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Biomedical subjects

E B Sansone

Publications and source records attributed to E B Sansone.

At least 19 recordsLinked to original sources

Photolytic destruction and polymeric resin decontamination of aqueous solutions of pharmaceuticals.

Amoxicillin, ampicillin, bleomycin, carmustine, cephalothin, dacarbazine, lomustine, metronidazole, norethindrone, streptozocin, sulfamethoxazole, and verapamil were completely degraded in solution, without the production of mutagenic residues, by photolysis using a medium-pressure mercury lamp in an all-quartz apparatus. A stream of air was passed through the solution and for amoxicillin, ampicillin, bleomycin, lomustine, metronidazole, and norethindrone it was necessary to add hydrogen peroxide. Dilute aqueous solutions of ampicillin, bleomycin, carmustine, cephalothin, lomustine, norethindrone, streptozocin, trimethoprim, and verapamil can be decontaminated using polymeric Amberlite resins.

Animals↗

Safe disposal of diisopropyl fluorophosphate (DFP).

Diisopropyl fluorophosphate (DFP), a volatile highly toxic enzyme inhibitor, in buffer (pH 3, pH 5, pH 7, pH 9, pH 11, Hank's, Dulbecco's, PBS, TBE, and HEPES) or water (10 mM), in DMF solution (200 mM), and bulk quantities can be degraded by adding 1M NaOH. The DFP was completely degraded, as determined by enzymatic assay, and the final reaction mixtures were not mutagenic.

Buffers↗

Degradation and disposal of some enzyme inhibitors. Scientific note.

Five enzyme inhibitors (phenylmethylsulfonyl fluoride, 4-amidinophenylmethanesulfonyl fluoride, 4-(2-aminoethyl)benzenesulfonyl fluoride, N alpha-p-tosyl-L-lysine chloromethyl ketone, and N-tosyl-L-phenylalanine chloromethyl ketone) in buffer, DMSO, or stock solutions were completely degraded by adding 1M NaOH and the final reaction mixtures were not mutagenic. The stability of these compounds decreased as the pH increased.

Chromatography, High Pressure Liquid↗

Oxidation of 1,1-dimethylhydrazine (UDMH) in aqueous solution with air and hydrogen peroxide.

The degradation of 1,1-dimethylhydrazine (UDMH), a component of some rocket fuels, was investigated using atmospheric oxygen and hydrogen peroxide. The reactions were carried out in the presence and absence of copper catalysis and at varying pH. Reactions were also carried out in the presence of hydrazine, a constituent, along with UDMH, of the rocket fuel Aerozine-50. In the presence of copper, UDMH was degraded by air passed through the solution; the efficiency of degradation increased as the pH increased but the carcinogen N-nitrosodimethylamine (NDMA) was formed at neutral and alkaline pH. Oxidation was not seen in the absence of copper. Production of NDMA occurred even at copper concentrations of < 1 ppm. Oxidation of UDMH with hydrogen peroxide also gave rise to NDMA. When copper was absent degradation of UDMH did not occur at acid pH but when copper was present some degradation occurred at all pH levels investigated. The production of NDMA occurred mostly at neutral and alkaline pH. In general, higher concentrations of hydrogen peroxide and copper favored the production of NDMA. Dimethylamine, methanol, formaldehyde dimethylhydrazone, formaldehyde hydrazone, and tetramethyltetrazene were also produced. The last three compounds were tested and found to be mutagenic.

Copper↗

Potassium permanganate can be used for degrading hazardous compounds.

Solutions of potassium permanganate in 3 M sulfuric acid, 1 M sodium hydroxide solution, and water can be used to degrade hazardous compounds. Excess oxidant can be removed by using sodium metabisulfite. Manganese, a carcinogen and mutagen, can be removed from the final reaction mixtures by making these mixtures strongly basic. Aqueous dilution causes the soluble potassium sulfate to dissolve while still allowing the insoluble manganese compounds to be removed by filtration and so reduces the weight of precipitate. In all cases the amount of manganese left in the filtrates was less than 2 ppm and the reaction mixtures were nonmutagenic. When ethanol was used as a test compound, degradation was much more rapid when the solvent was 3 M sulfuric acid or 1 M sodium hydroxide solution than when the solvent was water. However, the variation of the rate of reaction with pH depends on the nature of the substrate. Thus the effectiveness of the various methods may vary for other substrates. Potassium permanganate in sulfuric acid was used to degrade four polycyclic heterocyclic hydrocarbons. Destruction was greater than 99.9% and the final reaction mixtures contained no more than 0.5 ppm manganese and were not mutagenic. By modifying the work-up procedures to remove manganese from the final reaction mixture, procedures previously developed for degrading hazardous compounds can still be employed.

Chemical Phenomena↗

Removal of biological stains from aqueous solution using a flow-through decontamination procedure.

Chromatography columns filled with Amberlite XAD-16 were used to decontaminate, using a continuous flow-through procedure, aqueous solutions of the following biological stains: acridine orange, alcian blue 8GX, alizarin red S, azure A, azure B, brilliant blue G, brilliant blue R, Congo red, cresyl violet acetate, crystal violet, eosin B, eosin Y, erythrosin B, ethidium bromide, Giemsa stain, Janus green B, methylene blue, neutral red, nigrosin, orcein, propidium iodide, rose Bengal, safranine O, toluidine blue O, and trypan blue. Adsorption was most efficient for stains of lower molecular weight (< 600). Adsorption of stain increased as the flow rate decreased; column diameter had little effect on adsorption. Adsorption of stain was greatest when finely ground resin was used, but if the resin particles were too small, column clogging occurred. Limited grinding of the resin gave increased adsorption while retaining good flow characteristics. Amberlite XAD-16 saturated with methylene blue was regenerated to its initial adsorption capacity by passing methanol through the column. The technique described provides an economical, rapid means of removing stains from aqueous solution.

Animals↗

Reduced blood clearance and increased urinary excretion of N-nitrosodimethylamine in patas monkeys exposed to ethanol or isopropyl alcohol.

Low concentrations of N-nitrosodimethylamine are metabolized in rodent and human liver by cytochrome P450IIE1, an activity competitively inhibitable by ethanol. In rodents coadministration of ethanol with N-nitrosodimethylamine results in increased tumorigenicity in extrahepatic organs, probably as a result of reduced hepatic clearance. To test this concept in a primate, the effects of ethanol cotreatment on the pharmacokinetics of N-nitrosodimethylamine were measured in male patas monkeys. Ethanol, 1.2 g/kg given p.o. before i.v. N-nitrosodimethylamine (1 mg/kg) or concurrently with an intragastric dose resulted in a 10-50-fold increase in the area under the blood concentration versus time curves and a 4-13-fold increase in mean residence times for N-nitrosodimethylamine. Isopropyl alcohol, 3.2 g/kg 24 h before N-nitrosodimethylamine, also increased these parameters 7-10-fold; this effect was associated with persistence of isopropyl alcohol and its metabolic product acetone, both IIE1 inhibitors, in the blood. While no N-nitrosodimethylamine was detected in expired air, trace amounts were found in urine. Ethanol and isopropyl alcohol pretreatment increased the maximum urinary N-nitrosodimethylamine concentration 15-50-fold and the percentage of the dose excreted in the urine by 100-800-fold. Thus ethanol and isopropyl alcohol greatly increase systemic exposure of extrahepatic organs to N-nitrosodimethylamine in a primate.

1-Propanol↗

Aerial oxidation of hydrazines to nitrosamines.

When 1,1-dimethylhydrazine and N-aminopiperidine were deliberately exposed to air substantial amounts of the corresponding carcinogenic nitrosamines were formed. Unoxidized samples of 1,1-dimethylhydrazine were not mutagenic while oxidized samples (which contained much higher levels of nitrosamines) were mutagenic. Both unoxidized and oxidized samples of N-aminopiperidine were mutagenic.

1,2-Dimethylhydrazine↗

Validated methods for degrading hazardous chemicals: some halogenated compounds.

Two techniques were investigated for degrading a number of halogenated compounds of commercial and research importance. Reductive dehalogenation with nickel-aluminum alloy in potassium hydroxide solution was used to degrade iodomethane, chloroacetic acid, trichloroacetic acid, 2-chloroethanol, 2-bromoethanol, 2-chloroethylamine, 2-bromoethylamine, 1-bromobutane, 1-iodobutane, 2-bromobutane, 2-iodobutane, 2-bromo-2-methylpropane, 2-iodo-2-methylpropane, 3-chloropyridine, fluorobenzene, chlorobenzene, bromobenzene, iodobenzene, 4-fluoroaniline, 2-chloroaniline, 3-chloroaniline, 4-chloroaniline, 4-fluoronitrobenzene, 2-chloronitrobenzene, 3-chloronitrobenzene, 4-chloronitrobenzene, benzyl chloride, benzyl bromide, alpha,alpha-dichlorotoluene, and 3-aminobenzotrifluoride. The products were generally those obtained by replacing the halogen with hydrogen although concomitant reduction of the other groups was also observed. Bibenzyl was produced during the reduction of benzyl chloride, benzyl bromide, and alpha,alpha-dichlorotoluene. Refluxing with ethanolic potassium hydroxide was used to degrade iodomethane, chloroacetic acid, 2-fluoroethanol, 2-chloroethanol, 2-bromoethanol, 1-chlorobutane, 1-bromobutane, 1-iodobutane, 2-bromobutane, 2-iodobutane, 2-bromo-2-methylpropane, 2-iodo-2-methylpropane, benzyl chloride, benzyl bromide, 1-bromononane, 1-chlorodecane, and 1-bromodecane. The products were the corresponding ethyl ethers. 2-Methylaziridine was cleaved with nickel-aluminum alloy in potassium hydroxide solution to a mixture of isopropylamine and n-propylamine. In all cases, the compounds were completely degraded and only nonmutagenic reaction mixtures were produced.

Hazardous Substances↗

Decontamination of aqueous solutions of biological stains.

Aqueous solutions of a number of biological stains were completely decontaminated to the limit of detection using Amberlite resins. Amberlite XAD-16 was the most generally applicable resin but Amberlite XAD-2, Amberlite XAD-4, and Amberlite XAD-7 could be used to decontaminate some solutions. Solutions of acridine orange, alcian blue 8GX, alizarin red S, azure A, azure B, Congo red, cresyl violet acetate, crystal violet, eosin B, erythrosin B, ethidium bromide, Janus green B, methylene blue, neutral red, nigrosin, orcein, propidium iodide, rose Bengal, safranine O, toluidine blue O, and trypan blue could be completely decontaminated to the limit of detection and solutions of eosin Y and Giemsa stain were decontaminated to very low levels (less than 0.02 ppm) using Amberlite XAD-16. Reaction times varied from 10 min to 18 hr. Up to 500 ml of a 100 micrograms/ml solution could be decontaminated per gram of Amberlite XAD-16. Fourteen of the 23 stains tested were found to be mutagenic to Salmonella typhimurium. None of the completely decontaminated solutions were found to be mutagenic.

Acrylic Resins↗

Potential occupational exposure associated with parenteral administration of N-nitrosodiethylamine to Macaca mulatta: evidence of post-injection release to the atmosphere.

In order to assess the exposure of workers administering N-nitrosodiethylamine (NDEA) parenterally to Macaca mulatta, air samples were drawn through Thermosorb/N cartridges. Samples were analysed by gas chromatography-thermal energy analysis; the limit of detection was 0.02 micrograms/m3. Significant amounts of NDEA were found in those samples taken in the animal holding room. The NDEA recovered may be accounted for by its expiration by the animals (the contribution from excreta and leakage from the injection site is probably minor). On the basis of the total amount of NDEA administered (840 mg during the first experiment and 250 mg in the second) and the rate at which the animal holding room was ventilated, and assuming that the samples were representative, we estimate that 0.9% of the NDEA administered was released to the atmosphere in 5 h in the first experiment and that 2.7% and 0.8% were released in the first and second 24-h periods, respectively, in the second experiment. It should be noted that this potential source of exposure may be significant not only for workers but also for control or other experimental animals housed in the same room.

Air Pollutants, Occupational↗

Degradation and disposal of some antineoplastic drugs.

Bulk quantities and pharmaceutical preparations of the antineoplastic drugs carmustine (BCNU), lomustine (CCNU), chlorozotocin, N-[2-chloroethyl]-N'-[2,6-dioxo-3-piperidinyl]-N-nitrosourea (PCNU), methyl CCNU, mechlorethamine, melphalan, chlorambucil, cyclophosphamide, ifosfamide, uracil mustard, and spiromustine may be degraded using nickel-aluminum alloy in KOH solution. The drugs are completely destroyed and only nonmutagenic reaction mixtures are produced. Destruction of cyclophosphamide in tablets requires refluxing in HCl before the nickel-aluminum alloy reduction. Streptozotocin, chlorambucil, and mechlorethamine may be degraded using an excess of saturated sodium bicarbonate solution. The nitrosourea drugs BCNU, CCNU, chlorozotocin, PCNU, methyl CCNU, and streptozotocin were also degraded using hydrogen bromide in glacial acetic acid. The drugs were completely destroyed but some of the reaction mixtures were mutagenic and the products were found to be, in some instances, the corresponding mutagenic, denitrosated compounds.

Acetates↗

Decontamination and disposal of nitrosoureas and related N-nitroso compounds.

An improved procedure for chemically decontaminating residues of nitrosoureas and related N-nitroso compounds ("nitrosamides") commonly used in the cancer research laboratory is proposed. Treatment of accumulated wastes with aluminum:nickel alloy powder while progressively increasing the basicity of the medium consistently led to at least 99.98% destruction of each nitrosamide tested. Hazardous diazoalkanes were never detected in yields of greater than 0.1%. The mutagenicity of the completed reaction mixtures was never more than 3 times background except when the N-nitroso compound contained a 2-chloroethyl group. In most cases, the completeness of reaction could be determined chromatographically, not only to demonstrate the disappearance of the starting N-nitroso compound, but also to follow production of identifiable products in sufficient abundance to account for the starting material destroyed; none of the organic products observed was mutagenic in any of the four tester strains used. The procedure described herein proved reliable in two checker laboratories besides our own when applied to mixtures of seven N-nitroso compounds: N-methyl-N-nitroso-p-toluene-sulfonamide; N-methyl-N-nitrosourethane; N-methyl-N-nitrosourea; N-methyl-N'-nitro-N-nitrosoguanidine; N-ethyl-N-nitrosourea; N-ethyl-N'-nitro-N-nitrosoguanidine; and N-ethyl-N-nitrosourethane. All of the other procedures investigated for destruction of nitrosamides, including the widely used approach of dissolving the nitrosamides in alkali, were associated with important disadvantages.

Chemical Phenomena↗

Dealing with spills of hazardous chemicals: some nitrosamides.

Spills of N-methyl-N-nitrosourea, N-ethyl-N-nitrosourea, N-methyl-N-nitrosourethane and N-ethyl-N-nitrosourethane can be decontaminated using a mixture of ethanol and saturated aqueous sodium bicarbonate solution. Spills of N-methyl-N-nitroso-p-toluenesulphonamide, N-methyl-N'-nitro-N-nitrosoguanidine and N-ethyl-N'-nitro-N-nitrosoguanidine can be decontaminated with a solution of sulphamic acid in 2 M-hydrochloric acid. In all cases the nitrosamides are completely destroyed and only non-mutagenic reaction mixtures are produced.

Chromatography, High Pressure Liquid↗