O-Methylhydroxylamine

SLIGHTLY SOL IN BENZENE, PETROLEUM ETHER /N-METHYLHYDROXYLAMINE/

MISCIBLE WITH WATER, ALCOHOL, ETHER

Danger

H302+H312+H332 (96.6%): Harmful if swallowed, in contact with skin or if inhaled [Warning Acute toxicity, oral; acute toxicity, dermal; acute toxicity, inhalation]

P260, P261, P264, P264+P265, P270, P271, P280, P301+P317, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P354+P338, P316, P317, P321, P330, P362+P364, P363, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 29 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

...CORROSIVE TO SKIN & HIGHLY IRRITANT TO EYES & MUCOUS MEMBRANES. REPEATED EXPOSURE MAY ENHANCE ALLERGIC REACTION PARTICULARLY OF BACK OF HANDS & FOREARMS FROM 1-2 WK TO 2-5 YR AFTER COMMENCEMENT OF EXPOSURE & CASES OF ECZEMA...FOLLOWING PROLONGED CONTACT. ... NO CASES OF SYSTEMIC POISONING...IN WORKERS. /HYDROXYLAMINE/

/HYDROXYLAMINE IS/ ABOUT EQUIPOTENT TO NITRITE AS METHEMOGLOBIN FORMER, BUT IT HAS GREATER TENDENCY TO PRODUCE SULFHEMOGLOBIN, HEINZ BODIES & OTHER IRREVERSIBLE RED CELL DAMAGE. ... SYSTEMIC POISONING CHARACTERIZED BY CYANOSIS, CONVULSIONS & COMA. /HYDROXYLAMINE/

/HIGH CONCN/ IN ANIMALS...CAUSES CONVULSIONS FOLLOWED BY PARALYSIS & DEATH FROM CESSATION OF BREATHING... CHRONIC ABSORPTION OF MODERATE DOSES (1 MG/KG) MAY LEAD TO SLIGHT ANEMIA. /HYDROXYLAMINE/

...INHIBITOR OF CATALASE &...WHEN ADMIN PARENTERALLY, 40 MG CAUSING CONVULSIONS, NYSTAGMUS & DEATH IN RABBIT. LOCAL APPLICATION OF 10% SOLN...TO RABBIT EYES...CAUSED MODERATE INFLAMMATION OF CONJUNCTIVA. /HYDROXYLAMINE/

HYDROXYLAMINE ELEVATES BRAIN GABA /GAMMA-AMINOBUTYRIC ACID/ LEVELS IN RATS. /HYDROXYLAMINE/

O-METHYLHYDROXYLAMINE (2000 MCG/ML) INDUCED RESISTANCE MUTATION TO 8-AZAGUANINE. IT IS HIGHLY POTENT MUTAGEN FOR MICROORGANISMS AS WELL AS FOR MAMMALIAN CELLS.

REPLICATION OF PHAGE MS2 IN PRESENCE OF O-METHYLHYDROXYLAMINE (MUTAGENESIS IN VIVO) INCR REVERSION FREQUENCY OF 2 AMBER MUTATIONS IN MATURATION PROTEIN. PROBABLE MODE OF MUTAGENIC ACTION INVOLVES ENZYMATIC FORMATION OF MODIFIED PRECURSORS & INCORPORATION INTO RNA.

Methoyxamine is investigated for use as an adjunct to alkylating agents, reverse resistance to chemotherapy, and enhancing radiation therapy. Methoxyamine’s proposed mechanism of action is through blocking of the abasic sites (apurinic/apyrimidinic - AP sites) created by the cleavage of base excision repair (BER) glycoslyates. DNA alkylating agents cause cell death through excessive DNA damage by adduct formation. The human mechanism for DNA repair is very efficient and cancer therapeutics which use this mechanism are often ineffective due to resistance by efficient repair mechanisms such as base excision repair (BER). Alkylating agents such as tezmozolomide form methylated DNA adducts such as O6-methylguanine (O6mG), 7-methylguanine (N7mG) and 3-methyladenine (N3mA). O6mG is a cytotoxic and genotoxic adduct which is repaired by O6-methylguanine DNA-methyltransferase (MGMT). O6mG’s cytotoxicity is due to the mismatch repair mechanism (MMR), but cell induced defects in this repair pathway can lead to drug resistance. The N7mG (dominant lesions caused by methylating agents) and N3mA adducts are both repaired by the BER mechanism. Methoxyamine disrupts the BER pathway, increasing the amount of cytotoxic adducts, which results in cell death. Methoxyamine inhibits BER by stabilizing the AP sites created by cleavage of BER glysosylates, forming MX-AP lesions. Methoxyamine may be an effective adjunct to iododeoxyuridine(IUdR) induced radiosensitization and radiation treatment. IUdR is a halogenated pyrimidine which is incorporated into cellular DNA instead of thymidine, which enhances radiotumor sensitivity. Methoxyamine is proposed to have a dual action in this treatment as it alters cell cycle kinetics as well as prevents repair of DNA by BER, allowing increased sensitivity of tumor cells to DNA damage by radiation therapy. The efficiency of cell cycle repair has been shown to be cell cycle dependent, with the G1 phase being second most sensitive to ionizing radiation (the mitotic, M, phase is the most sensitive). Methoxyamine increases the amount of protein 53 (P53) and protein Rb (pRB), senescence factors which cause the cell to remain in the G1 phase. Methoxyamine also creates a stringent checkpoint at the G1/S boundary as well as an insufficient checkpoint at the G2 stage, preventing cells from going into the S phase. The increased number of G1 cells makes methoxyamine treated tumors more susceptible to ionizing radiation. The temozolomide and methoxyamine created lesion MX-AP not only disrupts the BER pathway but inhibits topoisomerase II alpha (topo II), an enzyme necessary for DNA replication, recombination and chromosome segregation. MX-AP sites block DNA replication and interfere with choromosome splitting. It is currently uncertain how what the interaction between topoisomerase II and methoxyamine causes cytotoxicity, but several mechanisms have been proposed, such as MX-AP sites binding to topo II, thus reducing their functionality by forming a toxic complex.

THE MAJOR MUTAGENIC EFFECT OF O-METHYLHYDROXYLAMINE ON VEGETATIVE SD PHAGE IN ESCHERICHIA COLI IS PROBABLY DUE TO REPLICATION ERRORS RESULTING FROM INCORPORATION OF ENZYMICALLY MODIFIED PRECURSORS INTO DNA.

THE DIPHOSPHATE REACTION PRODUCT (MO6A) OF O-METHYLHYDROXYLAMINE WAS PREPARED AND COPOLYMERIZED WITH CYTIDINE DIPHOSPHATE OR ADENOSINE DIPHOSPHATE. THE SPECIFIC CHANGED BASE PAIRING IS PROBABLY CAUSED BY A TAUTOMERIC SHIFT FROM THE AMINO TO THE IMINO. CHANGING THE TAUTOMERIC EQUILIBRIUM OF A PURINE BY A SUBSTITUTION REACTION WITH A MUTAGEN SHOULD BE CONSIDERED AS A CONTRIBUTING FACTOR FOR THE MECHANISM OF MUTATION OF HYDROXYLAMINES.

Used as an analytical reagent (mainly for ketones and aldehydes); [Hawley]

ANALYTICAL REAGENT

ANALYTICAL REAGENT FOR ALDEHYDES & KETONES

(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 HYDROXYLAMINE DISULFONIC ACID WITH METHYL SULFATE

BY HEATING HYDROXYLAMINE DISULFONIC ACID WITH METHYL SULFATE: GOLDFARB, J AM CHEM SOC 67: 1852 (1945). MAY ALSO BE PREPD FROM HYDROXYURETHAN.