Abstract  The acute toxicity of TNT, RDX, LAP (1.6 TNT/1.0 RDX), and/or LAP(I) (photolyzed LAP: 0.032 TNT/1.0 RDX, 10% undegraded RDX) was determined in mammalian species. In male and female rats, respectively, the acute oral LD50s were: TNT, 1320 and 794 mg/kg; RDX, 71 and about 70 mg/kg; and LAP, 574 and 594 mg/kg or lower, depending on particle size. In male and female mice, respectively, the LD50s were: TNT, 660 mg/kg (both sexes); RDX, < 75 and 86 mg/ kg; and LAP947 and 1131 mg/kg. LAP(I) was examined in mice only; the acute oral LD50s in males and females were: 585 and 684 mg/kg, respectively. LAP and LAP(I) produced conjunctivitis, iritis, and/or corneal opacity in rabbit eyes; the irritation was not totally reversed in unwashed eyes after 7 days and longer. In in vitro microbial assays using microsomal activation (Ames Test), TNT was mutagenic. LAP was also mutagenic, and photolysis increased its mutagenicity. In contrast, in vivo cytogenetics studies on rat bone marrow extracts failed to detect an effect of either TNT or LAP on somatic cells. The effects of repeated oral administration of TNT and of LAP were determined in 90-day studies in dogs, rats, and mice. Observations common to the three species treated with either test material were depressed body weight and/or weight gain and food intake, mild to moderate hemolytic anemia, enlarged spleens.

Abstract  In this study, the Fenton process was used to explore the possibility of treating explosives, namely 2,4,6-trinitrophenol (PA), ammonium picronitrate (AP), 2,4-dinitrotoluene (DNT), methyl-2,4,6-trinitrophenylnitramine (Tetryl) and 2,4,6-Trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX). The photo-Fenton process was also conducted to compare its oxidation efficiency with the Fenton process. The inhibition of hydroxyl radical and theory of crystal field stabilization energy were introduced in this study. Results show that oxidation efficiencies in Fenton system are in the following sequence: DNT > PA > AP > TNT > Tetryl > RDX > HMX. The degradation of the explosives obeys a pseudo-first-order behavior, and possible decomposing mechanisms are also discussed. For all explosives, the oxidation rates significantly increased with increasing the concentration of Fe(II), as well as illumination with UV light.

Abstract  The analysis of explosives with ion mobility spectrometry (IMS) directly from aqueous solutions was shown for the first time using an electrospray ionization technique. The IMS was operated in the negative mode at 250 degrees C and coupled with a quadrupole mass spectrometer to identify the observed IMS peaks. The IMS response characteristics of trinitrotoluene (TNT), 2,4-dinitrotoluene (2,4-DNT), 2-amino-4,6-dinitrotoluene (2-ADNT), 4-nitrotoluene (4-NT), trinitrobenzene (TNB), cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX), cyclo-tetramethylene-tetranitramine (HMX), dinitro-ethyleneglycol (EGDN) and nitroglycerine (NG) were investigated. Several breakdown products, predominantly NO(2)(-) and NO(3)(-), were observed in the low-mass region. Nevertheless, all compounds with the exception of NG produced at least one ion related to the intact molecule and could therefore be selectively detected. For RDX and HMX the [M+Cl(-)](-) cluster ion was the main peak and the signal intensities could be greatly enhanced by the addition of small amounts of sodium chloride to the sprayed solutions. The reduced mobility constants (K(0)) were in good agreement with literature data obtained from experiments where the explosives were introduced into the IMS from the vapor phase. The detection limits were in the range of 15-190 mug l(-1) and all calibration curves showed good linearity. A mixture of TNT, RDX and HMX was used to demonstrate the high separation potential of the IMS system. Baseline separation of the three compounds was attained within a total analysis time of 6.4 s.

Abstract  The detection and identification of 2,4,6-trinitrotoluene (TNT), 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX), and pentaerythritol tetranitrate (PETN) vapors have proven to be difficult and challenging due to the low vapor pressures of these high explosives. Detecting higher vapor pressure impurity compounds found in TNT and possible tagging agents mandated to be added to plastic explosives (RDX and PETN) would allow for easier vapor detection. The higher vapor pressure nitro compounds of interest are considered to be non-fluorescent; however, once reduced to their amino analogs, they have relatively high quantum yields. The standard reduction products, the reduction products obtained in solution, and the reduction products obtained in vapor phase were analyzed by conventional fluorescence, synchronous luminescence, and derivative spectroscopy. The nitro analogs of the isomers 1,3-diaminobenzene, 1,2-diaminobenzene, and 1,4-diaminobenzene are found as impurities in TNT. We provide for the first time the synchronous luminescence derivative spectra of these isomers; including their individual spectra and a spectrum of an isomeric mixture of the three. Using the standard reduction products associated with these isomers and other aromatic amines, our data suggest that the vapors of two signature impurities, 1,3-dinitrobenzene and 2,4-dinitrotoluene (2,4-DNT), minor impurity compounds, and two possible tagging agents, 2-nitrotoluene (2-NT) and 4-nitrotoluene (4-NT), can be detected and selectively identified using our fluorescence approach. To prove our methodology, we show that we were able to generate, collect, and reduce 2-NT, 4-NT, and 2,4-DNT vapors to their amino analogs. Using our fluorescence approach, these vapors could be detected and selectively identified both individually and in a mixture. Collectively, our data indicate that our method of detecting and identifying higher vapor pressure explosive-like compounds could potentially be used to detect and identify low vapor pressure explosives such as TNT, RDX, and PETN.

Abstract  Large-scale aerobic windrow composting has been used to bioremediate washout lagoon soils contaminated with the explosives TNT (2,4,6-trinitrotoluene) and RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) at several sites within the United States. We previously used 15N NMR to investigate the reduction and binding of T15NT in aerobic bench-scale reactors simulating the conditions of windrow composting. These studies have been extended to 2,4-dinitrotoluene (2,4DNT) and 2,6-dinitrotoluene (2,6DNT), which, as impurities in TNT, are usually presentwherever soils have been contaminated with TNT. Liquid-state 15N NMR analyses of laboratory reactions between 4-methyl-3-nitroaniline-15N, the major monoamine reduction product of 2,4DNT, and the Elliot soil humic acid, both in the presence and absence of horseradish peroxidase, indicated that the amine underwent covalent binding with quinone and other carbonyl groups in the soil humic acid to form both heterocyclic and non-heterocyclic condensation products. Liquid-state 15N NMR analyses of the methanol extracts of 20 day aerobic bench-scale composts of 2,4-di-15N-nitrotoluene and 2,6-di-15N-nitrotoluene revealed the presence of nitrite and monoamine, but not diamine, reduction products, indicating the occurrence of both dioxygenase enzyme and reductive degradation pathways. Solid-state CP/MAS 15N NMR analyses of the whole composts, however, suggested that reduction to monoamines followed by covalent binding of the amines to organic matter was the predominant pathway.

Abstract  Recent progress in analytical terahertz (THz) spectroscopy is reviewed with illustrative examples showing that it is an effective method for detecting and identifying intermolecular interactions in chemical compounds, such as hydrogen bonds. The unique and characteristic properties of THz waves, their significance to both science and industry, and the bases of one of the successful fields of analytical THz spectroscopy, namely THz time-domain spectroscopy and THz imaging for chemical analysis, are described. Preliminary quantitative studies are presented to show the potential of THz spectroscopy for the detection and identification of intermolecular hydrogen bonds in unknown mixture samples. The selective detection of intramolecular hydrogen bonds and the detection of intramolecular interactions in ice are also introduced. Some brief remarks are provided on future developments, the main issues, and the prospects for analytical THz spectroscopy.

Abstract  Guideline developers around the world are inconsistent in how they rate quality of evidence and grade strength of recommendations. As a result, guideline users face challenges in understanding the messages that grading systems try to communicate. Since 2006 the BMJ has requested in its “Instructions to Authors” on bmj.com that authors should preferably use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for grading evidence when submitting a clinical guidelines article. What was behind this decision? In this first in a series of five articles we will explain why many organisations use formal systems to grade evidence and recommendations and why this is important for clinicians; we will focus on the GRADE approach to recommendations. In the next two articles we will examine how the GRADE system categorises quality of evidence and strength of recommendations. The final two articles will focus on recommendations for diagnostic tests and GRADE’s framework for tackling the impact of interventions on use of resources. GRADE has advantages over previous rating systems. Other systems share some of these advantages, but none, other than GRADE, combines them all.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. RRM JOURNAL ARTICLE MOUSE HUMAN DRINKING WATER ENVIRONMENTAL POLLUTION TOXICOLOGY

Abstract  Explosives belonging to the group of nitrotoluenes may be readily extracted with C18 adsorbent in the off-line mode and also in on-line coupling of the extraction unit to HPLC, while polar explosives like hexyl, HMX, and RDX show a substantial breakthrough and low recoveries. However, these compounds are quantitatively extracted using a new polymeric phase, LiChrolut EN, in the off-line mode. Preliminary results show that this new adsorbent may in principle also be used in the on-line mode for explosives. In this case, the cartridges have to be eluted in the backflush mode. Method detection limits of | 0. 1 mug are achieved for on-line extraction of explosives and related compounds with water samples as small as 10 ... 30 mL.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. RRM LITERATURE REVIEW HUMAN WIENER INDEX CONNECTIVITY INDEX BALABAN INDEX

Abstract  The public depends on competent risk assessment from the federal government and the scientific community to grapple with the threat of pollution. When risk reports turn out to be overblown--or when risks are overlooked--public skepticism abounds. This comprehensive and readable book explores how the U.S. Environmental Protection Agency (EPA) can improve its risk assessment practices, with a focus on implementation of the 1990 Clean Air Act Amendments. With a wealth of detailed information, pertinent examples, and revealing analysis, the volume explores the "default option" and other basic concepts. It offers two views of EPA operations: The first examines how EPA currently assesses exposure to hazardous air pollutants, evaluates the toxicity of a substance, and characterizes the risk to the public. The second, more holistic, view explores how EPA can improve in several critical areas of risk assessment by focusing on cross-cutting themes and incorporating more scientific judgment. This comprehensive volume will be important to the EPA and other agencies, risk managers, environmental advocates, scientists, faculty, students, and concerned individuals.

Abstract  The expanded Second Edition of Dr. Rothman's acclaimed Modern Epidemiology reflects the remarkable conceptual development of this evolving science and the engagement of epidemiologists with an increasing range of current public health concerns. This landmark work is the most comprehensive and cohesive text on the principles and methods of contemporary epidemiologic research.Coauthored by two leading epidemiologists, with 15 additional contributors, the Second Edition presents a much broader range of concepts and methods than Dr. Rothman's single-authored original edition. Coverage of basic measures and study types is more thorough and includes a new chapter on field methods. New chapters on advanced topics in data analysis, such as hierarchical regression, are also included. A new section covers specific areas of research such as infectious disease epidemiology, ecologic studies, disease surveillance, analysis of vital statistics, screening, clinical epidemiology, environmental and occupational epidemiology, reproductive and perinatal epidemiology, genetic epidemiology, and nutritional epidemiology.

Abstract  In a continuing review of long-term toxicology and carcinogenesis studies in rats and mice, the National Toxicology Program (NTP) is confronted with many problems concerning the interpretation of tumor data. A frequently raised question is: "Should certain neoplasms be combined for overall assessment of rodent carcinogenesis data?" NTP policy is that certain neoplasms may be combined for statistical assessment of tumor data and that hyperplastic responses may be used as supportive evidence. The primary reason for combining neoplastic lesions is to gain more insight into the evidence of the carcinogenicity of a given chemical in that species of animal. This report gives the rationale, criteria, and guidelines used by the NTP for combining neoplasms for the evaluation of long-term rodent toxicology and carcinogenesis studies. The guidelines are based mainly on lesions occurring in the F344/N inbred rat and (C57BL/6 X C3H)F1 mouse and may or may not be appropriate for other strains or species. The concepts of combining neoplasms and sites should be viewed in terms of the study as a whole, since tumor formation is only one of many responses caused by chemicals in mammals. The resulting information becomes part of the "weight of the evidence" for estimating the potential hazard of a given chemical.

Abstract  An extensive search of the literature was conducted for articles concerning the toxicology and treatment of six compounds (Mace, TNT, Smokeless Powder, Dynamite, RDX, and C-4) used, or considered for use, in training devices in the USAF Military Dog Program. Published results of research in the laboratory animals and information from documented cases of human poisoning were used to: predict the toxicity of these compounds for dogs, outline the probable symptoms of acute and chronic toxicosis, and develop a suggested course of treatment for poisoning by each compound.

Abstract  The Report on Carcinogens (RoC) is an informational scienti.c and public health document that identifies and discusses agents, substances, mixtures, or exposure circumstances (hereinafter referred to as substances) that may pose a hazard to human health by virtue of their carcinogenicity. For each listed substance, the RoC contains a substance profile which provides information on (1) the listing status, (2) cancer studies in humans and animals, (3) studies of genotoxicity (ability to damage genes) and biologic mechanisms, (4) the potential for human exposure to these substances, and (5) Federal regulations to limit exposures. The RoC does not present quantitative assessments of the risks of cancer associated with these substances. Thus, the listing of substances in the RoC only indicates a potential hazard and does not establish the exposure conditions that would pose cancer risks to individuals in their daily lives.

Abstract  A PBPK/PD model was developed for the organophosphate insecticide chlorpyrifos (CPF) (O,O-diethyl-O-[3,5,6-trichloro-2-pyridyl]-phosphorothioate), and the major metabolites CPF-oxon and 3,5,6-trichloro-2-pyridinol (TCP) in rats and humans. This model integrates target tissue dosimetry and dynamic response (i.e., esterase inhibition) describing uptake, metabolism, and disposition of CPF, CPF-oxon, and TCP and the associated cholinesterase (ChE) inhibition kinetics in blood and tissues following acute and chronic oral and dermal exposure. To facilitate model development, single oral-dose pharmacokinetic studies were conducted in rats (0.5-100 mg/kg) and humans (0.5-2 mg/kg), and the kinetics of CPF, CPF-oxon, and TCP were determined, as well as the extent of blood (plasma/RBC) and brain (rats only) ChE inhibition. In blood, the concentration of analytes followed the order TCP > CPF > CPF-oxon; in humans CPF-oxon was not quantifiable. Simulations were compared against experimental data and previously published studies in rats and humans. The model was utilized to quantitatively compare dosimetry and dynamic response between rats and humans over a range of CPF doses. The time course of CPF and TCP in both species was linear over the dose range evaluated, and the model reasonably simulated the dose-dependent inhibition of plasma ChE, RBC acetylcholinesterase (AChE), and brain (rat only) AChE. Model simulations suggest that rats exhibit greater metabolism of CPF to CPF-oxon than humans do, and that the depletion of nontarget B-esterase is associated with a nonlinear, dose-dependent increase in CPF-oxon blood and brain concentration. This CPF PBPK/PD model quantitatively estimates target tissue dosimetry and AChE inhibition and is a strong framework for further organophosphate (OP) model development and for refining a biologically based risk assessment for exposure to CPF under a variety of scenarios.

Abstract  Clandestine bomb-makers are exposed to significant amounts of explosives and allied materials. As with any ingested xenobiotic substance, these compounds are subject to biotransformation. As such, the potential exists that characteristic suites of biomarkers may be produced and deposited in matrices that can be exploited for forensic and investigative purposes. However, before such assays can be developed, foundational data must be gathered regarding the toxicokinetics, fate, and transport of the resulting biomarkers within the body and in matrices such as urine, hair, nails, sweat, feces, and saliva. This report presents an in vitro method for simulation of human metabolic transformations using human liver microsomes and an assay applicable to representative nitro-explosives. Control and metabolized samples of TNT, RDX, HMX, and tetryl were analyzed using high-performance liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) and biomarkers identified for each. The challenges associated with this method arise from solubility issues and limitations imposed by instrumentation, specifically, modes of ionization.

Abstract  Concerns have been raised over potential bioavailability and biotransfer of energetic materials such as hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). The present study assessed plant-incorporated [14C]RDX and plant-derived [14C]RDX-metabolite ingestion by the prairie vole (Microtus ochrogaster). The animals were fed labeled chow (maximum, < or =10 g/d) for 5 or 7 d, followed by a 6- or 4-d chase period. More than 95% of all label presented was recovered in the summed excreta, with 74% of this in the fecal nonabsorbed bulk. Greater than 20% of the presented [14C]RDX and plant-derived [14C]RDX metabolites were absorbed by the animals' digestive tracts. These materials were either metabolized to (14)CO2 (8-10% of the total label) or removed as nitrogenous waste through the kidneys (10-14%). Both 14C-urine and (14)CO2 excretion continued after the feces cleared, indicating ongoing metabolism of the labeled material. Approximately 4% was retained within the tissues at death, with the highest total activity in the liver and the highest specific activity in the testes. Other labeled tissues included the lung, heart, brain, spleen, skeletal muscle, bone, and pancreas. All these tissues containing [14C]RDX-derived materials are available to subsequent predators, indicating a potential for transfer to a higher trophic level.

Abstract  Contamination by hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) has been identified at areas of explosive manufacturing, processing, storage, and usage. Anaerobic conversion of RDX to N-nitroso metabolites (hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX), hexahydro-1,3-dinitroso-5-nitro-1,3,5-triazine (DNX), and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX)) has been demonstrated in the environment and in gastrointestinal tracts of mammals in vivo. Thus, potential exists for exposure to these N-nitroso compounds. While exposed to TNX via drinking water ad libitum, deer mice (Peromyscus maniculatus) were bred in three generations to produce cohorts F1A-D, F2A-B, and F3A. TNX was administered at four exposure levels: control (0 microg L(-1)), 10 microg L(-1), 100 microg L(-1), and 1000 microg L(-1). Endpoints investigated include: offspring production, offspring survival, offspring weight gain, and offspring organ weights. TNX exposure decreased litter size and increased postpartum mortality of offspring at the highest exposure level.

Abstract  Cyclotrimethylenetrinitramine (RDX) has been used extensively as an explosive. Prior to this study no data were available on the metabolism of RDX in animals. Metabolism of 14C-RDX was studied in male and female miniature pigs after a one-time gavage with 41 to 44 mg/kg, (0.8 to 0.9 mCi/animal) in an aqueous suspension of 0.1% carboxymethyl cellulose. Metabolic profiles and identification of 14C-RDX-derived radioactivity in plasma, liver and urine were performed utilizing HPLC radio-scanning and LC/MS/MS analysis. Analytical standards were available for all proposed metabolites. Two HPLC columns with differing elution profiles were used for separation, quantification and tentative identification. Identifications were confirmed using LC/MS/MS. Two metabolites were isolated and identified as 4-nitro-2, 4-diazabutanal and a novel metabolite, 4-nitro- 2-4 diaza-butanamide. Analysis also revealed trace levels of 1-nitroso-3,5-dinitro-1,3,5-triazacyclohexane (MNX), 1,3-dintroso-5-nitro-1,3,5-triazacyclohexane (DNX) and 1,3,5-trinitroso- 1,3,5-triazacyclohexane (TNX) in plasma and showed trace levels of MNX and DNX in urine. No metabolites were detected in the liver samples. Thus RDX was metabolized primarily by a method that accomplished both denitration and oxidative cleavage of the ring structure of this compound to form butanal and butanamide metabolites.

Abstract  CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane or HNIW) is a high-energy nitramine explosive. To improve atomistic understanding of the thermal decomposition of CL-20 gas and solid phases, we performed a series of ab initio molecular dynamics simulations. We found that during unimolecular decomposition, unlike other nitramines (e.g., RDX, HMX), CL-20 has only one distinct initial reaction channelhomolysis of the N-NO2 bond. We did not observe any HONO elimination reaction during unimolecular decomposition, whereas the ring-breaking reaction was followed by NO 2 fission. Therefore, in spite of limited sampling, that provides a mostly qualitative picture, we proposed here a scheme of unimolecular decomposition of CL-20. The averaged product population over all trajectories was estimated at four HCN, two to four NO2, two to four NO, one CO, and one OH molecule per one CL-20 molecule. Our simulations provide a detailed description of the chemical processes in the initial stages of thermal decomposition of condensed CL-20, allowing elucidation of key features of such processes as composition of primary reaction products, reaction timing, and Arrhenius behavior of the system. The primary reactions leading to NO2, NO, N 2O, and N2 occur at very early stages. We also estimated potential activation barriers for the formation of NO2, which essentially determines overall decomposition kinetics and effective rate constants for NO2 and N2. The calculated solid-phase decomposition pathways correlate with available condensed-phase experimental data.

Abstract  The two members of peroxide-based explosives, triacetone triperoxide (TATP) and hexamethylene triperoxide diamine (HMTD), can be manufactured from readily accessible reagents, and are difficult to detect by conventional analytical methods. TATP and HMTD were securely synthesized, taken up with acetone, hydrolyzed with 4 M HCl to hydrogen peroxide, the acidic solution containing H(2)O(2) was neutralized, and assayed by the copper(II)-neocuproine spectrophotometric method. The chromophore of the reaction was the Cu(I)-neocuproine chelate responsible for light absorption at 454 nm. The molar absorptivity (epsilon) of the method for TATP and HMTD was 3.45 x 10(4) and 4.68 x 10(4) L mol(-1) cm(-1), respectively. The TATP recovery from a synthetically contaminated loamy clay soil was 91-99%. The colorimetric method was also applied to a Cu(ii)-neocuproine-impregnated polymeric Nafion membrane sensor developed for the first time in this work for peroxide explosive assay. The absorbance-concentration response was perfectly linear, and the limit of detection (LOD) of the procedure for both TATP and HMTD was approximately 0.2 mg L(-1). Neither common soil ions (Ca(2+), K(+), Cl(-), SO(4)(2-), Mg(2+) and NO(3)(-)) at 100-fold amounts nor military-purpose nitro-explosives of TNT, RDX, and PETN at 10-fold amounts interfered with the proposed assay. Active oxygen constituents of laundry detergents (perborates and percarbonates), which normally interfered with the assay, could easily be separated from the analytes by solubility differences. The method was statistically validated against standard reference methods of TiOSO(4) colorimetry and GC-MS.