ABSTRACT
SAFETYNET is a European Thematic Network on Process Safety funded under the Brite-Euram Programme. The aim of this network is to reduce the time delay between research results and their practical use in industry in order to stimulate further development and adoption of technologies in the field of process safety. This is mainly done in areas related both to the safe operation of process plants and production facilities and to the prevention of accidents.
Subject(s)
Accident Prevention , Diffusion of Innovation , Hazardous Substances , Safety , Europe , Explosions , Humans , InternetABSTRACT
Reversed-phase HPLC conditions for the separation of 4-(2-pyridyl)-1-piperazinethiocarboxylic acid 2-[1-(pyridyl)-ethylidene]hydrazide dihydrochloride (NSC 348977, I), a synthetic thiosemicarbazone with antitumor activity, from mouse plasma have been investigated. Following denaturization and precipitation of the spiked plasma with acetonitrile, an aliquot of the supernatant was diluted with aqueous buffer and subjected to analysis on a Nova-Pak C18 column (150 x 3.9 mm I.D.) by isocratic elution with 50 mM aqueous potassium phosphate buffer (pH 6.8, containing 1 mM EDTA)-acetonitrile (60:40, v/v). The column effluent was monitored for UV absorption at 310 nm. Problems identified in the sample preparation and separation of I include sensitivity to oxygen, light, non-neutral pH and the presence of metal ions. These factors were seen to adversely influence sample recovery, and attempts were made to find conditions which minimize their effects.
Subject(s)
Antineoplastic Agents/isolation & purification , Chromatography, High Pressure Liquid/methods , Hydrazones/analysis , Piperazines/analysis , Animals , MiceABSTRACT
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.
Subject(s)
Isoflurophate/chemistry , Sodium Hydroxide/chemistry , Waste Disposal, Fluid/standards , Buffers , Chymotrypsin/chemistry , Hydrolysis , Isoflurophate/toxicity , Mutagenicity Tests , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Solvents/chemistry , Spectrophotometry, Ultraviolet , Tyrosine/analogs & derivatives , Tyrosine/metabolismABSTRACT
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.
Subject(s)
Dimethylhydrazines/chemistry , Hydrogen Peroxide , Oxygen , Copper , Dimethylhydrazines/pharmacology , Mutagenicity Tests , Oxidation-Reduction , Salmonella typhimurium/drug effectsABSTRACT
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.
Subject(s)
Hazardous Waste , Pharmaceutical Preparations/radiation effects , Photolysis , Resins, Plant/chemistry , Animals , Chromatography, High Pressure Liquid , Hydrogen Peroxide , In Vitro Techniques , Medical Waste Disposal , Mutagens/chemistry , Mutagens/toxicity , Rats , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Solutions , Spectrophotometry, Ultraviolet , Ultraviolet Rays , WaterABSTRACT
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.
Subject(s)
Enzyme Inhibitors/chemistry , Chromatography, High Pressure Liquid , Drug Stability , Hydrogen-Ion Concentration , Mutagens , Phenylmethylsulfonyl Fluoride/chemistry , Sodium Hydroxide/pharmacology , Tosyl Compounds/chemistry , Tosyllysine Chloromethyl Ketone/chemistry , Tosylphenylalanyl Chloromethyl Ketone/chemistryABSTRACT
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.
Subject(s)
Hazardous Substances , Hazardous Waste , Potassium Permanganate , Sodium Hydroxide , Sulfuric Acids , Chemical Phenomena , Chemistry, Physical , Drug Combinations , Hydrogen-Ion Concentration , Manganese/chemistry , Polycyclic Compounds/chemistry , Refuse DisposalABSTRACT
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.
Subject(s)
Coloring Agents/chemistry , Animals , Chromatography, Ion Exchange , Coloring Agents/isolation & purification , Coloring Agents/toxicity , In Vitro Techniques , Ion Exchange Resins , Methylene Blue/chemistry , Mutagenicity Tests , Particle Size , Polymers , Rats , Resins, Plant , Solutions , Spectrometry, Fluorescence , Spectrophotometry, UltravioletSubject(s)
3,3'-Diaminobenzidine , Carcinogens , Hazardous Waste , Mutagens , Waste Disposal, Fluid/methods , 3,3'-Diaminobenzidine/chemistry , 3,3'-Diaminobenzidine/toxicity , Ascorbic Acid , Carcinogens/chemistry , Carcinogens/toxicity , Horseradish Peroxidase , Hydrogen Peroxide , Mutagens/chemistry , Mutagens/toxicity , Oxidation-Reduction , Potassium Permanganate , SafetyABSTRACT
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.
Subject(s)
Hazardous Substances/chemistry , Hydrocarbons, Halogenated/chemistry , Mutagenicity TestsABSTRACT
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.
Subject(s)
Coloring Agents , Hazardous Substances , Ion Exchange Resins , Staining and Labeling , Acrylic Resins , Coloring Agents/toxicity , Decontamination/methods , Mutagenicity Tests , Polymers , Polystyrenes , PolyvinylsABSTRACT
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.
Subject(s)
Dimethylhydrazines/chemistry , Hydrazines/chemistry , Mutagens/chemistry , Nitrosamines , Piperidines/chemistry , 1,2-Dimethylhydrazine , Animals , Biotransformation , Chromatography, Gas , Cricetinae , Dimethylhydrazines/pharmacology , Male , Mesocricetus , Microsomes, Liver/metabolism , Mutagenicity Tests , Oxidation-Reduction , Piperidines/pharmacology , Rats , Rats, Inbred Strains , Salmonella typhimurium/drug effectsABSTRACT
The behaviour of cows in cubicles was studied in two dairy herds which were under the same ownership and had similar buildings and management systems. One of the herds had an annual problem of lameness due to laminitis leading to solar ulceration in the replacement first lactation heifers. There were considerable behavioural differences between the cows in the two herds. In the problem herd the heifers and cows stood for significantly longer, more heifers were seen not to use the cubicles, and there were more examples of aberrant behaviour than in the other herd. Less straw was used for cubicle bedding in the problem herd and when the amount used was increased to one bale per 10 cows per day no new cases of laminitis and solar ulceration occurred in the heifers.
Subject(s)
Behavior, Animal , Cattle/physiology , Hoof and Claw , Housing, Animal , Lameness, Animal/etiology , Animals , Cattle Diseases/etiology , Female , Foot Diseases/etiology , Foot Diseases/veterinary , SyndromeABSTRACT
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.
Subject(s)
Antineoplastic Agents/analysis , Acetates , Aluminum , Animals , Antineoplastic Agents/toxicity , Bicarbonates , Chemical Phenomena , Chemistry , Chromatography, High Pressure Liquid , In Vitro Techniques , Magnetic Resonance Spectroscopy , Mechlorethamine/analysis , Mutagenicity Tests , Mutagens , Nickel , Nitrosourea Compounds/analysis , Nitrosourea Compounds/toxicity , Oxidation-Reduction , Rats , Salmonella/genetics , Sodium , Sodium Bicarbonate , ThiosulfatesABSTRACT
The metabolism and distribution of the parkinsonian syndrome inducing neurotoxin MPTP has been studied in non-human primates and mice housed in controlled environmental chambers. 14C6-MPTP was prepared and injected at concentrations normally employed for lesioning experiments (30 mg/kg in mice, 0.3 mg/kg in monkeys). All interior surfaces of the chambers which could be reached by animals or their excreta were contaminated with radiolabeled metabolites. Vapor born unmetabolized MPTP was negligible, although significant amounts of MPTP were found in the excreta of mice (less than or equal to 15% injected dose) and small amounts from rhesus monkeys (less than 2%). Procedures to minimize contact with animal fur, bedding and excreta should protect investigators working with MPTP over extended periods. Permanganate oxidation effectively detoxifies solutions of MPTP. MPTP, MPP+, common synthetic intermediates, and the products of MPTP's oxidation are not mutagenic as measured by a Salmonella-microsome assay.