Phenylhydroxylamin

NEEDLES FROM SATURATED SODIUM CHLORIDE SOLN

NEEDLES FROM WATER, BENZENE OR PETROLEUM ETHER SOLN

Soluble in hot water (NTP, 1992)

VERY SOL IN CHLOROFORM; INSOL IN PETROLEUM ETHER; FREELY SOL IN ALCOHOL, CARBON DISULFIDE, DIL MINERAL ACID, ETHER, HOT BENZENE, ACETIC ACID

181 to 183 °F (NTP, 1992)

82 °C

N-phenylhydroxylamine appears as tan to brown crystals. (NTP, 1992)

Solid; [Merck Index] Tan to brown solid; [CAMEO]

Danger

H301 (97.6%): Toxic if swallowed [Danger Acute toxicity, oral]

P264, P270, P301+P316, P321, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 42 reports by companies from 2 notifications to the ECHA C&L Inventory.

Occupational cases of severe poisoning have been reported; Markedly increases sister chromatid exchange in cultured human fibroblasts; Causes methemoglobinemia in rats and mice; Lethal-dosed rats did not exhibit methemoglobin levels sufficiently high to cause death by anoxia, suggesting that methemoglobinemia is not responsible for acute toxicity; Emergency treatment: Methemoglobinemia; [HSDB] An irritant; [CAMEO] Irritating to human skin; Causes hematuria and methemoglobinemia in subcutaneous, lethal-dose studies of rats and rabbits; Repeated dose studies of rats produce weight loss and changes to blood; [RTECS] May cause irritation; [Aldrich MSDS]

N-PHENYLHYDROXYLAMINE neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen may be generated in combination with strong reducing agents, such as hydrides.

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, you should dampen the solid spill material with alcohol, then transfer the dampened material to a suitable container. Use absorbent paper dampened with alcohol 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 alcohol followed by washing with a strong soap and water solution. Do not reenter the contaminate area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

AGMENELLUM QUADRUPLICATUM STRAIN PR-6 AND OSCILLATORIA SP STRAIN JCM WERE GROWN PHOTOAUTOTROPHICALLY IN THE PRESENCE OF ANILINE. CYANOBACTERIUM WAS EXTREMELY SENSITIVE TO THE ANILINE DERIVATIVE PHENYLHYDROXYLAMINE. ANILINE AND DERIVATIVES HAVE BEEN FOUND IN THE EFFLUENT FROM DYE MANUFACTURING PLANTS.

.../THERE HAVE BEEN/ RATHER SEVERE POISONINGS FROM PHENYLHYDROXYLAMINE /IN INDUSTRIAL PLANTS/, & STILL HAVE NOT OBSERVED IN MAN CONCN BEYOND APPROX 75% METHEMOGLOBIN.

METHEMOGLOBIN LEVELS TO 40% MAY EXIST WITHOUT SYMPTOMS OTHER THAN SENSE OF WELL-BEING. @ HIGHER CONCN HEADACHE MAY BECOME SEVERE; WEAKNESS, ATAXIA & LIGHTHEADEDNESS OCCUR. WITH INCREASING CONCN...DYSPNEA, TACHYCARDIA & ALARMING CYANOSIS ARE NOTED. EVEN @...LEVELS APPROXIMATING 75%, HOWEVER, RECOVERY WITHOUT SPECIFIC THERAPY HAS BEEN THE RULE. /AROMATIC AMINO COMPD/

HUMAN FIBROBLASTS WERE ALLOWED TO ATTACH TO PLASTIC PETRI DISHES FOR 4 HOURS AND EXPOSED IN SERUM-FREE MEDIUM FOR 2 HOURS TO N-PHENYLHYDROXYLAMINE (0.001-0.5 MMOL). THE TREATMENT MEDIUM WAS REPLACED WITH COMPLETE MEDIUM CONTAINING 5-BROMODEOXYURIDINE (10 MUMOL), AND CELLS WERE ALLOWED TO GROW FOR 48 HOURS WITH COLCEMIDE PRESENT FOR THE FINAL 4.5 HOURS. CELL CYCLE ANALYSES (PERCENTAGE OF CELLS IN 1ST, 2ND, OR 3RD DIVISION) REVEALED THAT N-PHENYLHYDROXYLAMINE INHIBITED CELL PROLIFERATION. CELL DEATH WAS SEEN AT DOSES OF 0.5 MMOL. SIGNIFICANT INCREASES IN SISTER CHROMATID EXCHANGE WERE FOUND. N-PHENYLHYDROXYLAMINE INDUCED A DOSE-RELATED INCREASE IN SISTER CHROMATID EXCHANGE FREQUENCY WITH A 1.4-FOLD ELEVATION.

THE NONENZYMATIC REDUCTION OF NITROSOBENZENE BY NADPH AND NADH IN AQUEOUS BUFFER SOLUTION AT 25 °C IS DESCRIBED. BOTH REACTANTS QUANTITATIVELY CONVERT NITROSOBENZENE TO PHENYLHYDROXYLAMINE. THE OXIDATION OF PHENYLHYDROXYLAMINE BY NAD(P) TO NITROSOBENZENE IS ONLY STIMULATED BY A FACTOR OF 1.2 OVER OXIDATION IN ITS ABSENCE (WHEN THE RATIO OF NADP:PHENYLHYDROXYLAMINE WAS 8:1).

...RATS /DIED WHEN DOSED WITH/...BETA-PHENYLHYDROXYLAMINE...BUT LEVELS OF METHEMOGLOBIN WERE INSUFFICIENT TO CAUSE DEATH BY ANOXIA. .../IT WAS/ CONCLUDED THAT METHEMOGLOBINEMIA PLAYS NO IMPORTANT PART IN ACUTE TOXICITY OF /THIS COMPD/...

AS TESTED IN MICE, PHENYLHYDROXYLAMINE, N-HYDROXY-P-AMINOTOLUENE & N-HYDROXY-P-ACETOPHENONE WERE ALL ABOUT EQUIPOTENT, IE GENERATED EQUIVALENT PEAK CONCENTRATIONS OF METHEMOGLOBIN AT EQUAL DOSES. AT SAME TIME THEY WERE 10 OR MORE TIMES MORE POTENT THAN NITRITE, HYDROXYLAMINE, OR SIMPLE AMINOPHENOLS.

AROMATIC NITRO AND AMINO COMPOUNDS PROBABLY ARE NOT, IN THEMSELVES, CYANOSIS PRODUCERS, BUT BIOCHEMICAL REDOX PROCESSES CREATE DERIVATIVES WHICH HINDER OXYGEN TRANSPORT TO TISSUES BY FORMING HB-COMPLEXES. ENZYME SYSTEMS CATALYZE OXIDATION OF AMINE GROUP...TO KNOWN CYANOPATHIC NITROSO-...DERIVATIVES. PHENYLHYDROXYLAMINES ARE PROBABLY MOST POTENT CYANOSIS PRODUCERS IN REDOX SERIES. /AROMATIC NITRO AND AMINO COMPOUNDS/

A MECHANISM IS PROPOSED IN WHICH CYCLIC CONVERSION OF PHNO TO PHENYLHYDROXYLAMINE WITHIN ERYTHROCYTE LEADS TO ACCUM OF H2O2 WHICH REACTS WITH FERRO-HB, INITIATING OXIDATIVE DEGRADATION OF HEME.

For more Non-Human Toxicity Excerpts (Complete) data for N-PHENYLHYDROXYLAMINE (6 total), please visit the HSDB record page.

...INTRAERYTHROCYTIC RECYCLING ACCOUNTS FOR THE HIGH POTENCY /AS METHEMOGLOBIN FORMER/ OF PHENYLHYDROXYLAMINE RELATIVE TO OTHER COMPOUNDS. ...PHENYLHYDROXYLAMINE & HEMOGLOBIN REACT TO FORM METHEMOGLOBIN & NITROSOBENZENE. IN INTACT NORMAL RED CELL PROVIDED WITH SUBSTRATE, MECHANISMS EXIST FOR REDUCTION OF NITROSOBENZENE TO REGENERATE PHENYLHYDROXYLAMINE.

UNDER ANAEROBIC CONDITIONS, PHENYLHYDROXYLAMINE REACTS WITH THE MODEL NUCLEOPHILE BISULFITE TO FORM ANILINE, O-AMINOPHENOL, 0-AMINOBENZENESULFONIC ACID, AND P-AMINOBENZENESULFONIC ACID. ALL PRODUCTS RESULT FROM IMTERMEDIATES FORMED FROM NUCLEOPHILIC ATTACK OF BOTH BISULFITE AND SULFITE ON THE ARYLHYDROXYLAMINE WITH SUBSEQUENT COVALENT ADDITION-ELIMINATION PROCESSES LEADING TO PRODUCTS. THIS SCHEME IS A POSSIBLE ALTERNATIVE PATHWAY FOR DESCRIBING THE MECHANISM FOR CARCINOGENIC ARYLATION OF NUCLEIC ACID RESIDUES BY ARYLHYDROXYLAMINES NOT REQUIRING THE INTERMEDIACY OF SHORT-LIVED FREE RADICALS OR NITRENIUM IONS.

THE MECHANISM OF SULFHEMOGLOBIN FORMATION AND SPECIES DIFFERENCES IN THE FORMATION OF SULFHEMOGLOBIN AND METHEMOGLOBIN WERE INVESTIGATED. ERYTHROCYTES OR HEMOLYZATES WERE INCUBATED WITH PHENYLHYDROXYLAMINE, ANILINE-HCL OR ITS MONOCHLORO DERIVATIVES IN THE PRESENCE OR ABSENCE OF LIVER MICROSOMES FROM MICE, RATS, GUINEA PIGS, RABBITS, CATS, DOGS, AND MONKEYS. SULFHEMOGLOBIN WAS NOT INDUCED VIA METHEMOGLOBIN. SPECIES DIFFERENCES IN THE PRODUCTION RATES OF N-HYDROXY METABOLITES FROM ANILINE AND ITS DERIVATIVES BY LIVER MICROSOMES (AS WELL AS THE SUSCEPTIBILITY OF ERYTHROCYTES TO N-HYDROXY COMPOUNDS) IN VITRO WERE NOT REFLECTED IN SPECIES DIFFERENCES IN METHEMOBGLOBIN AND SULFHEMOGLOBIN FORMATION IN VIVO.

PHENYLHYDROXYLAMINE IS BIOSYNTHESIZED FROM ANILINE & N-ETHYLANILINE IN PIG & RABBIT: HEINZE E, HLAVICA P, KIESE M & LIPOWSKY G; BIOCHEM PHARMAC 19: 641 (1970). HLAVICA P, KIESE M; BIOCHEM PHARMAC 18: 1501 (1969) /FROM TABLE/

PHENYLHYDROXYLAMINE IS METABOLIZED TO ANILINE IN PIG: KADLUBAR FF, MCKEE EM, ZIEGLER DM; ARCHS BIOCHEM BIOPHYS 156: 46 (1973) /FROM TABLE/

CYTOCHROME P-450 COMPLEX WAS FORMED BY DIRECT INTERACTION OF NITROSOBENZENE WITH NADPH-REDUCED RAT LIVER MICROSOMES IN ANAEROBIC CONDITIONS, AND BY REACTION OF PHENYLHYDROXYLAMINE WITH AEROBIC MICROSOMES.

DETOXIFICATION BY REARRANGEMENT OF THE PHENYLHYDROXYLAMINE TO ORTHO- AND PARA-AMINOPHENOLS OF LOWER POTENTIAL FOR EXCRETION THROUGH THE KIDNEYS PROBABLY IS RESPONSIBLE FOR RESTORATION OF THE OXYGEN TRANSPORT BALANCE /FOLLOWING CYANOSIS/.

For more Metabolism/Metabolites (Complete) data for N-PHENYLHYDROXYLAMINE (7 total), please visit the HSDB record page.

N-Hydroxyaniline is a known human metabolite of aniline.

Used as intermediate for cupferron and p-aminophenol; Not commercially produced in the US; [HSDB]

CHEMICAL INTERMEDIATE FOR CUPFERRON (A REAGENT) & P-AMINOPHENOL

(1972) No Data

(1975) No Data

(1972) No Data

(1975) No Data

(1972) NOT PRODUCED COMMERCIALLY IN US

(1975) NOT PRODUCED COMMERCIALLY IN US

REACTION OF AN ALCOHOLIC SOLUTION OF NITROBENZENE WITH ZINC DUST AND A SMALL QUANTITY OF CALCIUM CHLORIDE

PREPD BY ZINC REDUCTION OF NITROBENZENE IN AMMONIUM CHLORIDE SOLN: KAMM, ORG SYNTH 4, 57 (1925).