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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

To assess the effectiveness of directional air flow and the influence of a disturbance such as opening and closing doors on the airborne transfer of contamination, the concentration of a tracer gas (ethane) was measured at various locations in a model consisting of four adjacent rooms between two corridors. Each room had two doors opening into the corridor. Ethane concentrations were measured as a function of pressure drop (0, +/- 0.005, +/- 0.01, and +/- 0.02 in. H2O) and time of door opening and closing (3, 6, and 9 sec). A hydrocarbon analyzer was used to measure the concentration of ethane. Contamination was transferred in the direction of decreasing static pressure and was proportional to the magnitude of the pressure differential. Opening and closing a door led to exchange of air between the spaces separated by the door regardless of the sign of the pressure differential that existed when the door was closed. The extent to which a space was contaminated by opening and closing a door was directly proportional to the time the door was open. Contaminant concentration differences between adjacent spaces were greatest when the connecting door was kept closed and the pressure differential was least. The findings indicate that modification of current practices may lead to improved protection of personnel, animals, and experiments from contamination.

A simple one-step procedure for chemically degrading nitrosamine residues generated in the research laboratory is described. Treatment with aluminum-nickel alloy powder and aqueous alkali rapidly reduced all 11 nitrosamines studied to the corresponding amines. Hydrazines were produced as transitory intermediates, but these potential carcinogens were also easily reduced under the conditions employed, and no products except amines, ammonia, and, in some cases, alcohols were detected in the final reaction mixtures. Reduction proceeded smoothly in every other solvent system tested, except that reactions in acetone or dichloromethane solution were sometimes slow, incomplete, and/or led to unidentified products; therefore, we cannot recommend the procedure for use in these solvents. Otherwise, the method was efficient, reliable, and inexpensive and has been recommended as one of the preferred means of degrading potentially carcinogenic nitrosamines to innocuous products. Details of its application to some decontamination and disposal problems commonly encountered in the research laboratory are provided. Data illustrating this procedure's advantages over six other reducing systems are also presented.

The effect of moisture on the ability of a granular activated carbon to adsorb chloroform vapor from a flowing airstream was studied under three test conditions: (1) chloroform and water vapor were introduced concurrently into a dry carbon bed; (2) dry chloroform was introduced into a humidified carbon bed; (3) humidified chloroform was introduced into a carbon bed at the same relative humidity. The criterion for bed performance was the time when the downstream chloroform concentration was 1% of that in the inlet stream. Chloroform concentration was essentially constant at 108 +/- 2 micrograms/cm3; relative humidities (RH) varied from 0 to 97%. No RH effect on the adsorption of chloroform by the carbon was observed in test (1); tests (2) and (3) showed monotonic decreases in chloroform adsorption for RH greater than 40%. These results indicated that, for a dry carbon bed, the 1% breakthrough time for chloroform adsorbed from atmospheres of RH from 13% to 95% was essentially the same as that when RH = 0%. For humidified carbon beds, no change in 1% breakthrough time for chloroform was observed until RH was greater than 40%.

N-Nitrosomorpholine (NMOR) and N-nitrosodiethanolamine (NDELA) were painted on the clipped upper dorsal skin of male F344 rats. NDELA was applied undiluted, dissolved in water, and dissolved in cutting oil; NMOR was applied dissolved in water and in ethyl acetate. Aqueous solutions of the nitrosamines were used for gavage. Rats were housed individually. Blood and urine samples were analyzed for nitrosamines by chromatography combined with a Thermal Energy Analyzer. Maximum penetration of NMOR was approximately equal to 34% 2 hours after application of 5 mg to the skin or by gavage; less than 1% appeared in the urine in 24 hours. Skin painting with NDELA in water (20 mg/100 microliters) and in cutting oil (25 mg/25 microliters) yielded small concentrations of NDELA (always < 25 micrograms/ml blood). When 50 mg of undiluted NDELA was painted on the skin, 130 to 220 micrograms/ml of blood was recovered after 1 hour. Administering 50 mg NDELA in water by gavage yielded similar blood concentrations. Maximum skin penetration observed with NDELA was 78% 1 hour after application of 50 mg. From 20 to 30% of the NDELA applied undiluted and by gavage appeared in the urine in 24 hours. Although animals and humans differ, skin exposure to NMOR or NDELA represents a risk due to absorption.

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.

N-Nitrosomorpholine (NMOR) and N-nitrosodiethanolamine (NDELA) were applied to the clipped dorsal skin (about 3.5 X 3.5 cm) of adult male Fischer 344 rats. NDELA was applied undiluted, dissolved in water and dissolved in cutting oil; NMOR was applied dissolved in water and in ethyl acetate. To compare the extent of absorption through the skin with that from the stomach, aqueous solutions of the nitrosamines were used for gavage. Blood and urine samples were analysed for nitrosamines, using GC-TEA or HPLC-TEA. Maximum skin penetration observed with NMOR was 56%, following application of 5 mg, whereas a similar proportion of the dose was regularly present after gavage of 5 mg. Less than 1% was recovered from the urine. Skin painting of NDELA in water (20 mg in 100 microliter) and in cutting oil (25 mg in 25 microliter) yielded small concentrations of NDELA in the blood; less than 25 mg/l in all cases. However, when 50 mg NDELA was painted on the skin undiluted, from 130 to 220 mg/l of blood were recovered after one hour. fifty mg NDELA in water yielded similar blood concentrations when administered by gavage. From 20 to 30% of the NDELA applied undiluted and by gavage were recovered in the urine. It is concluded that, although there are differences between animals, exposure to NMOR or NDELA represents a risk due to absorption through the skin.

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.

As part of the joint International Agency for Research on Cancer-National Cancer Institute program for the evaluation and development of methods for the degradation of chemical carcinogens, four oxidative techniques for the degradation of hydrazines were investigated. The oxidizing agents used were as follows: sodium hypochlorite, calcium hypochlorite, potassium iodate, and potassium permanganate in sulfuric acid. In each case, at least 99% of the hydrazine initially present was destroyed; however, the potential usefulness of these methods was compromised by the formation (in some reaction mixtures) of carcinogenic N-nitroso compounds and/or unknown mutagenic species. Oxidative degradation of hydrazines is recommended only for the decontamination of glassware and for the treatment of spills, for which reductive degradation methods are not suitable.

To assess the potential risks to personnel preparing feed for carcinogen bioassay research, a tracer was mixed with a meal diet to yield 10 kg batches of 100, 3,000 and 5,890 ppm. Wipe samples were obtained from horizontal and vertical surfaces, equipment and personnel before operations began, after they were completed, and following clean-up. Total and respirable suspended particulate matter samples were obtained. All operations led to contamination of clothing and equipment; cleaning did not remove all contamination. These results, obtained in a well controlled environment in which trained and well protected personnel were working, suggest that a higher level of process control may be required for adequate protection of personnel performing material handling operations with known or suspected carcinogens.

The permeability coefficient of benzene vapor in air was calculated from experimentally measured values of solubility coefficient and diffusion coefficient for natural rubber, nitrile, neoprene, natural rubber plus neoprene, butyl rubber, polyvinyl chloride and polyethylene membranes. The permeability coefficient for natural rubber at room temperature (approximately 23 degrees C) was 4.2 x 10(-10) cm2/sec when the concentration of benzene in air was 10 ppm. This means that a worker (1.8 m2 surface area) completely clothed in a 0.0254 cm (10 mil) natural rubber suit would be exposed via the skin to 0.3 microgram benzene in an 8-hour shift if the benzene concentration were 10 ppm. In the same time period and with the same benzene concentration the worker would inhale 1600 microgram benzene if his tidal volume were 700 cm3, his breathing rate were 15 min-1, and he was wearing a respiratory with a protection factor of 100. Permeability coefficients for other vapor-membrane systems available in the literature suggest that exposure to vapors penetrating protective garments are in general negligible when compared with inhalation exposures for low vapor concentrations.

Samples of laboratory gloves of various composition and thicknesses were used as barriers between 0.136 M solutions of nitrosamines (dimethyl-, ethylmethyl-, diethyl-8 n-butylmethyl-, di-n-propyl-, di-iso-propyl- and di-sec-butyl- in dichloromethane, acetone, ethanol and double-distilled, deionized water) and water. The concentration of permeated nitrosamine was measured periodically. Nearly all gloves tested were permeable to the nitrosamine solutions. The results indicate that: (1) gloves should not be assumed to provide full protection, (2) gloves should be discarded immeidately following overt contamination and (3) gloves should not be reused.

Cyanogen bromide in water and seven organic solvents and sodium cyanide in water may safely and efficiently (greater than 99.7%) be destroyed using sodium hydroxide (1 M) solution and commercially available sodium or calcium hypochlorite. Details are given of an analytical procedure which can be used to check the final reaction mixture for the presence of residual cyanogen bromide or cyanide.

It has been reported that dimethyl sulfate (DMS) can be degraded with sodium hydroxide solution (1 mol/L), sodium carbonate solution (1 mol/L), or ammonium hydroxide solution (1.5 mol/L). This has now been confirmed. Complete destruction of undiluted DMS or DMS in solvents miscible with water (methanol, ethanol, DMSO, DMF, acetone) or solvents partially miscible or immiscible with water (toluene, p-xylene, benzene, 1-pentanol, ethyl acetate, chloroform, carbon tetrachloride, acetonitrile) could be obtained using any of the above methods. Reaction times were 15 min after homogeneity was obtained for undiluted DMS, 15 min for solutions in methanol, ethanol, DMSO, and DMF, one hour for solutions in acetone, three hours for acetonitrile, and one day for the other solvents listed above. The final reaction mixtures were tested for mutagenicity, and when the solutions were not cytotoxic, no mutagenic response was obtained. DMS in solution was determined by a colorimetric method. The products of the reactions were found to be methanol when NaOH and Na2CO3 were used and methylamine, dimethylamine, trimethylamine, and methanol when ammonium hydroxide was used. The stability of DMS in various solvents was also determined.

The chemical degradation of five N-nitrosamides used widely for the experimental induction of cancer has been studied with the goal of identifying, and experimentally validating, reliable methods that can be recommended for the destruction of carcinogenic N-nitrosoureas and related compounds in laboratory wastes. Although data are not yet complete, preliminary evidence indicates that none of the five methods studied thus far is ideal for hazard-control purposes. Decomposition with 1 mol/L potassium hydroxide solution destroyed the N-nitrosamides, but generated diazoalkanes, which are carcinogenic, toxic and potentially explosive. Treatment with strong acid in the presence of sulfamic acid or iron filings completely decomposed all N-nitrosamides without forming diazoalkanes, but failed in the presence of solvents which were immiscible with water. Cleavage with hydrogen bromide in glacial acetic acid proceeded to a point of maximum degradation, following which gradual reformation of the N-nitrosamide was observed; this resynthesis could be avoided by carefully bubbling nitrogen through the reaction mixture, but degradation was slow or failed completely in the presence of hydroxylic solvents. Permanganate oxidation was effective in sulfuric acid solution, but was incomplete when an alcohol or dimethyl sulfoxide was present. Salmonella typhimurium tester strains TA1535, TA1530 and TA100, which detect base-pair substitutions in DNA, detected mutagenic degradation products in each of the destruction methods, with the exception of the hydrobromic acid/acetic acid procedure.

Estimates of occupational exposure to chemical carcinogens in biomedical research based on environmental monitoring data, efficiency of containment devices, and accident data suggest that workers may be exposed to a few tenths of a microgram of these carcinogens per work day. Environmental exposure to carcinogenic polycyclic aromatic hydrocarbons and N-nitroso compounds exceeds one microgram per day. Because occupational exposure to chemical carcinogens in the laboratory can be readily controlled and because environmental exposure appears to be greater than the occupational exposure that does occur, the relative risk of occupational exposure does not seem to constitute a major health problem.

Proper design of fermentation facilities and equipment modification can control the risks associated with largescale production and purification of microbially produced cytotoxic agents and oncogenic viruses. The primary biohazard risks to operators and the environment are generation of aerosols and accidental spills. Fermentation and recovery facilities can be constructed to contain these agents by installing fermentation equipment within a HEPA-filter-exhausted biological barrier. Within this barrier system, large-scale processing that generates potentially hazaradous areosols (filtration, centrifugation of transformed cells or crystal slurries, and banding of viruses) should be isolated from other operations. Isolation of equipment is often required, with provision for both chemical and biological decontamination of process wastes. Failsafe fermentor over-pressure sensors, parallel exhaust gas filtration, welded transfer lines, and modified sampling systems for elimination of aerosols can be installed on most fermentation equipment. Aerosol and spill containment by proper equipment design, coupled with appropriate personnel protective equipment and medical monitoring, make possible safe production of experimental growth factors and viruses from large-scale culture of transformed mammalian cells and production of cytotoxic antitumor antibiotics.

Selected references on laboratory design, use of hoods, and the potential hazards of specific common laboratory procedures have been culled from the microbiological safety literature. It is suggested that this information may be usefully applied to work with chemical carcinogens.

Reductive destruction of dacarbazine, procarbazine hydrochloride, isoniazid, and iproniazid using nickel-aluminum alloy in basic solution is described. Solutions of dacarbazine 10 mg/mL were prepared by adding dacarbazine 100 mg, citric acid 100 mg, and mannitol 50 mg to 10 mL of water. Aqueous solutions of procarbazine hydrochloride 10 mg/mL were prepared from commercially available capsules, and aqueous solutions of isoniazid 10 mg/mL and iproniazid 5 mg/mL were prepared from powdered drug. Reductive destruction of drugs was accomplished by mixing each solution with an equal volume of 1 M potassium hydroxide solution and adding 1 g of nickel-aluminum alloy for each 20 mL of basified solution. The resulting mixtures were stirred for 20 hours (96 hours for iproniazid) and analyzed by high-performance liquid chromatography and gas chromatography for the presence of residual drug and degradation products. Dacarbazine solutions were also subjected to destruction by photolysis and by oxidation using potassium permanganate in sulfuric acid, and the results were compared with those obtained by reductive destruction. All reaction mixtures were tested for mutagenicity in Salmonella strains. All drugs subjected to reductive destruction were completely degraded to the limits of detection of the assay and produced only nonmutagenic reaction mixtures. The only acceptable results for dacarbazine were obtained by the reductive destruction method. Reduction of dacarbazine, procarbazine hydrochloride, isoniazid, and iproniazid with nickel-aluminum alloy in dilute base appears to be a good method for the destruction of these toxic compounds.

Scraping TLC plates in a hood leads to contamination of the hood, equipment, worker, and the environment. The magnitude of contamination is presented as a fraction of the chemical delivered, and the effects of plate thickness, dryness, and adsorbent material are examined. Frequent clean-up and decontamination are recommended.

Formaldehyde used for the disinfection of a laminar-flow biological safety cabinet was oxidatively degraded by using a catalyst. This technique reduced the formaldehyde concentration in the cabinet from about 5,000 to about 45 mg/m3 in 8 h. This technique should prove useful in other applications.