Alkylating agents toxicity

Vascular Tone Immune Surveillance Cellular Adhesion Vascular Permeability Neurotransm ission Bronchodilation Platelet Adhesion Inhibition Renal Function Antioxidant Leukocyte Adhesion Inhibition Protection Against TNF Toxicity Enzyme Function Inhibition DNA Damage Induction Lipid Peroxidation Induction Increased Susceptibility to Radiation Alkylating Agents Toxic Metals Antioxidant Stores Depletion... 

Ethyl trifluoromethanesulfonate [425-75-2] M 178.1, b 115 /atm, 118-120 /atm, d 1.378, Hp 1.336. The ester reacts slowly with H2O and aqueous alkali. If its IR has no OH bands (-3000 cm" ) then purify by redistillation. If OH bands are present then dilute with dry Et20 and shake (carefully) with aqueous NaHC03 until effervescence ceases, then wash with H2O and dry (MgSOa), filter, evaporate and distil the residue under slight vacuum then at atmospheric pressure in a N2 atmosphere. IT IS A POWERFUL ALKYLATING AGENT, AND THE FUMES ARE VERY TOXIC - CARRY ALL OPERATIONS IN AN EFFICIENT FUME CUPBOARD. [Gramstad and Hazeldine J Chem Soc 173 7956 Howells and McCown Chem Rev 77 69 1977.]... 

Alkylation Hazards arise from the alkylating agents, e.g. dimethyl sulphate (suspected human carcinogen), hydrogen fluoride (highly toxic irritant gas) Thermal alkylation processes require higher temperatures and pressures, with associated problems... 

As alkylating agent an alkyl halide, alkyl tosylate or dialkyl sulfate is used in most cases the latter type of reagent is often used in the preparation of methyl and ethyl ethers by employing dimethyl sulfate and diethyl sulfate respectively. Dimethyl sulfate is an excellent methylating agent, but is acutely toxic as well as carcinogenic." ... 

Benzothiepins react with strong alkylating agents, such as methyl fluorosulfonate (caution toxic), to give the corresponding 1-benzothiepinium salts 2.88... 

Alkylating Agents. Figure 2 Biotransformation of cyclophosphamide - formation of inactive ( ) and toxic ( metabolites. 

Other examples of esterification with trialkyloxonium salts have been reported.7,8 The present procedure offers the advantages that the reactive carboxylate ion is generated in sitv and that a low-boiling, nonaqueous solvent is employed, whereby the experimental procedure is considerably simplified. A related method has been reported which utilizes a hindered amine wdth dimethyl sulfate [Sulfuric acid, dimethyl csterj as the alkylating agent.9 The present procedure is carried out under somewhat milder conditions and avoids the use of highly toxic reagents. 

Each category of chemotherapy drugs has similar side effects. Anthracyclines cause cardiac toxicity, which is related to the cumulative dose. Tubulin interactive agents are associated with neuropathy and ileus. Alkylating agents are associated with secondary malignancies. 

Possible increased toxicity when given concurrently with alkylating agents, radiation, purine analogs, and methotrexate. 

HD is a vesicant (blister agent) and alkylating agent producing cytotoxic action on the hematopoietic (blood-forming) tissues which are especially sensitive. The rate of detoxification of HD in the body is very slow, and repeated exposures produce a cumulative effect. It causes blisters, irritates the eyes, and it is toxic when inhaled. HD has been determined to be a human carcinogen by the International Agency for Research on Cancer. 

Ifosfamide -alkylating agent noncell cycle specific -bone marrow suppression -hemorrhagic cystitis (need Mesna uroprotection) -nausea and vomiting—mild to moderate -mucocutaneous effects (mucositis, stomatitis, diarrhea) -CNS toxicity—lethargy, stupor, coma, seizures... 

Procarbazine -alkylating agent cell cycle independent -bone marrow suppression—prolonged -nausea and vomiting—severe tolerance often develops with repeated dosing -mucocutaneous effects (mucositis, stomatitis, diarrhea) -rash, hives, photosensitivity -interstitial pneumonitis -CNS toxicity—seizures, lethargy, headache, ataxia -flu-like syndrome -azoospermia and amenorrhea almost universal... 

Field First Aid Decontaminate At Once for All Exposed Victims Although sulfur mustards cause cellular changes within minutes of contact, the onset of pain and other clinical effects are delayed for one to twenty-four hours. Sulfur mustards are alkylating agents that may cause bone marrow suppression and neurologic and gastrointestinal toxicity. However, the biochemical mechanisms of action are not clearly understood by anyone. The death rate from exposure to sulfur mustard during World War I was 2-3 percent,... 

To [Co(en)2((S)-GluOBzl)]I2 (5.0 g, 7.3 X 10 3 mol) in dry trimethyl-phosphate (18 ml, 4A sieves) contained in a conical flask equipped with a drying tube was added methyl trifluoromethane sulfonate (8.0 g, 4.9 x 10 2 mol) and the mixture was stirred at room temperature for 30 min (Caution The alkylating agent is believed to be extremely toxic. Use a hood and avoid skin and vapor contact). The deep orange solution was then slowly poured into rapidly stirred dry ether (600 ml) and the precipitated semisolid recovered by decantation. The residue was dissolved in the minimum volume of dry methanol (10-20 ml), the product reprecipitated using further dry ether (400 ml), and the solid recovered as before. A further precipitation using methanol (10-20 ml) and dry ether (800 ml) produced the complex as a finely divided solid. This was recovered by filtration (porosity 4 sin-... 

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