Acetylphenylhydrazine

150.18

150.18

742880

204-055-3

C818L19FMP

229032|2847|2064

2811

DTXSID1020015

Hexagonal prisms

29280090

41.1

log Kow = 0.74 /Estimated/

1-acetyl-2-phenylhydrazide appears as colorless prisms or white solid. (NTP, 1992)

1.1392 (rough estimate)

131 °C

271.72°C (rough estimate)

1.6180 (estimate)

Water insoluble .

Store at +15°C to +25°C.

7.3X10-5 mm Hg at 25 °C /Estimated/

Oral-Mouse LD50: 270 mg/kg; Abdominal cavity-mouse LDL0: 150 mg/kg

Flammable; decomposes by heating to release toxic nitrogen oxide fumes

Henry's Law constant = 2.6X10-11 atm-cu m/mol at 25 °C /Estimated/

Hydroxyl radical reaction rate constant = 4.8X10-11 cu cm/molec-sec at 25 °C /Estimated/

Water insoluble.

Amides and Imides

1-ACETYL-2-PHENYLHYDRAZIDE is an amide and an amine. Organic amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx).

III

6.1

UN 2811 6.1/PG 3

3

22-36/37/38-43-20/21/22

22-26-36-24/25-36/37

AJ2900000

Xn

Warehouse ventilated, low temperature and dry

Stable under normal temperatures and pressures.

P280-P305 + P351 + P338

H301-H315-H317-H319-H335

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Flash point data for this compound are not available. It is probably combustible. (NTP, 1992)

|Danger|H301 (99.48%): Toxic if swallowed [Danger Acute toxicity, oral]|P261, P264, P270, P271, P272, P280, P301+P310, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P333+P313, P337+P313, P362, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 765 companies from 16 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. 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. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. RECOMMENDED GLOVE MATERIALS: Suggested Glove Type(s): Butyl rubber (to 70 minutes) (NTP, 1992)|...Vinyl coated hand protection, natural or reclaimed rubber protection, rubber aprons, and plastic eye and face protection... used when working with small quantities. Where possibility of gross splashing exists, full protective clothing made of rubber, neoprene or vinyl-coated materials should be worn. For respiratory protection in situations where recommended tolerance limits are ... exceeded, respiratory protective equipment ... must be used. /Hydrazine and derivatives/

highly toxic

Xylitol was investigated for its ability to ameliorate hemolytic anemia induced by acetylphenylhydrazine in rabbits. Animal experiments were performed using two different concentrations of xylitol, a 5% and a 10% solution with a total dose of 2 g/kg bw and infusion rates of 10 mg and 20 mg xylitol/kg bw/min respectively. Two doses of acetylphenylhydrazine (APH), 5 and 10 mg/kg, were injected ip as hemolytic inducers in different groups of rabbits. All the rabbits infused with xylitol showed significantly less acute APH-induced hemolysis. The isotonic 5% xylitol solution was found to maintain and restore the hematological parameters (packed cell volume, hemoglobin concentration, reduced glutathione (GSH) content, and reticulocyte counts) better than the 10% xylitol solution. Increased 51CR-red cell survival confirmed the beneficial effect of xylitol. The survival of erythrocytes as represented by chromium-labeling in rabbits infused with 5% xylitol after treatment with 10 mg/kg APH increased from about 33% (the survival of red cells in rabbits injected with APH alone) to 67% of normal rabbits' red cell survival. Erythrocytes in APH-treated animals took up xylitol more readily than erythrocytes from control animals.|One millimolar ascorbic acid and alpha-mercaptopropionylglycine significantly (p<0.005) protected against RBC Heinz body formation during incubation with acetylphenylhydrazine, while cysteine, cysteamine, and methionine did not. The effect of ascorbic acid was concentration dependent with concentrations as low as 0.1 mM having significant antioxidant effects.|The effect of pteroyl glutamate (PGA) on the distribution of folates during hemolysis induced by acetyl-phenylhydrazine (APH) was investigated. One group of rabbits received daily APH injections, 1 mL of a 2.5% solution/kg; another group received 3 injections each of 10 mg PGA in addition to APH. Blood samples were collected for blood count and folate activity determinations. Animals were killed on day 8, and bone marrow and liver were analyzed for folate activity by 3 different bioassays. Packed red blood cells were incubated with radio labeled PGA to measure uptake. As reticulocytosis due to APH increased to 87% on day 7, there was a gradual rise in red blood cell folate activity. Serum folate activities were normal, liver activities were somewhat depressed, and bone marrow folate activity was elevated compared to untreated controls. When rabbits were treated with PGA as well, folate activity was 2-5 fold higher, and its rise more pronounced in 2 of 3 bioassays, but not when determined with Pediococcus-cerevisiae. Similar results were seen when serum folate activity was measured. All 3 bioassays showed an increase in folate with APH and PGA compared to APH alone, while with liver folate there was significant difference between the two control groups. The mean uptake of labeled PGA by packed red blood cells was 2.7% of folates present in the incubation when rabbits were treated with APH alone, and 0.72% when they were given both APH and PGA. /It was concluded/ that while the hemolytic stimulus brings about a substantial transfer of folates from the bone marrow, the hemopoietic tissue can utilize more folate when additional amounts are made available by parenteral administration of PGA.|The reaction of oxyhemoglobin and acetylphenylhydrazine, which results in hemoglobin denaturation and precipitation, was found to be influenced by H202 and superoxide (O2-.) generated during the reaction. By analysing the different hemoglobin oxidation products, it was found that by influencing the rate at which oxyhemoglobin was oxidized, H2O2 accelerated the overall hemoglobin breakdown, and O2-. inhibited it. By adding GSH (reduced glutathione) or ascorbate, it was possible to slow down the rates of both oxyhemoglobin oxidation and O2-. production, and the overall rate of hemoglobin breakdown. These results are compatible with a mechanism involving production of the acetylphenylhydrazyl free radical, and with GSH, ascorbate and O2-. acting as radical scavengers and preventing its further reactions. The reaction produced choleglobin, as well as acetylphenyldiazine and methemoglobin, which combined to form a hemichrome. The hemichrome was less stable and precipitated first. It was also less stable than the hemichrome formed by direct reaction of acetylphenyldiazine with methemoglobin, and it is proposed that this is because the methemoglobin produced from oxyhemoglobin and acetylphenylhydrazine was modified by the free radicals and H2O2 produced in the reaction.

LD50 Mouse oral 270 mg/kg

/Persons with X-linked inherited glucose-6-phosphate dehydrogenase deficiency./|The fetal red blood cell appears to be more susceptible to oxidative damage /from acetylphenylhydrazine/ than its adult counterpart. There is a potential health hazard associated with administering oxidant drugs to expectant mothers or newborn infants.|Biological half-lives were significantly different among the three acetylation phenotypes (analysis of variance, P < 0.05): 3.94+/-1.70 hours for slow acetylators, 2.25+/-0.37 hours for intermediate acetylators, and 1.86+/-0.67 hours for rapid acetylators. /Hydrazine/

/Former use:/ Treatment of polycythemia.

ACUTE/CHRONIC HAZARDS: When heated to decomposition this compound emits toxic fumes. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . Cover skin burns with dry, sterile dressings after decontamination ... . /Hydrazine and Related Compounds/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors for hypotension with a normal fluid volume. Watch for signs of fluid overload ... . Treat seizures with diazepam ... . Monitor for signs of hypoglycemia (decreased level of consciousness, tachycardia, pallor, dilated pupils, diaphoresis, and/or a dextrose strip or glucometer reading less than 50 mg/dl) and administer 50% dextrose if necessary. Draw blood sample before administration ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Hydrazine and Related Compounds/

/OTHER TOXICITY INFORMATION/ A reduced glutathione stability test was carried out in 8 healthy men and 12 known glucose-6-phosphate dehydrogenase deficient men and women (ages 11-70 yr) whose blood samples were incubated with solutions of acetylphenylhydrazine (5 mg/mL of blood)... . Reduced glutathione levels were measured before and after drug incubation. The results indicated that acetylphenylhydrazine... produced a significant decrease in reduced glutathione levels in glucose-6-phosphate dehydrogenase deficient red cells compared to the reduction seen in normal red cells incubated with these drugs.|/OTHER TOXICITY INFORMATION/ Ascorbate inhibited oxidation of HbO2 and Heinz body formation in glucose-6-phosphate dehydrogenase deficient (human) red cells incubated with acetylphenylhydrazine (APH). Ascorbate may substitute for the glutathione (GSH) which is depleted and act as a scavenger for drug free radicals generated during the reaction. Ascorbate was protective at concentrations only a little higher than that in normal blood... .|/OTHER TOXICITY INFORMATION/ The effects of acetylphenylhydrazine (APH) on the rate of oxidation of hemoglobin to methemoglobin and reduced glutathione (GSH) concentrations were studied in human blood. Erythrocytes were obtained from human fetal blood and normal adult blood and incubated in a medium containing 2 mg/mL APH for up to 1 hr. Samples were obtained at 15, 30, 45, and 60 min and assayed for methemoglobin and GSH. Reduced nicotinamide-adenine-dinucleotide (NADH)/methemoglobin reductase activity of fetal and adult erythrocytes was determined. The rate of oxidation of hemoglobin to methemoglobin in the presence of APH was faster in fetal than in adult erythrocytes. APH decreased the rate of dose appearance of GSH from fetal erythrocytes, relative to adult erythrocytes. The mean NADH/methemoglobin reductase of APH treated fetal erythrocytes was only 46% of the adult value. /It was concluded/ that the rate of oxidation of hemoglobin to methemoglobin in erythrocytes from fetal blood is apparently faster than that of normal adult erythrocytes. This may be due to the difference in structure of hemoglobin-F, the major hemoglobin component in the erythrocytes of the newborn, and hemoglobin-A.

1-acetyl-2-phenylhydrazine

Acetic acid, 2-phenylhydrazide: ACTIVE