Abstract  BIOSIS COPYRIGHT: BIOL ABS. RRM MEETING

Abstract  Individuals may be exposed to solvent mixtures and fuel either at work or home, through air, water and food contamination. Few studies have addressed the genotoxic effects of mixed, low-level exposure to fuel and solvent. This was an optimally designed study where each subject was sampled prior to exposure and after 15 and 30 weeks while exposed, in a repeated measures design with each subject serving as his own control. Fifty men aged between 18 and 50, working on aircraft equipment operation and maintenance at a military installation were included. Eight unexposed men were concurrently sampled. Sister-chromatid exchanges (SCE) and micronuclei (MN) frequency were measured in conjunction with air sampling and expired breath analysis for jet fuel (JP-4), 1,1,1-trichloroethane, methyl ethyl ketone, xylenes, toluene and methylene chloride. Exposure levels measured by industrial hygiene were very low (all means <6 p.p.m.), <10% of the OSHA standard. Expired breath levels were also low, <25 p.p.b. A small but statistically significant increase in the frequency of SCE occurred after 30 weeks of exposure for sheet metal workers (P = 0.003) and for painters (P = 0.05). The MN frequency in the sheet metal workers initially showed a statistically significant increase, but by 30 weeks had decreased. Cigarette smoking, alcohol and caffeine use were not associated with changes from baseline for either MN or SCE. Smokers, however, had significantly higher values of SCEs at baseline than did nonsmokers. In summary, these findings suggest that small increases in SCEs in particular, may serve as a sensitive biologic indicator of low level hydrocarbon exposure in as much as statistically significant changes occurred in the highest exposed groups but not in the low or no exposure groups. Chance occurrence or exposures to other occupational or non-occupational agents cannot be eliminated as a cause of the study findings.

Abstract  Slurry bioremediation testing was conducted on waste sludges from petrochemical production. The study concludes that the apparent mechanism for remediation of the waste involves an initial dissolution of the waste constituents into the aqueous phase followed by actual biodegradation. The test reactor most successful in the solubilization and dispersal of waste constituents and possibly most effective in reducing waste sludge mass during treatment is the reactor with the lowest waste sludge-to-microorganism ratio.

Abstract  The association between indoor exposure to volatile organic, compounds (VOC), prevalence of allergic sensitization and cytokine secretion profile of peripheral T cells was studied in 3 year old children of the LARS study (Leipzig Allergy Risk Children Study) to investigate the role of VOC exposure as a risk factor for the development of atopic disease. Indoor VOC exposure was measured over a period of 4 weeks in infants' bedrooms using a passive sampling system. Specific IgE antibodies to food, indoor and outdoor allergens were measured by the Pharmacia CAP system and correlated to VOC exposure (n= 120). In addition, cytokine producing peripheral T cells (interleukin(IL)-4, inrerferon(IFN)-y) were measured in a subgroup of 28 children by means of intracellular cytokine staining. For the first time we were able to show that exposure to alkanes (C6, C9, ClO) and aromatic compounds (toluene, o-xylene, m + p-xylene, 2-, 3- and 4-ethyl-toluene, chlorobenzene) may contribute to the risk of allergic sensitization to the food allergens milk and egg white (Odds ratios between 5.7 and 11.2). Moreover, significantly reduced numbers of CD3 +/ CD8 + peripheral T cells were found in children exposed to alkanes (C9-C13), naphthalene and chlorobenzene. Exposure to benzene, ethylbenzene and chlorobenzene was associated with higher percentages of IL-4 producing CD3+T cells. Both an increase in IL-4 producing type 2 T cells and a reduction of IFN-y producing type 1 T cells may contribute to a type 2 skewed memory in response to allergens. Therefore, we suggest exposure to VOCs in association with allergic sensitization to be mediated by a T cell polarization toward the type 2 phenotype.

Abstract  The volatile organic compounds of forest air (Kälbelescheuer, Southern Black Forest) and, for comparison, suburban air (Tübingen) were qualitatively analyzed by gas chromatographic and mass spectrometric methods. 94 Individual compounds were identified, 6 of them belonged to biogenic monoterpenes (α-pinene, Δ3-carene, myrcene, limonene, eucalyptol, camphene). While the monoterpenes were enriched in forest air, a similar collection of the pollution products was observed in both locations. Predominant substances were aromatic compounds (toluene, ethylbenzene, benzene, xylenes, ethyltoluenes, pseudocumene and naphthalene) which can be regarded as constituents of vehicle exhaust fumes and incineration processes. Other important substances in forest air were various solvents, of which butyl acetate, isobutyl acetate, tetrachloroethylene and trichloroethylene, butanol-1, and several ketones were prominent species.

Abstract  HEEP COPYRIGHT: BIOL ABS. An analytical method is described in which trace quantities of organic materials in air are adsorbed on a porous polymer of high temperature stability. The trapped substances are subsequently heat desorbed and transferred to a short precolumn which is kept at subambient temperature. Separation is effected by gas chromatography with efficient capillary columns. Identification of the separated compounds is established by gas chromatography-mass spectrometry. Profiles established over a period of approximately 18 mo. are remarkably constant for samples collected in urban environments. Once a profile is qualitatively made, quantitative results can be obtained for a large number of substances with a high degree of accuracy. The absolute concentrations of substances vary within wide limits; weather conditions being the prime factor. The overall picture does not suggest large compositional variations within samples taken from heavily industrialized areas and urban environments. Several hundred substances can be recognized, ranging from C5 to C16. Almost 100 compounds, mostly alkanes and substituted aromatic hydrocarbons were identified. Other substances present in trace quantities are aldehydes and chlorinated hydrocarbons. Volatiles, eluting before benzene, can be determined only qualitatively, since displacement occurs by less volatile substances with increasing sample size. The new method has significant advantages over existing procedures such as ease of handling, versatility, simplicity and economy.

Abstract  Toxic Combustion By-Products Consortium of Companies; the National Science Foundation; U.S. Environmental Protection Agency; University of California. Gas phase concentrations of individual polycyclic aromatic hydrocarbons (PAHs) were measured in real time in combustion products from a co-flow diffusion flame using laser photoionization (LP) time-of-flight mass spectrometry (TOF/MS). In particular, a naphthalene detection sensitivity of 4 parts per billion (ppb) was demonstrated. The use of calibration mixtures with argon indicated the feasibility of naphthalene detection at about 45 parts per trillion (ppt) at a signal-to-noise (S/N) ratio of 20. This suggests the possibility of low-ppt level detection at a S/N of 1. The novelty of the system is the use of a heated sampling probe and a continuously purged, heated-pulse valve that was positioned close to the ionization zone, thereby allowing the generation of photoions in the high-density region of the sample jet, where concentrations of PAH are high. Because the system developed allows for the real time detection of select species, it represents a useful tool in continuous emissions monitoring (CEM) for environmental compliance as well as direct process control.

Abstract  The concentrations of 86 vapor-phase, semivolatile, and particle-phase aromatic compounds are measured during a severe Los Angeles photochemical smog episode. The measurements are part of a larger experiment designed to acquire a nearly complete description of organic air pollutants for use in verifying the predictions of photochemical airshed models for organics. Compound classes formed by grouping all aromatic hydrocarbons having the same number of aromatic rings show progressively declining concentrations as the number of aromatic rings is increased. Examination of the partitioning of the polycyclic aromatic hydrocarbons (PAH) between the gas and particle phases shows the transition from purely gaseous PAH at low molecular weight to purely particle-phase PAH at high molecular weight, with compounds such as the mutagencyclopenta[cd]pyrene present about equally in both gas and particle phases. Primary aromatics, both the vapor-phase monoaromatics and the PAH, show evidence of depletion by atmospheric chemical reaction over downwind transport with apparent depletion rates generally increasing as the degree of substitution of the aromatic rings increases. In contrast, many nitro-PAH and some oxy-PAH accumulate during downwind transport. consistent with their likely formation as products of atmospheric chemical reactions. Historical data generally show that aromatics concentrations declined substantially from the 1950s to the 1980s, but that concentrations measured during the present1993 experiment are very similar to those measured during the mid-1980s including the August episode of the 1987SCAQS experiment The present experiment provides baseline data prior to the introduction of California Phase II reformulated gasoline that can be used in future years to examine the effect of the reduced aromatic content of that Phase II gasoline.

Abstract  Canadian Department of National Defence.

Abstract  Atmospheric contamination of spacecraft cabins has been a toxicological concern since this country began its efforts in manned space flight (1). Procedures have been developed and utilized for determining the identities and quantities of contaminant gases present in the cabin. Methods have also been developed for assessing and controlling the trace gas contaminant buildup within the closed cabins. Although more than 100 contaminant gases have been detected in the Shuttle cabin, for the most part the concentrations of these gases have been maintained below a toxicity hazard level.

Abstract  The effects of polybrominated biphenyls (PBB), beta-naphthoflavone (6051872) (NF), and phenobarbital (50066) on the activity of arylhydrocarbon-hydroxylase (AHH) in liver and kidney were studied in male C57BL/6J-mice (C57-mice) and male DBA/2J-mice (DBA-mice). The effect of these compounds on chloroform (67663) induced hepatotoxicity and nephrotoxicity was also examined. NF was fed to C57-mice and DBA-mice at a concentration of 1 gram per kilogram of diet for 5 days before exposure to chloroform. Control animals received regular diet. Another group of mice was fed 0 or 100 parts per million PBB for 28 days before chloroform exposure. Phenobarbital was injected in another group at the rate of 80 milligrams per kilogram body weight intraperitoneally (ip) on 3 consecutive days. Twenty four hours after the final injection, mice were exposed to chloroform. After pretreatment with NF, PBB, or phenobarbital, mice received 0.025, 0.05, 0.1, or 0.25 milliliter of chloroform per kilogram body weight ip in peanut oil. Controls were injected with peanut oil alone. All animals were killed after 24 hours. Blood, liver, and kidneys were removed from each animal and used to assay for serum glutamic-pyruvic-transaminase (SGPT) activity, blood urea nitrogen (BUN), and the ability to accumulate organic cations as tetraethylammonium (66400) (TEA), and organic anions as para-aminohippurate (61789) (PAH). A dose related increase in SGPT activity was observed in previously untreated mice following exposure to chloroform. Administration of chloroform to phenobarbital or PBB treated C57-mice or DBA-mice caused a marked increase in SGPT activity. After a single dose of chloroform, accumulation of PAH and TEA was depressed in a dose related manner. Dietary PBB enhanced this depression in C57-mice only. A dose dependent increase in BUN was observed after exposure to chloroform. Only PBB treatment of C57-mice enhanced this response. AHH activity was stimulated in liver after treatment of both strains with phenobarbital and PBB. The authors conclude that the nephrotoxic metabolite of chloroform is generated in the kidneys.

Abstract  The overall goal of this project is the development of a new methodology for translating advances in molecular level understanding of toxicological responses into a predictive tool for dose response in whole animals and humans exposed to single compounds or mixtures of compounds. The methodology incorporates a mechanistic cellular level model into a PBPK (physiologically based pharmacokinetic) model which simultaneously guides the development of an in vitro cell culture analog (CCA) to the PBPK. Where the PBPK specifies an organ, (e.g., liver) the in vitro or CCA system contains a compartment with the appropriate cell or cell population (e.g., hepatocytes for the liver). The CCA has significant advantages over other in vitro systems and PBPK systems used independently for evaluating metabolic responses to drugs or potentially toxic chemicals where the exchange of metabolites between organs is likely to be important. The CCA system is superior to a PBPK because an a priori description of complete metabolism is not required and secondary, unexpected interactions can be detected. The CCA system, unlike other in vitro systems, gives a dynamic response that realistically simulates in vivo interactions between organs. Furthermore, the CCA allows dosing on the same basis as animal tests (e.g., milligrams per kilogram of body mass equivalent). Because the construction of a CCA is guided by a PBPK, this approach allows extrapolation to low doses and across species, including extrapolation to humans. We have constructed a prototype system and have conducted proof-of-concept experiments using naphthalene as a test chemical. These experiments clearly demonstrate the ability to generate a reactive metabolite in one compartment and detect its effects (on LDH release and glutathione depletion) in a second compartment. However, this prototype device would be expensive to replicate and requires nearly constant supervision from a trained investigator. For this concept to replace animals an inexpensive, self-regulating device is needed. An initial design to accomplish this goal is described as well as the corresponding model using naphthalene as a test compound. (c) 1996 John Wiley & Sons, Inc.

Abstract  Sodium Polynaphthalenesulfonate (SPNS) and Sodium Naphthalenesulfonate (SNS) are sodium salts of naphthalene sulfonic acid. SPNS was used as an emulsion stabilizer, surfactant—hydrotrope, and/or surfactant—suspending agent at concentrations between 0.1% and 0.4%, in a wide range of products, including one lipstick. SNS is described as a surfactant—hydrotrope; no current uses were reported, but information was provided indicating that use concentrations would be typically below 2%. SNS is manufactured by reacting naphthalene with sulfuric acid to produce a sulfonic acid, which is then reacted with sodium hydroxide to produce the final product. The polymer form uses the sulfonic acid intermediate in a reaction with formaldehyde and water under conditions of heat and pressure to form the polymer sulfonic acid form, to which sodium hydroxide is added to make the final SPNS. The residue level of formaldehyde was 0.09%. Only around 1% of SNS in a 1-mg/ml solution applied to porcine skin penetrated the skin after 24 h, a similar amount was found noncovalently bound to the skin, and the concentration of material applied to the surface of the skin was largely unchanged. Both chemicals were not toxic in acute oral or dermal studies. In a subchronic oral toxicity study in rats, the effects noted were increases in urinary sugar in females and urine protein concentrations in males. Although undiluted SPNS was not a significant eye irritant in rabbits, undiluted SNS was a moderate eye irritant in rabbits. At 2%, SNS was a minimal eye irritant in rabbits. Undiluted SNS was at most a mild irritant in Guinea pigs, and was nonirritating at 20% and 2%. In a delayed contact hypersensitivity test in Guinea pigs, 30% SNS used in the induction phase and in the challenge phase produced no reactions. In a Guinea pig maximization test, 1% SNS used with Freund's complete adjuvant (FCA) injected in the initial sensitization, 50% SNS applied topically in the second sensitization, and up to 30% SNS applied topically in the challenge phase did not produce any irritation or sensitization. Bothingredients were negative in Ames mutagenesis assays. In clinical studies, SNS was neither an irritant (tested up to 2%), cumulative irritant (tested up to 1%), nor a sensitizer (tested up to 1%). The Panel considered the low penetration in concert with the low concentrations of use of theseingredients and the absence of significant overall toxicity and the limited negative genotoxicity findings sufficient to support a conclusion that SNS and SPNS are safe as used in cosmetic formulations intended to be applied to the skin. Use of SPNS in a lipstick formulation, was not considered to be different from application to the skin in that the barrier properties of the skin do not apply when theseingredients may contact mucous membranes or may beingested. Accordingly, the Panel concluded that the available data are insufficient to support the safety of SNS and SPNS in cosmetic formulations that may contact mucous membranes or beingested. The additional data needed to make a safety assessment for these uses include dermal reproductive and developmental toxicity data and one genotoxicity assay in a mammalian system, and if that study is positive, then a 2-year dermal carcinogenicity study using National Toxicology Program (NTP) methods may be needed.

Abstract  BACKGROUND: Arsenite oxidase from Alcaligenes faecalis NCIB 8687 is a molybdenum/iron protein involved in the detoxification of arsenic. It is induced by the presence of AsO(2-) (arsenite) and functions to oxidize As(III)O(2-), which binds to essential sulfhydryl groups of proteins and dithiols, to the relatively less toxic As(V)O(4)(3-) (arsenate) prior to methylation.

RESULTS: Using a combination of multiple isomorphous replacement with anomalous scattering (MIRAS) and multiple-wavelength anomalous dispersion (MAD) methods, the crystal structure of arsenite oxidase was determined to 2.03 A in a P2(1) crystal form with two molecules in the asymmetric unit and to 1.64 A in a P1 crystal form with four molecules in the asymmetric unit. Arsenite oxidase consists of a large subunit of 825 residues and a small subunit of approximately 134 residues. The large subunit contains a Mo site, consisting of a Mo atom bound to two pterin cofactors, and a [3Fe-4S] cluster. The small subunit contains a Rieske-type [2Fe-2S] site.

CONCLUSIONS: The large subunit of arsenite oxidase is similar to other members of the dimethylsulfoxide (DMSO) reductase family of molybdenum enzymes, particularly the dissimilatory periplasmic nitrate reductase from Desulfovibrio desulfuricans, but is unique in having no covalent bond between the polypeptide and the Mo atom. The small subunit has no counterpart among known Mo protein structures but is homologous to the Rieske [2Fe-2S] protein domain of the cytochrome bc(1) and cytochrome b(6)f complexes and to the Rieske domain of naphthalene 1,2-dioxygenase.

Abstract  In recent years, different approaches have been attempted to study the microbial transformation of micropollutants in soil and aquifer systems, namely (i) field studies; (ii) investigations on a laboratory scale in which field situations are imitated, by using percolation columns, saturated flow aquifer columns or microcosms; and (iii) with pure and mixed cultures of microorganisms. Using alkylated and halogenated compounds as examples, this paper qualitatively and quantitatively compares field data with laboratory results. Pure cultures studies are discussed with respect tot he findings in laboratory soil systems. Some data are also presented about the survival of a pure culture which degrades halogenated aromatic compounds in systems mimicking natural conditions.

Abstract  A broad range of pollutants such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated hydrocarbons (PCHs), polynitrohydrocarbons (PNHs), polychlorinated biphenyls (PCBs) and organochlorine (OCs) insecticides were simultaneously analyzed in spiked soil, water or plasma samples by using gas chromatography-mass spectrometry (GC-MS). Water and plasma samples containing the pollutants were extracted by a solid-phase extraction (SPE) method using florisil columns. The soil samples, fortified with the toxicants, were extracted with water, methanol or dichloromethane (DCM). The water extract was processed by the SPE method. The methanol and DCM samples were dried, dissolved in acetonitrile and subjected to the SPE extraction. The extracted samples were analyzed by GC-MS programmed to monitor selected ions. The deuterium labelled compounds were used as the internal standards. The chromatographic profile of total ions indicated complete separation of some compounds such as

Abstract  HEEP COPYRIGHT: BIOL ABS. Sediment samples from the western portion of Lake Ontario were analyzed for chlorinated organic compounds using gas chromatographic mass spectrometry. Electron impact and negative chemical ionization mass spectrometry were employed. Many chlorinated compounds previously found to be leaking into the Niagara River from waste disposal sites in the city of Niagara Falls were identified in the sediments of Lake Ontario. Two unique chlorofluorinated compounds were found in the lake's sediment, showing that stable compounds introduced into the Niagara River accumulated to detectable levels 100 km away in Lake Ontario. Chlorinated styrenes and several highly chlorinated polycyclic aromatic hydrocarbons were also found. Their exact origin was uncertain.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. RRM IDIOPATHIC LIVER DISEASE NEOPLASM CELLULAR ALTERATION FOCI MEGALOCYTIC HEPATOSIS

Abstract  A simple, selective and sensitive high performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of naproxen and its main degradation products such as 1-(6-methoxy-2-naphthyl) ethanol (MNE), 2-methoxy-6-ethyl naphthalene (MEN) and 2-acetyl-6-methoxy naphthalene (AMN). The separation of these compounds was achieved on porous graphitic carbon (PGC) column using tetrahydrofuran-methanol as the mobile phase, and the effluent from the column was monitored at 272 nm. At a flow rate of 1 ml min(-1), the retention time of the last eluting compound was less than 10 min. Correlation coefficient for calibration curves in the ranges 2-25 microg ml(-1) for all compounds studied were greater than 0.999. The sensitivity of detection is 0.05 microg l(-1) for naproxen, MNE and MEN and 0.20 microg ml(-1) for AMN. The reproducibility of the peak area of these compounds using isocratic elution were quite high, and the standard deviations (S.D.) were below 2% (n=5). The reproducibility of retention times of these compounds was within 1% (n=5). The proposed liquid chromatographic method was successfully applied to the analysis of commercially available naproxen sodium (NS) dosage forms with recoveries of 98.8-102%. A comparative study shows that the selectivity of these compounds on PGC column was different to that obtained with octadecyl silica (ODS) columns.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. As part of NOAA's National Status and Trends Mussel Watch Program, oysters were sampled along the Gulf of Mexico coast each winter from 1986 to 1992 and analyzed for trace metal, polynuclear aromatic hydrocarbon (PAH), and pesticide body burden. We identified contaminant variables for which large-scale climate processes played an important role in establishing the interannual variation in body burden by examining cases where body burdens rose or fell more or less in unison over broad geographic body burden of organic contaminants had a much stronger regional component. All but two of the 11 organic contaminants had scales of concordancy of 200 km or greater and six exceeded 400 km. Concordancy was strongest either in the southern, northwestern, or northcentral Gulf, depending upon the contaminant. For all contaminants, bays tended to vary independently in the northeastern Gulf. For three contaminants, total chlordanes, dieldrin and Cd, regional concordancy may originate from a widespre the similarity in interannual variation between south Texas and southern Florida; (3) ENSO-related climate responses in the Gulf follow the southwestern/northeastern trend that would establish the northwestern Gulf focus in concordancy so prominent in many of the contaminants; and (4) deviations in yearly mean body burden from the Gulf-wide mean track the Southern Oscillation Index in some cases.

Abstract  The TLV-TWA 10 ppm (52 mg/m3) and TLV-STEL of 15 ppm (79 mg/m3) are recommended for occupational exposure to naphthalene. These values are intended to minimize the potential for eye and respiratory tract irritation and ocular toxicity that can include cataract formation, optical neuritis, lens opacities, and retinal degeneration. Other adverse effects may include headache, loss of appetite, nausea, and blood dyscrasia, such as hemolytic anemia and hemoglobinuria. Systemic poisoning following dermal contact and absorption of naphthalene warrants a Skin notation. Based on the very limited evidence of carcinogenicity in rodents, pulmonary adenomas in female mice but not in the male mice or in rats of either sex, exposed by inhalation for 2 years, an A4, Not Classifiable as a Human Carcinogen, notation is assigned. Sufficient data were not available to recommend a SEN notation.

Abstract  In foundry industry, the millions tones of spent sands weresuccessfully used as landfill materials for many years. Butthis practise is becoming a problem as the disposal costsincrease rapidly and legislation gets tighter. However, thereis not much experimental data to describe their chemicalcharacteristics, especially for the leaching behaviour andtoxic compounds of the different kinds of spent sands. Thisarticle aims to present the analysis of organic compounds andleaching characteristics of the spent foundry sands. Based onthe evaluation of the chemistry of spent sands, the contentsof the selected 32 polyaronmatic hydrocarbon (PAH) and otherorganic compounds in 11 different spent foundry sands wereanalysed. The concentrations of As, Ba, Cd, Cr, Pb, Hg, Se,Ag, Cu and Zn in 11 different spent foundry sands were alsomeasured with regard to leaching characteristics. ThepH-dependent leaching characteristics of chromium were furtherinvestigated. It was found that all spent foundry sandscontain PAHs in which naphthalene is about 30%. The PAHs ingreen sands are much higher than those in chemical binderspent sands, even though phenolic/ester sands have higher PAHsthan furan/acid and silicate sands. The leaching metals arevery low in all spent foundry sands. The leached Cr increaseswith increasing pH of the eluted solution, which can be usedin practise for shortening the leaching time of the spentfoundry sands.

Abstract  The mechanism of intramolecular triplet-triplet (T-T) energy transfer and subsequent reaction in N,O-diacylhydroxylamines was investigated using the model compounds N-(1-naphthoyl)-N-phenyl-O-(benzoyl-substitu benzoyl)hydroxylamines (NPB) with self-sensitization abilities. An examination of the UV absorption and phosphorescence behavior as well as of energy-minimized conformations of these relatively flexible model compounds established that T-T energy transfer from the benzophenone chromophore to the naphthoyl chromophore occurs in a nearly unit efficiency exhibiting only phosphorescence derived from the latter chromophore in both methanol-ethanol (1:1 v/v) and 2-chlorobutane at 77 K and is more likely to proceed by a ''through-space'' mechanism than by a ''through-bond'' mechanism. The self-sensitized photolysis of NPB with 366 nm light in methanol at room temperature was found to give the fragmentation products, N-phenyl-1-naphthalenecarboxamide (PNA), benzophenone (BP), and benzoyl-substituted benzoic acids (BBA), whereas no BBA was detected in the photolysis in 1,2-dichloroethane and acetonitrile. The finding that the reaction of NPB is efficiently quenched by trans-stilbene according to the Stern-Volmer equation in both methanol and 1,2-dichloroethane indicates that all the products come from the first excited triplet state of the naphthoyl chromophore. On the other hand, the enhanced hydrogen bonding ability of the medium resulted in an increase in the quantum yield for the formation of BBA (Phi(BBA)) accompanied by a decrease in Phi(BA) holding the magnitude of Phi(BBA) + Phi(BA) nearly constant. But neither Phi(PNA) nor the quantum yield for the disappearance of NPB was subject to such a hydrogen-bonding effect. This intriguing result was explained in terms of a mechanism in which the N-O bond cleavage in triplet NPB gives a vibrationally excited tripler radical pair whose relaxation is very slow compared to decarboxylation of the caged benzoyl-substituted benzoyloxyl radical in 1,2-dichloroethane. Solvation of this vibrationally hot radical pair through hydrogen bonding substantially promotes its relaxation eventually affording BBA.

Abstract  Primary cultures of rat hepatocytes were used in a screen in vitro for agents which protect against the toxic effects of the hepatoxin microcystin-LR. Exposure of cells to microcystin-LR, a cyclic heptapeptide produced by blue-green algae, resulted in clustering of hepatocytes within 15 min of addition. This initial response was followed by disruption of cellular function (measured by a protein synthesis assay) and eventual loss of membrane integrity, resulting in leakage of cytosolic enzymes (measured by LDH release). The antibiotic rifampicin was effective in reducing LDH release and preventing cell clustering at concentrations as low as 2.0 mum. Cytochalasins provided some protection at 10 mum. However, microscopy revealed disruption of hepatocytes in the presence of cytochalasins alone, at or above this concentration. Bile acids, cholic acid and deoxycholate were protective at higher concentrations (0.1 mm), but when given alone caused some leakage of cytosolic enzymes. Di-naphthalene dyes, trypan blue and trypan red, had no detrimental effects on hepatocytes and showed some protection at 20 mum. Hepatic uptake of tritium-labelled microcystin-LR was suppressed by bile acids and rifampicin, providing further evidence that blocking or competing with bile acid uptake also prevents microcystin-LR association with, and toxicity in, isolated hepatocytes. Although all drugs tested worked to varying degrees, rifampicin was most effective in providing protection of hepatocytes from toxin at lower concentrations while having no detrimental effects on the cells when added alone.