1-아세틸-2-페닐히드라진

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.

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.

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.

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.

...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/

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.

/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.

/LABORATORY ANIMALS: Acute Exposure/ The hematological effects of phenylhydrazine (PH) were investigated in rabbits. Blood studies of total white and total red blood cell counts, hemoglobin and hematocrit determinations, reticulated red blood cell counts, differential counts, and fragility tests were performed daily. Nine rabbits were given an ip injection of PH and were killed on successive days. Acetylphenylhydrazine was similarly injected into an additional 9 rabbits. ...Anemia developed in all animals after 24 hours. Effects of acetylphenylhydrazine were the same as for PH. ...

/LABORATORY ANIMALS: Acute Exposure/ The role of the spleen in the removal of Heinz bodies from circulation and in the regeneration of erythrocytes following acetylphenylhydrazine (APH) induced anemia was assessed in rats. Normal and splenectomized Sprague-Dawley-rats were injected sc with a single dose of APH at 5-90 mg/kg. Blood was taken repeatedly over the 17 to 18 day observation period and erythrocytes were counted for percentage of Heinz body containing cells. Hematocrits were performed and reticulocytes were counted. Another group of rats with intact spleens were given radioactive iron by iv injection, followed by the same doses of APH. Four days after APH administration, animals were sacrificed and livers and spleens were removed, and weighed. Accumulated radioactive iron was determined by scintillation counting. Erythrocyte survival was determined by iv injection of radioactively tagged erythrocytes in another group of normal and splenectomized rats followed in 2 hr by a sc injection of 15 mg/kg APH and periodic sampling and counting of surviving radioactive cells. The rate of Heinz body removal was more rapid in intact rats. As the dose of APH increased, the rate of removal of Heinz bodies increased in both normal and splenectomized animals. Hematocrits fell significantly in both groups at 90 mg/kg APH. At 15 and 30 mg/kg APH, hematocrits were lower in normal rats than in splenectomized rats. Regenerative response was higher in normal rats. Reticulocyte increases were greatest at the higher doses and greater in those animals with spleens. Dose related increase in spleen size was seen with APH treated animals but no increase in liver weight was noted. Radioactive iron accumulated in the spleen in amounts related to doses of APH and an increase in iron was noted in the liver at 90 mg/kg. There was a more rapid removal of radioactively tagged erythrocytes in intact rats.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Twenty female Sprague-Dawley-rats received sc injections of 10 to 40 mg/kg /acetylphenylhydrazine/ over a period of 94 days; doses were administered daily after the twentieth day. Twenty matched controls received injections of physiological saline. ...After 94 days of treatment, the 39 surviving animals were autopsied. The combined gastrocnemius and soleus muscles of both legs were assayed for myoglobin. Mean body weights of animals in both groups were about the same until the last week when the treated group showed a moderate weight loss. Hemoglobin concentration and packed cell volume were lower in the treated group. After 65 days, the mean fecal urobilinogen excretion of treated animals was 4 times that of the controls, and the mean urinary urobilinogen was 1.5 times the control values. Mean myoglobin concentration of muscle from control animals was 1.31 mg/g and decreased to 0.87 mg/g in treated animals; the state of muscle hydration was the same in both groups. Spleens in treated animals were about 8 times larger than in controls.

/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/

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/