HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
Altretamin
HMM · HTM · Hemel · NC 195 · RB-1515 · Hexylen · Hexalen · WR-95704
Identifikatoren & physikalische Daten
| CAS No. | 645-05-6 |
|---|---|
| Summenformel | C9H18N6 |
| Durchschnittliche Molmasse | 210,28 g/mol |
| Monoisotopische Masse | 210,15929458 g/mol |
| SMILES | CN(C)c1nc(N(C)C)nc(N(C)C)n1 |
| InChIKey | UUVWYPNAQBNQJQ-UHFFFAOYSA-N |
| PubChem CID | 2123 |
| ChEMBL | CHEMBL1455 |
| ChEBI | CHEBI:24564 |
| EC No. | 211-428-4 |
| DTXSID | DTXSID4022579 |
| Lokaler Name | Altretamin |
Chemische & physikalische Eigenschaften
| XLogP | 2,7 |
|---|---|
| Polarare Oberfläche (TPSA) | 48,4 |
| H-Brücken-Donoren | 0 |
| H-Brücken-Akzeptoren | 6 |
| Frei drehbare Bindungen | 3 |
| Schwere Atome | 15 |
| Formalladung | 0 |
| Komplexität | 148 |
| Arzneimittel | Pharmaceuticals -> Listed in ZINC15 |
| SpringerMaterials Properties | Fusion temperature |
| LogP (Verteilungskoeffizient) | log Kow = 2.731.7 |
| Color/Form | Needles from absolute ethanolSolid |
| Löslichkeit | Insoluble (NTP, 1992)Soluble in acetoneIn water, 91 mg/L at 25 °C3.10e+00 g/LWater 0.92 (mg/mL)Chloroform (Sparingly), Methanol (Slightly, Heated) |
| Human Drugs | FDA approved drugs -> Active ingredient |
| Schmelzpunkt | 172-174 °C172 - 174 °C171-175 °C (lit.) |
| Physical Description | Hexamethylmelamine is a colorless crystalline solid. Insoluble in water. (NTP, 1992) |
| Stability/Shelf Life | Bulk: The bulk drug is stable at room temperature. Solution: Aqueous solutions at pH 4, 7, and 10 are stable for 24 hours at room temperature (UV). |
| Collision Cross Section | 152.33 Ų [M+K]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]145.6 Ų [M+H]+ [CCS Type: TW |
| Siedepunkt | 339.81°C (rough estimate) |
| Dichte | 1.0441 (rough estimate) |
| Brechungsindex | 1.6100 (estimate) |
| Lagerbedingungen | Keep in dark place,Inert atmosphere,Room temperature |
| pKa (Säurekonstante) | pKa 10.3 (Uncertain) |
| Aggregatzustand | solid |
| Farbe | White to Off-White |
| Merck | 13,318 |
| InChI | 1S/C9H18N6/c1-13(2)7-10-8(14(3)4)12-9(11-7)15(5)6/h1-6H3 |
| InChIKey | UUVWYPNAQBNQJQ-UHFFFAOYSA-N |
| SMILES | CN(C)c1nc(nc(n1)N(C)C)N(C)C |
| CAS Datenbank | 645-05-6(CAS DataBase Reference) |
| NIST chemische Informationen | Altretamine(645-05-6) |
| EPA chemische Informationen | Altretamine (645-05-6) |
Sicherheit & Vorschriften
| GHS-Einstufung | WarningH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 41 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| Regulatorische Informationen | Hazard Traits - Developmental ToxicityReproductive Toxicity |
| Gesundheitsgefahren | SYMPTOMS: Nausea and vomiting, possibly parathesia, numbness, depression, confusion, drowsiness and hallucinations. |
| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl altretamine approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
| Reaktive Gruppe | Amines, Phosphines, and Pyridines |
| Reactivity Profile | HEXAMETHYLMELAMINE 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. |
| Air and Water Reactions | Insoluble in water. |
| Hazard Classes and Categories | Acute Tox. 4 (100%) |
| Shipment Methods and Regulations | /PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Methods for transporting hazardous drugs to the health-care setting should be consistent with environmental protection and national or local regulations for transporting hazardous substances. When hazardous drugs are being transported to the home-care setting, appropriate containers (eg, lined cardboard boxes) and procedures should be used to prevent breakage and contain leakage. ... The drugs must be securely capped or sealed and properly packaged and protected during transport to reduce further the chance of breakage and spillage in a public area such as a corridor or elevator. /Antineoplastic agents/ |
| Erste Hilfe | 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. |
| Lagerbedingungen | Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. |
| Freisetung ohne Brand | 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 ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 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 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. |
| Entsorgungsverfahren | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices./PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All contaminated disposables should be contained in sealable bags for transfer to larger waste containers. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All bottles must be discarded as contaminated waste after decontamination of the biohazard cabinet. All protective apparel (gown, gloves, goggles, and respirator) should be discarded as contaminated waste. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The contaminated filters must be removed, bagged in thick plastic and prepared for disposal in a hazardous waste dump site or incinerator licensed by the Environmental Protection Agency (EPA). /Antineoplastic agents/For more Disposal Methods (Complete) data for ALTRETAMINE (8 total), please visit the HSDB record page. |
| Preventive Measures | /PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Accidental contamination of the health-care environment, resulting in exposure of personnel, patients, visitors, and family members to hazardous substances, is prevented by maintaining the physical integrity and security of packages of hazardous drugs. 1. Access to all areas where hazardous drugs are stored is limited to specified authorized staff. 2. A method should be present for identifying to personnel those drugs that require special precautions (eg, cytotoxics). One way to accomplish this is to apply appropriate warning labels to all hazardous drug containers, shelves, and bins where the drug products are stored. ... 3. A method of identifying, for patients and family members, those drugs that require special precautions in the home should be in place. This may be accomplished in the health-care setting, by providing specific labeling for discharge medications, along with written instructions. 4. Methods for identifying shipping cartons of hazardous drugs should be required from manufacturers and distributors of these drugs. 5. Written procedures for handling damaged packages of hazardous drugs should be maintained. Personnel involved in shipping and receiving hazardous drugs should be trained in these procedures, including the proper use of protective garments and equipment. Damaged shipping cartons of hazardous drugs should be received and opened in an isolated area (eg, in a laboratory fume hood, if available, not in a vertical laminar airflow biological safety cabinet used for preparing sterile products). /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Facilities (eg, shelves, carts, counters, and trays) for storing hazardous drugs are designed to prevent breakage and to limit contamination in the event of leakage. Bins, shelves with barriers at the front, or other design features that reduce the chance of drug containers falling to the floor should be used. Hazardous drugs requiring refrigeration should be stored separately from nonhazardous drugs in individual bins designed to prevent breakage and to contain leakage. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Until the reproductive risks (or lack thereof) associated with handling hazardous drugs within a safety program have been substantiated, staff who are pregnant or breast-feeding should be allowed to avoid contact with these drugs. Policies should be in effect that provide these individuals with alternative tasks or responsibilities if they so desire. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The pharmacy should provide access to information on toxicity, treatment of acute exposure (if available), chemical inactivators, solubility and stability of hazardous drugs (including investigational agents) used in the workplace. /Antineoplastic agents/For more Preventive Measures (Complete) data for ALTRETAMINE (20 total), please visit the HSDB record page. |
| Personal Protective Equipment (PPE) | 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. (NTP, 1992)/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Protective apparel: Disposable closed-front gown or coveralls, disposable utility gloves over disposable latex gloves, NIOSH-approved air-purifying half-mask respirator equipped with a high efficiency filter, and eye protection should be worn. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Class 100 clean-air work stations, both horizontal and vertical airflow (with no containment characteristics), are inappropriate engineering controls for handling hazardous drugs because they provide no personnel protection and permit environmental contamination. Although there are no engineering controls designed specifically for the safe handling of hazardous chemicals as sterile products, Class II contained vertical-flow biological safety cabinets (biohazard cabinets) have been adopted for this use. Biohazard cabinetry is, however, designed for the handling of infectious agents, not hazardous chemicals. ... Based on design, ease of use, and cost considerations, Class II contained-vertical-flow biohazard cabinetry is currently recommended for use in preparing sterile doses of hazardous drugs. Class II cabinetry design and performance specifications are defined in NSF Standard 49. Biological safety cabinets selected for use with hazardous drugs should meet NSF Standard 49 specifications to ensure the maximum protection from these engineering controls. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers should wear powder free, disposable surgical latex gloves of good quality when preparing hazardous drugs. Selection criteria for gloves should include thickness (especially at the fingertips where stress is the greatest), fit, length, and tactile sensation. ... The practice of double gloving is supported by research that indicates that many glove materials vary in drug permeability even within lotstherefore, double gloving is recommended. ... In general, surgical latex gloves fit better, have appropriate elasticity for double gloving and maintaining the integrity of the glove-gown interface, and have sufficient tactile sensation (even during double gloving) for stringent aseptic procedures. ... Powdered gloves should be avoided. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers who are not protected by the containment environment of a biohazard cabinet should use respiratory protection when handling hazardous drugs. Respiratory protection should be an adjunct to and not a substitute for engineering controls. Surgical masks of all types provide no respiratory protection against powdered or liquid aerosols of hazardous drugs. In situations where workers may be exposed to potential eye contact with hazardous drugs, an appropriate plastic face shield or splash goggles should be worn. /Antineoplastic agents//PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ During compounding of hazardous drugs (eg, crushing, dissolving, and preparing an ointment), workers should wear low permeability gowns and double gloves. Compounding should take place in a protective area such as a disposable glove box. If compounding must be done in the open, an area away from drafts and traffic must be selected, and the worker should use appropriate respiratory protection. /Antineoplastic agents/ |
| Wechselwirkungen | Blood dyscrasia causing medications (leukopenic and/or thrombocytopenic effects of altretamine may be increased with concurrent or recent therapy if these medications cause the same effectsdosage adjustment of altretamine, if necessary, should be based on blood counts)Additive bone marrow depression may occur /with radiation therapy/dosage reduction may be required when two or more bone marrow depressants, including radiation, are used concurrently or consecutively.Concurrent use of altretamine with monoamine oxidase (MAO) inhibitors, including furazolidone, procarbazine, and selegiline use may result in severe orthostatic hypotension.Because normal defense mechanisms may be suppressed by altretamine therapy, the patient's antibody response to /a killed/ vaccine may be decreased. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factorsestimates vary from 3 months to 1 year)For more Interactions (Complete) data for ALTRETAMINE (6 total), please visit the HSDB record page. |
| Hepatotoxicity | Altretamine therapy is associated with a low rate of serum enzyme elevations, but these are generally mild and self limited, not requiring dose adjustment. Rare instances of clinically apparent acute liver injury attributed to altretamine have been reported, but the clinical features have not been characterized. Altretamine has not been linked specifically to sinusoidal obstruction syndrome, but it is rarely used in high doses in neoplastic disease or in conditioning regimens for bone marrow transplantation, situations in which alkylating agents are commonly associated with this complication. |
| Milk Concentrations | It is not known whether altretamine or its metabolites are distributed into breast milk. |
| Medical Surveillance | /PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ There is no method available for routine monitoring of personnel for evidence of hazardous drug exposure. Tests for the presence of mutagens or chromosomal damage are not drug specific and are of value only in controlled studies. Chemical analysis of urine for the presence of hazardous drugs at the sensitivity level needed to detect occupational exposure is limited to a few drugs and is not yet commercially available. /Antineoplastic agents/ |
| Human Toxicity Excerpts | /CASE REPORTS/ This case report describes a 76-year-old white woman who was found to have ovarian cancer and underwent chemotherapy with hexamethylmelamine. After 34 months of therapy, she developed an acute myelocytic leukemia. |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)AltretamineAmbiguous-DILI-concernAdverse reactionsDOI:10.1016/j.drudis.2016.02.015 |
| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ No adverse effect on fertility was found in female rats when altretamine was administered from 14 days prior to breeding through the gestation period. Administration to male rats in doses of 120 mg per square meter of body surface area per day for 60 days prior to mating resulted in testicular atrophy, reduced fertility, and a possible dominant lethal mutagenic effectdoses of 450 mg per square meter of body surface area per day for 10 days caused decreased spermatogenesis, atrophy of testes, seminal vesicles, and ventral prostate./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Altretamine is embryotoxic and teratogenic in rats and rabbits given 2 to 10 times the human dose./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The antineoplastic drug hexamethylmelamine (HMM) was evaluated for effects on reproduction and postnatal development in the rat and on embryonal and fetal development in the rat and rabbit. Daily po treatment of male rats for 62 days with doses of 0, 10, 20, or 40 mg/kg/day resulted in testicular atrophy, reduced fertility, and a possible dominant lethal mutagenic effect at the higher two dose levels. Alterations in morphology and function of the beta cells of the pancreatic islets were observed after treatment of males for more than 28 days with 20 or 40 mg/kg/day. The same dose levels administered to female rats for 14 days prior to breeding and through Day 13 or 20 of gestation had no adverse effects on fertility, but the highest dose was embryocidal and postnatal survival was decreased at both the 20- and 40-mg/kg/day dose levels. Similar effects on postnatal survival were observed when the drug was administered by gavage to rats during the last week of gestation and throughout the lactation period. Treatment of pregnant rats throughout organogenesis (Days 6 to 15) or for 4-day intervals during organogenesis (Days 6 to 9, 9 to 12, or 12 to 15) with po doses ranging from 20 to 80 mg/kg/day resulted in decreased body weight gain and food consumption, an increased resorption rate in dams receiving 80 mg/kg/day on Days 6 to 9, and decreased fetal weights at all dose levels and most treatment intervals. The incidence of minor skeletal defects was increased among litters of HMM-treated groups. Major fetal malformations were limited in number but were considered treatment related. Treatment of pregnant rabbits po on Days 6 to 18 of gestation with doses of 0, 20, 40, or 60 mg/kg/day did not result in an embryocidal or teratogenic effect. Treatment with 60 mg/kg/day did, however, result in decreased kit weights, indicating a mild embryo-fetotoxic effect./GENOTOXICITY/ It is of great interest to elucidate the mechanisms by which cytostatic drugs exert their mutagenic and/or carcinogenic activity besides the anticancer effect and the possible relationship among them. A useful and informative approach to this problem is the analysis of the mutation spectra induced by these drugs in eukaryotic organisms. Sequence analysis of the mutations induced by hexamethylmelamine, a crosslinking agent extensively used in the treatment of ovarian cancer, in male germ cells of Drosophila was conducted using the v locus as reporter gene. Both intra-locus and multi-locus deletions were induced whereas based changes were almost absent. Thus, it is proposed that deletions are likely to be involved in the generation of second malignancies in hexamethylmelamine-treated patients. It has to be stressed that systems, such as v, capable of efficiently recovering mutations caused by big losses of DNA, should be used for the study of mutational spectra induced by cross-linking agents./GENOTOXICITY/ Hexamethylmelamine (HEMLA) is a metabolism-dependent formaldehyde-releasing agent ... known to be mutagenic to Drosophila. ... The present paper describes the mutagenicity of HEMLA to strain TA100 of Salmonella typhimurium. Activity is dependent upon both the use of a pre-incubation assay protocol and on high concentrations of Aroclor-induced rat liver in the S9 mix. ... |
| Probable Routes of Human Exposure | /PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ ... exposure may be through inadvertent ingestion of the drug on foodstuffs (eg, workers' lunches), inhalation of drug dusts or droplets or direct skin contact. /Antineoplastic agents/ |
| Environmental Water Concentrations | While data specific to altretamine were not located(SRC, 2007), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). |
| Antidote and Emergency Treatment | Emergency and supportive measures. Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotensin, and arrhythmias if they occur. Treat nausea and vomiting with metoclopramide and fluid loss caused by gastroenteritis with intravenous crystalloid fluids. /Antineoplastic agents/Bone marrow depression should be treated with the assistance of an experienced hematologist or oncologist. /Antineoplastic agents/Decontamination. Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. /Antineoplastic agents/Enhanced elimination. Because of the rapid intracellular incorporation of most of these agents, dialysis and other extracorporeal removal procedures are generally not effective. /Antineoplastic agents/ |
| Toxicity Data | Human(po): TDL0 8 mg/kgRat(po): LD50 350 mg/kgRat(ip): LD50 265 mg/kgMouse(po): LD50 437 mg/kgMouse(ip): LD50 200 mg/kgMouse(iv): LD50 171 mg/kg |
| Non-Human Toxicity Values | LD50 Rat oral 350 mg/kgLD50 Guinea pig oral 255 mg/kg |
| Wassergefährdungsklasse (WGK) | 3 |
| Zollcode | 2933690000 |
| RTECS-Nr. | OS1050000 |
| R-Sätze (R) | 22-36/37/38 |
| Toxizität | LD50 in rats, guinea pigs (mg/kg): 350, 255 orally (Jasper) |
| Gefahrensymbole | Xn |
| Sicherheitshinweise (S) | 26-36 |
| Lagerklasse | 11 - Combustible Solids |
| Gefahrstoffdaten | 645-05-6(Hazardous Substances Data) |
| Gefahrenklasse | Acute Tox. 4 OralEye Irrit. 2Skin Irrit. 2STOT SE 3 |
Anwendungen & Verwendung
Verwenden
An antitumor agent which also acts as a chemosterilant for male houseflies and other insects. Antineoplastic.