Carcinogens Methylation

Ghloromethylation. The reactive intermediate, 1-chloromethylnaphthalene [86-52-2] has been produced by the reaction of naphthalene in glacial acetic acid and phosphoric acid with formaldehyde and hydrochloric acid. Heating of these ingredients at 80—85°C at 101.3 kPa (1 atm) with stirring for ca 6 h is required. The potential ha2ard of such chloromethylation reactions, which results from the possible production of small amounts of the powerhil carcinogen methyl chloromethyl ether [107-30-2J, has been reported (21). 

Newbold, R.F., Warren, W., Medcalf, A.S.C. Amos, J. (1980) Mutagenicity of carcinogenic methylating agents is associated with a specific DNA modification. Nature, 283, 596-599... 

Damjanov, I., R. Cox, D.S. Sarma, and E. Farber. Patterns of damage and repair.of liver DNA induced by carcinogenic methylating agents in vivo. Cancer Res. 33 2122-2128, 1973. 

CLA was effective for both the direct-acting carcinogen methyl-nitrosourea (MNU) and the indirect-acting DMBA, suggesting the action of CLA was independent of carcinogen activation. 

Smith IA, Seybold PG. Substituent effects in chemical carcinogens Methyl derivatives of the benzacridines. J Hetero Chem 1979 16 421-5. 

Chronic administration of 20 pi cayenne extract (2.5 mg/ml capsaicin) to the cheek pouch of hamsters induced shrunken eyeballs and closing of the eyelids in 23% of the animals. This effect was not observed in hamsters that received a single application of the potent carcinogen methyl(acetoxymethyl) nitrosamine prior to repeated treatment with the cayenne extract (Agrawal et al. 1985). 

DNA treated with carcinogenic methylating agents on a strong cation-97... 

Chloromethylation can be efficiently effected using chloromethyl methyl ether, in the presence of Lewis acids. However, due to its carcinogenic nature, extreme care should be exercised in its use (46). Alternatively, paraformaldehyde—HCl/ZnCl2 can be used as the chloromethylating agent. 

P-Hydroxy acids lose water, especially in the presence of an acid catalyst, to give a,P-unsaturated acids, and frequendy P,y-unsaturated acids. P-Hydroxy acids do not form lactones readily because of the difficulty of four-membered ring formation. The simplest P-lactone, P-propiolactone, can be made from ketene and formaldehyde in the presence of methyl borate but not from P-hydroxypropionic acid. P-Propiolactone [57-57-8] is a usehil intermediate for organic synthesis but caution should be exercised when handling this lactone because it is a known carcinogen. 

Among the aromatics, it was found that 4-nitroquinoline N-oxide [56-57-5] is a powerful carcinogen producing malignant tumors when painted on the skin of mice (80). It was further estabUshed that the 2-methyl, 2-ethyl, and 6-chloro derivatives of 4-nitro quinoline oxide are also carcinogens (81). 

CH3OCH2CI, i-Pr2NEt, 0 , 1 h 25°, 8 h, 86% yield. This is the most commonly employed procedure for introduction of the MOM group. The reagent chloromethyl methyl ether is reported to be carcinogenic. 

H2NCON(NO)Me, KOH, DME, H2O, 0°, 75% yield. This method generates diazomethane in situ. A -Methyl-A -nitrosourea is a proven carcinogen. 

CH3OCH2OCH3, Zn/BrCH2C02Et, 0° CH3COCI, 0-20°, 2 h, 75-85%. A number of methoxymethyl esters were prepared by this method, which avoids the use of the carcinogen chloromethyl methyl ether. 

Zn, (CH30)2CH2, BrCH2C02Et, 80-82% yield. Formation of the meth-oxymethyl thioether with dimethoxymethane avoids the use of the carcinogen chloromethyl methyl ether. The reaction forms an intermediate zinc thiolate, which then forms the monothioacetal. 

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." ... 

Carboiimide-polystyrene, 95, 99 Carbonyl compounds, 36 Carcinogens, OSHA list of, 128 Carveol [2-Cyclohexen-l-ol, 2-methyl-5-(1-methylethenyl)-], 106 Carveol acetate [2-Cyclohexene-l-ol, 2-... 

N-Nitroso-N-methyl-N -nitroguanidine, diazomethane from, 41, 10 Nitrosomethylurethane, warning because a carcinogen, 43, 86 o-Nitrotoluene, condensation with ethyl oxalate, 43,40... 

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