We indude in this review an assessment of the formation, environmental fate, and mammalian and ecotoxicity of CW agent degradation products relevant to environmental and occupational health.These parent CW agents indude several vesicants: sulfur mustards [undistilled sulfur mustard (H), sulfur mustard (HD), and an HD/agent T mixture (HT)]; nitrogen mustards [ethylbis(2-chloroethyl)amine (HN1), methylbis(2-chloroethyl)amine (HN2), tris(2-chloroethyl)amine (HN3)], and Lewisite; four nerve agents {O0ethyl S.[2-(diisopropylamino)ethyl] methylphosphonothioate (VX), tabun (GA), sarin (GB), and soman (GD)}; and the blood agent cyanogen chloride. The degradation processes considered here include hydrolysis, microbial degradation, oxidation, and photolysis. We also briefly address decontamination but not combustion processes. Because CW agents are generally not considered very persistent, certain degradation products of significant persistence, even those that are not particularly toxic, may indicate previous CW agent presence or that degradation has occurred. Of those products for which there are data on both environmental fate and toxicity, only a few are both environmentally persistent and highly toxic. Major degradation products estimated to be of significant persistence (weeks to years) indude thiodiglycol for HD; Lewisite oxide for Lewisite; and ethyl methyl phosphonic acid, methyl phosphonic acid, and possibly S.(2-diisopropylaminoethyl) methylphosphonothioic acid (EA 2192) for VX. Methyl phosphonic acid is also the ultimate hydrolysis product of both GB and GD. The GB product, isopropyl methylphosphonic acid, and a dosely related contaminant of GB, diisopropyl methylphosphonate, are also persistent. Of all of these compounds, only Lewisite oxide and EA 2192 possess high mammalian toxicity. Unlike other CW agents, suifur mustard agents (e.g., HD) are somewhat persistent; therefore, sites or conditions involving potential HD contamination should include an evaluation of both the agent and thiodiglycol.
The nerve agents, GA, GB, and VX are organophosphorus esters that form a major portion of the total agent volume contained in the U.S. stockpile of unitary chemical munitions. Congress has mandated the destruction of these agents, which is currently slated for completion in 2004. The acute, chronic, and delayed toxicity of these agents is reviewed in this analysis. The largely negative results from studies of genotoxicity, carcinogenicity, developmental, and reproductive toxicity are also presented. Nerve agents show few or delayed effects. At supralethal doses, GB can cause delayed neuropathy in antidote-protected chickens, but there is no evidence that it causes this syndrome in humans at any dose. Agent VX shows no potential for inducing delayed neuropathy in any species. In view of their lack of genotoxcity, the nerve agents are not likely to be carcinogens. The overreaching concern with regard to nerve agent exposure is the extraordinarily high acute toxicity of these substances. Furthermore, acute effects of moderate exposure such as nausea, diarrhea, inability to perform simple mental tasks, and respiratory effects may render the public unable to respond adequately to emergency instructions in the unlikely event of agent releaase, making early warning and exposure avoidance important. Likewise, exposure or self-contamination of first responders and medical personnel must be avoided. Control limits for exposure via surface contact of drinking water are needed, as are detection methods for low levels in water or foodstuffs.ImagesFigure 2.
Amnestic mild cognitive impairment (aMCI) often is an early stage of Alzheimer’s disease (AD). MCI is characterized by cognitive decline departing from normal cognitive aging but that does not significantly interfere with daily activities. This study explores the potential of scalp EEG for early detection of alterations from cognitively normal status of older adults signifying MCI and AD. Resting 32-channel EEG records from 48 age-matched participants (mean age 75.7 years)–15 normal controls (NC), 16 early MCI, and 17 early stage AD–are examined. Regional spectral and complexity features are computed and used in a support vector machine model to discriminate between groups. Analyses based on three-way classifications demonstrate discrimination accuracies of 83.9%–96.8% for MCI vs. NC (p-value<0.0029), 71.9%–96.9% for AD vs. NC (p-value<0.0333), and 87.9%–90.9% for AD vs. MCI (pvalue<0.0136), depending on the EEG protocol condition employed. These results demonstrate the great promise for scalp EEG spectral and complexity features as noninvasive biomarkers for detection of MCI and early AD.
The decontamination of chemical warfare agents (CWA) from structures, environmental media, and even personnel has become an area of particular interest in recent years due to increased homeland security concerns. In addition to terrorist attacks, scenarios such as accidental releases of CWA from U.S. stockpile sites or from historic, buried munitions are also subjects for response planning. To facilitate rapid identification of practical and effective decontamination approaches, this paper reviews pathways of CWA degradation by natural means as well as those resulting from deliberately applied solutions and technologies; these pathways and technologies are compared and contrasted. We then review various technologies, both traditional and recent, with some emphasis on decontamination materials used for surfaces that are difficult to clean. Discussion is limited to the major threat CWA, namely sulfur mustard (HD, bis[2-chloroethyl]sulfide), VX (O-ethyl S-[2-diisopropylaminoethyl] methylphosphonothioate), and the Gseries nerve agents. The principal G-agents are GA (tabun, ethyl N,N-dimethylphosphoramidocyanidate), GB (sarin, isopropyl methylphosphonofluoridate), and GD (soman, pinacolyl methylphosphonofluoridate). The chemical decontamination pathways of each agent are outlined, with some discussion of intermediate and final degradation product toxicity. In all cases, and regardless of the CWA degradation pathway chosen for decontamination, it will be necessary to collect and analyze pertinent environmental samples during the treatment phase to confirm attainment of clearance levels.
BackgroundNoninvasive and effective biomarkers for early detection of amnestic mild cognitive impairment (aMCI) before measurable changes in behavioral performance remain scarce. Cognitive event-related potentials (ERPs) measure synchronized synaptic neural activity associated with a cognitive event. Loss of synapses is a hallmark of the neuropathology of early Alzheimer’s disease (AD). In the present study, we tested the hypothesis that ERP responses during working memory retrieval discriminate aMCI from cognitively normal controls (NC) matched in age and education.MethodsEighteen NC, 17 subjects with aMCI, and 13 subjects with AD performed a delayed match-to-sample task specially designed not only to be easy enough for impaired participants to complete but also to generate comparable performance between subjects with NC and those with aMCI. Scalp electroencephalography, memory accuracy, and reaction times were measured.ResultsWhereas memory performance separated the AD group from the others, the performance of NC and subjects with aMCI was similar. In contrast, left frontal cognitive ERP patterns differentiated subjects with aMCI from NC. Enhanced P3 responses at left frontal sites were associated with nonmatching relative to matching stimuli during working memory tasks in patients with aMCI and AD, but not in NC. The accuracy of discriminating aMCI from NC was 85% by using left frontal match/nonmatch effect combined with nonmatch reaction time.ConclusionsThe left frontal cognitive ERP indicator holds promise as a sensitive, simple, affordable, and noninvasive biomarker for detection of early cognitive impairment.
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