, made ill by
fumes, were treated and released from a local hospital. A stretch of U.S.
Highway 101 was closed resulting in a 10 mile long traffic jam. /Hydrazine hydrate/
Immediately Dangerous to Life or Health:
NIOSH considers hydrazine to be a
potential occupational carcinogen.
Protective Equipment & Clothing:
Recommendations for respirator selection. Condition: At concentrations above
the NIOSH REL, or where there is no REL, at any detectable concentration.
Respirator Class(es): Any self-contained breathing apparatus that has a full
facepiece and is operated in a pressure-demand or other positive-pressure mode.
Any supplied-air respirator that has a full facepiece and is operated in a
pressure-demand or other positive-pressure mode in combination with an auxiliary
self-contained breathing apparatus operated in pressure-demand or other
positive-pressure mode.
Recommendations for respirator selection. Condition: Escape from suddenly
occurring respiratory hazards: Respirator Class(es): Any appropriate
escape-type, self-contained breathing apparatus.
Wear appropriate personal protective clothing to prevent skin contact.
Wear appropriate eye protection to prevent eye contact.
Eyewash fountains should be provided in areas where there is any possibility
that workers could be exposed to the substance; this is irrespective of the
recommendation involving the wearing of eye protection.
Facilities for quickly drenching the body should be provided within the
immediate work area for emergency use where there is a possibility of exposure.
(Note: It is intended that these facilities provide a sufficient quantity or
flow of water to quickly remove the substance from any body areas likely to be
exposed. The actual determination of what constitutes an adequate quick drench
facility depends on the specific circumstances. In certain instances, a deluge
shower should be readily available, whereas in others, the availability of water
from a sink or hose could be considered adequate.)
Preventive Measures:
If material not on fire and not involved in fire: Keep sparks, flames, and
other sources of ignition away. Keep material out of water sources and sewers.
Build dikes to contain flow as necessary. Attempt to stop leak if without undue
personnel hazard. Use water spray to diperse vapors and dilute standing pools of
liquid. /Hydrazine, anhydrous; hydrazine, aqueous solution/
SRP: Contaminated protective clothing should be segregated in such a manner
so that there is no direct personal contact by personnel who handle, dispose, or
clean the clothing. Quality assurance to ascertain the completeness of the
cleaning procedures should be implemented before the decontaminated protective
clothing is returned for reuse by the workers. Contaminated clothing should not
be taken home at end of shift, but should remain at employee's place of work for
cleaning.
Personnel protection: Avoid breathing vapors. Keep upwind. ... Avoid bodily
contact with the material. Do not handle broken packages unless wearing
appropriate protective equipment. Wash away any material which may have
contacted the body with copious amounts of water or soap and water. /Hydrazine, anhydrous; hydrazine, aqueous solution/
Contact lenses should not be worn when working with this chemical.
SRP: The scientific literature for the use of contact lenses in industry is
conflicting. The benefit or detrimental effects of wearing contact lenses depend
not only upon the substance, but also on factors including the form of the
substance, characteristics and duration of the exposure, the uses of other eye
protection equipment, and the hygiene of the lenses. However, there may be
individual substances whose irritating or corrosive properties are such that the
wearing of contact lenses would be harmful to the eye. In those specific cases,
contact lenses should not be worn. In any event, the usual eye protection
equipment should be worn even when contact lenses are in place.
PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or
of food & beverage containers or utensils, & the application of
cosmetics should be prohibited in any laboratory. All personnel should remove
gloves, if worn, after completion of procedures in which carcinogens have been
used. They should ... wash ... hands, preferably using dispensers of liq
detergent, & rinse ... thoroughly. Consideration should be given to
appropriate methods for cleaning the skin, depending on nature of the
contaminant. No standard procedure can be recommended, but the use of organic
solvents should be avoided. Safety pipettes should be used for all pipetting.
/Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth &
purification ... should be carried out under well ventilated hood. Analytical
procedures ... should be carried out with care & vapors evolved during ...
procedures should be removed. ... Expert advice should be obtained before
existing fume cupboards are used ... & when new fume cupboards are
installed. It is desirable that there be means for decreasing the rate of air
extraction, so that carcinogenic powders can be handled without ... powder being
blown around the hood. Glove boxes should be kept under negative air pressure.
Air changes should be adequate, so that concn of vapors of volatile carcinogens
will not occur. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Vertical laminar flow biological safety
cabinets may be used for containment of in vitro procedures ... provided that
the exhaust air flow is sufficient to provide an inward air flow at the face
opening of the cabinet, & contaminated air plenums that are under positive
pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where
filtered air is blown across the working area towards the operator, should never
be used ... Each cabinet or fume cupboard to be used ... should be tested before
work is begun (eg, with fume bomb) & label fixed to it, giving date of test
& avg air flow measured. This test should be repeated periodically &
after any structural changes. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Principles that apply to chem or biochem lab
also apply to microbiological & cell-culture labs ... Special consideration
should be given to route of admin. ... Safest method of administering volatile
carcinogen is by injection of a soln. Admin by topical application, gavage, or
intratracheal instillation should be performed under hood. If chem will be
exhaled, animals should be kept under hood during this period. Inhalation
exposure requires special equipment. ... unless specifically required, routes of
admin other than in the diet should be used. Mixing of carcinogen in diet should
be carried out in sealed mixers under fume hood, from which the exhaust is
fitted with an efficient particulate filter. Techniques for cleaning mixer &
hood should be devised before expt begun. When mixing diets, special protective
clothing, & possibly, respirators may be required. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": When ... admin in diet or applied to skin,
animals should be kept in cages with solid bottoms & sides & fitted with
a filter top. When volatile carcinogens are given, filter tops should not be
used. Cages which have been used to house animals that received carcinogens
should be decontaminated. Cage cleaning facilities should be installed in area
in which carcinogens are being used, to avoid moving of ... contaminated
/cages/. It is difficult to ensure that cages are decontaminated, &
monitoring methods are necessary. Situations may exist in which the use of
disposable cages should be recommended, depending on type & amt of
carcinogen & efficiency with which it can be removed. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": To eliminate risk that ... contamination in
lab could build up during conduct of expt, periodic checks should be carried out
on lab atmospheres, surfaces, such as walls, floors & benches, & ...
interior of fume hoods & airducts. As well as regular monitoring, check must
be carried out after cleaning up of spillage. Sensitive methods are required
when testing lab atmospheres. ... Methods ... should ... where possible, be
simple & sensitive. ... /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Rooms in which obvious contamination has
occurred, such as spillage, should be decontaminated by lab personnel engaged in
expt. Design of expt should ... avoid contamination of permanent equipment. ...
Procedures should ensure that maintenance workers are not exposed to
carcinogens. ... Particular care should be taken to avoid contamination of
drains or ventilation ducts. In cleaning labs, procedures should be used which
do not produce aerosols or dispersal of dust, ie, wet mop or vacuum cleaner
equipped with high efficiency particulate filter on exhaust, which are avail
commercially, should be used. Sweeping, brushing & use of dry dusters or
mops should be prohibited. Grossly contaminated cleaning materials should not be
re-used ... If gowns or towels are contaminated, they should not be sent to
laundry, but ... decontaminated or burnt, to avoid any hazard to laundry
personnel. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Doors leading into areas where carcinogens are
used ... should be marked distinctively with appropriate labels. Access ...
limited to persons involved in expt. ... A prominently displayed notice should
give the name of the Scientific Investigator or other person who can advise in
an emergency & who can inform others (such as firemen) on the handling of
carcinogenic substances. /Chemical Carcinogens/
The worker should immediately wash the skin when it becomes contaminated.
Work clothing that becomes wet should be immediately removed due to its
flammability hazard.
Shipment Methods and Regulations:
No person may /transport,/ offer or accept a hazardous material for
transportation in commerce unless that person is registered in conformance ...
and the hazardous material is properly classed, described, packaged, marked,
labeled, and in condition for shipment as required or authorized by ... /the
hazardous materials regulations (49 CFR 171-177)./
The International Air Transport Association (IATA) Dangerous Goods
Regulations are published by the IATA Dangerous Goods Board pursuant to IATA
Resolutions 618 and 619 and constitute a manual of industry carrier regulations
to be followed by all IATA Member airlines when transporting hazardous
materials.
The International Maritime Dangerous Goods Code lays down basic principles
for transporting hazardous chemicals. Detailed recommendations for individual
substances and a number of recommendations for good practice are included in the
classes dealing with such substances. A general index of technical names has
also been compiled. This index should always be consulted when attempting to
locate the appropriate procedures to be used when shipping any substance or
article.
PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should
be avoided. To avoid spilling, carcinogens should be transported in securely
sealed glass bottles or ampoules, which should themselves be placed inside
strong screw-cap or snap-top container that will not open when dropped &
will resist attack from the carcinogen. Both bottle & the outside container
should be appropriately labelled. ... National post offices, railway companies,
road haulage companies & airlines have regulations governing transport of
hazardous materials. These authorities should be consulted before ... material
is shipped. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following
procedure must be adopted. The carcinogen should be enclosed in a securely
sealed, watertight container (primary container), which should be enclosed in a
second, unbreakable, leakproof container that will withstand chem attack from
the carcinogen (secondary container). The space between primary & secondary
container should be filled with absorbent material, which would withstand chem
attack from the carcinogen & is sufficient to absorb the entire contents of
the primary container in the event of breakage or leakage. Each secondary
container should then be enclosed in a strong outer box. The space between the
secondary container & the outer box should be filled with an appropriate
quantity of shock-absorbent material. Sender should use fastest & most
secure form of transport & notify recipient of its departure. If parcel is
not received when expected, carrier should be informed so that immediate effort
can be made to find it. Traffic schedules should be consulted to avoid ...
arrival on weekend or holiday ... /Chemical Carcinogens/
Storage Conditions:
IN ORDER TO REDUCE FLAMMABILITY HAZARD & MAINTAIN PURITY, IT IS USUALLY
STORED UNDER NITROGEN.
Detached storage is preferred. Inside storage should be in a standard
flammable liquids storage warehouse, room, or cabinet. Provide water for
flushing spills or leaks. Tanks should be located in water-filled dikes.
Separate from acids, oxidizing materials, metal oxides. Normally stored under
nitrogen.
Cleanup Methods:
HYDRAZINE REMOVAL FROM NUCLEAR POWER
PLANT WASTEWATER USING ACTIVATED CARBON & COPPER ION CATALYSTS.
In the event of a spill, remove all ignition sources, soak up the hydrazine with a spill pillow or absorbent
material, place in an appropriate container, and dispose of properly. Evacuation
and cleanup using respiratory protection may be necessary in the event of a
large spill or release in a confined area.
Spill or leak procedures: Eliminate all ignition sources. Approach release
from upwind. Use water spray to cool & disperse vapors, protect personnel,
& dilute spills to form nonflammable mixtures. Control runoff & isolate
discharged material for proper disposal.
Disposal Methods:
Generators of waste (equal to or greater than 100 kg/mo) containing this
contaminant, EPA hazardous waste number U133, must conform with USEPA
regulations in storage, transportation, treatment and disposal of waste.
Hydrazine is a waste chemical stream
constituent which may be subjected to ultimate disposal by controlled
incineration with facilities for effluent scrubbing to abate any ammonia formed
in the combustion process.
Hydrazine is a potential candidate
for liquid injection incineration with a temperature range of 650 to 1600 deg C
and residence times of 0.1 to 2 seconds. Also a potential candidate for rotary
kiln incineration with a temperature range of 820 to 1,600 deg C and residence
times of seconds for liquids and gases; hours for solids. Also a potential
candidate for fluidized bed incineration with a temperature range of 450 to 980
deg C and residence times of seconds for liquids and gases; longer for solids.
Recommendable method: Incineration. Peer-review: Dilute well with alcohol,
hydrocarbon solvent before burning. Concentrated hydrazine may explode if heated. Hydrazine is a powerful reductant but should
be well diluted prior to oxidizing. (Peer-review conclusions of an IRPTC Expert
Consultation (May 1985))
PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that
has been proved satisfactory for all carcinogenic compounds & specific
methods of chem destruction ... published have not been tested on all kinds of
carcinogen containing waste. ... summary of avail methods & recommendations
... /given/ must be treated as guide only. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method
for disposal of contaminated laboratory waste from biological expt. However, not
all incinerators are suitable for this purpose. The most efficient type ... is
probably the gas fired type, in which a first stage combustion with a less than
stoichiometric air:fuel ratio is followed by a second stage with excess air.
Some ... are designed to accept ... aqueous & organic solvent solutions,
otherwise it is necessary ... to absorb soln onto suitable combustible material,
such as sawdust. Alternatively, chem destruction may be used, esp when small
quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": HEPA (high efficiency particulate arrestor)
filters ... can be disposed of by incineration. For spent charcoal filters, the
adsorbed material can be stripped off at high temp & carcinogenic wastes
generated by this treatment conducted to & burned in an incinerator. ...
LIQUID WASTE: ... Disposal should be carried out by incineration at temp that
... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage
litter, & misc solid wastes ... should be disposed of by incineration at
temp high enough to ensure destruction of chem carcinogens or their metabolites.
/Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Small quantities of ... some carcinogens
can be destroyed using chem reactions ... but no general rules can be given. ...
As a general technique ... treatment with sodium dichromate in strong sulfuric
acid can be used. The time necessary for destruction ... is seldom known ... but
1-2 days is generally considered sufficient when freshly prepd reagent is used.
... Carcinogens that are easily oxidizable can be destroyed with milder
oxidative agents, such as saturated soln of potassium permanganate in acetone,
which appears to be a suitable agent for destruction of hydrazines or of
compounds containing isolated carbon-carbon double bonds. Concn or 50% aqueous
sodium hypochlorite can also be used as an oxidizing agent. /Chemical
Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are alkylating, arylating or
acylating agents per se can be destroyed by reaction with appropriate
nucleophiles, such as water, hydroxyl ions, ammonia, thiols, & thiosulfate.
The reactivity of various alkylating agents varies greatly ... & is also
influenced by sol of agent in the reaction medium. To facilitate the complete
reaction, it is suggested that the agents be dissolved in ethanol or similar
solvents. ... No method should be applied ... until it has been thoroughly
tested for its effectiveness & safety on material to be inactivated. For
example, in case of destruction of alkylating agents, it is possible to detect
residual compounds by reaction with 4-(4-nitrobenzyl)-pyridine. /Chemical
Carcinogens/
Neutralization of hydrazine fuels
with hypochlorite is a recommended procedure for the treatment of fuel spills
prior to disposal. Previous research has shown that incomplete reaction of
hypochlorite with the methylated hydrazine fuels monomethylhydrazine and
unsymmetrical dimethylhydrazine leads to a wide variety of byproducts, including
N-nitrosoamines, which are believed to be highly carcinogenic. The results
presented in this paper were obtained as part of a program to assess the
environmental implications of using the hypochlorite method for the treatment
and disposal of hydrazine fuel spills.
The fuels examined were hydrazine,
monomethylhydrazine, unsymmetrical dimethylhydrazine and Aerozine-50. The
neutralization products were determined under experimental conditions comparable
to those expected for actual spills. The effects of varying the temperature and
the pH as well as of aging the final reaction mixture were determined.
Quantitative measurements of nitrosoamines produced are presented. Major and
environemntally significant minor products were identified using gas
chromatography/mass-spectrometry.
Occupational Exposure Standards:
OSHA Standards:
Permissible Exposure Limit: Table Z-1 8-hr Time-Weighted Avg: 1 ppm (1.3
mg/cu m). Skin Designation.
Vacated 1989 OSHA PEL TWA 0.1 ppm (0.1 mg/cu m), skin designation, is still
enforced in some states.
Threshold Limit Values:
8 hr Time Weighted Avg (TWA) 0.01 ppm, skin
A3. A3= Confirmed animal carcinogen with unknown relevance to humans.
Excursion Limit Recommendation: Excursions in worker exposure levels may
exceed three times the TLV-TWA for no more than a total of 30 min during a work
day, and under no circumstances should they exceed five times the TLV-TWA,
provided that the TLV-TWA is not exceeded.
NIOSH Recommendations:
NIOSH considers hydrazine to be a
potential occupational carcinogen.
NIOSH usually recommends that occupational exposures to carcinogens be
limited to the lowest feasible concn.
Recommended Exposure Limit: 2-Hr Ceiling Value: 0.03 ppm (0.04 mg/cu m).
Immediately Dangerous to Life or Health:
NIOSH considers hydrazine to be a
potential occupational carcinogen.
Manufacturing/Use Information:
Major Uses:
REACTANT IN FUEL CELLS IN MILITARY USES; REDUCING AGENT IN ELECTRODLESS
NICKEL PLATING; CHAIN EXTENDER IN URETHANE POLYMERIZATIONS; REDUCING AGENT IN
PLUTONIUM EXTRACTION FROM REACTOR WASTE; WATER TREATMENT AGENT-EG, FOR THE
REMOVAL OF HALOGENS
CHEM INT FOR BLOWING AGENTS-EG, AZOBIS(ISOBUTYRONITRILE); CHEM INT FOR
PHOTOGRAPHY CHEMS-EG, TRIAZOLES; CHEM INT FOR PHARMACEUTICALS-EG,
ANTITUBERCULANTS; CHEM INT FOR TEXTILE DYES-EG, 2-HYDROXYNAPHTHAZINE; CHEM INT
FOR HEAT STABILIZERS; CHEM INT FOR EXPLOSIVES-EG, HYDRAZINIUM AZIDE; CHEM INT
FOR HYDRAZINE SALTS USED IN SOLDERING
FLUXES; CHEM INT FOR HYDRAZINIUM SULFATE
/Hydrazine/ reacts with
beta-bicarbonyl compounds to form pyrazole derivatives.
Hydrazine is employed during nuclear
power plants start-up operations to ensure that oxygen is not present to induce
the stress-corrosion reaction
Reducing agent for many transition metals and some nonmetals (arsenic,
selenium, tellurium), as well as uranium and plutonium; nuclear fuel
reprocessing; redox reaction; polymerization catalyst; short stopping agent;
component of high-energy fuels; corrosion inhibitor in boiler feedwater &
reactor cooling water; wastewater treatment; electrolytic plating of metals on
glass & plastics; rocket propellent; manufacture drugs & agricultural
chemicals (maleic hydrazide); scavenger for gases; fuel cells; blowing agent.
It is used for metal plating, and for reducing noble-metal catalysts and
unsaturated bonds in organic compounds
Chemical intermediate /Hydrazine
hydrate/
Soldering flux /Hydrazine
monobromide/
Rocket propellant /Hydrazine
perchlorate hemihydrate/
Reducing agent; solvent for inorganic chemicals; manufacture Helman catalyst,
consisting of 80% hydrazine hydrate,
19.5% ethanol, 0.5 to 0.05% copper, used to decompose hydrogen peroxide in V-2
type rockets /Hydrazine hydrate/
Explosive /Hydrazine nitrate/
Chemical intermediate in manufacture of agricultural chemicals, spandex
fibers and antioxidants. Reducing agent; organic hydrazine derivs; rocket fuel.
Chlorine scavenger for HCl gas streams /Dihydrochloride/
Oxygen scavenger (boiler water treatment); electrodeless nickel coating
reagent; rocket propellant.
Used as a chemical intermediate for the synthesis of acetazolamide; adipic
acid dihydrazide; allopurinol; alprazolam; aminoguanidine bicarbonate;
2,2'-azobisisobutyronitrile; azodicarbonamide; benzene-1,3-disulphohydrazide;
benzenesulphohydrazide; t-butylhydrazinium chloride; clofentezine;
N,N'-dibenzaloxalyldihydrazide; 1,4-dichlorophthalazine-6-carboxyl chloride;
dihydralazine; 2,5-dimercapto-1,3,4-thiadiazole; 1,1-dimethylhydrazine;
diphenylene oxide-3,6-disulphohydrazide;
diphenylsulphone-3,3'-disulphohydrazide; N,N'-disalicylhydrazide; elastane;
guanoclor; hydramethylnon;
hydrazinobis(3-(3,5-di-t-butyl-4-hydroxyphenyl)propionate); hydriodic acid;
isoniazid; maleic hydrazide; metamitron; metazachlor; methidathion; 2-methyl
thiosemicarbazide; metribuzin; nifuratel; nitrofurantoin; oxadiazon;
4,4'-oxybis(benzenesulphohydrazide); Pigment Yellow 101;
poly(p-benzhydrazoterephthalamide); polyols, polyurea dispersion; pyrazophos;
pyridate; robenidine; N-salicylidene-N'-salicoylhydrazine; semicarbazide
hydrochloride; thiosemicarbazide; p-toluenesulphohydrazide;
N,N',N"-triaminoguanidine nitrate; triazolam; 1,2,4-triazole; tricyclazole;
trihydrazinotriazine.
MEDICATION
Manufacturers:
Olin Corporation, Hq, 1501 Merritt 7, PO Box 4500, Norwalk, CT (203)
750-3000; Olin Chemicals, (address same as Hq); Production site: PO Box 2896,
Interstate 10, (318) 491-3000, Lake Charles, LA 70602
Methods of Manufacturing:
Prepn from hydrazine hydrate.
In the Olin Raschig process, sodium hypochlorite solution is mixed with a
threefold excess of ammonia at 5 deg C to form chloramine, which is then rapidly
added to a 30-fold molar excess of anhydrous ammonia under pressure and heated
to 130 deg C. The reaction liquor containing 1-2% hydrazine hydrate, is treated as in the
conventional Raschig process to give hydrazine hydrate. Anhydrous hydrazine is obtained by removing the water by
azeotropic distillation with aniline in a column at atmospheric pressure.
In the Bayer process, sodium hypochlorite, acetone, and a 20% aqueous
solution of ammonia are fed simultaneously and continuously into a reactor at
ca. 35 deg C and 200 kPa. Excess ammonia is removed from the reaction mixture by
stripping, quenched with water, and recycled to the reactor as an aqueous
solution. The aqueous dimethyl ketazine solution, freed from ammonia but
containing unreacted acetone, sodium chloride, and organic impurities, is fed
into a distillation column where the dimethyl ketazine is recovered as an
aqueous azeotrope at atmospheric pressure. The dimethyl ketazine is then
hydrolyzed in a distillation column under pressure giving acetone, which is
recycled to the reactor, and a 10% aqueous solution of hydrazine. The latter is then concentrated to
a hydrazine content of 64%.
Hydrogen peroxide is activated by acetamide and disodium hydrogen phosphate.
The overall reaction results in the formation of methyl ethyl ketazine in high
yield. Methyl ethyl ketazine is separated by decantation; it is then purified by
distillation. The purified ketazine is hydrolyzed under pressure to give
concentrated aqueous hydrazine and
overhead methyl ethyl ketone.
General Manufacturing Information:
World capacity was about 44,100 metric tons hydrazine in 1992.
Available commercially as anhydrous grade, hydrate, or sulfate.
Hydrazine is available in anhydrous
form as well as aqueous solutions, typically 35, 51.2, 54.4, and 64 wt% N2H4.
A century after its discovery, hydrazine is still difficult to synthesize,
mainly for thermodynamic reasons... most hydrazine is produced by variations of the
Raschig process, the oxidation of ammonia by hypochlorite. Only one new
industrial process has been introduced recently(1980), using hydrogen peroxide
as oxidant.
Formulations/Preparations:
HYDRAZINE IS PRODUCED IN USA IN A
PROPELLANT GRADE WHICH CONTAINS A MINIMUM OF 97.5% OF ACTIVE INGREDIENT.
Grade: to 99% pure
Anhydrous propellant grade
Liquid grade, 55%, 85%, 100% hydrate solutions
17%, 25%, 35%, 55%, 75%, 85%, 100% hydrate grades
Hydrazine is available in anhydrous
form as well as aqueous solutions, typically 35, 51.2, 54.4, and 64 wt% N2H4.
Hydrazine hydrate is a colorless
liquid containing 63.4% hydrazine (1:1
N2H4:H2O). Aqueous solutions with lower hydrazine contents are also available. A 35%
aqueous solution is commonly used for boiler treatment applications.
Hydrazine, greater than or equal to
98.5 wt%; water, less than or equal to 1.0 wt%; chloride, less than or equal to
5 ppm; iron, less than or equal to 20 ppm; aniline, less than or equal to 0.5
wt%; non-volatile residue, less than or equal to 0.005 wt%; carbon dioxide, less
than 0.02 wt%; carbon volatile, greater than 0.02 wt%; density 1.008-1.002 g/ml
at 25 deg C.
Impurities:
MAJOR IMPURITY IS WATER (UP TO 2.5%), AND UP TO 0.2% OF UNDEFINED INSOL
MATERIAL ...
Consumption Patterns:
CHEM INT FOR PESTICIDES, 40%; CHEM INT FOR BLOWING AGENTS, 33%; CORROSION
INHIBITOR & WATER TREATMENT AGENT, 15%; OTHER USES, 12% (1980)
In 1982, 40% of hydrazine output was
used in agricultural chemicals, about 33% for blowing agents, 15% for water
treatment, and 5% as an aerospace propellant.
U. S. Production:
(1977) AT LEAST 9.08X10+8 G
Laboratory Methods:
Clinical Laboratory Methods:
A simple micromethod for the determination of hydrazine in biological samples was
demonstrated using samples from male albino rats. Rats were injected
intraperitoneally with 1 ml/kg of 1 molar (M) hydrazine or 5 ml/kg 0.45M isoniazid.
Determinations were made of hydrazine
concentrations in the liver, brain, and serum, as well as of the glutathione
content of the liver and brain of the treated rats. Hydrazine was determined by reacting samples
with 4 percent p-dimethylaminobenzaldehyde for 20 minutes at room temperature,
and assaying the colored product of the reaction at 470 nm using a double beam
spectrophotometer. Data of extenction plotted against concentration showed
adherence to Beer's law from 0.17 to 1 micromolar hydrazine concentration. ...
Analytic Laboratory Methods:
CHEMILUMINESCENT REACTIONS OF OZONE WITH HYDRAZINE, METHYLHYDRAZINE AND
DIMETHYLHYDRAZINE WERE USED TO DETERMINE METHYLHYDRAZINE, AEROZINE (50:50
METHYLHYDRAZINE-DIMETHYLHYDRAZINE), AND NITROUS OXIDE IN AIR AT CONCN OF 0.1-100
PPM.
In a liquid chromatographic method for the determination of hydrazine in polyvinylpyrrolidone. The
polyvinylpyrrolidone is dissolved in acetate buffer, hydrazine is derivated with benzaldehyde to
form benzalazine, and is quantitated on a silica column using p-nitrobenzene as
the internal standard. Reproducibility on repeat analysis is about +/- 10%.
Recoveries from spiked samples in most cases were 84% or better.
This work characterizes a newly developed, sensitive and convenient
spectrophotometric procedure for determination of sub-ppm concentrations of
hydrazine and its organic derivatives
The method is based on formation of the cuprous neocuproine chelate after
reaction of hyrazines with a prepared aqueous solution of the copper (II)
neocuproine complex. The cuprous chelate is then directly measured in aqueous
solution at 458 nm. The effect of several experimental conditions influencing
the reaction are presented and the method was employed for the analysis of 5
different hydrazine compounds. The
standard deviation did not exceed + or - 0.47%.
NIOSH Method 3503. Determination of Hydrazine by Visible Absorption
Spectrophotometry. DL= 0.009 mg/cu m.
DOE Method S0010R. Collection of Liquid Samples for Effluent Monitoring of
Operations Facilities.
Sampling Procedures:
Air samples containing hydrazine are
taken with a glass tube, 5 cm x 6 mm ID, packed loosely with glass wool, and a
glass midget bubbler with 15 ml HCl. A sampling pump is connected to this tube
and accurately calibrated at a flow rate of 0.2 to 1 l/min for a total sample
size of 7 to 100 liters. This technique has an overall precision of 0.094, over
a studied range of 0.59 to 3.4 mg/cu m using 91 liter samples.
Naval Research Laboratory scientists have developed a dosimeter badge for
passive hydrazine detection. The new NRL
dosimeter badge satisfies the requirement for a small device that provides
quantitative personal monitoring without interfering with the person's work and
should eliminate larger, more cumbersome detectors presently in use. The badge
consists of a diffusion barrier and a critic acid substrate that collects and
stabilizes hydrazine and
monomethylhydrazine, until it can be analyzed using wet chemical methods.
Special References:
Special Reports:
KIMBALL RF; MUTAT RES 39 (2): 111 (1977). A REVIEW OF THE MUTAGENICITY OF
HYDRAZINE DERIVATIVES IS PRESENTED.
BACK KC ET AL; AVIAT, SPACE ENVIRON MED 49 (4): 591 (1978). A REVIEW OF
HAZARDS ASSOCIATED WITH USE OF HYDRAZINE
PROPELLANTS IN MISSILE OPERATIONS.
TOTH B; FALK SYMP 31 (COLONIC CARCINOG): 165 (1982). REVIEW OF HYDRAZINE COMPOUNDS ON COLON & INTESTINE
CARCINOGENESIS.
SCHABACHER W; VGB KRAFTWERKSTECH 62 (2): 139 (1982). REVIEW OF OCCUPATIONAL
EXPOSURE TO HYDRAZINE & SAFETY
GUIDELINES.
Houston WE et al; Toxic Hazards Research Unit Annual Report (1986); Govt
Report Announcements & Index Iss 22 (1987).
Keller WC; Toxicity Assessment of Hydrazine Fuels; Aviation, Space, and
Environmental Medicine: 59 (11): A100 (1988).
Stone DA and Niseman FL; Proceedings of the Conference on the Environ
Chemistry of Hydrazine Fuels (1987);
Govt Reports Announcements & Index Iss 24 (1988).
U.S. Department of Health & Human Services/National Toxicology Program;
9th Report on Carcinogens. National Institute of Environmental Health Sciences,
Research Triangle Park, NC. (2000)
Synonyms and Identifiers:
Synonyms:
DIAMINE **PEER REVIEWED**
HYDRAZINE ANHYDROUS **PEER
REVIEWED**
HYDRAZINE BASE **PEER
REVIEWED**
HYDRAZYNA (POLISH) **PEER
REVIEWED**
LEVOXINE **PEER
REVIEWED**
Oxytreat 35 **PEER REVIEWED**
Formulations/Preparations:
HYDRAZINE IS PRODUCED IN USA IN A
PROPELLANT GRADE WHICH CONTAINS A MINIMUM OF 97.5% OF ACTIVE INGREDIENT.
Grade: to 99% pure
Anhydrous propellant grade
Liquid grade, 55%, 85%, 100% hydrate solutions
17%, 25%, 35%, 55%, 75%, 85%, 100% hydrate grades
Hydrazine is available in anhydrous
form as well as aqueous solutions, typically 35, 51.2, 54.4, and 64 wt% N2H4.
Hydrazine hydrate is a colorless
liquid containing 63.4% hydrazine (1:1
N2H4:H2O). Aqueous solutions with lower hydrazine contents are also available. A 35%
aqueous solution is commonly used for boiler treatment applications.
Hydrazine, greater than or equal to
98.5 wt%; water, less than or equal to 1.0 wt%; chloride, less than or equal to
5 ppm; iron, less than or equal to 20 ppm; aniline, less than or equal to 0.5
wt%; non-volatile residue, less than or equal to 0.005 wt%; carbon dioxide, less
than 0.02 wt%; carbon volatile, greater than 0.02 wt%; density 1.008-1.002 g/ml
at 25 deg C.
Shipping Name/ Number DOT/UN/NA/IMO:
UN 2029; Hydrazine, anhydrous and
hydrazine aqueous solutions, with more
than 64% hydrazine, by weight.
UN 2030; Hydrazine, aqueous solution
with not more than 64% hydrazine, by
weight
IMO 3.1; Hydrazine, anhydrous and
hydrazine aqueous solutions, with more
than 64% hydrazine by weight.
IMO 8.2; Hydrazine aqueous solutions,
with not more than 64%, by weight
NA 9188; Hydrazine 35%
Standard Transportation Number:
49 062 25; Hydrazine, anhydrous
49 350 30; Hydrazine, aqueous
solution
EPA Hazardous Waste Number:
U133; A toxic waste when a discarded commercial chemical product or
manufacturing chemical intermediate or an off-specification commercial chemical
product.
RTECS Number:
NIOSH/MU7175000