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METHYLHYDRAZINE CASRN: 60-34-4 See Occupational Exposure Standards
Human Health Effects:
Evidence for Carcinogenicity: A3; Confirmed animal carcinogen with unknown relevance to humans.
Human Toxicity Excerpts: METHYLHYDRAZINE IS STRONGEST
CONVULSANT & MOST TOXIC OF METHYL /SUBSTITUTED HYDRAZINE/ DERIVATIVES.
MONOMETHYLHYDRAZINE IS A STRONG
METHEMOGLOBIN FORMER & BLOOD PIGMENTS ARE EXCRETED IN URINE. LIVER CHANGES
ARE PRIMARILY OF FATTY DEGENERATION TYPE, SELDOM PROGRESSING TO NECROSIS ...
MONOMETHYLHYDRAZINE ... IN HIGH DOSES
CAN CAUSE EXTENSIVE KIDNEY DAMAGE. CHANGES IN HEART MUSCLE ARE PRIMARILY OF
FATTY CHARACTER. NAUSEA OBSERVED WITH ALL ... HYDRAZINES IS OF CENTRAL ORIGIN
& REFRACTORY TO MEDICATION. ... A GROUP OF MALE VOLUNTEERS WERE EXPOSED (HEAD ONLY) TO 90 PPM ... FOR 10
MIN TO EVALUATE EMERGENCY EXPOSURE LIMIT (EEL). ... THERE WAS SOME EYE REDNESS
& SLIGHT TICKLING SENSATION OF THE NOSE. ... THE ONLY HEMATOLOGIC
ABNORMALITY WAS HEINZ BODY FORMATION IN 3-5% OF ERYTHROCYTES BY SEVENTH DAY
POST-EXPOSURE ... Mushrooms inducing headache about 6 hr after ingestion: This intoxication is
assoc most often with Gyromitra exculenta, which may be mistaken for the edible
morel. ... The toxin is monomethylhydrazine, which antagonizes
pyridoxine. The toxin is volatile, & the mushroom may be made edible by air
drying or by extraction of the toxin with boiling water, which is then
discarded. Onset of symptoms /from monomethylhydrazine produced in mushrooms/ is
sudden, usually about 6 to 8 hr after ingestion or inhalation of vapor from
cooking mushrooms. It is characterized by headache, malaise, abdominal fullness,
& emesis (but not diarrhea). Generally, the patient recovers completely
within 2 to 6 days. However, fatal hepatic necrosis has developed.
Severe health hazard. May be fatal if absorbed through skin or inhaled.
Strong sensitizer. Corrosive. Causes severe eye & skin burns. Symptoms of
overexposure include convulsions, damage to liver & kidneys, death.
Liquid will burn skin & eyes. Chromosome damage in vitro in humans and rats has been reported, and Ehrlich
ascites liver cells show chromosome lesions after incubation with methyl hydrazine.
Skin, Eye and Respiratory Irritations: Vapor is irritating to eyes, nose & throat. Skin irritation is pronounced with the propellant hydrazines ... /Hydrazine
& derivatives/ All hydrazines have similar toxic local effects due to their irritant
properties. The vapor is highly irritating to the eyes, upper respiratory tract,
& skin ... /Hydrazines/
Medical Surveillance: Placement medical examinations shall include at least: comprehensive medical
and work histories; comprehensive physical examination; specific clinical tests
including complete and differential blood count; liver function tests including
serum glutamic-pyruvic transaminase (SGPT), urinalysis including specific
gravity, glucose, protein, and microscopic examination, and a 14 x 17 inch
posteroanterior chest roentenogram; a judgement of the worker's ability to use
positive pressure respirators; and urobilinogen and serum bilirubin tests shall
be considered by the responsible physician. Periodic examinations shall be made
available at least annually to those working with hydrazines. /Hydrazines/
Probable Routes of Human Exposure: Monomethylhydrazine ... is a
decomposition product of the mushroom toxin, gyromitrin (Gyromitra esculenta)
... /when/ generated in vivo is believed to be responsible for the toxicity of
gyromitrin. Human exposure to methylhydrazine
most likely results from its use as a component of aerospace propellants. NIOSH
(NOES Survey 1981-1983) has estimated that 1,473 workers (230 of these are
female) are exposed to methylhydrazine
in the USA(1). The general population may be exposed to methylhydrazine via dermal contact with vapors
and other products containing methylhydrazine(SRC).
Emergency Medical Treatment:
Emergency Medical Treatment:
Antidote and Emergency Treatment: 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: A3; Confirmed animal carcinogen with unknown relevance to humans.
Non-Human Toxicity Excerpts: WHEN /MONOMETHYLHYDRAZINE/ ...
APPLIED TO SKIN OF DOGS, IT IS ABSORBED & CARRIED BY BLOODSTREAM TO EYES
WHERE IT ENTERS AQ HUMOR & INJURES ENDOTHELIUM OF CORNEA, CAUSING CORNEAL
EDEMA IN 5-6 HR. IN EXCISED CORNEAS SOLN AS DIL AS 1X10-7 MOLAR ... /PROMOTED/
SWELLING OF CORNEA ... METHYLHYDRAZINE WAS MUTAGENIC AFTER
ACTIVATION IN MICROBIAL REVERSION TESTS, CONDUCTED AS SUSPENSION TESTS WITH
SALMONELLA TYPHIMURIUM TA-1535. DOGS WERE EXPOSED AT 1, 2, 5 & 10 PPM. A 2 PPM EXPOSURE FOR 6 MO PRODUCED
5.7% ERYTHROCYTE HEMOLYSIS THROUGH METHEMOGLOBIN HEINZ BODY TRANSFORMATION
MECHANISM. THIS EFFECT WAS FOLLOWED BY RETICULOCYTOSIS. CONTINUOUS 90 DAY
EXPOSURE PRODUCED MEASURABLE EFFECTS IN DOGS & RATS. BEAGLE DOGS SHOWED
SIGNIFICANT INCR IN SERUM PHOSPHORUS & ALKALINE PHOSPHATASE LEVELS DURING
THE EXPOSURE PERIOD. TERATOGENIC EFFECTS OF METHYLHYDRAZINE IN CONCN IN EXCESS OF 10 MG/L
ON EMBRYOS OF THE SOUTH AFRICAN CLAWED TOAD WAS STUDIED. MALFORMATIONS OF THE
HEAD, TRUNK, & TAIL OF OCCURRED. THE MOST COMMON ABNORMALITY OBSERVED WAS
TAIL KINKS. OTHER ABNORMALITIES OBSERVED WERE MICROCEPHALY, CYCLOPIA, SHORTENING
OF TRUNK, & EDEMA. A 0.01% SOLN OF METHYLHYDRAZINE WAS
ADMIN DAILY IN DRINKING WATER TO 6 WK OLD SYRIAN GOLDEN HAMSTERS FOR LIFE.
TREATMENT GAVE RISE TO MALIGNANT HISTIOCYTOMAS OF LIVER & TUMORS OF CECUM.
MONOMETHYLHYDRAZINE INDUCED
ABNORMALITIES IN MORPHOLOGY OF SPERM IN THE CAUDA EPIDIDYMIDES OF MICE WHICH
REACHED MAX LEVELS 3 WEEKS AFTER CHEM TREATMENT. IT IS NOT REPORTED TO BE SKIN SENSITIZER BUT IT CAUSES MANY HEMATOLOGIC
ABNORMALITIES IN VARIETY OF TEST SPECIES. THESE INCL HEMOLYTIC ANEMIA (WITH REDN
IN ERYTHROCYTES, HEMOGLOBIN, HEMATOCRIT VALUES) INCR IN METHEMOGLOBIN, AN INCR
IN HEINZ BODIES & LIVER, KIDNEY, & SPLEEN HEMOSIDEROSIS, AS WELL AS
LIVER CHOLESTASIS ... METHYLHYDRAZINE GAVE NEGATIVE RESULTS
IN AMES TESTS WITH SALMONELLA TYPHIMURIUM TA100 AS INDICATOR STRAIN. IN HOST
MEDIATED ASSAY, METHYLHYDRAZINE SHOWED
MARGINAL MUTAGENIC ACTIVITY. SALMONELLA TYPHIMURIUM TA1950 WAS THE INDICATOR
STRAIN. AN IMPORTANT FEATURE OF THE ACUTE SEIZURE MODEL INVOLVING EXPOSURE TO THE
CONVULSANT, MONOMETHYLHYDRAZINE (MMH),
IS THE LATENCY IN MINUTES POSTINJECTION TO THE ONSET OF GENERALIZED TONIC CLONIC
CONVULSIONS. POSTOPERATIVE MONOMETHYLHYDRAZINE LATENCIES IN 8 NAIVE CATS
WERE COMPARED WITH SUBSEQUENT AFTER DISCHARGE THRESHOLDS OBTAINED FROM
BASOLATERAL AMYGDALA KINDLING ELECTRODES. THE CORRELATION BETWEEN THOSE 2
INDICES WAS STATISTICALLY SIGNIFICANT. CATS DIVIDED ON BASIS OF MEDIAN
POPULATION VALUE INTO HIGH OR LOW MONOMETHYLHYDRAZINE SEIZURE LATENCIES DIFFERED
SIGNIFICANTLY FROM ONE ANOTHER ON THAT INDEX. ANIMALS WITH PROLONGED SEIZURE
LATENCIES SHOWED SIGNIFICANTLY HIGHER AFTERDISCHARGE THRESHOLDS, WHEREAS SHORTER
LATENCIES ACCOMPANIED LOWER AFTER DISCHARGE THRESHOLDS. THE GENDER, WT,
ELECTRODE IMPEDANCE OR ELECTRODE SITES OF INDIVIDUALS DID NOT ACCOUNT FOR THIS
RELATIONSHIP. RESULTS SUGGEST ENDOGENOUS DIFFERENCES IN SEIZURE SUSCEPTIBILITY
THAT ARE DEFINABLE REGARDLESS OF PROCEDURE. METHYLHYDRAZINE INDUCED MUTATIONS IN
SEVERAL STRAINS OF ESCHERICHIA COLI INDEPENDENTLY OF THE REC A & LEX A LOCI,
INDICATING THAT THE MUTAGENIC EFFECT WAS NOT DEPENDENT ON ERROR PRONE REPAIR
ACTIVITY. 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.
SELECTED HYDRAZINES WERE EXAMINED FOR THEIR MUTAGENIC ACTIVITY IN SALMONELLA
TYPHIMURIUM STRAINS TA15357 TA1537. THESE IN VITRO ASSAYS WERE CONDUCTED WITH
& WITHOUT METABOLIC ACTIVATION BY AROCLOR INDUCED RAT LIVER ENZYMES. HIGH
LEVEL OF MUTAGENICITY WAS OBSERVED WITH METHYLHYDRAZINE & PHENYLHYDRAZINE
HYDROCHLORIDE. GROUPS OF DOGS, MONKEYS, & RATS WERE EXPOSED CONTINUOUSLY TO MONOMETHYLHYDRAZINE FOR 90 DAYS IN THOMAS DOME
CHAMBERS TO ESTABLISH SPECIFIC EXPOSURE SAFETY STD. ANIMALS WERE ALSO EXPOSED TO
DURATIONS UP TO 24 HR IN CONFINED WORKING AREAS. RESULTS INDICATE THAT
ATMOSPHERIC CONCN OF 0.04 PPM MONOMETHYLHYDRAZINE IS SAFE FOR CONTINUOUS
EXPOSURE IN CONFINED WORKING AREAS. A LEVEL OF 1 PPM MONOMETHYLHYDRAZINE IS SAFE CONCN FOR 24 HR
EMERGENCY EXPOSURE LIMIT. With oral doses of 20 mg/kg when admin on days 8 through 12 of mouse
pregnancy ... 36% of offspring /were/ malformed. A dose of 200 mg/kg in rabbit
on 14th day produced an equal number of /abnormal/ offspring. The anomalies
consisted of anencephaly, eye defects & complex facial bone deformities.
Methylhydrazine was tested for
mutagenicity in the Salmonella/microsome preincubation assay using the standard
protocol approved by the National Toxicology Program. Methylhydrazine was tested at doses of 1.0,
3.3, 10, 33, and 100 ug/plate in as many as 5 Salmonella typhimurium strains
(TA1535, TA1537, TA97, TA98, and TA100) in the presence and absence of rat or
hamster liver S-9. Methylhydrazine was
negative in these tests and the highest ineffective dose tested in any S
typhimurium strain was 100 ug/plate. SC INFUSION OF 30 UMOL/KG/HR OF METHYLHYDRAZINE FOR 14 HR INTERFERED WITH
GLYCOLYSIS IN RATS BY INHIBITING PHOSPHOFRUCTOKINASE. CHRONIC EXPOSURE TO MORE
THAN 0.6 UMOL/KG/HR OBSTRUCTED METHYLAMINE OXIDN. PUTRESCINE OXIDN WAS LESS
SENSITIVE. The embryotoxicity and teratogenicity of monomethylhydrazine, unsymmetrical
dimethylhydrazine and symmetrical dimethylhydrazine were investigated in Fischer
344 rats. On days 6 to 15 of gestation, rats were given ip injections of 2.5,
5.0, or 20 mg/kg monomethylhydrazine;
10, 30, or 60 mg/kg unsymmetrical dimethylhydrazine; or 2.0, 5.0, or 10.0 mg/kg
symmetrical hydrazine. Animals were sacrificed on day 20 of gestation, and uteri
were opened. Numbers and positions of implants, dead and live fetuses, and
resorptions were recorded. Live fetuses were examined for abnormalities.
Visceral and skeletal examinations were performed. Maternal weight gain was
significantly depressed in rats given monnomethylhydrazine and unsymmetrical
dimethylhydrazine; symmetrical dimethylhydrazine had an inconsistent effect on
maternal weight gain. Treatment with monomethylhydrazine had an inconsistent effect
on litter parameters. At doses of 5.0 or 10 mg/kg monomethylhydrazine there was an insignificant
increase in litters exhibiting 33% or more resorptions and in incidence of
abnormalities. Treatment with 60 mg/kg unsymmetrical dimethylhydrazine produced
a significant reduction in mean fetal weight; numbers of implants and viable
fetuses were less than in untreated controls. Nearly 50% of rats treated with 60
mg/kg unsymmetrical dimethylhydrazine had a resorption incidence of greater than
33%, and malformations were increased. Treatment with 10 mg/kg symmetrical
dimethylhydrazine caused a moderate decrease in mean viable fetuses per litter,
and mean fetal weight was significantly reduced. A slight reduction was seen in
incidence of malformations and litters with 33% or more resorption. No
teratogenic effects were seen in any of the derivatives. The /results/ conclude
that unsymmetrical dimethylhydrazine and symmetrical dimethylhydrazine are
embryotoxic in rats. Acute toxicity is characterized by convulsions, neurological
hyperexcitability, hypoglycemia, vomiting, anemia, bilirubinemia,
methemoglobinemia, and ocular and upper respiratory tract irritation.
Pathological changes in the lungs, liver, kidneys, and brain were observed in
animals receiving acutely toxic doses. Treated skin sites exhibited erythema, edema, and a blanched appearance /in
acute dermal studies/. Methyl hydrazine applied to the skin
of dogs was carried by the bloodstream to the eyes where it entered the aq humor
and caused corneal edema. Dilute soln as low as 10-7 M applied directly to
corneal explants caused corneal swelling. A 6-mo inhalation study was performed in which rats, mice, dogs, and monkeys
were exposed at 0, 0.2, 1, 2, or 5 ppm methyl hydrazine
for 6 hours/day, 5 days/wk. ... Body weight reductions occurred
in rats exposed at 1 to 5 ppm; compound-related effects at 0.2 ppm were not
observed. Hemolytic anemia and the presence of Heinz bodies were observed in
dogs inhaling 0.2 ppm and higher. Dogs exposed at 2 ppm and 5 ppm had incr
methemoglobin formation, but both the anemia and methemoglobin were reversible.
Alkaline phosphatase and bilirubin were also elevated in dogs in a dose-related
manner at all exposure concn and were considered indicative of liver damage.
Suppression of the flow of bile (hepatic cholestasis) was observed in dogs
exposed at 0.2 ppm and higher, and hepatic and renal tubular hemosiderosis were
observed at 2 ppm and 5 ppm. Incr mortality at 2 ppm and 5 ppm was noted in
mice. Concn-related incr in hepatic, splenic, and renal tubular hemosiderosis
were observed in mice. AT 2 ppm or 5 ppm, mice had periportal or centrilobular
cholestasis and bile duct proliferation. Hemolysis and Heinz bodies formation in
erythrocytes were observed in monkeys inhaling 5 ppm; however, compound-related
effects at lower doses were not observed. ... When rats, dogs, and monkeys inhaled methyl
hydrazine 24 hours/day, 7 days/wk for 90 days at vapor concn of
0, 0.04, or 0.1 ppm methyl hydrazine,
hematological effects in rats and dogs were seen at 0.1 ppm,
discoloration of the liver occurred at 0.1 ppm in dogs, and serum phosphorus was
elevated in rats at 0.04 and 0.1 ppm. No compound-related effects were reported
in monkeys. ... Methyl hydrazine was found to
produce pulmonary tumors in mice and malignant histiocytoma of the liver and
cecal tumors in hamsters when admin in the drinking water at concn of 0.01%.
Exposures to methyl hydrazine at
concn of 0 ppm and 0.02 ppm (rats and mice only) and 0.2, 2, or 5 ppm (rats and
hamsters only) were conducted for 6 hours/day, 5 days/wk, over a period of 1 yr
and were followed by observation for 1 yr. Rats that inhaled 0.02 ppm and above
experienced a decr rats of growth which persisted through the postexposure
observation period. A cmpd-related incr in tumors was not detected in rats at
any dose. Mice exposed at 0.02 ppm and above exhibited nasal irritation and
plasmacytosis. Renal cysts and hydronephrosis were observed in mice that inhaled
0.2 ppm and 2 ppm, respectively, and mice exposed at 2 ppm had a significantly
higher incidence of lung tumors, nasal adenomas, nasal polyps, nasal osteomas,
hemangiomas, and liver adenomas and carcinomas compared with control mice.
Rhinitis and an incr number of biliary cysts were observed in hamsters
exposed at 0.2 ppm or greater of methyl hydrazine.
The numbers of nasal polyps, interstitial fibrosis of the
kidney, and benign adrenal adenoma were incr in hamsters that inhaled 2 ppm or 5
ppm. Hamsters exposed at 5 ppm exhibited reduced body weights and an incr
incidence of nasal adenomas. Dogs exposed to methyl
hydrazine failed to develop pathological changes; however,
exposure at 0.2 ppm and above caused transient anemia, reduced hematocrit, and
reduced hemoglobin. Exposure of dogs at 2 ppm also results in a reversible incr
in methemoglobin, alkaline phosphatase, bilirubin, and serum glutamic-pyruvic
transaminase (SGPT) ... . Methyl hydrazine was given to
pregnant female rats by ip injection at doses of 2.5, 5.0, or 10 mg/kg on days 6
through 15 of gestation. Methyl hydrazine
was assoc with a reduction in maternal body weights and some
evidence for embryo-toxicity. There was an equivocal incr in ocular
abnormalities. Mice receiving daily, repeated ip injections for 5 days of methyl hydrazine (at fractional doses of 0.25
or 0.4 mg/kg of the 3 mg/kg LD50) had a significantly greater percentage of
mature sperm with abnormal head shapes observed 1 to 3 wk following treatment.
Abnormalities were reversible within 7 wk following cessation of treatment.
Methyl hydrazine is generally
inactive in test designed to measure mutagenic activity ... However, a spot test
in E. coli was weakly positive, and mutations have been described in that
organism following methyl hydrazine
treatment. ... Chromosome damage in vitro in humans and rats has
been reported, and Ehrlich ascites liver cells show chromosome lesions after
incubation with methyl hydrazine. Liver
DNA damage in vivo using DNA alkaline elution techniques has been both positive
and negative. Isolated hepatocytes and liver microsomes incubated with monomethylhydrazine, 1,1-dimethylhydrazine and
1,2-dimethylhydrazine produced free radical intermediates which were detected by
ESR spectroscopy by using 4-pyridyl-1-oxide-t-butyl nitrone as spin trapping
agent. The spectral features of the spin adducts derived from all three
hydrazine derivatives corresponded to the values reported for the methyl free
radical adduct of 4-pyridyl-1-oxide-t-butyl nitrone. In the microsomal
preparatons, inhibitors of the mixed function oxidase system and the destruction
of cytochrome p450 by pretreating the rats with cobalt chloride all decreased
the free radical formation. Methimazole, an inhibitor of FAD-containing
monoxygenase system, similarly decreased the activation of
1,1-dimethylhydrazine, but not that of monomethylhydrazine and 1,2-dimethylhydrazine.
The addition to liver microsomes of physiological concentrations of glutathione
(GSH) lowered by approx 80% the intensities of the ESR signals. Consistently,
incubation of isolated hepatocytes with methylhydrazine decreased the intracellular
GSH content, suggesting that GSH can effectively scavenge the methyl free
radicals. The results obtained suggest that methyl free radicals could be the
alkylating species responsible for the toxic and/or carcinogenic effect of
methylhydrazines. 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: LC50 Rat inhalation 74-78 ppm/4 hr (calculated) LC50 Mouse inhalation 56-65 ppm/4 hr (calculated)
LC50 Hamster inhalation 143 ppm/4 hr (calculated)
LD50 Mouse intravenous 33 mg/kg LD50 Mouse oral 33 mg/kg LD50 Rat intravenous 33 mg/kg LD50 Rat oral 33 mg/kg LD50 Guinea pig percutaneous 49 mg/kg LD50 Rabbit intravenous 12 mg/kg LD50 Dog intravenous 12 mg/kg LC50 Monkey inhalation 162 ppm/1 hour LC50 Dog inhalation 96 ppm/1 hour LD50 Rabbit dermal 93 mg/kg LD50 Guinea pig dermal 47 mg/kg LD50 Hamster dermal 239 mg/kg LD50 Rat dermal 183 mg/kg
Ecotoxicity Values: LC50 Hyalella azteca (amphipod) 1.2 mg/l/48 hr. /Conditions of bioassay not
specified/ LC50 Guppies 2.6-6.7 mg/l/24 hr. /Conditions of bioassay not specified/
Metabolism/Pharmacokinetics:
Metabolism/Metabolites: N-OXIDATION OF METHYLHYDRAZINE
CATALYZED BY PURIFIED MOUSE LIVER MICROSOMAL MIXED FUNCTION AMINE OXIDASE IS
SHOWN. AT PH 7.7 & 25 DEG C, METHYLHYDRAZINE HAS NEARLY THE SAME MAXIMAL
N-OXIDATION RATE AS DIMETHYLANILINE. ALTHOUGH METHANE CAN BE DETECTED AS A
PRODUCT OF N-OXIDATION OF METHYLHYDRAZINE, IT MAY REPRESENT THE CHEMICAL
DECOMP PRODUCT OF A N-OXIDIZED INTERMEDIATE. FLAVOPROTEIN N-OXYGENASE ... CATALYZES FORMATION OF ... N-OXIDES OF METHYLHYDRAZINE /&/ 1,1-DIMETHYLHYDRAZINE
...
Absorption, Distribution & Excretion: METHYLHYDRAZINE IS ABSORBED FROM THE
LUNG, GI TRACT, INJECTION SITES, & SKIN. 1.5 MG/MIN OF MONOMETHYLHYDRAZINE
INFUSED IV INTO DOGS WAS EXCRETED BY COMBINATION OF GLOMERULAR FILTRATION,
PASSIVE DIFFUSION MEDIATED REABSORPTION, & SIMULTANEOUS TUBULAR SECRETION.
(14)C LABELED METHYLHYDRAZINE WAS
ADMIN TO MICE, DOGS, & MONKEYS. ALL SPECIES EXCRETED 25-40% OF THE DOSE IN
URINE WITHIN 24 HR. IN MICE ... APPROX THE SAME AMT WAS EXCRETED IN RESPIRED
AIR. BOTH CARBON DIOXIDE AND RADIOACTIVE METHANE WERE FOUND.
... WHEN MONOMETHYLHYDRAZINE ...
APPLIED TO SKIN OF DOGS, IT IS ABSORBED & CARRIED BY BLOODSTREAM TO EYES
WHERE IT ENTERS AQ HUMOR ... The resp & urinary excretion of ip admin monomethylhydrazine (MMH) by rats was studied
by means of radiotracer technique. Rats given 0.12 mM/kg respired approx 45% of
the labeled carbon during the following 24 hr. Of the respired radioactivity,
20-25% was (14)C labeled carbon dioxide & the remainder was (14)C-methane.
At the subconvulsive dose, 40% of the admin radioactivity was excreted in the
urine. The percentage of urinary excretion from (14)C from higher doses was
less, but the net amt excreted was slightly higher. Undiluted methyl hydrazine applied to
dog skin at doses of 14.7-264.5 mg/kg was detected in the blood within 30 sec
following application.
Mechanism of Action: The enzyme systems in rat liver and lung responsible for the oxidative
metabolism of hydrazine derivatives were studied to determine whether these
enzymes, cytochrome p450 and monoamine oxidase, were responsible for
metabolically activating hydrazines to carcinogenic/toxic metabolites.
Cytochrome p450 preferentially oxidized the nitrogen to nitrogen bond of
1,2-disubstituted hydrazines and hydrazides, while monoamine oxidase oxidized
the nitrogen to nitrogen bond of all the classes of hydrazine derivatives that
were tested. Oxidation of the nitrogen to nitrogen bond led to the formation of
stable azo intemediates in the case of 1,2-disubstituted hydrazines and to
unstable monoazo (diazene) metabolites in the case of monosubstituted hydrazines
and hydrazides. /Substituted hydrazines/
Interactions: ADMIN OF METHYLHYDRAZINE TO MICE DECR
SURVIVAL OF ANIMALS AFTER X-IRRADIATION, INHIBITED GROWTH OF EHRLICH ASCITES
TUMOR, & INCR NUMBER OF CELLS WITH CHROMOSOME ABERRATIONS. DECR IN THE SH
LEVEL WAS SUGGESTED AS RESPONSIBLE FOR RADIOSENSITIZING ACTIVITY.
METHYLHYDRAZINE WAS TESTED FOR
SYNERGISM IN PROMOTING IN VITRO ONCOGENIC TRANSFORMATION OF SWISS MOUSE 3T3
CELLS BY HERPES SIMPLEX TYPE 2 VIRUS (HSV-2). METHYLHYDRAZINE ENHANCED LEVEL OF ONCOGENIC
TRANSFORMATION APPROX 2-FOLD. Several inhibitors of the FAD-containing monooxygenase (FAD-MO) system from
rat liver microsomes (imipramine, chloropromazine, mercaptoethylamine,
dithiothreitol, naphthylthiourea, phenylthiocarbamide) and one inhibitor of the
liver microsomal cytochrome p450-mediated biotransformations, were tested as
possible inhibitors of monomethylhydrazine (MMH) biotransformation to
carbon dioxide and to reactive metabolites that bind covalently to nucleic acids
and proteins. Results confirm previous suggestions that both FAD-containing
monooxygenase system and p450 are involved in monomethylhydrazine metabolism to carbon
dioxide and suggest a similar participation of both systems for production of
reactive metabolites interacting wth macromolecules. EXPTL USE: SINGLE SC INJECTIONS OF SUBSTITUTED HYDRAZINES WERE GIVEN ALONE
& JOINTLY WITH PYRIDOXINE HYDROCHLORIDE TO SWISS MICE. THE CONVULSIVE, TOXIC
& LETHAL EFFECTS OF METHYLHYDRAZINE
WERE SUCCESSFULLY PREVENTED BY ADMIN OF PYRIDOXINE HYDROCHLORIDE BEFORE &/OR
AFTER INJECTION. EXPTL USE: THE EFFECTIVENESS OF MUSCIMOL, DIAZEPAM, & PYRIDOXINE &
CERTAIN COMBINATIONS OF THESE COMPOUNDS AGAINST CONVULSIONS INDUCED BY MONOMETHYLHYDRAZINE WAS EXAM IN MICE. ALL
DRUGS HAD A PROTECTIVE EFFECT BUT COMBINATIONS CONTAINING DIAZEPAM & EITHER
PYRIDOXINE OR MUSCIMOL WERE THE MOST EFFECTIVE ANTAGONISTS TO MONOMETHYLHYDRAZINE POISONING.
Repeated, large doses of pyridoxine can control methyl hydrazine-induced convulsions ... The
recommended dose of pyridoxine can be reduced when concurrent admin of diazepam
is employed.
Pharmacology:
Interactions: ADMIN OF METHYLHYDRAZINE TO MICE DECR
SURVIVAL OF ANIMALS AFTER X-IRRADIATION, INHIBITED GROWTH OF EHRLICH ASCITES
TUMOR, & INCR NUMBER OF CELLS WITH CHROMOSOME ABERRATIONS. DECR IN THE SH
LEVEL WAS SUGGESTED AS RESPONSIBLE FOR RADIOSENSITIZING ACTIVITY.
METHYLHYDRAZINE WAS TESTED FOR
SYNERGISM IN PROMOTING IN VITRO ONCOGENIC TRANSFORMATION OF SWISS MOUSE 3T3
CELLS BY HERPES SIMPLEX TYPE 2 VIRUS (HSV-2). METHYLHYDRAZINE ENHANCED LEVEL OF ONCOGENIC
TRANSFORMATION APPROX 2-FOLD. Several inhibitors of the FAD-containing monooxygenase (FAD-MO) system from
rat liver microsomes (imipramine, chloropromazine, mercaptoethylamine,
dithiothreitol, naphthylthiourea, phenylthiocarbamide) and one inhibitor of the
liver microsomal cytochrome p450-mediated biotransformations, were tested as
possible inhibitors of monomethylhydrazine (MMH) biotransformation to
carbon dioxide and to reactive metabolites that bind covalently to nucleic acids
and proteins. Results confirm previous suggestions that both FAD-containing
monooxygenase system and p450 are involved in monomethylhydrazine metabolism to carbon
dioxide and suggest a similar participation of both systems for production of
reactive metabolites interacting wth macromolecules. EXPTL USE: SINGLE SC INJECTIONS OF SUBSTITUTED HYDRAZINES WERE GIVEN ALONE
& JOINTLY WITH PYRIDOXINE HYDROCHLORIDE TO SWISS MICE. THE CONVULSIVE, TOXIC
& LETHAL EFFECTS OF METHYLHYDRAZINE
WERE SUCCESSFULLY PREVENTED BY ADMIN OF PYRIDOXINE HYDROCHLORIDE BEFORE &/OR
AFTER INJECTION. EXPTL USE: THE EFFECTIVENESS OF MUSCIMOL, DIAZEPAM, & PYRIDOXINE &
CERTAIN COMBINATIONS OF THESE COMPOUNDS AGAINST CONVULSIONS INDUCED BY MONOMETHYLHYDRAZINE WAS EXAM IN MICE. ALL
DRUGS HAD A PROTECTIVE EFFECT BUT COMBINATIONS CONTAINING DIAZEPAM & EITHER
PYRIDOXINE OR MUSCIMOL WERE THE MOST EFFECTIVE ANTAGONISTS TO MONOMETHYLHYDRAZINE POISONING.
Repeated, large doses of pyridoxine can control methyl hydrazine-induced convulsions ... The
recommended dose of pyridoxine can be reduced when concurrent admin of diazepam
is employed.
Environmental Fate & Exposure:
Environmental Fate/Exposure Summary: Methylhydrazine's production and use
as a rocket fuel may result in its direct release to the environment during
refueling and transfer operations. It may also be released in various waste
streams during the production or use of this compound as an intermediate in
chemical synthesis and as a solvent. If released to the atmosphere, methylhydrazine will exist solely in the vapor
phase in the ambient atmosphere, based on a measured vapor pressure of 50 mm Hg
at 25 deg C. Vapor-phase methylhydrazine
is degraded in the atmosphere by reaction with photochemically-produced hydroxyl
radicals and ozone with estimated half-lives of about 6 hours and 1-12 minutes,
respectively. Both vapor phase methylhydrazine and methylhydrazine dissolved in aerosols are
expected to react rapidly with ozone. An estimated Koc value of 6 suggests that
methylhydrazine will have very high
mobility in soil. Hydrazines are weak bases and should exist predominantly in
their protonated form at pH values below their pKa value. A positive charge on
the hydrazine could either increase or decrease the adsorption capacity of this
compound depending on the soil and pH. Some chemical decomposition of methylhydrazine was reported in soil.
Volatilization from moist soil surfaces is not expected to occur based on an
estimated Henry's Law constant of 3.2X10-8 atm-cu m/mole. Volatilization from
dry soil surfaces may be significant given the vapor pressure of this compound.
Methyl hydrazine may also undergo direct
photolysis on soil and water surfaces since hydrazines strongly absorb UV light
in the environmentally significant range. Based on limited data, methylhydrazine may biodegrade in soil and
water under aerobic conditions. In water, methylhydrazine is not expected to adsorb to
sediment and particulate matter based on its Koc value although it may adsorb
strongly to clay particulates and organic matter based on soil studies. This
compound should not volatilize from water surfaces given its estimated Henry's
Law constant. Estimated half-lives of methylhydrazine present at 9.5 mM in pond and
sea water are 18.0 and 24.1 days, respectively, and at 19.0 mM are 13.1 days in
both pond and sea water. Release to water is expected to result in oxidation by
dissolved oxygen, especially at high pH values; the half-life of the reaction
between methylhydrazine and dissolved
oxygen in water is about 2 hr at 30 deg C and pH 9.16. Bioconcentration in
aquatic organisms should be low based on an estimated BCF value of 0.1.
Occupational exposure may occur through inhalation or dermal contact at sites
where methylhydrazine is produced or
used. The general population may be exposed to methylhydrazine via dermal contact with vapors
and products containing methylhydrazine.
(SRC)
Probable Routes of Human Exposure: Monomethylhydrazine ... is a
decomposition product of the mushroom toxin, gyromitrin (Gyromitra esculenta)
... /when/ generated in vivo is believed to be responsible for the toxicity of
gyromitrin. Human exposure to methylhydrazine
most likely results from its use as a component of aerospace propellants. NIOSH
(NOES Survey 1981-1983) has estimated that 1,473 workers (230 of these are
female) are exposed to methylhydrazine
in the USA(1). The general population may be exposed to methylhydrazine via dermal contact with vapors
and other products containing methylhydrazine(SRC).
Natural Pollution Sources: It has been found in nature in an edible mushroom Gyrimitia esculenta.
Artificial Pollution Sources: Methylhydrazine's use in rocket fuel,
as an intermediate in chemical synthesis(1) and as a solvent(2), may result in
environmental release in a variety of waste streams(SRC). Methylhydrazine's production and use as a
rocket fuel may result in its direct release to the environment during refueling
and transfer operations(3).
Environmental Fate: TERRESTRIAL FATE: Based on a recommended classification scheme(1), an
estimated Koc value of 6(SRC), determined from a measured log Kow(2) and a
recommended regression-derived equation(3), indicates that methylhydrazine will have very high mobility
in soil(SRC). Hydrazines are weak bases and should exist predominantly in their
protonated form at pH values below their pKa value. A positive charge on the
hydrazine could either increase or decrease the adsorption capacity of this
compound depending on the soil and pH(SRC). Of the initial amount of methylhydrazine in 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) samples, 0%,
5%, 20%, and 8%, respectively, was possibly degraded in less than 1 hour (mainly
due to chemical decomposition)(4). Methylhydrazine may decompose in soils high in
organic carbon and clay and tightly adsorb to clay soils; it may, however, leach
from sandy soils(4). Methylhydrazine's
measured value for vapor pressure, 50 mm Hg(5), indicates that volatilization
from dry soil surfaces should be significant although adsorption to clay soils
and soils containing organic matter may attenuate the rate of this process(SRC).
Volatilization from moist soil surfaces is not expected based on the estimated
Henry's Law constant, 3.2X10-8(6,SRC), for this compound(SRC). Based on limited
data, it is possible that this compound may biodegrade in soil(7,SRC).
AQUATIC FATE: The estimated half-lives of methylhydrazine present at 9.5 mM in pond and
sea water are 18.0 and 24.1 days, respectively, and at 19.0 mM are 13.1 days in
both pond and sea water(1). The half-life of the reaction between methylhydrazine and dissolved oxygen in water
is about 2 hr at 30 deg C and pH 9.16(2). Based on a recommended classification
scheme(3), an estimated Koc value of 6(SRC), determined from a measured log
Kow(4) and a recommended regression-derived equation(3), indicates that methylhydrazine should not adsorb to suspended
solids and sediment in water(SRC). Based on results from soil studies, however,
this compound may adsorb strongly to clay particles and organic matter in
water(1). Methylhydrazine is not
expected to volatilize from water surfaces(3,SRC) based on an estimated Henry's
Law constant of 3.2X10-8 atm-cu m/mole(SRC), developed using a fragment constant
estimation method(5). According to a classification scheme(6), an estimated BCF
value of 0.1(3,SRC), from a measured log Kow(4), suggests that bioconcentration
in aquatic organisms is low(SRC). Based on limited data, it is possible that
this compound may biodegrade in water(7,SRC). ATMOSPHERIC FATE: According to a model of gas/particle partitioning of
semivolatile organic compounds in the atmosphere(1), methylhydrazine, which has a measured vapor
pressure of 50 mm Hg at 25 deg C(2), will exist solely as a vapor in the ambient
atmosphere. Vapor-phase methylhydrazine
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). Assuming an ozone concentration of 7X10+11 molecules/cu cm, a
maximum half life of about 3.3 min for the reaction of methylhydrazine with ozone was estimated from
a minimum rate constant of 5X10-15 cu cm/molecule sec(4,SRC). The half life for
the reaction between ozone and methylhydrazine was estimated to be <1 min
during ozone pollution episodes and <12 min in the 'natural' troposphere(5).
Reaction of methylhydrazine with ozone
is expected to be the predominant fate of methylhydrazine in the atmosphere(SRC).
Environmental Biodegradation: No data were available, but the toxicity of methylhydrazine to microbial species was found
to be sufficiently high to prevent its degradation by biological waste
treatment(1). Large amounts of methylhydrazine, such as might be released
from a spill, are not expected to biodegrade. However, biodegradation of lower
methylhydrazine concn may occur(SRC).
Methylhydrazine at 500 mg/l, present in
a wastewater mixture of hydrazine compounds, was incubated with an inoculum
prepared from a trickling filter plant; following a 24 hour lag period, this
mixture of compounds was biodegraded as measured by oxygen uptake(2). No
specific information on the fate of methylhydrazine alone was available(2).
Environmental Abiotic Degradation: The rate constant for the vapor-phase reaction of methylhydrazine with photochemically-produced
hydroxyl radicals has been measured as 6.50X10-11 cu cm/molecule-sec at 25 deg
C(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). Dark
decay of 11.5 ppm methylhydrazine in a
6400 l chamber at 10% relative humidity (RH) and 24 deg C proceeded with a half
life of 19.8 hr(2). Dark decay in a 3800 l chamber of 11.5 ppm methylhydrazine at 10% RH and 24 deg C
proceeded with a half life of 49.8 hr and 10.3 ppm methylhydrazine at 17% RH and 22 deg C
proceeded with a half life of 30.1 hr(2). The products were ammonia and
methyldiazene. Ammonia accounted for only 2% and 4% of the methylhydrazine lost in dry and humidified
air, respectively(2). The estimated concentration of methyldiazene in the 3800 l
chamber experiments was about 0.3 ppm(2). A minimum reaction rate of about
5X10-15 cu cm/molecule sec was obtained for the reaction between methylhydrazine and ozone in a large chamber
with 14-28% RH and from 22-24 deg C(2). Assuming an ozone concentration of
7X10+11 molecules/cu cm, the maximum half-life for the reaction of methylhydrazine with ozone is about 3.3
min(SRC). Major products observed were methylhydroperoxide, methyldiazene,
formaldehyde, diazomethane and hydrogen peroxide(2). The half-life for the
reaction between ozone and methylhydrazine was estimated to be < 1 min
during ozone pollution episodes and < 12 min in the 'natural' troposphere(3).
The upper limit for the rate of reaction of methylhydrazine with nitrogen dioxide is about
1.4X10-18 cu cm/molecule sec(2). Nitrous oxide does not react significantly with
methylhydrazine(2). The lifetime of
methylhydrazine in aerosols upon
exposure to ozone is about 1 min(4). The aqueous oxidation of methylhydrazine results in methanol,
nitromethane and nitrosodimethylamine(4). At a pH of 9.16 and 30 deg C, the
first order rate constant for the reaction between dissolved oxygen and methylhydrazine is 5.6X10-3 1/min giving a
half-life of about 2 hr(SRC,5). Methyl hydrazine
may also undergo direct photolysis on soil and water surfaces
since hydrazines strongly absorb UV light in the environmentally significant
range(SRC).
Environmental Bioconcentration: An estimated BCF value of 0.1 was calculated for methylhydrazine(SRC), using a measured log Kow
of -1.05(1) and a recommended regression-derived equation(2). According to a
classification scheme(3), this BCF value suggests that bioconcentration in
aquatic organisms is low(SRC).
Soil Adsorption/Mobility: Of the initial amount of methylhydrazine in 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), 3%, 46%,
26%, and 64% was adsorbed, respectively(1). Passage of 2 liters of distilled,
deionized water through columns containing sand, VAFB soil, organic soil and
clay (10% clay plus 90% pure sand) treated with 10 ml of a 0.1 v/v solution of
methylhydrazine resulted in 86.9%, 5.5%,
6.5%, 6.3% recovery of methylhydrazine,
respectively(1). Based on a log Kow of -1.05(2), a Koc of 6 for methylhydrazine has been calculated from a
regression-derived equation(3,SRC). According to a recommended classification
scheme(3), this estimated Koc value suggests that methylhydrazine has very high mobility in
soil(SRC).
Volatilization from Water/Soil: The Henry's Law constant for methylhydrazine is estimated as 3.2X10-8
atm-cu m/mole(SRC) using a fragment constant estimation method(1). This value
indicates that methylhydrazine will be
essentially nonvolatile from water surfaces(2,SRC). Methylhydrazine's measured value for vapor
pressure, 50 mm Hg at 25 deg C(3) indicates that volatilization from dry soil
surfaces should be significant although adsorption to clay soils and soils
containing organic matter may attenuate the rate of this process(SRC).
Volatilization from moist soil surfaces is not expected based on the estimated
Henry's Law constant(1,SRC) for this compound(SRC).
Environmental Standards & Regulations:
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 10 lb or 4.54 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. Methyl hydrazine
is an extremely hazardous substance (EHS) subject to reporting
requirements when stored in amounts in excess of its threshold planning quantity
(TPQ) of 500 lbs.
RCRA Requirements: P068; As stipulated in 40 CFR 261.33, when methyl
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 container or inner liner used to hold this waste or 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(e)).
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. Methyl hydrazine
is included on this list.
State Drinking Water Guidelines: (FL) FLORIDA 10 ug/l
Chemical/Physical Properties:
Molecular Formula: C-H6-N2
Molecular Weight: 46.07
Color/Form: Clear liquid Fuming, colorless liquid.
Odor: ODOR CHARACTERISTIC OF SHORT CHAIN, ORGANIC AMINES
Ammonia-like odor.
Boiling Point: 87.5 DEG C
Melting Point: -52.4 DEG C
Critical Temperature & Pressure: CRITICAL TEMPERATURE: 594 DEG F= 312, DEG C= 585 DEG K; CRITICAL PRESSURE:
1,195 PSIA = 81.3 ATM = 8.25 MN/SQ M
Density/Specific Gravity: 0.874 @ 25 DEG C
Heat of Combustion: -12,178 BTU/LB = -6,766 CAL/G = -283.1X10+5 J/KG
Heat of Vaporization: 376 BTU/LB= 209 CAL/G= 8.75X10+5 J/KG
Octanol/Water Partition Coefficient: Log Kow= -1.05
pH: MILDLY ALKALINE BASE
Solubilities: >10% in ethyl ether >10% in ethanol >10% in water SOL IN PETROLEUM ETHER MISCIBLE WITH HYDRAZINE AND WATER, LOW MOL WT MONOHYDRIC ALCOHOLS; SOL IN
HYDROCARBONS Miscible in alcohol; soluble in water, ether, and carbon tetrachloride.
Spectral Properties: IR PRISM: 7650 (Sadtler Research Laboratories Prism Collection)
NMR: 6865 (Sadtler Research Laboratories Spectral Collection)
MASS: 4 (National Bureau of Standards EPA-NIH Mass Spectra Data Base,
NSRDS-NBS-63) Index of refraction: 1.4325 @ 20 deg C/d
Surface Tension: 34.3 dynes/cm= 0.0343 N/m at 20 deg C (liquid)
Vapor Density: 1.6 (AIR= 1)
Vapor Pressure: 50 mm Hg at 25 deg C
Viscosity: 0.771 millipascal second @ 25 deg C
Other Chemical/Physical Properties: CONVERSION FACTORS: 1 MG/L= 532 PPM; 1 PPM= 1.88 MG/CU M
HEAT CAPACITY AT 25 DEG C: 32.25 CAL/MOLE/DEG C; STRONG REDUCING AGENT
HYGROSCOPIC Heat of fusion: 10.42 kJ/mole; heat of formation: 53.97 kJ/mole; free energy
of formation: 179.9 kJ/mole; entropy of formation: 165.9 J/mole/deg C
Ionization potential: 7.67 eV The kinetics of oxidation of methylhydrazine and 1,1-dimethylhydrazine by
dissolved oxygen in water was measured at various acidities as a function of
catalyst (cupric ion) concentration. In dilute solutions the oxidation occurred
through a cupric ion catalyzed process and by an uncatalyzed step. The extent of
formation of the carcinogen nitrosodimethylamine depended on the initial
1,1-dimethylhydrazine concentration. In dilute solutions nitrosodimethylamine
was not formed, but in more concentrated solutions, nitrosodimethylamine
formation increased with increasing 1,1-dimethylhydrazine content, reached a
maximum at 60-80% 1,1-dimethylhydrazine (by volume) and then decreased. The
nitrosodimethylamine yield appeared to approximately parallel the viscosity of
the medium, and it was speculated that the factors which controlled viscosity
may also have been responsible for governing nitrosodimethylamine formation.
Chemical Safety & Handling:
DOT Emergency Guidelines: Health: Toxic; may be fatal if inhaled, ingested or absorbed through skin.
Inhalation or contact with some of these materials will irritate or burn skin
and eyes. Fire will produce irritating, corrosive and/or toxic gases. Vapors may
cause dizziness or suffocation. Runoff from fire control or dilution water may
cause pollution. Fire or explosion: Highly flammable: Will be easily ignited by heat, sparks
or flames. Vapors may form explosive mixtures with air. Vapors may travel to
source of ignition and flash back. Most vapors are heavier than air. They will
spread along ground and collect in low or confined areas (sewers, basements,
tanks). Vapor explosion and poison hazard indoors, outdoors or in sewers. Those
substances designated with a "P" may polymerize explosively when heated or
involved in a fire. Runoff to sewer may create fire or explosion hazard.
Containers may explode when heated. Many liquids are lighter than water.
Public safety: Call Emergency Response Telephone Number. ... Isolate spill or
leak area immediately for at least 100 to 200 meters (330 to 660 feet) in all
directions. Keep unauthorized personnel away. Stay upwind. Keep out of low
areas. Ventilate closed spaces before entering. Protective clothing: Wear positive pressure self-contained breathing
apparatus (SCBA). Wear chemical protective clothing which is specifically
recommended by the manufacturer. It may provide little or no thermal protection.
Structural firefighters' protective clothing provides limited protection in fire
situations ONLY; it is not effective in spill situations.
Evacuation: ... Fire: If tank, rail car or tank truck is involved in a fire,
isolate for 800 meters (1/2 mile) in all directions; also, consider initial
evacuation for 800 meters (1/2 mile) in all directions. Fire: CAUTION: All these products have a very low flash point. Use of water
spray when fighting fire may be inefficient. Small fires: Dry chemical, CO2,
water spray or alcohol-resistant foam. Large fires: Water spray, fog or
alcohol-resistant foam. Move containers from fire area if you can do it without
risk. Dike fire control water for later disposal; do not scatter the material.
Use water spray or fog; do not use straight streams. Fire involving tanks or
car/trailer loads: Fight fire from maximum distance or use unmanned hose holders
or monitor nozzles. Cool containers with flooding quantities of water until well
after fire is out. Withdraw immediately in case of rising sound from venting
safety devices or discoloration of tank. ALWAYS stay away from tanks engulfed in
fire. For massive fire use unmanned hose holders or monitor nozzles; if this is
impossible, withdraw from area and let fire burn. Spill or leak: Fully encapsulating, vapor protective clothing should be worn
for spills and leaks with no fire. ELIMINATE all ignition sources (no smoking,
flares, sparks or flames in immediate area). All equipment used when handling
the product must be grounded. Do not touch or walk through spilled material.
Stop leak if you can do it without risk. Prevent entry into waterways, sewers,
basements or confined areas. A vapor suppressing foam may be used to reduce
vapors. Small spills: Absorb with earth, sand or other non-combustible material
and transfer to containers for later disposal. Use clean non-sparking tools to
collect absorbed material. Large spills: Dike far ahead of liquid spill for
later disposal. Water spray may reduce vapor; but may not prevent ignition in
closed spaces. First aid: Move victim to fresh air. Call 911 or emergency medical service.
Apply artificial respiration if victim is not breathing. Do not use
mouth-to-mouth method if victim ingested or inhaled the substance; induce
artificial respiration with the aid of a pocket mask equipped with a one-way
valve or other proper respiratory medical device. Administer oxygen if breathing
is difficult. Remove and isolate contaminated clothing and shoes. In case of
contact with substance, immediately flush skin or eyes with running water for at
least 20 minutes. Wash skin with soap and water. Keep victim warm and quiet.
Effects of exposure (inhalation, ingestion or skin contact) to substance may be
delayed. Ensure that medical personnel are aware of the material(s) involved,
and take precautions to protect themselves.
Odor Threshold: 1.75 mg/cu m (low); 5.25 mg/cu m (high) The warning properties (irritation & odor) of the hydrazines are probably
sufficient to prevent acute poisoning from short exposures. However, in view of
the chronic toxicity properties, the warning properties should not be considered
adequate for prolonged exposures. They ... have median detectable odor levels of
1 to 10 ppm, but these levels are levels above all the TLVs adopted for
hydrazines except phenylhydrazine. /Hydrazines/
Skin, Eye and Respiratory Irritations: Vapor is irritating to eyes, nose & throat. Skin irritation is pronounced with the propellant hydrazines ... /Hydrazine
& derivatives/ All hydrazines have similar toxic local effects due to their irritant
properties. The vapor is highly irritating to the eyes, upper respiratory tract,
& skin ... /Hydrazines/
Fire Potential: DANGEROUS, WHEN EXPOSED TO HEAT OR FLAME.
NFPA Hazard Classification: Health: 4. 4= Materials that, on very short exposure, could cause death or
major residual injury, including those that are too dangerous to be approached
without specialized protective equipment. A few whiffs of the vapor or gas can
cause death, or contact with the vapor or liquid may be fatal, if it penetrates
the fire fighter's normal protective gear. The normal full protective clothing
and breathing apparatus available to the typical fire fighter will not provide
adequate protection against inhalation or skin contact with these materials.
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: 2. 2= This degree includes materials that are normally unstable
and readily undergo violent chemical change, but are not capable of detonation.
This includes materials that can undergo chemical change with rapid release of
energy at normal temperatures and pressures and materials that can undergo
violent chemical changes at elevated temperatures and pressures. This also
includes materials that may react violently with water or that may form
potentially explosive mixtures with water. In advanced or massive fires
involving these materials, fire fighting should be done from a safe distance or
from a protected location.
Flammable Limits: Lower flammable limit: 2.5% by volume; Upper flammable limit: 97% by volume
Flash Point: -8 deg C, 17 deg F (closed cup)
Autoignition Temperature: 196 DEG C (385 DEG F)
Fire Fighting Procedures: 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.
Toxic Combustion Products: Toxic oxides of nitrogen are produced during combustion of this material.
Firefighting Hazards: VAPORS ARE HEAVIER THAN AIR & MAY TRAVEL TO A SOURCE OF IGNITION &
FLASH BACK. Prolonged exposure of the containers of the material to fire or heat may
result in the spontaneous decomposition of the material & violent rupture of
the container.
Explosive Limits & Potential: 2.5 & 97% + OR - 2% BY VOL Ignites on contact with hydrogen peroxide or nitrogen dioxlde among other
oxidants.
Hazardous Reactivities & Incompatibilities: Reacts violently with oxidizing materials, oxygen, & peroxides; sometimes
resulting in autoignition. Oxides of iron; copper; manganese; lead; copper alloys; porous materials such
as earth, asbestos, wood & cloth; strong oxidizers such as fluorine &
chlorine; nitric acid; hydrogen peroxide. Spontaneous ignition may occur if in contact with oxidizing materials.
A powerful reducing agent & fuel, hypergolic with many oxidants such as
dinitrogen tetraoxide or hydrogen peroxide. Contact of dicyanofurazan, or its N-oxide (dicyanofuroxan), with hydrazine,
mono or dimethylhydrazine ... is instantaneously explosive.
IGNITES SPONTANEOUSLY ON CONTACT WITH STRONG OXIDIZING AGENTS SUCH AS
FLUORINE, CHLORINE TRIFLUORIDE, NITROGEN TETRAOXIDE, FUMING NITRIC ACID.
Immediately Dangerous to Life or Health: NIOSH considers methyl hydrazine to
be a potential occupational carcinogen.
Protective Equipment & Clothing: Wear special protective clothing and positive pressure self-contained
breathing apparatus. Breakthrough times greater than one hour reported by (normally) two or more
testers for butyl rubber and polyvinyl chloride. Some data suggesting
breakthrough times of approximately an hour for chlorinated polyethylene and
viton. ... VINYL COATED HAND PROTECTION, NATURAL OR RECLAIMED RUBBER PROTECTION,
RUBBER APRONS, AND PLASTIC EYE AND FACE PROTECTION ... USED WHEN WORKING WITH
SMALL QUANTITIES. WHERE POSSIBILITY OF GROSS SPLASHING EXISTS, FULL PROTECTIVE
CLOTHING MADE OF RUBBER, NEOPRENE OR VINYL-COATED MATERIALS SHOULD BE WORN. FOR
RESPIRATORY PROTECTION IN SITUATIONS WHERE RECOMMENDED TOLERANCE LIMITS ...
EXCEEDED, RESPIRATORY PROTECTIVE EQUIPMENT SUCH AS APPROVED CANISTERS OR A GAS
MASK OR SELF CONTAINED BREATHING APPARATUS MUST BE USED. /HYDRAZINE &
DERIVATIVES/ All systems or equipment containing the hydrazines shall be designed to
minimize the possibility of vapor or aerosol inhalation, skin or eye contact,
and spill or leaks; such as full face shields, goggles, and full body protection
clothing, including gloves and boots. /Hydrazines/ 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.) 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.
Preventive Measures: 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.
Evacuation: If fire becomes uncontrollable or container is exposed to direct
flame consider evacuation of one (1/3) mile radius.
Personnel protection: Avoid breathing vapors. Keep upwind. ... Avoid bodily
contact with the material. ... Do not handle broken packages unless wearing
appropriate personal protective equipment. Wash away any material which may have
contacted the body with copious amounts of water or soap and water.
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. Inhalation of salt dusts should be avoided. /Hydrazine & derivatives/
Engineering controls, such as process enclosure or local exhaust ventilation,
shall be used when needed to keep concentrations of airborne hydrazines within
acceptable levels. Ventilation systems shall be designed to prevent accumulation
or recirculation of airborne hydrazines in the workplace environment and to
remove hydrazines from the breathing zone of workers. /Hydrazines/
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. 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.
Storage Conditions: Store in a cool, dry, well-ventilated location. Separate from acids,
oxidizing materials, halogens, & air. Outside or detached storage is
preferred.
Cleanup Methods: Wear butyl rubber gloves, self-contained breathing apparatus, eye protection
and impervious clothing. Body shield should be available. Eliminate all sources
of ignition and flammables. On skin or clothing. Wash skin immediately. Remove
contaminated clothing at once. Spills: Cover spill with a 1:1:1 mixture by
weight of sodium carbonate or calcium carbonate, clay cat litter (bentonite) and
sand. Scoop the solid into a container, transport to the fume hood and slowly
add to water allowing 20 ml water for each 1 g of methylhydrazine. Filter off the clay and sand.
For each 1 g of methylhydrazine, place
41 ml (about 25% excess) of commercial laundry bleach (containing about 5.25%
sodium hypochlorite) into a 3-necked round-bottom flask equipped with a stirrer,
thermometer and dropping funnel. Add the aqueous methylhydrazine dropwise to the stirred
hypochlorite solution, monitoring the rate of addition by rise in temperature.
The temperature is maintained at 45-50 deg C and addition takes about 1 hour.
Stirring is continued for 2 hours until the temperature gradually falls to room
temperature.
Disposal Methods: Generators of waste (equal to or greater than 100 kg/mo) containing this
contaminant, EPA hazardous waste number P068, must conform with USEPA
regulations in storage, transportation, treatment and disposal of waste.
Methyl hydrazine is a good candidate
for liquid injection incineration with a temperature range of 650 to 1600 deg C
and a residence time of 0.1 to 2 seconds. Also a good 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; for solids hours. Also a good candidate
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.
Small Quantities. Wear butyl rubber gloves, laboratory coat and eye prolection. Work in the fume hood. Prepare a dilute (5%) aqueous solution of methylhydrazine by adding slowly to the appropriate volume of water. For each 1 g of methylhydrazine, place 41 ml (about 25% excess) of household laundry bleach (5.25% sodium hypochlorite) into a 3-necked round-bottom flask equipped with a stirrer, thermometer and dropping funnel. Add the aqueous methylhydrazi |