Fugitive Emissions of Volatile Organic Compounds from a Tailings Pond in the Oil Sands Region of Alberta.

Tailings ponds in the oil sands (OS) region in Alberta, Canada, have been associated with fugitive emissions of volatile organic compounds (VOCs) and other pollutants to the atmosphere. However, the contribution of tailings ponds to the total fugitive emissions of VOCs from OS operations remains uncertain. To address this knowledge gap, a field study was conducted in the summer of 2017 at Suncor's Pond 2/3 to estimate emissions of a suite of pollutants including 68 VOCs using a combination of micrometeorological methods and measurements from a flux tower. The results indicate that in 2017, Pond 2/3 was an emission source of 3322 ± 727 tons of VOCs including alkanes, aromatics, and oxygenated and sulfur-containing organics. While the total VOC emissions were approximately a factor of 2 higher than those reported by Suncor, the individual VOC species emissions varied by up to a factor of 12. A chemical mass balance (CMB) receptor model was used to estimate the contribution of the tailings pond to VOC pollution events in a nearby First Nations and Metis community in Fort McKay. CMB results indicate that Suncor Pond 2/3 contributed up to 57% to the total mass of VOCs measured at Fort McKay, reinforcing the importance of accurate VOC emission estimation methods for tailings ponds.

Improving Insights on Air Pollutant Mixtures and Their Origins by Enhancing Local Monitoring in an Area of Intensive Resource Development.

An "event-based" approach to characterize complex air pollutant mixtures was applied in the Oil Sands region of northern Alberta, Canada. This approach was developed to better-inform source characterization and attribution of the air pollution in the Indigenous community of Fort McKay, within the context of the lived experience of residents. Principal component analysis was used to identify the characteristics of primary pollutant mixtures, which were related to hydrocarbon emissions, fossil fuel combustion, dust, and oxidized and reduced sulfur compounds. Concentration distributions of indicator compounds were used to isolate sustained air pollution "events". Diesel-powered vehicles operating in the mines were found to be an important source during NOx events. Industry-specific volatile organic compound (VOC) profiles were used in a chemical mass balance model for source apportionment, which revealed that nearby oil sands operations contribute to 86% of the total mass of nine VOC species (2-methylpentane, hexane, heptane, octane, benzene, toluene, m,p-xylene, o-xylene, and ethylbenzene) during VOC events. Analyses of the frequency distribution of air pollution events indicate that Fort McKay is regularly impacted by multiple mixtures simultaneously, underscoring the limitations of an exceedance-based approach relying on a small number of air quality standards as the only tool to assess risk.

Diol it up: The influence of NaCl on methylglyoxal surface adsorption and hydration state at the air-water interface.

Methylglyoxal (MG)-an atmospherically important α-dicarbonyl implicated in aqueous-phase secondary organic aerosol formation-is known to be surface-active. Due to the presence of carbonyl moieties, MG can hydrate to form geminal diols in solution. Recently, it has been shown that MG exists predominantly as a monohydrate at the neat air-water interface. However, inorganic aerosol constituents have the potential to "salt-out" MG to the interface, shift its hydration equilibria, and catalyze self- and cross-oligomerization reactions. Here, we study the influence of the non-reactive salt, sodium chloride (NaCl), on the MG's surface adsorption and hydration state using vibrational sum frequency spectroscopy. The presence of NaCl is found to enhance MG's surface activity but not to the extent that water is fully excluded from the interface. Perturbations in the interfacial water structure are attributed to shifts in MG's hydration equilibrium at higher ionic strengths. Evidence of surface-active MG oligomer species is presented, but such oligomers are not thought to contribute significantly to the interfacial population. This work builds on the published studies on MG in pure water and gives insight into the interface's perturbation by NaCl, which has important implications for understanding MG's atmospheric fate.

Model Behavior: Characterization of Hydroxyacetone at the Air-Water Interface Using Experimental and Computational Vibrational Sum Frequency Spectroscopy.

Small atmospheric aldehydes and ketones are known to play a significant role in the formation of secondary organic aerosols (SOA). However, many of them are difficult to experimentally isolate, as they tend to form hydration and oligomer species. Hydroxyacetone (HA) is unusual in this class as it contributes to SOA while existing predominantly in its unhydrated monomeric form. This allows HA to serve as a valuable model system for similar secondary organic carbonyls. In this paper the surface behavior of HA at the air-water interface has been investigated using vibrational sum frequency (VSF) spectroscopy and Wilhelmy plate surface tensiometry in combination with computational molecular dynamics simulations and density functional theory calculations. The experimental results demonstrate that HA has a high degree of surface activity and is ordered at the interface. Furthermore, oriented water is observed at the interface, even at high HA concentrations. Spectral features also reveal the presence of both cis and trans HA conformers at the interface, in differing orientations. Molecular dynamics results indicate conformer dependent shifts in HA orientation between the subsurface (∼5 Šdeep) and surface. Together, these results provide a picture of a highly dynamic, but statistically ordered, interface composed of multiple HA conformers with solvated water. These results have implications for HA's behavior in aqueous particles, which may affect its role in the atmosphere and SOA formation.

A pinch of salt is all it takes: chemistry at the frozen water surface.

Chemical interactions at the air-ice interface are of great importance to local atmospheric chemistry but also to the concentrations of pollutants deposited onto natural snow and ice. However, the study of such processes has been hampered by the lack of general, surface-specific probes. Even seemingly basic chemical properties, such as the local concentration of chemical compounds, or the pH at the interface, have required the application of assumptions about solute distributions in frozen media. The measurements that have been reported have tended for the most part to focus on entire ice or snow samples, rather than strictly the frozen interface with the atmosphere. We have used glancing-angle laser spectroscopy to interrogate the air-ice interface; this has yielded several insights into the chemical interactions there. The linear fluorescence and Raman spectra thus measured have the advantage of easy interpretability; careful experimentation can limit their probe depth to that which is relevant to atmospheric heterogeneous processes. We have used these techniques to show that the environment at the interface between air and freshwater ice surfaces is distinct from that at the interface between air and liquid water. Acids such as HCl that adsorb to ice surfaces from the gas phase result in significantly different pH responses than those at liquid water surfaces. Further, the solvation of aromatic species is suppressed at freshwater ice surfaces compared with that at liquid water surfaces, leading to extensive self-association of aromatics at ice surfaces. Photolysis kinetics of these species are much faster than at liquid water surfaces; this can sometimes (but not always) be explained by red shifts in the absorption spectra of self-associated aromatics increasing the extent to which solar radiation is absorbed. The environment presented by frozen saltwater surfaces, in contrast, appears to be reasonably well-described by liquid water. The extent of hydrogen bonding and the solvation of adsorbed species are similar at liquid water surfaces and at frozen saltwater surfaces. Adsorbed acids and bases evoke similar pH responses at frozen saltwater ice surfaces and liquid water surfaces, and photochemical kinetics of at least some aromatic compounds at frozen saltwater ice surfaces are well-described by kinetics in liquid water. These differences are not observed in experiments that interrogate the entire ice sample (i.e., that do not distinguish between processes occurring in liquid regions within bulk ice and those at the air-ice interface). Our work has shown that in general, the chemistry occurring at salty frozen interfaces is well described as being cold aqueous chemistry, whereas that seen at the pure ice interface is not. These findings have significant implications for heterogeneous atmospheric processes in ice-covered environments.

A means to an interface: investigating monoethanolamine behavior at an aqueous surface.

The use of amine scrubbers to trap carbon dioxide from flue gas streams is one of the most promising avenues for atmospheric carbon dioxide reduction. However, modifications are necessary to efficiently scale these scrubbers for use in fossil fuel plants. Current advances in tailoring amines for CO2 capture involve improvements of bulk kinetic and thermodynamic parameters, with little consideration to surface chemistry and behavior. Aqueous alkanolamine solutions, such as monoethanolamine (MEA), are currently highly favored sorbents in CO2 post-combustion capture. Although numerous studies have explored MEA-CO2 chemistry at the macroscopic scale, few have investigated the role of the interface in the gas adsorption process. Additionally, as these amines become more industrially ubiquitous, their presence on and the need to understand their behavior at atmospheric and environmental surfaces will increase. This study investigates the surface behavior of monoethanolamine at the vapor/water interface, with particular focus on MEA's surface orientation and footprint. Using vibrational sum frequency spectroscopy, surface tensiometry, and computational techniques, MEA is found to adopt a constrained gauche interfacial conformation with its methylene backbone oriented toward the vapor phase and its functional groups solvated in the bulk solution. Computational and experimental analysis agree well, giving a complete picture with vibrational mode assignments and surface orientation of MEA. These findings can assist in the tailoring of amine structures or to facilitate improvements in engineering design to exploit favorable surface chemistry, as well as to serve as a starting point toward understanding aqueous amine surface behavior relevant to environmental systems.

Hydration, Orientation, and Conformation of Methylglyoxal at the Air-Water Interface.

Aqueous-phase processing of methylglyoxal (MG) has been suggested to constitute an important source of secondary organic aerosol (SOA). The uptake of MG to aqueous particles is higher than expected because its carbonyl moieties can hydrate to form geminal diols, as well as because MG and its hydration products can undergo aldol condensation reactions to form larger oligomers in solution. MG is known to be surface active, but an improved description of its surface behavior is crucial to understanding MG-SOA formation. These studies investigate MG adsorption, focusing on its hydration state at the air-water interface, using a combined experimental and theoretical approach that involves vibrational sum frequency spectroscopy, molecular dynamics simulations, and density functional theory calculations. Together, the experimental and theoretical data show that MG exists predominantly in a singly hydrated state (diol) at the interface, with a diol-tetrol ratio at the surface higher than that for the bulk. In addition to exhibiting a strong surface activity, we find that MG significantly perturbs the water structure at the interface. The results have implications for understanding the atmospheric fate of methylglyoxal.

Total organic carbon measurements reveal major gaps in petrochemical emissions reporting.

Anthropogenic organic carbon emissions reporting has been largely limited to subsets of chemically speciated volatile organic compounds. However, new aircraft-based measurements revealed total gas-phase organic carbon emissions that exceed oil sands industry-reported values by 1900% to over 6300%, the bulk of which was due to unaccounted-for intermediate-volatility and semivolatile organic compounds. Measured facility-wide emissions represented approximately 1% of extracted petroleum, resulting in total organic carbon emissions equivalent to that from all other sources across Canada combined. These real-world observations demonstrate total organic carbon measurements as a means of detecting unknown or underreported carbon emissions regardless of chemical features. Because reporting gaps may include hazardous, reactive, or secondary air pollutants, fully constraining the impact of anthropogenic emissions necessitates routine, comprehensive total organic carbon monitoring as an inherent check on mass closure.

Aircraft and satellite observations reveal historical gap between top-down and bottom-up CO2 emissions from Canadian oil sands.

Measurement-based estimates of greenhouse gas (GHG) emissions from complex industrial operations are challenging to obtain, but serve as an important, independent check on inventory-reported emissions. Such top-down estimates, while important for oil and gas (O&G) emissions globally, are particularly relevant for Canadian oil sands (OS) operations, which represent the largest O&G contributor to national GHG emissions. We present a multifaceted top-down approach for estimating CO2 emissions that combines aircraft-measured CO2/NOx emission ratios (ERs) with inventory and satellite-derived NOx emissions from Ozone Monitoring Instrument (OMI) and TROPOspheric Ozone Monitoring Instrument (TROPOMI) and apply it to the Athabasca Oil Sands Region (AOSR) in Alberta, Canada. Historical CO2 emissions were reconstructed for the surface mining region, and average top-down estimates were found to be >65% higher than facility-reported, bottom-up estimates from 2005 to 2020. Higher top-down vs. bottom-up emissions estimates were also consistently obtained for individual surface mining and in situ extraction facilities, which represent a growing category of energy-intensive OS operations. Although the magnitudes of the measured discrepancies vary between facilities, they combine such that the observed reporting gap for total AOSR emissions is ≥(31 ± 8) Mt for each of the last 3 years (2018-2020). This potential underestimation is large and broadly highlights the importance of continued review and refinement of bottom-up estimation methodologies and inventories. The ER method herein offers a powerful approach for upscaling measured facility-level or regional fossil fuel CO2 emissions by taking advantage of satellite remote sensing observations.

Glancing-angle Raman spectroscopic probe for reaction kinetics at water surfaces.

We report glancing-angle Raman spectra acquired at the surface of aqueous dimethyl sulfoxide solutions and demonstrate that this technique can be used to measure the surface concentration of solutes. The presence of some solute molecules at the surface suppresses the intensity of the OH-stretching band of water there. We used this phenomenon to study the interfacial reaction of gas-phase ozone with aqueous NaX solutions (X = Br, I) by monitoring the decrease in intensity of the OH-stretching band of water over time. UV-VIS analysis of the product solutions indicates that X(3)(-), formed from X(2) evolved in the ozonation reaction, is the species most likely responsible for the decrease in OH-stretching intensity at the surface. The dependence of the rate of OH-Raman signal loss at the water surface on the bulk halide concentration is well described by a Langmuir-Hinshelwood kinetic model. The Langmuir-Hinshelwood parameters indicated that iodide has a approximately 50 times greater propensity for the surface compared to bromide.

Fullerene C60 nanomaterial induced oxidative imbalance in gonads of the freshwater fish, Anabas testudineus (Bloch, 1792).

The engineered carbon nanomaterial, fullerene C60, with unique physicochemical properties, released into the aquatic environment is known to formulate high risk factor for the aquatic life. The present study was aimed to investigate fullerene C60 induced oxidative imbalance in ovary and testis of the freshwater fish, Anabas testudineus. The median lethal concentration (96 h-LC50) of fullerene C60 in Anabas testudineus was 50 mg/ L, and fish exposed to two sublethal concentrations i.e., 5 mg/ L and 10 mg/ L (one-tenth and one-fifth of LC50) for short-term (24, 48, 72 and 96 h) and long-term (7, 15, 30 and 60 d) durations. The antioxidant parameters such as the activities of superoxide dismutase (SOD), catalase, glutathione reductase, glutathione peroxidase, the levels of hydrogen peroxide generation and lipid peroxidation were analyzed along with histopathological alterations in gonadal tissues. Both sublethal concentrations of fullerene C60 caused significant (P < 0.05) decrease in the activities of antioxidant enzymes, whereas the levels of hydrogen peroxide generation and lipid peroxidation increased significantly (P < 0.05) in gonads. Fullerene exposure significantly (P < 0.05) increased the mucous deposition with significant (P < 0.05) reduction in the weights of gonads and gonado-somatic index. The histopathological analysis showed prominent alterations in testis and ovary of treated fishes when compared to the control groups. After 60 d of sublethal exposure of fullerene C60, fish were left in the toxicant-free water for another 60 d, in which the changes in the activities of the gonadal antioxidant enzymes and histological alterations were not completely recovered. Hence, from the present study, it was illustrated that fullerene C60 caused oxidative imbalance in the gonads, which may possibly affect the reproductive potential of the fish, Anabas testudineus.

In-Vitro Subtype-Specific Modulation of HIV-1 Trans-Activator of Transcription (Tat) on RNAi Silencing Suppressor Activity and Cell Death.

Human immunodeficiency virus (HIV) is a global health concern affecting millions of individuals with a wide variety of currently circulating subtypes affecting various regions of the globe. HIV relies on multiple regulatory proteins to modify the host cell to promote replication in infected T cells, and these regulatory proteins can have subtle phenotypic differences between subtypes. One of these proteins, HIV-1 Trans-Activator of Transcription (Tat), is capable of RNA interference (RNAi) Silencing Suppressor (RSS) activity and induction of cell death in T cells. However, the subtype-specific RSS activity and induction of cell death have not been explored. We investigated the ability of Tat subtypes and variants to induce RSS activity and cell death. TatB, from HIV-1 subtype B, was found to be a potent RSS activator by 40% whereas TatC, from HIV-1 subtype C, showed 15% RSS activity while subtype TatC variants exhibited varying levels. A high level of cell death (50-53%) was induced by subtype TatB when compared to subtype TatC (25-28%) and varying levels were observed with subtype TatC variants. These differential activities could be due to variations in the functional domains of Tat. These observations further our understanding of subtype-specific augmentation of Tat in HIV-1 replication and pathogenesis.

Genetic Polymorphisms in the Open Reading Frame of the CCR5 gene From HIV-1 Seronegative and Seropositive Individuals From National Capital Regions of India.

C-C chemokine receptor type 5 (CCR5) serves as a co-receptor for Human immunodeficiency virus (HIV), enabling the virus to enter human CD4 T cells and macrophages. In the absence of CCR5, HIV strains that require CCR5 (R5 or M-tropic HIV) fail to successfully initiate infection. Various natural mutations of the CCR5 gene have been reported to interfere with the HIV-CCR5 interaction, which influences the rate of AIDS progression. Genetic characterization of the CCR5 gene in individuals from the National Capital Regions (NCRs) of India revealed several natural point mutations in HIV seropositive/negative individuals. Furthermore, we identified novel frame-shifts mutations in the CCR5 gene in HIV seronegative individuals, as well as the well reported CCR5Δ32 mutation. Additionally, we observed a number of mutations present only in HIV seropositive individuals. This is the first report to describe the genetic variations of CCR5 in individuals from the NCRs of India and demonstrates the utility of investigating understudied populations to identify novel CCR5 polymorphisms.

Extensive first-principles molecular dynamics study on Li encapsulation into C60 and its experimental confirmation.

The aim of increasing the production ratio of endohedral C60 by impinging foreign atoms against C60 is a crucial matter of the science and technology employed towards industrialization of these functional building block materials. Among these endohedral fullerenes, Li+@C60 exhibits a wide variety of physical and chemical phenomena and has the potential to be applicable in areas spanning the medical field to photovoltaics. However, currently, Li+@C60 can be experimentally produced with only ∼1% ratio using the plasma shower method with a 30 eV kinetic energy provided to the impinging Li+ ion. From extensive first-principles molecular dynamics simulations, it is found that the maximum production ratio of Li+@C60 per hit is increased to about 5.1% (5.3%) when a Li+ ion impinges vertically on a six-membered ring of C60 with 30 eV (40 eV) kinetic energy, although many C60 molecules are damaged during this collision. On the contrary, when it impinges vertically on a six-membered ring with 10 eV kinetic energy, the production ratio remains at 1.3%, but the C60 molecules are not damaged at all. On the other hand, when the C60 is randomly oriented, the production ratio reduces to about 3.7 ± 0.5%, 3.3 ± 0.5%, and 0.2 ± 0.03% for 30 eV, 40 eV, and 10 eV kinetic energy, respectively. Based on these observations we demonstrate the possibility of increasing the production ratio by fixing six-membered rings atop C60 using the Cu(111) substrate or UV light irradiation. In order to assess the ideal experimental production ratio, the 7Li solid NMR spectroscopy measurement is also performed for the multilayer randomly oriented C60 sample irradiated by Li+ using the plasma shower method combined with inductively coupled plasma atomic emission spectroscopy (ICP-AES). Time-of-flight mass spectroscopy measurements are also performed to cross check whether Li+@C60 molecules are produced in the sample. The resulting experimental estimate, 4% for 30 eV incident kinetic energy, fully agrees with our simulation results mentioned above, suggesting the consistency and accuracy of our simulations and experiments.

p53 protein aggregation promotes platinum resistance in ovarian cancer.

High-grade serous ovarian carcinoma (HGSOC), the most lethal gynecological cancer, often leads to chemoresistant diseases. The p53 protein is a key transcriptional factor regulating cellular homeostasis. A majority of HGSOCs have inactive p53 because of genetic mutations. However, genetic mutation is not the only cause of p53 inactivation. The aggregation of p53 protein has been discovered in different types of cancers and may be responsible for impairing the normal transcriptional activation and pro-apoptotic functions of p53. We demonstrated that in a unique population of HGSOC cancer cells with cancer stem cell properties, p53 protein aggregation is associated with p53 inactivation and platinum resistance. When these cancer stem cells differentiated into their chemosensitive progeny, they lost tumor-initiating capacity and p53 aggregates. In addition to the association of p53 aggregation and chemoresistance in HGSOC cells, we further demonstrated that the overexpression of a p53-positive regulator, p14ARF, inhibited MDM2-mediated p53 degradation and led to the imbalance of p53 turnover that promoted the formation of p53 aggregates. With in vitro and in vivo models, we demonstrated that the inhibition of p14ARF could suppress p53 aggregation and sensitize cancer cells to platinum treatment. Moreover, by two-dimensional gel electrophoresis and mass spectrometry we discovered that the aggregated p53 may function uniquely by interacting with proteins that are critical for cancer cell survival and tumor progression. Our findings help us understand the poor chemoresponse of a subset of HGSOC patients and suggest p53 aggregation as a new marker for chemoresistance. Our findings also suggest that inhibiting p53 aggregation can reactivate p53 pro-apoptotic function. Therefore, p53 aggregation is a potential therapeutic target for reversing chemoresistance. This is paramount for improving ovarian cancer patients' responses to chemotherapy, and thus increasing their survival rate.

Activation of p38 mitogen-activated protein kinase and caspases in UVB-induced apoptosis of human keratinocyte HaCaT cells.

Exposure of human keratinocyte HaCaT cells to ultraviolet B-irradiation induced apoptotic morphologic changes. In this study, we found that the ultraviolet B irradiation (0.25 J per cm2) induced phosphorylation of p38 mitogen-activated protein kinase and c-jun N-terminal protein kinase, and also significant activation of caspase-3 (CPP32-like protease) and a small increase of caspase-1 (ICE-like protease) activity in the early stages of ultraviolet B-induced apoptosis. Pretreatments of the cells with a p38 mitogen-activated protein kinase inhibitor, SB203580, and a caspase-3 inhibitor, Ac-Asp-Met-Gln-Asp-1-aldehyde, suppressed the ultraviolet B irradiation-induced apoptosis by approximately 60% as estimated by nuclear staining and DNA laddering. Pretreatment with caspase-1 inhibitor, Ac-Tyr-Val-Lys-Asp-aldehyde was without effect. Ultraviolet B-induced caspase-3 activation resulted in cleavage of poly(ADP) ribose polymerase, which was abolished by the caspase-3 inhibitor. SB203580 pretreatment prevented activation of caspase-3 and caspase-1, and also suppressed the cleavage of poly(ADP) ribose polymerase. Neither ceramide generation nor sphingomyelinase activation (neutral and acid) was observed in the ultraviolet B-irradiated HaCaT cells. Also various antioxidants did not affect the caspase activation induced by ultraviolet B irradiation. These results indicated that activation of p38 mitogen-activated protein kinase upstream of caspases may play an important part in the apoptotic process of keratinocytes exposed to ultraviolet B irradiation.

Enhancement of the clastogenicity of N-nitrosodialkylamines plus near-ultraviolet irradiation by ethanol in Chinese hamster lung fibroblasts.

Early work from our laboratory showed a synergistic action of N-nitrosodialkylamines and near-ultraviolet light (UVA, 320-400 nm) to cause mutations in bacteria and phages. Recently we reported that N-nitrosodialkylamines + UVA induces chromosome aberrations in Chinese hamster lung cells in culture. We have now found that ethanol can potentiate this clastogenic action of N-nitrosodialkylamines + UVA. When the cells were treated with N-nitrosopyrrolidine (NPYR) or N-nitrosodiethylamine (NDEA) + UVA for 2 hours in the presence of 1% ethanol, approximately 2-fold increase in the numbers of cells with aberrant chromosomes was observed, compared to those found without the ethanol. NPYR/NDEA only ethanol only, or ethanol + UVA did not cause the aberrations. The enhancement was dependent on the concentration of ethanol. Treatment of cells with ethanol before the NPYR + UVA was ineffective. By contrast, treatment of cells with NPYR-UVA and then with ethanol was as effective as with the simultaneous treatment. Methanol showed synergistic effects similar to those of ethanol, but mannitol did not. Intracellular hydrogen peroxide was found to be increased twofold over that in the background by a treatment with ethanol + UVA. The alcohol-mediated enhancement of the clastogenic action of N-nitrosodialkylamines + UVA may be a consequence of an increase in intracellular oxidative stress, or simply due to increased membrane permeability.

Effect of inoculum size and frequency on the establishment of Streptococcus mutans in the oral cavities of experimental animals.

SPF Sprague-Dawley rats and ICR mice were inoculated with either Streptococcus mutans MT8148R (serotype c) or 6715 (g), and the influence of inoculum size, inoculum frequency, and sucrose on the establishment of S. mutans in the oral cavity was examined. Successful colonization of S. mutans in the experimental animals was absolutely dependent on the number of the cells introduced orally. Furthermore, inoculum frequency and sucrose seemed to act as secondary factors to modify the establishment of S. mutans, and it is suggested that high inoculum frequency may decrease the inoculum size necessary for the colonization of S. mutans in the oral cavity.

Synergistic action of N-nitrosodialkylamines and near-UV in the induction of chromosome aberrations in Chinese hamster lung fibroblasts in vitro.

N-Nitrosodialkylamines are promutagens and proclastogens, requiring metabolic activation for their actions. Previously, we showed that direct-acting bacterial mutagens can be formed from N-nitrosodialkylamines on exposure to near-UV. We have now found that N-nitrosodialkylamines with near-UV irradiation are clastogenic to Chinese hamster lung cells. When the cells in culture were irradiated with near-UV for 3 h in the presence of N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR), N-nitrosopiperidine (NPIP) or N-nitrosomorpholine (NMOR), and then further incubated for a total period of 24 h with the N-nitrosodialkylamines, chromosome aberrations were induced. Neither the N-nitrosodialkylamine nor near-UV alone were clastogenic. Severe clastogenicity (> 50% of cells examined showing aberrations) was observed for 0.5 mM NDEA, NPYR and NPIP. The order of the clastogenic activity was NDEA, NPYR > NPIP, NDMA > NMOR. This order differed from that of bacterial mutagenicity previously reported for these N-nitrosodialkylamines plus near-UV, in which NMOR gave the strongest activity. The chromosome aberrations induced by the NPYR and NDEA plus near-UV in CHL-cells were inhibited by superoxide dismutase, glutathione and L-cysteine. Dimethylsulfoxide or D-mannitol, scavengers of hydroxy radical, and L-histidine, a scavenger of single oxygen, were ineffective. These results suggest that superoxide formed by a synergistic action of an N-nitrosodialkylamine and near-UV is the cause of the chromosome aberrations observed, an assumption consistent with the known ability of superoxide to cleave DNA.

[Single dose toxicity studies of lactitol (NS-4) in mice and rats].

The single dose toxicity studies of lactitol, a hepatic encephalopathy drug, were performed in ddY mice and SD rats of both sexes by administering the drug orally, intravenously or subcutaneously. The drug was administered as a single dose followed by a 14-day observation. Oral LD50 values of lactitol were estimated to be between 23 and 30 g/kg in male mice, approximately 30 g/kg in female mice, and more than 30 g/kg in male and female rats. Lethal dose was more than 10 g/kg intravenously and subcutaneously in mice and rats of both sexes. The signs of toxicity in mice and rats observed following the administration of this drug included the following: decreased spontaneous movement [p.o., i.v., s.c.]; diarrhea, oligopnea or prone position, transient decreased body weight [p.o]. There were no treatment-related changes in gross examination. Based on these results, it was found that lactitol had a very low acute toxicity when administered by a single dose method in mice and rats.