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PDF1,1-DIMETHYLHYDRAZINESee Occupational Exposure Standards
Human Health Effects:
Evidence for Carcinogenicity:
Evaluation: No epidemiological data on the carcinogenicity of
1,1-dimethylhydrazine were available. There is sufficient evidence in
experimental animals for the carcinogenicity of 1,1-dimethylhydrazine. Overall
evaluation: 1,1-Dimethylhydrazine is possibly carcinogenic to humans (Group 2B).
A3. Confirmed animal carcinogen with unknown relevance to humans.
Human Toxicity Excerpts:
... WORKERS EXPERIENCED RESPIRATORY DISTRESS AND LATER, NAUSEA AND VOMITING
AFTER ACCIDENTAL EXPOSURE TO ... /1,1-DIPHENYLHYDRAZINE/ VAPOR. OTHERS HAVE
OBSERVED THAT ACUTE ACCIDENTAL EXPOSURES WILL PRODUCE NOSE AND THROAT
IRRITATION, MILD CONJUNCTIVITIS, AND NAUSEA. /1,1-DIPHENYLHYDRAZINE/
... 6 CASES OF FATTY LIVER ASSOCIATED WITH A RISE IN SGPT LEVELS IN 26
PERSONNEL WORKING WITH LIQUID ROCKET FUELS FOR UP TO 5 YEARS /WERE DESCRIBED/.
... Symptoms: ... dyspnea; lethargy; ... anoxia; convulsions; liver injury.
The Carcinogen Assessment Group (CAG), Office of Health and Environmental
Assessment in EPA'S Research and Development Office, has prepared a list of
chemical substances for which substantial or strong evidence exists showing that
exposure to these chemicals, under certain conditions, causes cancer in humans,
or can cause cancer in animal species which in turn, makes them potentially
carcinogenic in humans. Substances are placed on the CAG list only if they have
been demonstrated to induce malignant tumors in one or more animal species or to
induce benign tumors that are generally recognized as early stages of
malignancies, and/or if positive epidemiologic studies indicated they were
carcinogenic. 1,1-Dimethylhydrazine is on that list.
HIGHLY CORROSIVE & IRRITATING TO SKIN, EYES, AND MUCOUS MEMBRANES.
CONVULSANT POISON.
/A case history/ is presented /regarding/ extensive burns associated with
1,1-dimethylhydrazine (UDMH) toxicity in
a 31-year-old man. Neurological symptoms dominated early developments. Specific
treatment with pyridoxine, while begun late, effected a quite rapid resolution
and the subsequent progression of treatment was straightforward. In reviewing
previous reported findings, the distinctive characteristics of UDMH toxicity /have been elucidated/. The
methods for its detection and modes of treatment /is also considered/. ...
Several incidents of human inhalation exposure to UDMH /1,1-dimethylhydrazine/ has occurred.
Exposure levels were not determined. Symptoms of exposure incl respiratory
effects, nausea, vomiting, neurological effects, pulmonary edema, and incr SGPT.
Conclusions: There are no data on human exposures that would serve to
identify a critical effect of exposure to either 1,1-dimethylhydrazine or
1,2-dimethylhydrazine. Judging from animal experiments, the critical effect of
both substances is cancer. Acute exposure can have effects on breathing and on
the nervous system. Dimethylhydrazine (both isomers) is readily absorbed through
the skin.
Skin, Eye and Respiratory Irritations:
... IRRITATING TO SKIN, EYES, MUCOUS MEMBRANES.
Highly corrosive and irritating to skin, eyes, mucous membranes.
Medical Surveillance:
Consider the point of attack /CNS, liver, gastrointestinal system, blood,
respiratory system, eyes, skin/ in placement and periodic physical exam.
Probable Routes of Human Exposure:
Human exposure to 1,1-dimethylhydrazine will most likely result from its use
as a component of aerospace propellants. NIOSH (NOES Survey 1981-1983) has
estimated that 2,917 workers are exposed to 1,1-dimethylhydrazine in the US(1).
Exposure of workers to 1,1-dimethylhydrazine at the Rocky Mountain Arsenal
Hydrazine Facility was mainly through inhalation(2). The general population may
be exposed to 1,1-dimethylhydrazine through the ingestion of food, and dermal
contact with vapors, food and other products containing this compound(SRC).
Emergency Medical Treatment:
Emergency Medical Treatment:
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The following Overview, *** DIMETHYLHYDRAZINE ***, 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 Dimethylhydrazine (UDMH) has lesser oral and greater
inhalational toxicity than does hydrazine. This review
is based on the properties of methylhydrazine and
hydrazines, with effects specific for UDMH identified.
o The following effects may occur with UDMH: systemic
absorption by any exposure route, strong irritation or
burns of the skin and eyes, CNS stimulation (tremors
and convulsions), methemoglobinemia, hemolysis, and
liver or kidney damage.
o Dimethylhydrazine is an experimental animal carcinogen
and a suspected human carcinogen.
VITAL SIGNS
0.2.3.1 ACUTE EXPOSURE
o Anoxia, cyanosis, or fever may occur.
HEENT
0.2.4.1 ACUTE EXPOSURE
o METHYL HYDRAZINE causes irritation of the eyes, nose,
and throat. Vapors may cause eye irritation. Direct
contact with the liquid may cause severe eye damage and
burns of the mucous membranes. Facial edema,
conjunctivitis, and excessive salivation have been
reported with hydrazine exposure.
RESPIRATORY
0.2.6.1 ACUTE EXPOSURE
o Respiratory distress without lower respiratory tract
irritation has been seen in exposed humans. Some
hydrazines may cause delayed death, bronchial mucosal
destruction, and pulmonary edema.
GASTROINTESTINAL
0.2.8.1 ACUTE EXPOSURE
o Nausea, vomiting, diarrhea, and anorexia are common.
HEPATIC
0.2.9.1 ACUTE EXPOSURE
o Increased serum liver enzyme levels may be seen after
acute exposure.
0.2.9.2 CHRONIC EXPOSURE
o Fatty liver has been seen in workers with occupational
exposure to rocket fuel and in monkeys.
GENITOURINARY
0.2.10.1 ACUTE EXPOSURE
o Diuresis was seen in rats. Renal function was not
impaired in dogs.
0.2.10.2 CHRONIC EXPOSURE
o Fatty infiltration in the renal tubular epithelium and
diuresis were seen in rats.
HEMATOLOGIC
0.2.13.1 ACUTE EXPOSURE
o Methemoglobinemia, Heinz bodies, and hemolytic anemia
have occurred in experimental animals.
DERMATOLOGIC
0.2.14.1 ACUTE EXPOSURE
o UDMH is corrosive to the skin. Second- and
third-degree burns can occur with brief exposure to the
liquid. Irritation may follow vapor exposure. Some
hydrazines are skin sensitizers.
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.
PSYCHIATRIC
0.2.18.1 ACUTE EXPOSURE
o Confusion, lethargy, and agitation have been reported.
IMMUNOLOGIC
0.2.19.1 ACUTE EXPOSURE
o Cellular and humoral immunological responses were
depressed in hydrazine-exposed guinea pigs.
0.2.19.2 CHRONIC EXPOSURE
o Some hydrazines are skin sensitizers.
REPRODUCTIVE HAZARDS
o Fetotoxicity, but not teratogenicity, was seen with
exposure to high doses in rats. Methemoglobin inducers
may be especially hazardous to the fetus. Abnormal
sperm morphology has been seen in mice.
CARCINOGENICITY
0.2.21.2 HUMAN OVERVIEW
o Dimethylhydrazine is an experimental animal carcinogen.
It is a suspect human carcinogen, but epidemiological
data are lacking.
GENOTOXICITY
o Dimethylhydrazine has been genotoxic, inducing DNA
damage, mutations, sister chromatid exchanges, and
oncogenic transformation in vitro.
OTHER
0.2.23.1 ACUTE EXPOSURE
o Dimethylhydrazine can be hazardous by any route of
exposure. Vitamin B6 is antidotal for seizures (and
posibbly other manifestations) in rats, mice, dogs, and
monkeys. |
| 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 levels. |
| Treatment Overview: |
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 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 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 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.
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.
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.
DERMAL EXPOSURE
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. |
| Range of Toxicity: |
o Minimum lethal human exposure is unknown.
o Dimethylhydrazine (UDMH) is less toxic than methyl
hydrazine. |
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:
Evaluation: No epidemiological data on the carcinogenicity of
1,1-dimethylhydrazine were available. There is sufficient evidence in
experimental animals for the carcinogenicity of 1,1-dimethylhydrazine. Overall
evaluation: 1,1-Dimethylhydrazine is possibly carcinogenic to humans (Group 2B).
A3. Confirmed animal carcinogen with unknown relevance to humans.
Non-Human Toxicity Excerpts:
... DAILY DOSES OF 0.5 MG UNSYMMETRICAL 1,1-DIPHENYLHYDRAZINE IN WATER 5
DAYS/WEEK FOR 40 WEEKS /GIVEN BY GAVAGE/ TO A GROUP OF 25 FEMALE SWISS MICE.
LUNG TUMORS WERE FOUND IN 1/8 MICE (0.25 TUMOURS/MOUSE) DYING BETWEEN 40 AND 45
WEEKS AND IN 4/9 MICE (2.6 TUMOURS/MOUSE) DYING BETWEEN 50 AND 60 WEEKS. IN 85
CONTROLS, 2/37 MICE (0.05 TUMOURS/MOUSE) AND 6/42 MICE (0.2 TUMOURS/MOUSE)
DEVELOPED LUNG TUMORS WITHIN THE SAME PERIODS.
DOGS EXPOSED FOR APPROXIMATELY 3 HR TO A VAPOR CONCN OF 111 PPM OF
1,1-DIMETHYLHYDRAZINE SHOWED SALIVATION, VOMITING, RESPIRATORY DISTRESS, AND
CONVULSIONS. ALL 3 DIED ON THE DAY OF EXPOSURE. SIMILAR SYMPTOMS ... OBSERVED IN
2 OF 3 DOGS EXPOSED TO 52 PPM FOR 4 HOURS; 1 OF THESE DIED.
3 DOGS EXPOSED REPEATEDLY TO 25 PPM DEVELOPED DEPRESSION, SALIVATION,
VOMITING, DIARRHEA, ATAXIA, CONVULSIVE SEIZURES, AND HEMOLYTIC ANEMIA. THERE WAS
A DECREASE IN HEMATOCRIT, HEMOGLOBIN AND RED BLOOD CELL COUNTS AND HEMOSIDERIN
WAS DEPOSITED IN THE CELLS OF THE RETICULOENDOTHELIAL SYSTEM. ... NO SEVERE
TOXIC SIGNS WERE OBSERVED IN 3 DOGS EXPOSED TO 5 PPM FOR 6 HR/DAY, 5 DAYS A WK
FOR 26 WK. LETHARGY & WT LOSS DEVELOPED AFTER 2 OR 3 WK OF EXPOSURE. THERE
WAS EVIDENCE OF MILD ANEMIA AFTER 6 WK OF EXPOSURE. EXAMINATION, 2 WK AFTER
EXPOSURE SHOWED ONLY HEMOSIDERIN DEPOSITION IN SPLEEN WITH NO LESIONS IN THE
OTHER ORGANS.
ADMINISTRATION OF 0.01% OF /1,1-DIMETHYLHYDRAZINE/ IN THE DRINKING WATER OF
50 MALE AND 50 FEMALE SWISS MICE RESULTED IN A HIGH INCIDENCE OF ANGIOSARCOMAS
(79%), LOCATED IN VARIOUS ORGANS. BESIDES THESE ANGIOSARCOMAS, TUMORS OF LUNGS
(71%), KIDNEYS (10%) AND LIVER (6%) WERE OBSERVED. AVG LATENT PERIOD ... 42 TO
61 WEEKS FOR VARIOUS TUMORS. /NO DATA ON CONTROLS GIVEN./
IP INJECTIONS OF 80-100 MG/KG OF 1,1-DIMETHYLHYDRAZINE PRODUCED DIURESIS IN
RATS. INJECTIONS OF 10 MG RESULTED IN DIURESIS ONLY WHEN GIVEN BY INTRACEREBRAL
ROUTE.
IMMUNOLOGICAL RESPONSIVENESS OF GUINEA PIGS WAS DECR BY 1,1-DIMETHYLHYDRAZINE
BUT LESS THAN THAT CAUSED BY 6-MERCAPTOPURINE, A KNOWN IMMUNOSUPPRESSIVE AGENT.
BOTH DEPRESSED HUMORAL & CELLULAR RESPONSES TO TUBERCULIN.
EXPOSURE TO CONCN OF 1,1-DIMETHYLHYDRAZINE IN EXCESS OF 10 MG/L DURING
NEURULATION WAS TERATOGENIC TO XENOPUS LAEVIS EMBRYOS. ABNORMALITIES: KINKY
TAILS, ABNORMAL NOTOCHORD, MICROCEPHALY, CYCLOPIA, SHORTENING OF TRUNKS, &
EDEMA. EXPOSURE DURING LATER OR EARLIER PERIODS AFFECTED ONLY VIABILITY.
DAILY INJECTIONS OF 70, 50, 30 OR 10 MG 1,1-DIMETHYLHYDRAZINE (UDMH) PER KG INTO RATS RESULTED IN THE DEATH
OF 90, 60, 50, AND 0, RESPECTIVELY, OF THE ANIMALS WITHIN FIRST 3 DAYS. ANIMALS
SURVIVING FIRST 3 DAYS BEGAN TO GAIN WEIGHT EVEN THOUGH DAILY DOSING WAS
CONTINUED. ANIMALS RECEIVING MORE THAN 10 MG/KG/DAY WERE MARKEDLY DIURETIC
THROUGHOUT THE 21 DAY TEST PERIOD. BLOOD UREA NITROGEN AND SERUM GLUTAMIC
OXALACETIC TRANSAMINASE SGOT LEVELS WERE SIGNIFICANTLY ELEVATED IN THE 50 MG/KG
GROUP AT 21 DAYS AND SLIGHTLY ELEVATED IN THE 30 MG/KG/DAY GROUP.
HISTOPATHOLOGIC STUDIES SHOWED SOME EVIDENCE OF EARLY LIPID INFILTRATION IN THE
TUBULAR EPITHELIUM OF THE KIDNEY. THUS, ALTHOUGH SOME ANIMALS APPARENTLY ADJUST
TO RELATIVELY HIGH DAILY DOSES OF UDMH,
BIOCHEMICAL AND HISTOLOGIC EVIDENCE INDICATES MILD KIDNEY DAMAGE IN THESE
ANIMALS.
HEMATOLOGICAL EFFECTS WERE STUDIED IN RABBITS & MICE ADMIN
1,1-DIMETHYLHYDRAZINE IP (10 MG/KG/DAY) FOR 20 DAYS. IT DECR THE APPARENT HALF
LIFE OF RED BLOOD CELLS FROM 15 DAYS TO 6 DAYS IN RABBITS.
ANIMALS WERE EXPOSED FOR 6 MO TO 1,1-DIMETHYLHYDRAZINE AT CONCN OF 0.05, 0.5,
& 5 PPM. MICE EXPOSED TO HIGHEST CONCN HAD INCREASED INCIDENCE OF
HEMANGIOSARCOMAS & KUPFFER CELL SARCOMAS. SKIN, LUNG, PANCREAS, PITUITARY,
& LIVER TUMORS WERE INCREASED SIGNIFICANTLY IN RATS. TUMOR INCIDENCE WAS
HIGHER THAN IN CONTROLS.
1,1-DIMETHYLHYDRAZINE WAS MUTAGENIC IN VITRO USING BACTERIAL & MAMMALIAN
CELL CULTURES. RESPONSES WERE POSITIVE AFTER MICROSOMAL ENZYME ACTIVATION,
SUGGESTING FORMATION OF ACTIVE METABOLITE. DOMINANT LETHAL TEST WAS NEGATIVE IN
MICE.
DIMETHYLHYDRAZINES GAVE NEGATIVE RESULTS IN AMES TESTS. IN HOST MEDIATED
ASSAYS, 1,1-DIMETHYLHYDRAZINE WAS ALSO NEGATIVE. EVIDENTLY, MUTAGENIC ACTIONS OF
VARIOUS HYDRAZINE DERIVATIVES ALTHOUGH CHEMICALLY CLOSELY RELATED, DEPEND ON
DIFFERENT REACTION MECHANISMS.
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.
In a study of chronic intoxication (inhalation & ip) of mice, rats &
cats by 1,1-dimethylhydrazine, morphologic exam showed that the nervous tissue
& the bronchopulmonary system were damaged, especially in the case of
inhalation intoxication.
Hydrazine sulfate was more mutagenic in the histidine requiring auxotroph of
Salmonella typhimurium, strain TA1530, than 1,1-dimethylhydrazine.
... When /1,1-dimethylhydrazine/ was applied to dogs over a large area of the
chest it was absorbed, passed into the aqueous humor, & caused opacity of
the cornea.
The chemical carcinogen hydrazine is a potent stimulator of guanylate
cyclase. 1,1-Dimethylhydrazine & hydrazine sulfate, two chemical
carcinogens, structurally related to hydrazine decrease guanylate cyclase
activity in rat tissues. Hydrazine increased DNA synthesis, but
1,1-dimethylhydrazine & hydrazine sulfate decreased DNA synthesis. The
relationship, if any, linking the guanylate cyclase cyclic GMP system to DNA
synthesis & carcinogenesis remains to be explored.
HYDRAZINE DERIV WERE TESTED FOR THEIR ABILITY TO INHIBIT PENTOBARBITAL &
CARISOPRODOL OXIDN & AMINOPYRINE N-DEMETHYLATION BY RAT LIVER MICROSOMAL
SYSTEMS IN VITRO OR IN VIVO. 1,1-DIMETHYLHYDRAZINE WAS A WEAK OR NONINHIBITOR.
THE INHIBITORY ACTION OF THE COMPOUNDS GENERALLY PARALLELED THEIR LIPID
SOLUBILITY.
THE FRIEDMAN-STAUB ASSAY WAS USED TO STUDY THE INHIBITION OF TESTICULAR DNA
SYNTHESIS BY 100 COMPOUNDS. MALE MICE WERE ADMIN CMPD IP OR ORALLY. OF THE 100
TESTED SUBSTANCES APPROX 86% OF THE KNOWN CARCINOGENS &/OR MUTAGENS SHOW UP
POSITIVELY IN THIS TEST, WHEREAS ONLY 10% OF NONCARCINOGENIC & NONMUTAGENIC
COMPOUNDS DEPRESS DNA-SYNTHETIC ACTIVITY SIGNIFICANTLY. HYDRAZINE & MOST OF
ITS DERIVATIVES INHIBITED DNA SYNTHESIS. 71.3% INHIBITION OF THYMIDINE
INCORPORTION INTO TESTICULAR DNA OCCURRED WITH N,N-DIMETHYLHYDRAZINE (200 MG/KG,
ORALLY).
Induction of malignant periphral nerve sheath tumors by 1,1-dimethylhydrazine
was studied in hamsters. MHH:EPH hamsters were injected subcutaneously with 0 or
37.3 mg/kg UDMH (males) and 32.5 mg/kg
(females) once a week for life. All animals were necropsied. UDMH induced malignant peripheral nerve sheath
tumors in 43% males and 40% females. The tumors consisted of neurofibrosarcomas
and melanotic and unpigmented schwannomas. The schwannomas originated mainly
from the cranial nerves whereas the neurofibrosarcomas originated mostly in the
thoracic and lumbrosacral nerves. ... Tumor multiplicity was 1.5 in males and
1.33 in females. Malignant dermal melanomas, hepatocellular carcinomas, and
adenocarcinomas of the stomach were also found in the treated animals,
especially in the females. No peripheral nerve tumors were found in the
controls. The authors conclude that UDMH
when given sc continuously, induces periphral nerve sheath tumors in hamsters.
Since these findings support other evidence of UDMH carcinogenicity, efforts should be made
to curtail the widespread use of UDMH.
/In an acute dermal toxicity study/ Application of UDMH /1,1-dimethylhydrazine/ to dog skin also
produced opacity of the cornea, and erythema /of the test site/.
Toxic effects from acute exposure /to 1,1-dimethylhydrazine/ incl vomiting,
convulsions, other neurological effects, pulmonary edema and hemorrhage, and
hyperglycemia. /species not specified/
Rats, mice, and dogs were exposed by inhalation to vapors of UDMH /1,1-dimethylhydrazine/ for 6 hours/day,
5 days/wk. The exposure conc for both rats and mice were 75 ppm for 7 wk or 140
ppm for 6 wk. Dogs were exposed at 5 ppm for 26 wk or 25 ppm for 13 wk.
Mortality, neurological, and respiratory effects were observed in rats and mice
exposed at either 75 or 140 ppm; however, no morphological tissue changes were
observed. At the 25 ppm exposure level, one dog died, and the remaining dogs
exhibited neurological effects, decr bw, hemolytic anemia, and hemosiderosis of
the reticuloendothelial system. At 5 ppm exposure, dogs had slightly decr bw,
hemolytic anemia, and hemosiderosis of the spleen.
Mice, rats, and hamsters were admin UDMH /1,1-dimethylhydrazine/ in their drinking
water. In mice, a significant incr in tumors of the blood vessels, lungs,
kidneys, and liver was observed. Rats developed liver carcinomas, and hamsters
developed vascular and cecal tumors.
An inhalation study was conducted in which dogs, rats, mice, and hamsters
were exposed at 0, 0.05, 0.5, or 5 ppm UDMH /1,1-dimethylhydrazine/ 6 hours/day, 5
days/wk for 6 months. The rodents were sacrificed 17-20 mo postexposure. At the
time of the report, the dogs were still alive and undergoing observation.
However, the UDMH was contaminated with
0.12% dimethylnitrosamine, a carcinogen ... Dogs exposed at 5 ppm had slight
abnormalities in liver function tests and elevated SGPT ... no compound-related
effects were detected at lower doses. These parameters were reversible during
the postexposure period. A compound-related incr in tumors was not evident in
hamsters at any dose level. Mice exposed at 5 ppm had incr hemangiosarcomas and
Kupffer cell sarcomas; tumors were not observed at lower doses. Rats exposed at
5 ppm had incr lung tumors, squamous cell carcinomas, and hepatocellular
carcinomas. Islet cell adenomas of the pancreas were incr in rats exposed at 0.5
ppm but were only slightly (not statistically) incr at 5 ppm. Fibrous
histiocytomas were slightly incr and significantly incr at 0.5 and 5 ppm,
respectively, and chromophobe adenomas were incr at both 0.5 and 5 ppm in rats
... Dogs exposed at 5 ppm UDMH
containing 0.12% dimethylnitrosamine for 8.5 weeks exhibited increases in SGPT
... and marginal changes in hepatic morphology. However, dogs exposed to
purified UDMH (5 ppm) had normal liver
function parameters and no morphological liver effects.
Pregnant rats were admin ip doses of 10, 30, or 60 mg/kg UDMH /1,1-dimethylhydrazine/ on days 6 through
15 of gestation. UDMH was embryotoxic
but not teratogenic in pregnant rats. Maternal bw was also depressed as a result
of the treatment.
A significant, reversible incr in the percentage of abnormally shaped sperm
was observed in mice admin five daily ip injections of UDMH /1,1-dimethylhydrazine/ at doses of 10,
25, 40, 55, or 70% of the UDMH ip LD50
(dose not specified).
UDMH /1,1-dimethylhydrazine/ is
active in S. typhimurium. Mutations were produced by UDMH in L5178Y mouse lymphoma cells and V-79
liver cells. Nutritional-deficient strains of E. coli were altered, but UDMH did not induce lambda prophage mutation
in this organism. Unscheduled DNA synthesis was increased in hepatocytes. In
vivo animals test, incl production of micronuclei in dogs and dominant lethals
in mice, were negative, and sperm abnormalities were not produced in mice. DNA
interactions can be demonstrated as single-strand breaks in rat hepatocytes and
were seen following exposure to UDMH.
Hepatocyte damage was seen in vivo using alkaline elution techniques, and
fragmentation was seen in liver and lung DNA of mice treated with ip doses.
EXPERIMENTAL: TO REMEDY 1,1-DIMETHYLHYDRAZINE INTOXICATION 2 TYPES OF DRUGS
WERE EFFECTIVE: AN ANTICONVULSIVE, PHENYTOIN & TWO AMINO ACID SALTS,
ORNITHINE ALPHA-ACETOGLUTARATE & ARGININE ASPARTATE. FOR ACUTE INTOXICATION
THE COMBINATION OF PHENYTOIN & AMINO ACID SALTS DECREASED THE MORTALITY OF
MALE RATS. FOR CHRONIC INTOXICATIONS EITHER AMINO ACID SALT HELPED TO RESTORE
NERVOUS SYSTEM FUNCTION. THESE TWO TYPES OF TREATMENT ARE PROBABLY USEFUL
COMPLEMENTS TO BASIC PYRIDOXINE HYDROCHLORIDE THERAPY FOR 1,1-DIMETHYLHYDRAZINE
INTOXICATION.
Preneoplastic mucosal changes were studied at six different time-points
during dimethylhydrazine (DMH)-induced colorectal carcinogenesis in the rat.
After 40 weeks of treatment, seven of 10 animals were bearing a total of 11
colorectal adenocarcinomas. The crypt cell production rate in the normal mucosa
of DMH treated animals was greatly increased in the left colon and rectum and
further rose with the duration of the experiment. Focal disturbances of the
mucosal architecture could be detected as early as 4 weeks after the initiation
of DMH-treatment using a stereo microscope. Their incidence was greatest in the
left colon and rectum and increased strongly with the duration of carcinogen
exposure. Characterization of these mucosal alterations, by means of
conventional histology, morphometry after microdissection, cell kinetics, mucin
histochemistry and quantitative enzyme histochemistry performed with serial
sections, revealed mild epithelial dysplasia, a considerable elongation and
dilation of the crypts and a marked increase of the crypt cell production,
includig a shift of the main proliferative compartment from the basal to the
medial crypt segment as well as the occurrence of mitotic figures in the luminal
epithelium. In affected crypts, the goblet cells completely lacked sulfomucins
and exclusively contained sialomucins. The activities of the enzymes
diaminopeptidase IV (brushborder), succinate dehydrogenase (mitochondria) and
acid beta-galactosidase (lysosomes) were markedly reduced. ... Early mucosal
alterations are indeed preneoplastic lesions and indicate the existence of the
adenoma-carcinoma sequence in this animal model. The easy detection of these
microadenomas under the stereo microscope and the existence of similar findings
in man suggest possible clinical applications. /Dimethylhydrazine, not otherwise
specified/
The carcinogenicity of daminozide (succinic acid-2,2-dimethylhydrazide;
Alar), a plant growth regulator used primarily in apple orchards, has been the
subject of recent investigations by several national and international
organizations because of contradictory study results. The aim of the present
study was to assess the carcinogenicity of daminozide alone and in combination
with l,l-dimethylhydrazine (UDMH), its
major contaminant, in a novel medium-term bioassay in Fischer 344 rats, the
diethylnitrosamine-hepatectomy model. Rats were given diethylnitrosamine (DEN)
at 200 mg/kg body weight intraperitoneally and then 2 weeks later were given
daminozide at 20,000 ppm or daminozide plus 1,1-dimethylhydrazine at 75, 150, or
300 ppm in the diet for 6 weeks and were then killed; all rats underwent a
partial (two-thirds) hepatectomy (PH) at week 3. Hepatocarcinogenic potential
was assessed by comparing the number and area of preneoplastic foci positive for
the glutathione S-transferase placental form (GST-P+) in the liver of treated
rats, with those in controls given diethylnitrosamine alone. Daminozide,
1,1-dimethylhydrazine, and the combination were not carcinogenic in this model.
This novel medium-term bioassay for carcinogenicity is considered to be
practical for the rapid evaluation of both agrochemical formulations and
contaminants found in agrochemicals and other compounds.
Non-Human Toxicity Values:
LC50 Rat inhalation 252 ppm/4 hr
LC50 Mouse inhalation 172 ppm/4 hr
LC50 Hamster inhalation 392 ppm/4 hr
LD50 Mouse intraperitoneal 290 mg/kg (Std deviation +1)
LD50 Mouse intravenous 250 mg/kg (Std deviation +1)
LD50 Cats intraperitoneal 30-40 mg/kg
LD50 Mouse oral 265 mg/kg (Std deviation +1)
LD50 Rat intravenous 119 mg/kg (Std deviation +1)
LD50 Rat intraperitoneal 131 mg/kg (Std deviation +1)
LD50 Rat oral 122 mg/kg (Std deviation +1)
LD50 Dog intravenous 60 mg/kg (Std deviation +1)
LD50 Dogs dermal 1200-1680 mg/kg
LD50 Guinea pig dermal 1329 mg/kg
LD50 Rabbit dermal 1060 mg/kg /without occlusion/
LD50 Rabbit dermal 156 mg/kg /with occlusion/
Ecotoxicity Values:
LC50 Daphnia 38 mg/l/24 hr. /Conditions of bioassay not specified/
LC50 Ictalurus punctatus (channel catfish) 11.35 mg/l/96 hr. /Conditions of
bioassay not specified/
LC50 Notemigonus crysoleucas (golden shiner) 34.00 ug/l/96 hr. /Conditions of
bioassay not specified/
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
FORMALDEHYDE WAS FORMED BY OXIDATIVE DEMETHYLATION OF 1,1-DIMETHYLHYDRAZINE
BY RAT LIVER MICROSOMES. PHENOBARBITAL OR 3-METHYLCHOLANTHRENE PRETREATMENT
ENHANCED DEMETHYLASE ACTIVITY.
RATS ADMIN LOW DOSE OF (14)C 1,1-DIMETHYLHYDRAZINE METABOLIZED APPROX 30% TO
(14)C LABELED CARBON DIOXIDE IN 10 HR. CONVERSION OF CONVULSIVE DOSE TO CARBON
DIOXIDE AMOUNTED TO SLIGHTLY MORE THAN 13% @ END OF 20 HR. AT LEAST 50% OF ADMIN
RADIOACTIVITY APPEARED IN URINE IN 2 DAY PERIOD.
N-OXIDATION OF ALKYLHYDRAZINES WAS CATALYZED BY MOUSE LIVER MICROSOMAL MIXED
FUNCTION OXIDASE. AT PH 7.7 & 25 DEG C, METHYLHYDRAZINE &
1,1-DIMETHYLHYDRAZINE HAVE NEARLY THE SAME MAXIMAL N-OXIDATION RATE AS
DIMETHYLANILINE.
1,1-DIMETHYLHYDRAZINE WHEN ADDED TO SUSPENSION OF RAT LIVER MICROSOMES
EXHIBITED BINDING SPECTRA LIKE THOSE SEEN FOR NITROGENOUS LIGANDS TO CYTOCHROME
P450.
The present study provides the first evidence for in vitro metabolic
conversion of a 1,1-disubstituted hydrazine to the corresponding nitrosamine.
The study shows that superoxide radical which is generated by NADPH-cytochrome
reductase is involved in the oxidation of 1,1-diphenylhydrazine to
N-nitrosodiphenylamine catalyzed by rat liver microsomes. /1,1-Disubstituted
hydrazine/
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/
A fatty acid stimulated, NADPH-independent pathway for the N-demethylation of
1,1-dimethylhydrazine with the generation of formaldehyde was demonstrated in
10,000 g soluble fractions of colonic mucosal homogenates. Tetramethylhydrazine
and, to a lesser extent, aminopyrine, but not 1,2-dimethylhydrazine or
methylhydrazine, were also substrates for this reaction. Isolated superficial
colonic epithelial cells metabolized 1,1-DMH at a faster rate than proliferative
epithelial cells. Indomethacin, an inhibitor of cyclooxygenase activity, and
5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of both cyclooxygenase and
lipoxygenase activities, suppressed formaldehyde production from
1,1-dimethylhydrazine by 50 and 80%. However, in the presence of indomethacin or
5,8,11,14-eicosatetraynoic, acid arachidonate hydroperoxide stimulated
formaldehyde formation. This suggested a peroxidative mechanism for
1,1-dimethylhydrazine metabolism, related in part to prostaglandin synthesis. A
possible role for lipoxygenase activity in mediating 1,1-dimethylhydrazine
metabolism was suggested by the ability of linoleate, which did not increase
prostaglandin synthesis, to stimulate 1,1-dimethylhydrazine metabolism and by
the fact that 5,8,11,14-eicosatetraynoic acid was more effective than
indomethacin as an inhibitor of 1,1-dimethylhydrazine metabolism. The fatty acid
stimulated pathway for N-demethylation was clearly distinct from the mixed
function oxidase activities. NADPH did not stimulate 1,1-dimethylhydrazine
metabolism to formaldehyde. 7,8-Benzoflavone or SKF-525A, inhibitors of
cytochrome p450, and methimazole, an inhibitor of N-demethylation catalyzed by
the hepatic microsomal FAD-containing monooxygenase, did not suppress
formaldehyde formation. To the extent that 1,1-dimethylhydrazine and
tetramethylhydrazine reach the colon unchanged, the results suggest that fatty
acid stimulated cooxidation pathways in colonic mucosa may contribute to the
metabolism of these agents. Metabolism by superficial cells which are destined
to slough may be an important defense mechanism against the toxic and
carcinogenic actions of these hydrazines in colon.
Absorption, Distribution & Excretion:
IT IS RAPIDLY ABSORBED FROM THE LUNG, GASTROINTESTINAL TRACT AND INJECTION
SITES.
APPROXIMATELY 50% OF THE ABSORBED DOSE IS EXCRETED IN 24 HR.
UNSYMMETRICAL DIMETHYLHYDRAZINE IS
/BIOTRANSFORMED/ ... TO CARBON DIOXIDE & UNKNOWN METABOLITES WHICH ARE
EXCRETED WITH FREE ... /1,1-DIMETHYLHYDRAZINE/ INTO THE URINE.
AFTER 5-30 MMOLE/KG WAS APPLIED TO CANINE SKIN IT WAS DETECTABLE IN BLOOD
WITHIN 30 SECONDS. BLOOD LEVEL WAS NO HIGHER @ 5-10 MIN SAMPLING TIME. BLOOD
LEVELS INCR SLOWLY TO BROAD PEAK FOLLOWED BY SLOW DECLINE & WAS DOSE
RELATED.
UDMH /1,1-dimethylhydrazine/ was
absorbed rapidly through the skin of dogs and was detectable in the blood within
30 sec following application.
Mechanism of Action:
The target organ specificity of diethylnitrosamine (DBN) was studied. Male
Syrian golden hamsters were administered eight weekly injections of 20 mg/kg
diethylnitrosamine, 20 mg/kg dimethylhydrazine, or 300 mg/kg dibutylnitrosamine.
One group of treated animals was maintained after the eight weeks on basal diet,
the second group received diet supplemented with 1% butylated hydroxyanisole,
and the third group received repeat treatment with the carcinogen, but now in
the drinking water. No toxic lesions were observed at week nine in the livers of
hamsters treated with diethylnitrosamine or dimethylhydrazine. Tracheal lesions
were induced by both diethylnitrosamine and dibutylnitrosamine. Only weak
binding for glutathione-S-transferase was observed, and an increase in binding
for glucose-6-phosphate dehydrogenase was apparent in areas of papillomas in
which mitotic figures were increased. Adenomatous hyperplastic regions were
present in lungs of animals that received dibutylnitrosamine. Forestomach
tumors, in the form of solitary outgrowths, were induced by dimethylhydrazine
and dibutylnitrosamine. Adenomas and adenocarcinomas of the large intestine and
colon were induced only in the dimethylhydrazine treated groups. Butylated
hydroxyanisole had no significant effect on tumorigenesis, with the exception of
diethylnitrosamine initiated hepatocellular lesions, which were inhibited. All
three carcinogens gave rise to clear, glycogen storing liver foci and nodules.
No hepatocellular lesions were positive for gamma-glutamyl-transpeptidase.
Butylated hydroxyanisole tended to enhance the phenotypic instability and was
associated with a slight induction of glutathione-S-transferase placental form
protein in the hepatocytes of periportal zone one. The results demonstrate that
Syrian golden hamsters are suitable test animals for studying comparative
neoplasia. /Dimethylhydrazine, not otherwise specified/
Changes in the intestinal mucosa during carcinogenesis were investigated in
36 rats after ... sc injection of 20 mg dimethylhydrazine/kg bw. More changes
were seen in the large than in the small intestine. In the first week, 60% of
colonic lymphoid plaques displayed various crypt abscesses and glandular
regenerations. These mucosal changes correspond to the glands covering the lymph
follicles, in direct contact with lymphoid cells. Beginning in week 8,
dysplastic glands developed in these mucosal areas above the lymph follicles.
The number of lymphoid plaques with dysplastic glands in the large intestine
increased week by week, attaining 75% in week 20. At the end of week 12 the
first adenocarcinoma was detected in the cecum by light microscopy, and
classified as a poorly differentiated adenocarcinoma with signet ring cells
infiltrating the lymph follicles which contained endocrine cells. The majority
of adenocarcinomas (10 cases) occurred in week 20. Of these, 7 were localized
above the lymphatic plaques in the intestine. Endocrine cells were found in
varying numbers in 6 of 10 adenocarcinomas. Three endocrine cell carcinomas,
corresponding to human adenocarcinoids or goblet cell carcinoids, developed
within the intestinal mucosa; all were identified as poorly differentiated
intestinal adenocarcinomas, two of them situated above lymph follicles. These
suprafollicular tumors developing from the glandular base were composed of
mucoid cells, endocrine cells, and undifferentiated cells. Microacarcinomas are
considered as initial stages of endocrine cell carcinoma. The trend of tumor
development above colonic lymph follicles, and the histogenesis of endocrine
cell carcinomas and de novo carcinomas is discussed. /Dimethylhydrazine, not
otherwise specified/
Interactions:
This study investigates the influence of two formula diets containing 20
g/100 g diet of either whey protein concentrate or casein or Purina mouse chow,
on the humoral immune responsiveness and dimethylhydrazine induced colon
carcinogenesis in A/J mice. After 20 weeks of dimethylhydrazine treatment, the
number of plaque forming cells per spleen, following intravenous inoculation
with 5 cells, was nearly three times greater in the whey protein-fed group than
in the casein-fed mice although both values were substantially below normal.
After 24 weeks of dimethylhydrazine treatment the incidence of tumors in the
whey protein-fed mice was substantially lower than that in mice fed either the
casein or Purina diet. Similarly, the tumor area was less in the whey protein
group in comparison to either the casein or Purina groups, with some difference
between casein and Purina groups. Body weight curves were similar in all dietary
groups. In conclusion, a whey protein diet appears to significantly inhibit the
incidence and growth of chemically induced colon tumors in mice.
The morphological features of the intestine in monkeys on various diets with
and without carcinogen were studied. Seventy adult female vervet monkeys were
divided into seven treatment groups. Four groups received a Western high fat low
fiber diet; two a Prudent low fat higher fiber diet, and one a control low fat
high fiber diet. Three groups received dimethylhydrazine 10 mg/kg
intramuscularly at 14 day intervals. After 18 months, monkeys of two groups on
the Western high fat low fiberdiet were transferred to the prudent low fat
higher fiber diet and 30 months later all were terminated. Small and large
intestine were examined macroscopically, histologically with morphometry,
histochemically for acid and neutral, sialo- and sulphomucins and
enzyme-histochemically for mucosal gamma-glutamyltranspeptidase activity. Large
intestines in all other than control low fat high fiber diet particularly in
Western high fat low fiber diet treated animals were dilated, thin walled, less
corrugated and contained more residual contents. Diverticulosis was found to be
mostly associated with Western high fat low fiber diet. Apparently
histologically normal colonic mucosa showed changed mucin secretion,
predominantly in Western high fat low fiber diet. groups, and also GGT activity
in all but control low fat high fiber diet groups. Changes which could be
associated with pre-malignancy occurred predomiantly but not exclusively in
carcinogen treated animals. Within 4 years of feeding to monkeys, diets used by
affluent western man caused distinct changes suggestive of the development of
intestinal diseases such as megacolon, diverticulosis and cancer. Feeding a
prudent diet resulted in only a mild reduction of these signs, whereas they were
absent in a usual monkey diet that was much lower in animal products and refined
carbohydrates.
The effects of multiple dietary influences of 1,2-dimethylhydrazine induced
colon cancer in rats were studied. A 24 factorial experimental design was used
to examine the main and interactive effects of 15% wheat bran (WB), 1%
cholesterol (CH) with cholic acid, 20% beef tallow (BT), and 0.1%
indole-3-carbinol (IC) on 160 male F344 rats treated ip with DMH (10 mg/kg)
weekly for 16 weeks. The test diets were fed for 3 weeks before, 16 weeks
during, and 12 weeks after DMH administration. At necropsy, total weight gain,
liver and spleen weights, serum cholestrol levels, liver aryl hydrocarbon
hydroxylase (AHH) activity, and the size, number, incidence, and location of
intestinal tumors were analyzed for dietary factor effects. The most significant
inducer to tumors was the combination of cholesterol+beef
tallow+indole-3-carbinol acting in synergism. The single main effect most
responsible for tumor morbidity was indole-3-carbinol, which appeared to enhance
tumorigenesis via its role as an inducer of aryl hydrocarbon hydroxylase
activity. The wheat bran decreased tumor incidence and burden when added to
diets also containing cholesterol, but it otherwise increased tumor burden per
tumor-bearing animal and incidence in all other diets. This study demonstrated
the need for examining synergistic and antagonist interactions among dietary
initiators and/or promoters of colon carcinogenesis, as well as implicating
indole-3-carbinol as a significant factor in the development of DMH-induced
tumors in rats.
DNA damage induced by methylhydrazines (monomethylhydrazine,
l,l-dimethylhydrazine, and 1,2-dimethylhydrazine) in the presence of metal ions
was investigated by a DNA sequencing technique. 1,2-Dimethylhydrazine plus
manganese(III) caused DNA cleavage at every nucleotide without marked site
specificity. ESR-spin-trapping experiments showed that the hydroxyl free radical
(.OH) is generated during the manganese(III)-catalyzed autoxidation of
1,2-dimethylhydrazine. DNA damage and hydroxyl free radical generation were
inhibited by hydroxyl free radical scavengers and superoxide dismutase, but not
by catalase. The results suggest that 1,2-dimethylhydrazine plus manganese(III)
generates hydroxyl free radical, not via H202, and that hydroxyl free radical
causes DNA damage. In the presence of copper(II), DNA cleavage was caused by the
three methylhydrazines frequently at thymine residues, especially of the GTC
sequence. The order of copper(II)-mediated DNA damage (1,2-dimethylhydrazine
greater than monomethylhydrazine approximately l,l-dimethylhydrazine) was not
correlated with the order of methyl free radical (.CH3) generation during
copper(II)-catalyzed autoxidation (monomethylhydrazine greater than
l,l-dimethylhydrazine much greater than 1,2-dimethylhydrazine). Catalase and
bathocuproine, a Cu(I)-specific chelating agent, inhibited DNA damage while
catalase did not inhibit the methyl free radical generation. The order of DNA
damage was correlated with the order of ratio of H202 production to 02
consumption observed during copper(II)-catalyzed autoxidation of
methylhydrazines. These results suggest that the copper(I)-peroxide complex
rather than the methyl free radical plays a more important role in
methylhydrazine plus copper(II)-induced DNA damage.
The effects of l,l-dimethylhydrazine or several early events associated with
lymphocyte activation were examined. The concentration of intracellular calcium
((Ca2+)i) and membrane potential of murine lymphocytes were found to be altered
upon exposure to 1,1-dimethylhydrazine; intracellular calcium was increased in
murine thymocytes, while splenocytes exhibited membrane hyperpolarization. In
addition, interleukin-2 receptor expression induced by in-vitro concanavalin A
stimulation of murine splenocytes at 24 and 48 hr in ionic fluctuations, thus
contributing to altered immune responsiveness.
Iron-enriched diets caused an increase of tumor rate in two models of
dimethylhydrazine (DMH)-induced colon tumorigenesis in mice. The effect was
independent of the time the iron-diet was fed, ie, during
dimethylhydrazine-treatment or following the dimethylhydrazine-treatment period.
The increase of tumor rate depended on the iron concentration in the diet
(0.5-3.5%). The concentration-dependent iron accumulation in the colonic mucosa
of mice was paralleled by increments of malonaldehyde contents indicating lipid
peroxidation, another factor known to be involved in tumor development. It is
suggested that iron exerts cocarcinogenic activity in the
dimethylhydrazine-model by stimulating cell proliferation and inducing oxidative
stress in the colonic mucosa. This effect of iron is independent of the time of
tumor-initiation by dimethylhydrazine, as it is also observed in the period of
tumor-promotion/progression after dimethylhydrazine-treatment.
Pharmacology:
Interactions:
This study investigates the influence of two formula diets containing 20
g/100 g diet of either whey protein concentrate or casein or Purina mouse chow,
on the humoral immune responsiveness and dimethylhydrazine induced colon
carcinogenesis in A/J mice. After 20 weeks of dimethylhydrazine treatment, the
number of plaque forming cells per spleen, following intravenous inoculation
with 5 cells, was nearly three times greater in the whey protein-fed group than
in the casein-fed mice although both values were substantially below normal.
After 24 weeks of dimethylhydrazine treatment the incidence of tumors in the
whey protein-fed mice was substantially lower than that in mice fed either the
casein or Purina diet. Similarly, the tumor area was less in the whey protein
group in comparison to either the casein or Purina groups, with some difference
between casein and Purina groups. Body weight curves were similar in all dietary
groups. In conclusion, a whey protein diet appears to significantly inhibit the
incidence and growth of chemically induced colon tumors in mice.
The morphological features of the intestine in monkeys on various diets with
and without carcinogen were studied. Seventy adult female vervet monkeys were
divided into seven treatment groups. Four groups received a Western high fat low
fiber diet; two a Prudent low fat higher fiber diet, and one a control low fat
high fiber diet. Three groups received dimethylhydrazine 10 mg/kg
intramuscularly at 14 day intervals. After 18 months, monkeys of two groups on
the Western high fat low fiberdiet were transferred to the prudent low fat
higher fiber diet and 30 months later all were terminated. Small and large
intestine were examined macroscopically, histologically with morphometry,
histochemically for acid and neutral, sialo- and sulphomucins and
enzyme-histochemically for mucosal gamma-glutamyltranspeptidase activity. Large
intestines in all other than control low fat high fiber diet particularly in
Western high fat low fiber diet treated animals were dilated, thin walled, less
corrugated and contained more residual contents. Diverticulosis was found to be
mostly associated with Western high fat low fiber diet. Apparently
histologically normal colonic mucosa showed changed mucin secretion,
predominantly in Western high fat low fiber diet. groups, and also GGT activity
in all but control low fat high fiber diet groups. Changes which could be
associated with pre-malignancy occurred predomiantly but not exclusively in
carcinogen treated animals. Within 4 years of feeding to monkeys, diets used by
affluent western man caused distinct changes suggestive of the development of
intestinal diseases such as megacolon, diverticulosis and cancer. Feeding a
prudent diet resulted in only a mild reduction of these signs, whereas they were
absent in a usual monkey diet that was much lower in animal products and refined
carbohydrates.
The effects of multiple dietary influences of 1,2-dimethylhydrazine induced
colon cancer in rats were studied. A 24 factorial experimental design was used
to examine the main and interactive effects of 15% wheat bran (WB), 1%
cholesterol (CH) with cholic acid, 20% beef tallow (BT), and 0.1%
indole-3-carbinol (IC) on 160 male F344 rats treated ip with DMH (10 mg/kg)
weekly for 16 weeks. The test diets were fed for 3 weeks before, 16 weeks
during, and 12 weeks after DMH administration. At necropsy, total weight gain,
liver and spleen weights, serum cholestrol levels, liver aryl hydrocarbon
hydroxylase (AHH) activity, and the size, number, incidence, and location of
intestinal tumors were analyzed for dietary factor effects. The most significant
inducer to tumors was the combination of cholesterol+beef
tallow+indole-3-carbinol acting in synergism. The single main effect most
responsible for tumor morbidity was indole-3-carbinol, which appeared to enhance
tumorigenesis via its role as an inducer of aryl hydrocarbon hydroxylase
activity. The wheat bran decreased tumor incidence and burden when added to
diets also containing cholesterol, but it otherwise increased tumor burden per
tumor-bearing animal and incidence in all other diets. This study demonstrated
the need for examining synergistic and antagonist interactions among dietary
initiators and/or promoters of colon carcinogenesis, as well as implicating
indole-3-carbinol as a significant factor in the development of DMH-induced
tumors in rats.
DNA damage induced by methylhydrazines (monomethylhydrazine,
l,l-dimethylhydrazine, and 1,2-dimethylhydrazine) in the presence of metal ions
was investigated by a DNA sequencing technique. 1,2-Dimethylhydrazine plus
manganese(III) caused DNA cleavage at every nucleotide without marked site
specificity. ESR-spin-trapping experiments showed that the hydroxyl free radical
(.OH) is generated during the manganese(III)-catalyzed autoxidation of
1,2-dimethylhydrazine. DNA damage and hydroxyl free radical generation were
inhibited by hydroxyl free radical scavengers and superoxide dismutase, but not
by catalase. The results suggest that 1,2-dimethylhydrazine plus manganese(III)
generates hydroxyl free radical, not via H202, and that hydroxyl free radical
causes DNA damage. In the presence of copper(II), DNA cleavage was caused by the
three methylhydrazines frequently at thymine residues, especially of the GTC
sequence. The order of copper(II)-mediated DNA damage (1,2-dimethylhydrazine
greater than monomethylhydrazine approximately l,l-dimethylhydrazine) was not
correlated with the order of methyl free radical (.CH3) generation during
copper(II)-catalyzed autoxidation (monomethylhydrazine greater than
l,l-dimethylhydrazine much greater than 1,2-dimethylhydrazine). Catalase and
bathocuproine, a Cu(I)-specific chelating agent, inhibited DNA damage while
catalase did not inhibit the methyl free radical generation. The order of DNA
damage was correlated with the order of ratio of H202 production to 02
consumption observed during copper(II)-catalyzed autoxidation of
methylhydrazines. These results suggest that the copper(I)-peroxide complex
rather than the methyl free radical plays a more important role in
methylhydrazine plus copper(II)-induced DNA damage.
The effects of l,l-dimethylhydrazine or several early events associated with
lymphocyte activation were examined. The concentration of intracellular calcium
((Ca2+)i) and membrane potential of murine lymphocytes were found to be altered
upon exposure to 1,1-dimethylhydrazine; intracellular calcium was increased in
murine thymocytes, while splenocytes exhibited membrane hyperpolarization. In
addition, interleukin-2 receptor expression induced by in-vitro concanavalin A
stimulation of murine splenocytes at 24 and 48 hr in ionic fluctuations, thus
contributing to altered immune responsiveness.
Iron-enriched diets caused an increase of tumor rate in two models of
dimethylhydrazine (DMH)-induced colon tumorigenesis in mice. The effect was
independent of the time the iron-diet was fed, ie, during
dimethylhydrazine-treatment or following the dimethylhydrazine-treatment period.
The increase of tumor rate depended on the iron concentration in the diet
(0.5-3.5%). The concentration-dependent iron accumulation in the colonic mucosa
of mice was paralleled by increments of malonaldehyde contents indicating lipid
peroxidation, another factor known to be involved in tumor development. It is
suggested that iron exerts cocarcinogenic activity in the
dimethylhydrazine-model by stimulating cell proliferation and inducing oxidative
stress in the colonic mucosa. This effect of iron is independent of the time of
tumor-initiation by dimethylhydrazine, as it is also observed in the period of
tumor-promotion/progression after dimethylhydrazine-treatment.
Environmental Fate & Exposure:
Environmental Fate/Exposure Summary:
1,1-Dimethylhydrazine's production and use as a component of jet and rocket
fuels, in chemical synthesis, as a stabilizer for organic fuel additives, as an
absorbent for acid gases, in photography and as a plant growth control agent may
result in its release to the environment through various waste streams. If
released to the atmosphere, 1,1-dimethylhydrazine will exist solely in the vapor
phase in the ambient atmosphere, based on a measured vapor pressure of 123 mm Hg
at 20 deg C. 1,1-Dimethylhydrazine is expected to react very quickly with ozone
in the troposphere with a maximum estimated half-life of 16.5 min for the
reaction between vapor phase 1,1-dimethylhydrazine and ozone. Vapor-phase
1,1-dimethylhydrazine is degraded in the atmosphere more slowly by reaction with
photochemically-produced hydroxyl radicals with an estimated half-life of about
6 days. Based on soil studies, 1,1-dimethylhydrazine will generally be mobile in
most soils. Leaching of this compound may result upon release of
1,1-dimethylhydrazine to sandy soil; some degradation and adsorption to soils
containing clay and organic carbon may occur. 1,1-Dimethylhydrazine may also
undergo direct photolysis in soil and water surfaces since hydrazines strongly
absorb UV light in the environmentally significant range (> 290 nm).
Volatilization from moist soil surfaces is not expected based on an estimated
Henry's Law constant of 7.0X10-8 atm-cu m/mole. The potential for volatilization
of 1,1-dimethylhydrazine from dry soil surfaces may exist based on its vapor
pressure. Release to water is expected to result in oxidation at a rate directly
proportional to the pH with half-lives of 3.9 to 630 hr at pH values of 9 to 5.
The estimated half lives of 1,1-dimethylhydrazine in pond water and seawater
based upon experimental results are 16.3 to 22.2 and 12.6 days, respectively.
Based on soil studies, 1,1-dimethylhydrazine should not adsorb to sediment and
particulate matter in water. This compound is not expected to volatilize from
water surfaces given its estimated Henry's Law constant. Bioconcentration in
aquatic organisms should be low based on an estimated BCF value of 0.1. The
general population may be exposed to 1,1-dimethylhydrazine via ingestion of
food. Occupational exposure may occur through inhalation or dermal contact at
workplaces where 1,1-dimethylhydrazine is produced or used. (SRC)
Probable Routes of Human Exposure:
Human exposure to 1,1-dimethylhydrazine will most likely result from its use
as a component of aerospace propellants. NIOSH (NOES Survey 1981-1983) has
estimated that 2,917 workers are exposed to 1,1-dimethylhydrazine in the US(1).
Exposure of workers to 1,1-dimethylhydrazine at the Rocky Mountain Arsenal
Hydrazine Facility was mainly through inhalation(2). The general population may
be exposed to 1,1-dimethylhydrazine through the ingestion of food, and dermal
contact with vapors, food and other products containing this compound(SRC).
Natural Pollution Sources:
/1,1-Dimethylhydrazine/ has not been reported to occur as such in nature.
Artificial Pollution Sources:
It may be present in the waste streams from plants where it is produced or
used. One source has reported that the burning of rocket fuels based on
dimethylhydrazine & hydrazine produces exhaust gases which contain only
trace quantities of unchanged fuel.
1,1-Dimethylhydrazine's production and use as a component of jet and rocket
fuels, in chemical synthesis, as a stabilizer for organic fuel additives, as an
absorbent for acid gases, in photography and as a plant growth control agent(1)
may result in its release to the environment through various waste streams(SRC).
1,1-Dimethylhydrazine is also formed as a degradation product of daminozide, a
plant growth regulator(2).
Environmental Fate:
TERRESTRIAL FATE: Of the initial amount of 1,1-dimethylhydrazine in cleaned
sand (100% sand), Vandenburg Air Force Base soil (99.1% sand, 0.4% clay, pH
6.1), organic soil (96% sand, 1% clay, 1% carbon, pH 6.4), and clay (69.3% sand,
27.95% clay, pH 3.7), 0, 11, 11, and 50% was degraded in less than 1 hour,
respectively, due to abiotic factors(1). 1,1-Dimethylhydrazine is expected to
adsorb to and degrade in soils containing clay and organic carbon(1). During
decomposition of 1,1-dimethylhydrazine, the oxidative loss of two hydrogens
occurs and produces the diazene(1). Volatilization of 1,1-dimethylhydrazine
should not be important from moist soil surfaces(SRC) given an estimated Henry's
Law constant of 7.0X10-8 atm-cu m/mole(SRC), using a fragment constant
estimation method(2). The potential for volatilization of 1,1-dimethylhydrazine
from dry soil surfaces may exist(SRC) based on a measured vapor pressure of 123
mm Hg at 20 deg C(3). Biodegradation is not expected to be important in soil due
to the microbial toxicity of 1,1-dimethylhydrazine(4)and its rapid elimination
by physical processes(SRC).
AQUATIC FATE: The estimated half lives of 1,1-dimethylhydrazine, initially
present in pond water at 6.5 and 13.1 mM, are 16.3 and 22.2 days, respectively,
and in sea water at the same concentrations are both 12.6 days(1). Aqueous
oxidation of 1,1-dimethylhydrazine occurred with half-lives of 3.9-630 hr at pH
values of 9-5(2). Based on soil studies(1), 1,1-dimethylhydrazine is not
expected to strongly adsorb to suspended solids and sediment in water(SRC).
1,1-Dimethylhydrazine should not volatilize from water surfaces(3,SRC) based on
an estimated Henry's Law constant of 7.0X10-8 atm-cu m/mole(SRC), developed
using a fragment constant estimation method(3). According to a classification
scheme(4), an estimated BCF value of 0.1(5,SRC), from an estimated log
Kow(6,SRC), suggests that bioconcentration in aquatic organisms is low(SRC).
Biodegradation is not expected to be significant due to the microbial toxicity
of 1,1-dimethylhydrazine(7) and its rapid degradation by physical
processes(SRC).
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of
semivolatile organic compounds in the atmosphere(1), 1,1-dimethylhydrazine,
which has a measured vapor pressure of 123 mm Hg at 20 deg C(2), will exist
solely as a vapor in the ambient atmosphere. 1,1-Dimethylhydrazine is expected
to react very quickly with ozone in the troposphere; assuming an ozone
concentration of 7X10+11 molecules/cu cm, a minimum rate constant of 1X10-15 cu
cm/molecule sec(3) translates into a maximum half life of 16.5 min for the
reaction between vapor phase 1,1-dimethylhydrazine and ozone(SRC). The half life
for the reaction between 1,1-dimethylhydrazine and ozone is at most 1 min and
0.2 hr in an ozone pollution episode and in the natural troposphere,
respectively(4). Vapor-phase 1,1-dimethylhydrazine is also 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 days(5,SRC).
1,1-Dimethylhydrazine may also undergo direct photolysis in soil and water
surfaces since hydrazines strongly absorb UV light in the environmentally
significant range (> 290 nm)(SRC).
Environmental Biodegradation:
1,1-Dimethylhydrazine is sufficiently toxic to bacteria to prevent the
degradation of this compound by biological waste treatment(1). Biodegradation is
not expected to be significant in the environment(SRC).
Environmental Abiotic Degradation:
The kinetics of oxidation of methylhydrazine and 1,1-dimethylhydrazine (UDMH) 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 UDMH concentration. In dilute solutions
nitrosodimethylamine was not formed, but in more concentrated solutions,
nitrosodimethylamine formation increased with increasing UDMH content, reached a maximum at 60-80%
UDMH (by volume) and then decreased.
Dark decay of 1,1-dimethylhydrazine in a 3800 L chamber at 13.1 and 13.7 ppm
and respective relative humidities (RH) of 17% and 50% and 22 deg C proceeded
with half-lives of 341 and 70.9 hr, respectively. In a 6800 L chamber at 12.3
ppm, 11% RH and 24 deg C, dark decay occurred with a half-life of 841 hr(1).
Less than 5% of the total losses of 1,1-dimethylhydrazine were attributable to
ammonia formation(1). Reaction of 1,1-dimethylhydrazine with ozone occurred too
rapidly to measure the rate constant(1). Assuming an upper limit of 2 min for
the reaction time, the rate constant of the reaction was said to be greater than
1X10-15 cu cm/molecule sec(1). Assuming an ozone concentration of 7X10+11
molecules/cu cm, this minimum rate constant translates into a maximum half-life
of 16.5 min(SRC). The major product was N-nitrosodimethylamine. Hydrogen
peroxide, methyl hydroperoxide, and methyl diazene were also formed in
substantial amounts(1). An apparent rate constant of about 2X10-17 cu
cm/molecule sec was obtained for the reaction of 1,1-dimethylhydrazine with
nitrogen dioxide; 1,1-dimethylhydrazine did not react significantly with NO(1).
The half-life for the reaction between 1,1-dimethylhydrazine and ozone is at
most 1 min and 0.2 hr in an ozone pollution episode and in the natural
troposphere, respectively(2). Oxidation of 1,1-dimethylhydrazine in dry air
occurred with half-lives ranging from 10-21 hr at an initial
1,1-dimethylhydrazine partial pressure of 0.314 torr(3). The minimum half-life
observed was 0.5 hr measured at 31.9 torr 1,1-dimethylhydrazine(3). The lifetime
of 1,1-dimethylhydrazine in contact with ozone in atmospheric aerosols is about
1 min(4). The products of ozone oxidation of 1,1-dimethylhydrazine in water
include methanol, nitromethane and nitrosodimethylamine(4).
The rate constant for the vapor-phase reaction of 1,1-dimethylhydrazine with
photochemically-produced hydroxyl radicals has been estimated as 2.5X10-12 cu
cm/molecule-sec at 25 deg C(SRC) using a structure estimation method(1,SRC).
This corresponds to an atmospheric half-life of about 6 days at an atmospheric
concentration of 5X10+5 hydroxyl radicals per cu cm(1,SRC).
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(1). 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(1). 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(1). Aqueous oxidation of 1,1-dimethylhydrazine occurred with half
lives of 3.9-630 hr at pH values of 9-5(2). Oxidation of 1,1-dimethylhydrazine
by oxygen in water, catalyzed by Mn+3, was found to occur at a rate of 130
L/mole-sec(3).
Environmental Bioconcentration:
An estimated BCF value of 0.1 was calculated for 1,1-dimethylhydrazine(SRC),
using an estimated log Kow of -1.19(1,SRC) 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 1,1-dimethylhydrazine in 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), 5%, 20%, 15%, and 30% was adsorbed, respectively. Passage of 2
liters of distilled, deionized water at 5 ml/min through columns containing
sand, VAFB soil, organic soil and clay (10% clay soil plus 90% pure sand) in
equilibrium with 10 ml of a 0.1 v/v solution of 1,1-dimethylhydrazine resulted
in 99.9%, 42.5%, 21.9%, and 7.2% recovery of this compound, respectively(1). As
the hydrazines are all very basic chemicals, adsorption to acidic, clay soils is
expected(1).
Volatilization from Water/Soil:
The Henry's Law constant for 1,1-dimethylhydrazine is estimated as 7.0X10-8
atm-cu m/mole(SRC) using a fragment constant estimation method(1). This value
indicates that 1,1-dimethylhydrazine will be essentially nonvolatile from water
surfaces(2,SRC). 1,1-Dimethylhydrazine's Henry's Law constant(1,SRC) indicates
that volatilization from moist soil surfaces should not occur(SRC). The
potential for volatilization of 1,1-dimethylhydrazine from dry soil surfaces may
exist(SRC) based on a measured vapor pressure of 123 mm Hg at 20 deg C(3).
Atmospheric Concentrations:
SOURCE DOMINATED: Atmospheric samples taken in and around the hydrazine
facility at Rocky Mountain Arsenal in October 1976 and January 1977 contained
1,1-dimethylhydrazine at concentrations ranging from not detected (detection
limit= 0.001 ppm) to 1.66 ppm(1).
Food Survey Values:
Maximum 1,1-dimethylhydrazine concentrations of 0.062 ppm in applesauce,
0.041 ppm in apple juice, 0.007 ppm in frozen cherries, and 0.60 ppm in the
canned sour cherries. 1,1-Dimethylhydrazine was not detected in stored, fresh
apples or grape juice products (detection limit= 0.1 ppm for all products except
for grape juice which was 0.2 ppm)(1).
Other Environmental Concentrations:
1,1-DIMETHYLHYDRAZINE HAS BEEN ISOLATED FROM TOBACCO IN AMOUNTS FROM 60-174
PPB. ITS ORIGIN WAS NOT DETERMINED.
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. Dimethylhydrazine 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:
U098; As stipulated in 40 CFR 261.33, when 1,1-dimethylhydrazine, 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:
This action promulgates standards of performance for equipment leaks of
Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing
Industry (SOCMI). The intended effect of these standards is to require all newly
constructed, modified, and reconstructed SOCMI process units to use the best
demonstrated system of continuous emission reduction for equipment leaks of VOC,
considering costs, non air quality health and environmental impact and energy
requirements. Dimethylhydrazine is produced, as an intermediate or final
product, by process units covered under this subpart.
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. 1,1-Dimethylhydrazine is included on this list.
Chemical/Physical Properties:
Molecular Formula:
C2-H8-N2
Molecular Weight:
60.10
Color/Form:
CLEAR, COLORLESS LIQUID
Colorless liquid ...
Odor:
CHARACTERISTIC AMMONIA LIKE FISHY ODOR OF ALIPHATIC HYDRAZINES
... Ammonia or fish-like odor.
Boiling Point:
63.9 DEG C AT 760 MM HG
Melting Point:
-58 DEG C
Corrosivity:
Highly corrosive.
Critical Temperature & Pressure:
Critical temp: 250 deg C; Critical pressure: 5.42 MPa
Density/Specific Gravity:
0.782 at 25 deg C/25 deg C; 0.791 at 22 deg C/4 deg C
Dissociation Constants:
pKa= 7.21 @ 25 deg C
Heat of Combustion:
-1979 kJ/mol
Heat of Vaporization:
32.623 kJ/mol
pH:
STRONGLY ALKALINE LIQ
Solubilities:
VERY SOL IN METHANOL
>10% in water
Miscible with dimethylformamide, hydrocarbons, alcohol, ether; water
solubility = 1X10+6 mg/l
Spectral Properties:
INDEX OF REFRACTION: 1.40753 @ 22.3 DEG C/D
MASS: 40 (Atlas of Mass Spectral Data, John Wiley & Sons, New York)
NMR: 18721 (Sadtler Research Laboratories Spectral Collection)
IR: 7647 (Sadtler Research Laboratories Prism Collection)
MASS: 9 (National Bureau of Standards EPA-NIH Mass Spectra Data Base,
NSRDS-NBS-63)
Surface Tension:
24.09 dynes/cm at 25 deg C
Vapor Density:
1.94 (AIR= 1)
Vapor Pressure:
157 mm Hg at 25 deg C
Viscosity:
0.492 millipascal second @ 25 deg C
Other Chemical/Physical Properties:
CONVERSION FACTORS: 1 MG/L= 4.07 PPM AND 1 PPM= 2.5 MG/CU M
CMPD IS HIGHLY REACTIVE; EASILY OXIDIZABLE AND FORMS SALTS
HYGROSCOPIC /1,1-DIMETHYLHYDRAZINE HYDROCHLORIDE/
VAPOR (GAS) SPECIFIC GRAVITY: 2.1; RATIO OF SPECIFIC HEATS OF VAPOR (GAS):
(EST) 1.152; HEAT OF SOLUTION: (EST) -10 CAL/G
CRYSTALS FROM ABSOLUTE ETHANOL /1,1-DIMETHYLHYDRAZINE HYDROCHLORIDE/
SOL IN WATER, ETHANOL; PRACTICALLY INSOL IN ETHER /1,1-DIMETHYLHYDRAZINE
HYDROCHLORIDE/
FUMES IN AIR AND GRADUALLY TURNS YELLOW
DISSOLVES, SWELLS, AND DISINTEGRATES MANY PLASTICS
Ionization potential: 7.46 eV
Heat of fusion: 10.07 kJ/mole; heat capacity: 2.045 J/g.deg C @ 25 deg C;
heat of formation: 51.63 kJ/mole; free energy of formation: 206.69 kJ/mole;
entropy of formation: 197.99 J/mole.deg C
Heat of sublimation: 8.37 kcal/mole @ 298 deg K
The kinetics of oxidation of methylhydrazine (MMH) and 1,1-dimethylhydrazine
(UDMH) by dissolved O2 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 (NDMA) depended on the initial UDMH concentration. In dilute solutions NDMA
was not formed, but in more concentrated solutions, NDMA formation increased
with increasing UDMH content, reached a
maximum at 60-80% UDMH (by volume) and
then decreased. The NDMA 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 NDMA formation.
Vapor pressure= 22.3 kPa at 25 deg C
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. /1,1-Dimethylhydrazine; Dimethylhydrazine, symmetrical;
Dimethylhydrazine, unsymmetrical/
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.
/1,1-Dimethylhydrazine; Dimethylhydrazine, symmetrical; Dimethylhydrazine,
unsymmetrical/
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. /1,1-Dimethylhydrazine;
Dimethylhydrazine, symmetrical; Dimethylhydrazine, unsymmetrical/
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.
/1,1-Dimethylhydrazine; Dimethylhydrazine, symmetrical; Dimethylhydrazine,
unsymmetrical/
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. /1,1-Dimethylhydrazine;
Dimethylhydrazine, symmetrical; Dimethylhydrazine, unsymmetrical/
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. /1,1-Dimethylhydrazine;
Dimethylhydrazine, symmetrical; Dimethylhydrazine, unsymmetrical/
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. /1,1-Dimethylhydrazine; Dimethylhydrazine, symmetrical;
Dimethylhydrazine, unsymmetrical/
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. /1,1-Dimethylhydrazine;
Dimethylhydrazine, symmetrical; Dimethylhydrazine, unsymmetrical/
Initial Isolation and Protective Action Distances: Small Spills (from a small
package or small leak from a large package): First, ISOLATE in all Directions 30
meters (100 feet); then, PROTECT persons Downwind during DAY 0.2 kilometers (0.1
miles) and NIGHT 0.2 kilometers (0.1 miles). LARGE SPILLS (from a large package
or from many small packages): First, ISOLATE in all Directions 60 meters (200
feet); then, PROTECT persons Downwind during DAY 0.5 kilometers (0.3 miles) and
NIGHT 1.1 kilometers (0.7 miles). /1,1-Dimethylhydrazine; Dimethylhydrazine,
unsymmetrical/
Odor Threshold:
12.0 mg/cu m (low); 20.0 mg/cu m (high)
A FISHY OR AMINE LIKE ODOR OF 1,1-DIMETHYLHYDRAZINE CAN BE DETECTED BY MOST
INDIVIDUALS IN LESS THAN 1 MINUTE AT CONCENTRATIONS OF 6 TO 14 PPM. THE ODOR
OFFERS ADEQUATE WARNING OF EXPOSURES TO CONCN THAT WOULD BE DANGEROUS FOR SHORT
EXPOSURES.
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:
... IRRITATING TO SKIN, EYES, MUCOUS MEMBRANES.
Highly corrosive and irritating to skin, eyes, mucous membranes.
Fire Potential:
It is flammable over a wide range of vapor air concentrations.
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: 1. 1= Includes materials that are normally stable, but may become
unstable at elevated temperatures and pressures and materials that will react
with water with some release of energy, but not violently. Fires involving these
materials should be approached with caution.
Flammable Limits:
LOWER 2% BY VOL; UPPER 95% BY VOL
Flash Point:
-15 DEG C, 5 DEG F (CLOSED CUP)
Autoignition Temperature:
249 DEG C (480 DEG F)
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.
Evacuation: If fire becomes uncontrollable or container is exposed to direct
flame--consider evacuation of one (1) mile radius.
Toxic Combustion Products:
Toxic oxides of nitrogen are produced during combustion of this material.
Firefighting Hazards:
Prolonged exposure of containers of the material to fire or heat may result
in their violent rupturing and rocketing due to the decomposition of the
material. ... Vapors may travel to a source of ignition and a flame can flash
back to the source of vapors.
Explosive Limits & Potential:
UPPER 95 VOL %; LOWER 2 VOL %
VAPOR MAY EXPLODE IF IGNITED IN AN ENCLOSED AREA.
Hazardous Reactivities & Incompatibilities:
Contact of dicyanofurazan, or its N-oxide (dicyanofuroxan), with ...
dimethylhydrazine ... is instantaneously explosive.
Spontaneous ignition can occur on contact with oxidants like hydrogen
peroxide, and fuming nitric acid.
Combinations of unsymmetrical dimethylhydrazine,
aniline, or furfuryl alcohol as fuels with hydrogen peroxide or
a mixture of nitric acid-nitrogen tetroxide- sulfuric acid as oxidizers ignite
with little delay and are used as propellants.
Unsymmetrical dimethylhydrazine
/&/ nitric oxide ignite on sparking.
Oxidizers, halogens, metallic mercury, fuming nitric acid, hydrogen peroxide
[Note: May ignite SPONTANEOUSLY in contact with oxidizers].
VAPOR IS INFLAMMABLE IN AIR & IGNITES SPONTANEOUSLY WHEN IN CONTACT WITH
OXIDIZING AGENTS.
Ignites violently on contact with nitric acid, hydrogen peroxide and nitrogen
dioxide among other oxidants.
Hazardous Decomposition:
... When heated to decomp it emits highly toxic fumes of /nitrogen oxides/.
Immediately Dangerous to Life or Health:
NIOSH considers 1,1-dimethylhydrazine to be a potential occupational
carcinogen.
Protective Equipment & Clothing:
RUBBER GLOVES, BOOTS, AND APRON; PLASTIC FACE SHIELD. GAS MASK WITH AMMONIA
CANISTER PROTECTS FOR 30 MIN AGAINST 1% CONCN; FOR LONGER PERIODS OR HIGHER
CONCN, USE SELF-CONTAINED BREATHING APPARATUS.
PERMEATION MEASUREMENTS OF HYPERGOLIC FUELS & OXIDANTS, INCLUDING
1,1-DIMETHYLHYDRAZINE, THROUGH COMMERCIAL PROTECTIVE CLOTHING MATERIAL IS
DISCUSSED.
PRECAUTIONS FOR "CARCINOGENS": ... dispensers of liq detergent /should be
available./ ... Safety pipettes should be used for all pipetting. ... In animal
laboratory, personnel should ... wear protective suits (preferably disposable,
one-piece & close-fitting at ankles & wrists), gloves, hair covering,
& overshoes. ... In chemical laboratory, gloves & gowns should always be
worn ... however, gloves should not be assumed to provide full protection.
Carefully fitted masks or respirators may be necessary when working with
particulates or gases, & disposable plastic aprons might provide addnl
protection. ... gowns ... /should be/ of distinctive color, this is a reminder
that they are not to be worn outside the laboratory. /Chemical Carcinogens/
For 1,1-dimethylhydrazine breakthrough times greater than one hour reported
by (normally) two or more testers for butyl rubber; breakthrough times less
(usually significantly less) than one hour reported by (normally two or more
testers for neoprene and polyvinyl chloride some data (usually from immersion
tests) suggesting breakthrough times greater than one hour are not likely for
nitrile rubber.
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/
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 air-purifying,
full-facepiece respirator (gas mask) with a chin-style, front- or back-mounted
canister providing protection against the compound of concern. 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:
THE BASIC VENTILATION METHODS ARE LOCAL EXHAUST VENTILATION AND DILUTION OR
GENERAL VENTILATION.
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.
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.
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/
Evacuation: If material leaking (not on fire), downwind evacuation must be
considered.
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.
Stability/Shelf Life:
SOLN STORED IN DARK AND COLD ARE RELATIVELY STABLE IN ABSENCE OF OXIDANTS
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:
PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practicable
to lab in which carcinogens are to be used, so that only small quantities
required for ... expt need to be carried. Carcinogens should be kept in only one
section of cupboard, an explosion proof refrigerator or freezer (depending on
chemicophysical properties ...) that bears appropriate label. An inventory ...
should be kept, showing quantity of carcinogen & date it was acquired ...
Facilities for dispensing ... should be contiguous to storage area. /Chemical
Carcinogens/
Cleanup Methods:
Activated carbon, polyurethane foam and polypropylene fibers are the most
advantageous agents for cleanup of 1,1-dimethylhydrazine. Also Amberlite XAD
resins and Dowex 50WX8 or Amberlite IRA 900 may be used.
PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA)
or charcoal filters can be used to minimize amt of carcinogen in exhausted air
ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter
housing that is designed so that used filters can be transferred into plastic
bag without contaminating maintenance staff is available commercially. Filters
should be placed in plastic bags immediately after removal ... The plastic bag
should be sealed immediately ... The sealed bag should be labelled properly ...
Waste liquids ... should be placed or collected in proper containers for
disposal. The lid should be secured & the bottles properly labelled. Once
filled, bottles should be placed in plastic bag, so that outer surface ... is
not contaminated ... The plastic bag should also be sealed & labelled. ...
Broken glassware ... should be decontaminated by solvent extraction, by chemical
destruction, or in specially designed incinerators. /Chemical Carcinogens/
Wear butyl rubber gloves, laboratory coat, eye protection and self-contained
breathing apparatus. Impervious clothing recommended. 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 of water for each 1 g of dimethylhydrazine. Filter
off the clay and sand. For each 1 g of dimethylhydrazine, place 32 ml
(approximately 25% excess) of commercial laundry bleach (containing
approximately 5% sodium hypochlorite) into a 3-necked round-bottom flask
equipped with a stirrer, thermometer and dropping funnel. Add the aqueous
dimethylhydrazine 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 continues for 2 hr 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 U098, must conform with USEPA
regulations in storage, transportation, treatment and disposal of waste.
CATALYTIC REDUCTIVE DESTRUCTION OF HYDRAZINES, INCLUDING
1,1-DIMETHYLHYDRAZINE, AS AN APPROACH TO WASTE HAZARD CONTROL IS DISCUSSED.
Controlled incineration (oxides of nitrogen are removed from the effluent gas
by scrubbers and/or thermal devices).
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/
A potential candidate for fluidized bed incineration at a temperature range
of 450 to 980 deg C and residence times of seconds for liquids and gases, and
longer for solids. A potential candidate for rotary kiln incineration at a
temperature range of 820 to 1,600 deg C and residence times of seconds for
liquids and gases, and hours for solids. A potential candidate for liquid
injection incineration at a temperature range of 650 to 1,600 deg C and a
residence time of 0.1 to 2 seconds.
Small Quantities. Wear butyl rubber gloves, laboratory coat and eye
protection. Work in the fume hood. Prepare a dilute (5%) aqueous solution of
1,1-dimethylhydrazine by adding slowly to the appropriate volume of water. For
each 1 g of dimethylhydrazine, place 32 ml (approximately 25% excess) of
commercial laundry bleach (containing approximately 5% sodium hypochlorite) into
a 3-necked round-bottom flask equipped with a stirrer, thermometer and dropping
funnel. Add the aqueous dimethylhydrazine 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 continues for 2 hours until the temperature gradually falls to room
temperature.
Occupational Exposure Standards:
OSHA Standards:
Permissible Exposure Limit: Table Z-1 8-hr Time-Weighted Avg: 0.5 ppm (1
mg/cu m). Skin Designation.
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 ???CHEMICAL??? 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: 0.06 ppm (0.15 mg/cu m).
Immediately Dangerous to Life or Health:
NIOSH considers 1,1-dimethylhydrazine to be a potential occupational
carcinogen.
Manufacturing/Use Information:
Major Uses:
THE BASE IN ROCKET FUEL FORMULATIONS
STABILIZER FOR ORG PEROXIDE FUEL ADDITIVES; ABSORBENT FOR ACID GASES; IN
PHOTOGRAPHY; COMPONENT OF JET AND ROCKET FUEL; PLANT GROWTH CONTROL AGENT
CHEM INT FOR SUCCINIC ACID 2,2-DIMETHYLHYDRAZIDE
As a modifer for 1-butene polymers to improve isotacticity
Unsymmetrical dimethylhydrazine is
produced in commercial quantity for use as fuel in the USA space program ... .
Used as a chemical intermediate for the synthesis of daminozide.
Manufacturers:
Olin Corporation, 501 Merritt 7, PO Box 4500, Norwalk, CT 06856-4500 (203)
750-3000. Production Site: PO Box 2896, Interstate 10, Lake Charles, LA 70602
(318) 491-3000.
Methods of Manufacturing:
PREPD INDUSTRIALLY BY REACTION OF DIMETHYLAMINE & CHLORAMINE; BY REDN OF
NITROSODIMETHYLAMINE (OBTAINED BY TREATING DIMETHYLAMINE SALT WITH SODIUM
NITRITE).
... By reductive catalytic alkylation of a hydrazide, probably acetic acid
hydrazide, with formaldehyde & hydrogen, followed by basic hydrolysis of
acetic acid dimethylhydrazide to remove the acetyl qroup ... .
Catalytic oxidation of dimethylamine and ammonia.
Hydrazine + acetic anhydride + formaldehyde + hydrogen (amide
formation/reductive methylation/amide hydrolysis).
General Manufacturing Information:
N,N'-(METHYL-(14)C)-DIMETHYLHYDRAZINE DIHYDROCHLORIDE HAVING A SPECIFIC
ACTIVITY OF 112.5 MICROCURIE/MMOL WAS PREPARED IN 2 STEPS FROM ETHYL
HYDRAZINEDICARBOXYLATE IN DRY 1,1-DIMETHYLHYDRAZINE & (14)C-METHYL IODIDE
WITH A SPECIFIC ACTIVITY OF APPROX 58 MICROCURIE/MMOL.
Formulations/Preparations:
1,1-DIMETHYLHYDRAZINE IS AVAILABLE IN THE UNITED STATES AS A SINGLE GRADE
CONTAINING 98% (MINIMUM) ACTIVE INGREDIENT AND NORMALLY HAVING 1.9% (MAX)
DIMETHYLAMINE AND 0.3% (MAX) WATER CONTENT.
U. S. Production:
(1977) AT LEAST 4.54X10+7 G
(1982) PROBABLY GREATER THAN 4.54X10+6 G
Laboratory Methods:
Clinical Laboratory Methods:
... A COLORIMETRIC METHOD FOR MEASURING MICROGRAM QUANTITIES OF UNSYMMETRICAL
1,1-DIMETHYLHYDRAZINE IN BLOOD ... USING TRISODIUM PENTACYANOAMINOFERROATE AS
THE COLOR REAGENT; READINGS ARE TAKEN SPECTROPHOTOMETRICALLY AT 500 NM:
PINKERTON ET AL; AMER INDUST HYG ASS J 24: 239 (1963).
DETERMINATION OF 1,1-DIMETHYLHYDRAZINE IN URINE & PLASMA BY HIGH
PERFORMANCE LIQUID CHROMATOGRAPHY WITH ELECTROCHEMICAL DETECTION LIMIT AT 250
NG.
Analytic Laboratory Methods:
NIOSH S143: MATRIX: AIR; ANALYTE: 1,1-DIMETHYLHYDRAZINE; PROCEDURE: BUBBLER
COLLECTION, COLORIMETRIC (REACTED WITH PHOSPHOMOLYBDIC ACID TO FORM BLUISH GREEN
COLORED COMPLEX); RANGE: 0.506-2.22 MG/CU M. PRECISION (COEFFICIENT OF
VARIATION): 0.062. POTENTIAL INTERFERENCES ... STANNOUS ION, FERROUS ION, ZINC,
SULFUR DIOXIDE, & HYDROGEN SULFIDE. INTERFERNCES FROM OXIDN OF
1,1-DIMETHYLHYDRAZINE GIVING A DIMINISHED READING MAY OCCUR WITH HALOGENS &
OXYGEN ... OTHER HYDRAZINE DERIVATIVES WILL ALSO INTERFERE ... & HYDROGEN
PEROXIDE WILL POSSIBLY REOXIDIZE THE BLUE OXIDE GIVING A LOWER READING.
NIOSH 248: Matrix: air; analyte: 1,1-dimethylhydrazine; procedure: adsorption
on sulfuric acid-coated silica gel, elution with water, reaction with
2-furaldehyde, extraction with ethyl acetate, gas chromatographic analysis.
Precision: 0.04 RSD for 1,1-dimethylhydrazine at 1.6 & 3.8 mg/cu m; range:
4-12000 ug/sample; interferences: cmpd which have nearly the same retention time
on the gas chromatography column
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.
A SIMPLE THIN LAYER CHROMATOGRAPHY SYSTEM WHICH IS EFFECTIVE IN RESOLVING
DIHYDROCHLORIDES OF HYDRAZINE, METHYLHYDRAZINE, 1,1-DIMETHYLHYDRAZINE &
1,2-DIMETHYLHYDRAZINE WAS REPORTED. THE SYSTEM IS APPLICABLE TO ANALYTICAL (THIN
LAYER) AND PREPARATIVE (THICK LAYER) SEPARATIONS. THE FOLIN-CIOCALLTEAU REAGENT
WAS A SENSITIVE TOOL FOR DETECTION. IN A STUDY OF LIMITS OF DETECTABILITY, 0.36
UG/SQ CM OF SEPARATED HYDRAZINES WAS EASILY VISIBLE & 0.12 UG/SQ CM WAS
STILL DETECTABLE. THE COLOR DEVELOPED IS STABLE FOR AT LEAST A WK.
/1,1-DIMETHYLHYDRAZINE DIHYDROCHLORIDE/
AN ELECTROCHEMICAL CELL CAPABLE OF DETECTING LEVELS OF 1,1-DIMETHYLHYDRAZINE
IN AIR IS DESCRIBED. IT IS COUPLED WITH A DYNAMIC AIR SAMPLING SYSTEM &
ELECTRONIC CONTROL & AMPLIFICATION CIRCUITRY TO PROVIDE A DIRECT-READING
PORTABLE ANALYZER.
RECOVERY RATES FOR AIRBORNE UNSYMMETRICAL
DIMETHYLHYDRAZINE 0.588-15.68 UG, EQUIV ATMOSPHERIC CONCN OF
0.04-1.04 MG/CU M, ARE 93.74-93.93% USING A VENTABLE GAS CHROMATOGRAPHY
PRECOLUMN TRAP.
... A COLORIMETRIC METHOD FOR MEASURING UG QUANTITIES OF UDMH /UNSYMMETRICAL 1,1-DIMETHYLHYDRAZINE/ IN
... WATER AND AIR USING TRISODIUM PENTACYANOAMINOFERROATE AS THE COLOR REAGENT;
READINGS ARE TAKEN SPECTROPHOTOMETRICALLY AT 500 NM /IS DISCUSSED.
Determination of hydrazine and 1,1-dimethylhydrazine after derivatization
with salicylaldehyde was done using high performance liquid chromatography with
electrochemical detection. Less than 5 ng of the two could be detected. The
detection limits for hydrazine and 1,1-dimethylhydrazine solutions were
estimated to be 0.025 and 0.20 ppm, respectively.
A procedure that simultaneously determines hydrazine, methylhydrazine, and
1,1-dimethylhydrazine in air utilizes a chilled acetone collection medium which
quantitatively traps the hydrazines and converts them to stable derivatives in a
single step. The acetone solution is then assayed directly for the derivatives
by using a gas chromatograph with a nitrogen specific detector. The overall
precision of the methodology is better than 5% for 90 ppb hydrazine. The minimum
detectable concentration is estimated to be 4 ppb.
The detection of hydrazine has been described down to 0.002% in aqueous &
alcoholic soln via thin layer chromatography of the p-dimethylaminobenzaldehyde.
The basic ASTM D 1385-78 procedure is adaptable to the determination of
monomethylhydrazine & unsymmetrical 1,1-dimethylhydrazine as these form
colored hydrazones. For mixtures of the 3 hydrazines mentioned, the sample can
be derivatized with salicylaldehyde & separated by high pressure liq
chromatography, using uv for detection. ... Gas chromatographic techniques for
the propellant hydrazines (hydrazine, monomethylhydrazine, & unsymmetrical
1,1-dimethylhydrazine) have been developed for high concentrations as well as
for dilute aqueous solutions.
NIOSH Method 3515. Determination of 1,1-Dimethylhydrazine by Visible
Spectrophotometry. Detection Limit= 0.010 mg/cu m.
1,1-Dimethylhydrazine was detected in fruit and fruit products using GC/ECD
following derivatization with 2-nitrobenzaldehyde. Detection limit= 1 ppm (2 ppm
for grape juice).
Sampling Procedures:
NIOSH S143: Matrix: air; analyte: 1,1-dimethylhydrazine; sampler: midget
glass bubbler containing 0.1 M hydrochloric acid.
NIOSH 128: Matrix: air; analyte: 1,1-dimethylhydrazine; sampler: adsorption
on sulfuric acid-coated silica gel.
Special References:
Special Reports:
LUNN G ET AL; ENVIRON SCI TECHNOL 17 (4): 240-3 (1983). CATALYTIC REDUCTIVE
DESTRUCTION OF HYDRAZINES, INCLUDING 1,1-DIMETHYLHYDRAZINE, AS AN APPROACH TO
WASTE HAZARD CONTROL IS DISCUSSED.
Toth B; Teratogenic hydrazines: a review; In Vivo Jan-Feb 7 (1): 101-10
(1993). The review summarizes the results of 30 hydrazines, which were studied
in humans and in six animal species for teratogenic activities.
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:
AS-DIMETHYLHYDRAZINE **PEER REVIEWED**
ASYMMETRIC DIMETHYLHYDRAZINE **PEER REVIEWED**
DIMAZIN **PEER REVIEWED**
DIMAZINE **PEER
REVIEWED**
DIMETHYLHYDRAZINE **PEER REVIEWED**
ASYM DIMETHYLHYDRAZINE **PEER REVIEWED**
N,N-DIMETHYLHYDRAZINE **PEER REVIEWED**
U-DIMETHYLHYDRAZINE **PEER REVIEWED**
UNSYM-DIMETHYLHYDRAZINE **PEER REVIEWED**
DIMETHYLHYDRAZINE UNSYMMETRICAL **PEER
REVIEWED**
1,1-DIMETHYLHYDRAZIN (GERMAN) **PEER
REVIEWED**
N,N-dimetilidrazina (Italian) **PEER
REVIEWED**
DMH **PEER REVIEWED**
HYDRAZINE, 1,1-DIMETHYL- **PEER REVIEWED**
NIESYMETRYCZNA DWU METYLOHYDRAZYNA (POLISH) **PEER
REVIEWED**
UDMH **PEER
REVIEWED**
UNSYMMETRICAL-DIMETHYLHYDRAZINE
**PEER REVIEWED**
Associated Chemicals:
1,1-Dimethylhydrazine hydrochloride;593-82-8
Formulations/Preparations:
1,1-DIMETHYLHYDRAZINE IS AVAILABLE IN THE UNITED STATES AS A SINGLE GRADE
CONTAINING 98% (MINIMUM) ACTIVE INGREDIENT AND NORMALLY HAVING 1.9% (MAX)
DIMETHYLAMINE AND 0.3% (MAX) WATER CONTENT.
Shipping Name/ Number DOT/UN/NA/IMO:
UN 1163; 1,1-Dimethylhydrazine
IMO 3.2; 1,1-Dimethylhydrazine
Standard Transportation Number:
49 062 10; Dimethylhydrazine, unsymmetrical
EPA Hazardous Waste Number:
U098; A toxic waste when a discarded commercial chemical product or
manufacturing chemical intermediate or an off-specification commercial chemical
product or manufacturing chemical intermediate.
RTECS Number:
NIOSH/MV2450000