Formation of Additive-Containing Nanothermites and Modifications to their Friction Sensitivity

Nanothermites can provide high energy densities and reaction rates but can also display extreme friction sensitivities. Additives that provide friction modification offer the potential to reduce the friction sensitivity of nanothermites. In the present work, MoS₂, graphene, and hexadecane additives were dispersed in MoO₃ prior to nanothermite formation with the aim of reducing friction sensitivity. Nanothermites were subsequently prepared using a palmitic acid–passivated nano-aluminum (L-Al) and additive-containing nano-MoO₃ by the resonant acoustic mixing of dry powders. In general, the incorporation of additives results in a reduction in friction sensitivity with the baseline minimum ignition friction rising from 10 to 120 N using 0.5% wt/wt micrometer-sized MoS₂ or 5% wt/wt hexadecane. However, the relationships between loading and performance are complex and vary by additive; for example, the friction sensitivity dependence using micrometer-diameter MoS₂ displays a maximum at 0.5% wt/wt and declines to 7 N using 5% MoS₂.     

Identification and categorization of liver toxicity markers induced by a related pair of drugs

Drug-induced liver injury (DILI) is the primary adverse event that results in the withdrawal of drugs from the market and a frequent reason for the failure of drug candidates in the pre-clinical or clinical phases of drug development. This paper presents an approach for identifying potential liver toxicity genomic biomarkers from a liver toxicity biomarker study involving the paired compounds entacapone ("non-liver toxic drug") and tolcapone ("hepatotoxic drug"). Molecular analysis of the rat liver and plasma samples, combined with statistical analysis, revealed many similarities and differences between the in vivo biochemical effects of the two drugs. Six hundred and ninety-five genes and 61 pathways were selected based on the classification scheme. Of the 61 pathways, 5 were specific to treatment with tolcapone. Two of the 12 animals in the tolcapone group were found to have high ALT, AST, or TBIL levels. The gene Vars2 (valyl-tRNA synthetase 2) was identified in both animals and the pathway to which it belongs, the aminoacyl-tRNA biosynthesis pathway, was one of the three most significant tolcapone-specific pathways identified.     

Quantitative analysis of etheno-2'-deoxycytidine DNA adducts using on-line immunoaffinity chromatography coupled with LC/ES-MS/MS detection

Etheno DNA adducts, including 3,N4-etheno-2'-deoxycytidine (etheno-dC), are promutagenic lesions present in normal animal and human tissues. These DNA adducts are believed to be important in the etiology of cancer. Existing methods for quantifying etheno-dC use 32p. postlabeling. Although highly sensitive, postlabeling requires the use of an energetic radioisotope and considerable time and effort. The new methodology reported here permits automated quantification of trace levels of etheno-dC in crude DNA hydrolysates on the order of 5 adducts in 10(8) normal nucleotides from 100-microg samples of DNA. This was accomplished by using on-line immunoaffinity chromatography, a reverse-phase LC separation on graphitized carbon, tandem mass spectrometric detection, and an isotopically labeled internal standard. The automated procedures permitted analysis of 4 DNA hydrolysates/hr. The sensitivity using immunoaffinity cleanup was approximately 100-fold greater than that observed when using a silica-based trapping system. The validated method was applied to the analysis of etheno-dC in commercial calf thymus DNA, untreated mouse liver, and untreated rat liver DNA. The demonstrated level of performance suggests future applicability of this method in studies of cancer in humans and experimental animals.     

Structure of 7,12-dimethylbenz(a)anthracene-guanosine adducts

Arene oxides have been proposed as the reactive intermediates in the process of carcinogenesis induced by polycyclic aromatic hydrocarbons. The present study defines the structures of four guanosine adducts formed by the reaction of 7,12-dimethylbenz[a]anthracene-5,6-oxide with polyguanylic acid. The modified polymer was hydrolyzed to nucleotides and the hydrophobic guanosine adducts separated from unmodified guanosine by LH-20 column chromatograhy. The adducts were further resolved into four components (I-IV) by reverse phase high pressure liquid chromatography. Analysis of the ultraviolet, circular dichroism, mass, and proton magnetic resonance spectra of these compounds, or their acetate and free base derivatives, indicates that in all four compounds the aromatic hydrocarbon is present on the 2 amino group of guanine. Compounds I and IV, and II and III constitute diastereoisomeric pairs, respectively. In the I and IV pair, the adducts result from addition at the 6 position of the original dimethylbenz[a]anthracene oxide, whereas in the II and III pair, the addition occurs at the 5 position. Indirect evidence suggests that trans opening of the oxide occurred in all cases but this remains to be established.     

Arylamine-DNA adduct conformation in relation to mutagenesis

A considerable body of evidence has indicated that local conformational alterations induced by DNA adducts may provide the molecular basis for differences in mutational specificities exhibited by structurally similar adducts. To elucidate the relationships between adduct structure and mutation induction, the ability of several single-ring arylamines present in tobacco smoke (i.e., methylanilines, dimethylanilines, and ethylanilines) to form DNA adducts was investigated. In all cases, the major adducts were C8-substituted deoxyguanosine derivatives, which is consistent with what has been observed with more carcinogenic arylamines, such as 2-aminofluorene and 4-aminobiphenyl. Spectroscopic and theoretical data on the adducts indicated conformational differences depending upon the location of the alkyl substituents. Adducts containing alkyl groups ortho to the amino function (e.g., 2-methylaniline) had a greater percentage of syn conformers about the glycosyl bond than those not bearing such groups. Arylamines with ortho alkyl substituents tend to be more mutagenic and tumorigenic than analogues not containing an ortho alkyl substituent. This increase in biological activity may be due in part to the greater propensity of ortho alkylated adducts to adopt a syn conformation.     

Immune functions in beluga whales (Delphinapterus leucas): evaluation of mitogen-induced blastic transformation of lymphocytes from peripheral blood, spleen and thymus

A quantitative assay was developed to evaluate mitogen-induced lymphoblastic transformation in beluga whales (Delphinapterus leucas) using peripheral blood mononuclear cells, splenocytes and thymocytes. Optimal concentrations of four different mitogens (Con-A, PHA, LPS and PWM) were determined with the use of standard curves. Addition of human recombinant IL-2 (rhIL-2) after 48 h in culture with the different mitogens suggests that Con-A, PHA and PWM, but not LPS, stimulate T cells in belugas, as they do in other animal species. The addition of 2-mercaptoethanol did not enhance significantly the proliferation of cells stimulated by Con-A, PHA and LPS, while it did with the cells stimulated by PWM and those cultured without mitogen. The proliferative response of cells was suppressed when the culture medium was supplemented by beluga serum instead of fetal calf serum. This assay will be useful to assess the status of the immune functions in different populations of beluga whales as well for further in vitro immunotoxicological experiments.     

The reaction of (+/-)-7alpha, 8beta-dihydroxy-9beta, 10beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene with DNA

A total of 129 semen samples from 62 bulls were examined for the presence of mycelial yeasts. Nine species of mycelial yeasts were obtained from the semen; Candida parapsilosis and C. tropicalis were the most frequently isolated organisms. Semen samples from 30 of the bulls had mycelial yeasts present.     

Occurrence and reductions of pharmaceuticals and personal care products and estrogens by municipal wastewater treatment plants in Ontario, Canada

Over the last ten years there have been reports of pharmaceuticals and personal care product (PPCP) residuals in municipal wastewater treatment plant (WWTP) effluents. The principle goal of this study was specifically to expand and in some cases establish a Canadian database for the presence of selected acidic drugs, triclosan, polycyclic musks, and selected estrogens in MWWTP influent and effluent. The impact of treatment configuration (e.g. lagoons, conventional activated sludge (CAS), and CAS followed by media filtration (CAS+filtration)) was also examined. For CAS systems, the most prevalent treatment type, the effect of operating temperature and SRT was evaluated. Selected PPCPs included ten acidic pharmaceuticals (i.e. a group of pharmaceuticals that are extractable at a pH of 2 or less), triclosan, five polycyclic musks and two estrogens. The pharmaceuticals and musks were selected on the basis of levels of use in Canada; reported aquatic toxicity effects; and the ability to analyze for the compounds at low levels. Twelve MWWTPs discharging into the Thames River, the second largest river in southwestern Ontario, were surveyed. The only common characteristic of acidic drugs is their extraction pH as they differ in their intended biological function and chemical structure. Many organics degraded by WWTP processes benefit from warm temperatures and long SRTs so the impact of these variables warranted additional attention. Influent concentrations and reductions for acidic drugs reported by this study were compared to other Canadian studies, when available, and European investigations. The data of this study seems consistent with other reports. Ten acidic drugs were considered by this study. Three were consistently present at non-quantifiable levels (e.g. CLF, FNP and FNF). Additionally, one analyte, SYL, presented results that were so inconsistent that the values were not analysed. The remaining six acidic pharmaceuticals were placed into three categories. IBU and NPX members of the first category had consistently high reductions. At the level of reduction achieved (i.e. median reduction of greater than 93%) and any effect of treatment type or operating characteristics would be subtle and non-discernable given the analytical noise. In the second group are KTP and IND, and definitive comments are difficult to make on the impact of treatment type and operational considerations due to a sparse data set (i.e. many influent values were at non-quantifiable concentrations). Median reductions were in the 23% to 44% range. In the last category are GMF and DCF which have median reductions of 66% and -34%, respectively. Several negative reduction values in the data set (i.e. twelve of twenty six sampling events) suggest that DCF may be deconjugated under certain conditions. This warrants further evaluation when analytical methods for measuring human metabolites of DCF are available. For both GMF and DCF, reduction does not appear to be strongly influenced by SRTs up to 15 days, while SRTs over 30 days were associated with more frequent non-quantifiable effluent levels of DCF. This would suggest that better treatment would be provided by lagoons and CAS systems with extended aeration. Preliminary data suggests that temperature does not play a strong role in the reduction of these compounds. Triclosan (TCL) was detected at concentrations of 0.01-4.01 microg/L in influent samples and 0.01-0.324 microg/L in effluent samples. Reduction of TCL ranged from 74% to 98%. Lagoon treatment seems to be the best TCL reduction as it was present in the influent and effluent at quantifiable and non-quantifiable concentrations, respectively, on nine of nine sampling occasions. Influent and reduction values of five polycyclic musks (e.g. ADBI, AHMI, ATII, HHCB, and AHTN) were examined over the course of this study. AHMI was predominantly present at non-quantifiable concentrations. HHCB and AHTN were present at the highest concentrations. A comparison between Canadian values and those of European studies indicate that in general polycyclic musk concentrations in Canadian MWWTP effluents are 5-10 times lower. More extensive European and Canadian databases would be useful in confirming this initial observation. Median reductions for the five remaining musks range between 37% and 65% in CAS systems. CAS+filtration systems would be expected to have higher reductions if musks were bound to the effluent solids. This trend is not apparent but this may be due to the small size of the data set. In lagoon systems, musk reduction for HHCB and AHTN are approximately 98-99%. For ADBI and ATII musk, there are no numerical reduction values as most often the effluent concentration was non-quantifiable. In some instances, both the influent and effluent concentrations were non-quantifiable. The hormones 17-beta-estradiol (E2) and estrone (E1) were detected at concentrations of 0.006 to 0.014 and 0.016 to 0.049 microg/L, respectively. E2 was not detected in any effluent samples (<0.005 microg/L) whereas E1 was detected in effluent samples from CAS treatment plants (median of 0.008 microg/L), and in one sample from lagoons. These data demonstrate that there are detectable levels of PPCPs entering Canadian waterways at trace levels, and that only some of these compounds are being reduced in a significant proportion by municipal wastewater treatment processes.     

Nanoscale ZnO induces cytotoxicity and DNA damage in human cell lines and rat primary neuronal cells

The toxic effects of ZnO nanoparticles (nano-ZnO) (1-100 microg/mL) suspended in DMEM were examined in human A549 cells, HepG2 cells, human skin fibroblast cells, human skin keratinocytes, and rat primary neuronal cells for 24 h. Nano-ZnO induced dose dependent cytotoxicity and damaged cell membranes. Cell death was not mediated by reactive oxygen species (ROS) or apoptosis. Nano-ZnO induced DNA damage in rat primary neuronal cells, human fibroblasts, and A549 cells. The cytotoxicity of nano-ZnO in DMEM supplemented with 10% FBS, instead of serum free DMEM, was also examined in the A549 cells, human skin fibroblast cells, and human skin keratinocytes. The levels of cytotoxicity induced were similar to those tested without FBS; in addition, ROS was observed. These results indicate that the cause of cytotoxicity is medium dependent and imply that cellular growth conditions may play a significant role in induction of cytotoxicity and DNA damage by nano-ZnO.