Release and toxicity comparison between industrial- and ...

EPA Pesticide Factsheets

Many consumer products containing ZnO have raised concern for safety in regards toenvironmental impact and the public health. Widely used sunscreens for protectingagainst UV and avoiding sunburns represent a great exposure to nano-ZnO, one of theingredients commonly applied in sunscreens. Applying nano-products on beaches mayrelease nanoparticles unintentionally into the ocean. Despite the accumulation of suchnano-products in the ocean harming or being detrimental to critical marine organisms,few studies have investigated the release and potential toxicity of nanoparticlesextracted from products and compared them with those from industrial-typenanoparticles. Results show that the cytotoxicity of both industrial- and sunscreenderivednano-ZnO to the marine diatom algae, Thalassiosira pseudonana, increasedas exposure increases over time, as measured by growth inhibition (%) of the algae ata constant concentration of nano-ZnO (10 mg/L). The extent of toxicity appeared to behigher from industrial-type nano-ZnO compared to sunscreen-extracted nano-ZnO,though the extent becomes similar when concentrations increase to 50 mg/L. On theother hand, at a fixed exposure time of 48 hrs, the cytotoxicity increases asconcentrations increase with the higher toxicity shown from the industrial-typecompared to sunscreen-induced nano-ZnO. Results indicate that while industrial-typenano-ZnO shows higher toxicity than sunscreen-derived nano-ZnO, the release andextent of toxicity from n

Environmentally Safer, Less Toxic Fire-Extinguishing Agents

NASA Technical Reports Server (NTRS)

Parrish, Clyde F.

2003-01-01

Fire-extinguishing agents comprising microscopic drops of water microencapsulated in flame-retardant polymers have been proposed as effective, less toxic, non-ozone-depleting, non-globalwarming alternatives to prior fire-extinguishing agents. Among the prior fire-extinguishing agents are halons (various halocarbon fluids), which are toxic and contribute both to depletion of upperatmospheric ozone and to global warming. Other prior fire-extinguishing agents are less toxic and less environmentally harmful but, in comparison with halons, are significantly less effective in extinguishing fires. The proposal to formulate new waterbased agents is based on recent success in the use of water mist as a fire-suppression agent. Water suppresses a flame by reducing the flame temperature and the concentration of oxygen available for the combustion process. The temperature is reduced because the water droplets in the mist absorb latent heat of vaporization as they evaporate. The concentration of oxygen is reduced because the newly generated water vapor displaces air. Unfortunately, water mists are difficult to produce in confined spaces and can evaporate before they reach the bases of flames. The proposal addresses both of these issues: The proposed fire-extinguishing agents would be manufactured in microencapsulated form in advance, eliminating the problem of generating mists in confined spaces. Because of the microencapsulation, the droplets would not evaporate until exposed directly to the heat of flames. In addition, the proposal calls for the introduction of free radicals that would inhibit the propagation of the chemical reactions of the combustion reactions. Manufacturing of a fire-extinguishing agent according to the proposal would begin with the formulation of a suitable polymer (e.g., a polybromostyrene) that would contribute free radicals to the combustion process. The polymer would be dissolved in a suitable hydrocarbon liquid (e.g., toluene). Water would be

Toxicity reduction in industrial effluents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1990-01-01

Wastewater treatment technology is undergoing a profound transformation as a result of the fundamental changes in regulations and permit requirements. Established design procedures and criteria which have served the industry well for decades are no longer useful. Toxicity reduction requirements have forced reconsideration of design standards and caused practicing environmental engineers to seek additional training in the biological sciences. Formal academic programs have not traditionally provided the cross-training between biologists and engineers which is necessary to address these issues. This book describes not only the process of identifying the toxicity problem, but also the treatment technologies which are applicable tomore » reduction or elimination of toxicity. The information provided in this book is a compilation of the experience of ECK-ENFELDER INC. in serving the environmental needs of major industry, and the experience of the individual contributors in research and consultations.« less

Toxicity and biodegradability of high strength/toxic organic liquid industrial effluents and hazardous landfill leachates.

PubMed

Naidoo, V; du Preez, M; Rakgotho, T; Odhav, B; Buckley, C A

2002-01-01

Industrial effluents and leachates from hazardous landfill sites were tested for toxicity using the anaerobic toxicity assay. This test was done on several industrial effluents (brewery spent grain effluent, a chemical industry effluent, size effluent), and several hazardous landfill leachates giving vastly different toxicity results. The brewery effluent, spent grain effluent and size effluent were found to be less toxic than the chemical effluent and hazardous landfill leachate samples. The chemical industry effluent was found to be most toxic. Leachate samples from the H:h classified hazardous landfill site were found to be less toxic at high concentrations (40% (v/v)) while the H:H hazardous landfill leachate samples were found to be more toxic even at low concentrations of 4% (v/v). The 30 d biochemical methane potential tests revealed that the brewery effluent, organic spent grain effluent and size effluent were 89%, 63%, and 68% biodegradable, respectively. The leachate from Holfontein hazardous landfill site was least biodegradable (19%) while the chemical effluent and Aloes leachate were 29% and 32% biodegradable under anaerobic conditions.

Necessity of toxicity assessment in Turkish industrial discharges (examples from metal and textile industry effluents).

PubMed

Sponza, Delia Teresa

2002-01-01

Toxicity of some organic and inorganic chemicals to microorganisms is an important consideration in assessing their environmental impact against their economic benefits. Microorganisms play an important role in several environmental processes, both natural and engineered. Some organic and inorganics at toxic levels have been detected in industrial discharges resulting in plant upsets and discharge permit violations. In addition to this, even though in some cases the effluent wastewater does not exceed the discharge limits, the results of toxicity tests show potential toxicity. Toxicity knowledge of effluents can benefit treatment plant operators in optimising plant operation, setting pre-treatment standards, and protecting receiving water quality and in establishing sewer discharge permits to safeguard the plant. In the Turkish regulations only toxicity dilution factor (TDF) with fish is part of the toxicity monitoring program of permissible wastewater discharge. In various countries, laboratory studies involving the use of different organisms and protocol for toxicity assessment was conducted involving a number of discharges. In this study, it was aimed to investigate the acute toxicity of textile and metal industry wastewaters by traditional and enrichment toxicity tests and emphasize the importance of toxicity tests in wastewater discharge regulations. The enrichment toxicity tests are novel applications and give an idea whether there is potential toxicity or growth limiting and stimulation conditions. Different organisms were used such as bacteria (Floc and Coliform bacteria) algae (Chlorella sp.). fish (Lepistes sp.) and protozoan (Vorticella sp.) to represent four tropic levels. The textile industry results showed acute toxicity for at least one organism in 8 out of 23 effluent samples. Acute toxicity for at least two organisms in 7 out of 23 effluent sampling was observed for the metal industry. The toxicity test results were assessed with chemical analyses

Toxic Epidemics: Agent Orange Sickness in Vietnam and the United States.

PubMed

Uesugi, Tak

2016-01-01

Social scientists studying toxic epidemics have often endeavored to shed light on the differences between scientists' and nonscientists' epistemic perspectives. Yet, little attention has been paid to the processes through which a toxic epidemic emerges as a phenomenon. A Luoi Valley of Central Vietnam was extensively sprayed with chemical defoliants (including Agent Orange) during the Vietnam War. The latent toxic effects of these chemicals, however, went largely unnoticed until the late 1990s. By juxtaposing the history through which the notion of "Agent Orange Sickness" emerged in the United States with an ethnographic study of A Luoi, I explore the notion of poison under which Agent Orange became recognizable as a poison.

The sources, fate, and toxicity of chemical warfare agent degradation products.

PubMed Central

Munro, N B; Talmage, S S; Griffin, G D; Waters, L C; Watson, A P; King, J F; Hauschild, V

1999-01-01

We include 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 include 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 (O-ethyl 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) include 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 closely 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, sulfur mustard agents (e.g., HD) are somewhat persistent; therefore, sites or conditions involving potential HD contamination should include an

Toxicity assessment on combined biological treatment of pharmaceutical industry effluents.

PubMed

Inanc, B; Calli, B; Alp, K; Ciner, F; Mertoglu, B; Ozturk, I

2002-01-01

This paper describes the wastewater characterization and aerobic/anaerobic treatability (oxygen uptake rate and biogas production measurement) of chemical-synthesis based pharmaceutical industry effluents in a nearby baker's yeast industry treatment plant. Preliminary experiments by the industry had indicated strong anaerobic toxicity. On the other hand, aerobic treatability was also uncertain due to complexity and unknown composition of the wastewater. The work in this study has indicated that the effluents of the pharmaceutical industry can be treated without toxicity in the aerobic stage of the treatment plant. Methanogenic activity tests with anaerobic sludge from the anaerobic treatment stage of the wastewater treatment plant and acetate as substrate have confirmed the strong toxicity, while showing that 30 min aeration or coagulation with an alum dose of 300 mg/l is sufficient for reducing the toxicity almost completely. Powdered activated carbon, lime and ferric chloride (100-1,000 mg/l) had no effect on reduction of the toxicity. Consequently, the pharmaceutical industry was recommended to treat its effluents in the anaerobic stage of the nearby baker's yeast industry wastewater treatment plan at which there will be no VOC emission and toxicity problem, provided that pretreatment is done.

The role of oxidative stress in organophosphate and nerve agent toxicity

PubMed Central

Pearson, Jennifer N.; Patel, Manisha

2016-01-01

Organophosphate nerve agents exert their toxicity through inhibition of acetylcholinesterase. The excessive stimulation of cholinergic receptors rapidly causes neuronal damage, seizures, death, and long-term neurological impairment in those that survive. Owing to the lethality of organophosphorus agents and the growing risk they pose, medical interventions that prevent organophosphate toxicity and the delayed injury response are much needed. Studies have shown that oxidative stress occurs in models of subacute, acute, and chronic exposure to organophosphate agents. Key findings of these studies include alterations in mitochondrial function and increased free radical–mediated injury, such as lipid peroxidation. This review focuses on the role of reactive oxygen species in organophosphate neurotoxicity and its dependence on seizure activity. Understanding the sources, mechanisms, and pathological consequences of organophosphate-induced oxidative stress can lead to the development of rational therapies for treating toxic exposures. PMID:27371936

Development of Medical Technology for Contingency Response to Marrow Toxic Agents

DTIC Science & Technology

2012-03-31

Development of Medical Technology for Contingency Response to Marrow Toxic Agents - Final Performance/Technical Report for March 01, 2010 to February 28...Development of Medical Technology for Contingency Response To Marrow Toxic Agents FINAL REPORT March 1, 2010 – March 31, 2012 National...Buccal Swabs 38 IIB.1.5 Enhancing HLA Data for Selected Donors 43 IIB.1.6 Maintain a Quality Control Program 46 IIB.2.1 Collection of Primary Data

SCREENING FOR TOXIC INDUSTRIAL CHEMICALS USING SEMIPERMEABLE MEMBRANE DEVICES WITH RAPID TOXICITY ASSAYS

EPA Science Inventory

A time-integrated sampling device interfaced with two toxicity-based assays is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethylsulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor...

Development of spacecraft toxic gas removal agents

NASA Technical Reports Server (NTRS)

Moore, R. S.

1974-01-01

The development of agents suitable for removal of CO, NH3, NO2 SO2, and other spacecraft contaminants was approached. An extensive technology review was conducted, yielding a large number of potentially useful materials and/or concepts. Because the two toxic gases of greatest interest, CO and NH3, suggested the use of catalysis principles emphasis was placed on the intestigation of transition metals on various supports. Forty-three materials were prepared or obtained and 25 were tested. Gas chromatographic techniques were used to find seven candidates that effectively managed various combinations of the four toxic gases: none managed all. These candidates included six transition metal-containing preparations and a supported LiOH material. Three commercial charcoals showed some efficiency for the toxic gases and may constitute candidates for enhancement by doping with transition metals.

Toxicity evaluation of the process effluent streams of a petrochemical industry.

PubMed

Reis, J L R; Dezotti, M; Sant'Anna, G L

2007-02-01

The physico-chemical characteristics and the acute toxicity of several wastewater streams, generated in the industrial production of synthetic rubber, were determined. The acute toxicity was evaluated in bioassays using different organisms: Danio rerio (fish), Lactuca sativa (lettuce) and Brachionus calyciflorus (rotifer). The removal of toxicity attained in the industrial wastewater treatment plant was also determined upstream and downstream of the activated sludge process. The results obtained indicate that the critical streams in terms of acute toxicity are the effluents from the liquid polymer unit and the spent caustic butadiene washing stage. The biological treatment was able to partially remove the toxicity of the industrial wastewater. However, a residual toxicity level persisted in the biotreated wastewater. The results obtained with Lactuca sativa showed a high degree of reproducibility, using root length or germination index as evaluation parameters. The effect of volatile pollutants on the toxicity results obtained with lettuce seeds was assessed, using ethanol as a model compound. Modifications on the assay procedure were proposed. A strong correlation between the toxic responses of Lactuca sativa and Danio rerio was observed for most industrial effluent streams.

Enhanced toxic cloud knockdown spray system for decontamination applications

DOEpatents

Betty, Rita G [Rio Rancho, NM; Tucker, Mark D [Albuquerque, NM; Brockmann, John E [Albuquerque, NM; Lucero, Daniel A [Albuquerque, NM; Levin, Bruce L [Tijeras, NM; Leonard, Jonathan [Albuquerque, NM

2011-09-06

Methods and systems for knockdown and neutralization of toxic clouds of aerosolized chemical or biological warfare (CBW) agents and toxic industrial chemicals using a non-toxic, non-corrosive aqueous decontamination formulation.

The Impact of Toxic Agent Training on Combat Readiness

DTIC Science & Technology

1992-03-24

Desert Storm veterans, as well as Lessons Learned from the use of toxic chemicals in World War I. Conclusions reached arei (1) Live agent training is...Department of the Army staff. The report of our findings and conclusions is attached. After reviewing this report and the lessons learned from Desert Storm...analysis of feedback from soldiers in the grades of PVl to General, input from Desert Storm veterans, as well as lessons learned from the use of toxic

Toxic-Waste Disposal by Drain-in-Furnace Technique

NASA Technical Reports Server (NTRS)

Compton, L. E.; Stephens, J. B.; Moynihan, P. I.; Houseman, J.; Kalvinskas, J. J.

1986-01-01

Compact furnace moved from site to site. Toxic industrial waste destroyed using furnace concept developed for disposal of toxic munitions. Toxic waste drained into furnace where incinerated immediately. In furnace toxic agent rapidly drained and destroyed in small combustion chamber between upper and lower layers of hot ceramic balls

OVERVIEW OF RISK ASSESSMENT FOR TOXIC AND PATHOGENIC AGENTS

EPA Science Inventory

Risk assessment is a process that defines the adverse health consequences of exposure to toxic or pathogenic agents. hen used in regulatory decision making, risk assessment is an important component of risk management, which "combines the risk assessment with the directives of re...

Toxic industrial chemicals and chemical weapons: exposure, identification, and management by syndrome.

PubMed

Tomassoni, Anthony J; French, Robert N E; Walter, Frank G

2015-02-01

Toxidromes aid emergency care providers in the context of the patient presenting with suspected poisoning, unexplained altered mental status, unknown hazardous materials or chemical weapons exposure, or the unknown overdose. The ability to capture an adequate chemical exposure history and to recognize toxidromes may reduce dependence on laboratory tests, speed time to delivery of specific antidote therapy, and improve selection of supportive care practices tailored to the etiologic agent. This article highlights elements of the exposure history and presents selected toxidromes that may be caused by toxic industrial chemicals and chemical weapons. Specific antidotes for toxidromes and points regarding their use, and special supportive measures, are presented. Copyright © 2015 Elsevier Inc. All rights reserved.

USE OF TOXICITY IDENTIFICATION EVALUATION METHODS TO CHARACTERIZE IDENTIFY, AND CONFIRM HEXAVALENT CHROMIUM TOXICITY IN AN INDUSTRIAL EFFLUENT

EPA Science Inventory

A toxicity identification evaluation (TIE) was conducted on effluent from a major industrial discharger. Initial monitoring showed slight chronic toxicity to Ceriodaphnia dubia; later sample showed substantial toxicity to C. dubia. Chemical analysis detected hexavalent chromium ...

Physiologic Conditions Affect Toxicity of Ingested Industrial Fluoride

PubMed Central

Sauerheber, Richard

2013-01-01

The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity from ingestion is distinct from fully soluble toxic industrial fluorides. The toxicity of fluoride is determined by environmental conditions and the positive cations present. At a pH typical of gastric juice, fluoride is largely protonated as hydrofluoric acid HF. Industrial fluoride ingested from treated water enters saliva at levels too low to affect dental caries. Blood levels during lifelong consumption can harm heart, bone, brain, and even developing teeth enamel. The widespread policy known as water fluoridation is discussed in light of these findings. PMID:23840230

Physiologic conditions affect toxicity of ingested industrial fluoride.

PubMed

Sauerheber, Richard

2013-01-01

The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity from ingestion is distinct from fully soluble toxic industrial fluorides. The toxicity of fluoride is determined by environmental conditions and the positive cations present. At a pH typical of gastric juice, fluoride is largely protonated as hydrofluoric acid HF. Industrial fluoride ingested from treated water enters saliva at levels too low to affect dental caries. Blood levels during lifelong consumption can harm heart, bone, brain, and even developing teeth enamel. The widespread policy known as water fluoridation is discussed in light of these findings.

Toxicity identification evaluation of cosmetics industry wastewater.

PubMed

de Melo, Elisa Dias; Mounteer, Ann H; Leão, Lucas Henrique de Souza; Bahia, Renata Cibele Barros; Campos, Izabella Maria Ferreira

2013-01-15

The cosmetics industry has shown steady growth in many developing countries over the past several years, yet little research exists on toxicity of wastewaters it generates. This study describes a toxicity identification evaluation conducted on wastewater from a small Brazilian hair care products manufacturing plant. Physicochemical and ecotoxicological analyses of three wastewater treatment plant inlet and outlet samples collected over a six month period revealed inefficient operation of the treatment system and thus treated wastewater organic matter, suspended solids and surfactants contents consistently exceeded discharge limits. Treated wastewater also presented high acute toxicity to Daphnia similis and chronic toxicity to Ceriodaphnia dubia and Pseudokirchneriella subcapitata. This toxicity was associated with suspended solids, volatile or sublatable and non-polar to moderately polar organic compounds that could be recovered in filtration and aeration residues. Seven surfactants used in the largest quantities in the production process were highly toxic to P. subcapitata and D. similis. These results indicated that surfactants, important production raw materials, are a probable source of toxicity, although other possible sources, such as fragrances, should not be discarded. Improved treatment plant operational control may reduce toxicity and lower impact of wastewater discharge to receiving waters. Copyright © 2012 Elsevier B.V. All rights reserved.

Concentration rather than dose defines the local brain toxicity of agents that are effectively distributed by convection-enhanced delivery.

PubMed

Zhang, Rong; Saito, Ryuta; Mano, Yui; Kanamori, Masayuki; Sonoda, Yukihiko; Kumabe, Toshihiro; Tominaga, Teiji

2014-01-30

Convection-enhanced delivery (CED) has been developed as a potentially effective drug-delivery strategy into the central nervous system. In contrast to systemic intravenous administration, local delivery achieves high concentration and prolonged retention in the local tissue, with increased chance of local toxicity, especially with toxic agents such as chemotherapeutic agents. Therefore, the factors that affect local toxicity should be extensively studied. With the assumption that concentration-oriented evaluation of toxicity is important for local CED, we evaluated the appearance of local toxicity among different agents after delivery with CED and studied if it is dose dependent or concentration dependent. Local toxicity profile of chemotherapeutic agents delivered via CED indicates BCNU was dose-dependent, whereas that of ACNU was concentration-dependent. On the other hand, local toxicity for doxorubicin, which is not distributed effectively by CED, was dose-dependent. Local toxicity for PLD, which is extensively distributed by CED, was concentration-dependent. Traditional evaluation of drug induced toxicity was dose-oriented. This is true for systemic intravascular delivery. However, with local CED, toxicity of several drugs exacerbated in concentration-dependent manner. From our study, local toxicity of drugs that are likely to distribute effectively tended to be concentration-dependent. Concentration rather than dose may be more important for the toxicity of agents that are effectively distributed by CED. Concentration-oriented evaluation of toxicity is more important for CED. Copyright © 2013 Elsevier B.V. All rights reserved.

Molluscicidal properties and selective toxicity of surface-active agents

PubMed Central

Visser, S. A.

1965-01-01

Of over 100 commercially produced surface-active agents tested against the bilharziasis vector snail Biomphalaria sudanica, 13 were found to possess considerable and highly selective molluscicidal properties at concentrations of less than 1 ppm for exposures of 48 hours. Against crustacea, fish, water plants, mosquito larvae, mice, and the eggs of B. sudanica, the toxicities of the 13 surfactants were slight. The chemicals did not appear to be absorbed by organic matter to any appreciable extent. It is thought that the toxicity to B. sudanica is of both a chemical and a physical nature. PMID:5294185

Ocular toxicities associated with targeted anticancer agents: an analysis of clinical data with management suggestions

PubMed Central

Fu, Chen; Gombos, Dan S; Lee, Jared; George, Goldy C; Hess, Kenneth; Whyte, Andrew; Hong, David S

2017-01-01

Ocular toxicities are among the most common adverse events resulting from targeted anticancer agents and are becoming increasingly relevant in the management of patients on these agents. The purpose of this study is to provide a framework for management of these challenging toxicities based on objective data from FDA labels and from analysis of the literature. All oncologic drugs approved by the FDA up to March 14, 2015, were screened for inclusion. A total of 16 drugs (12 small-molecule drugs and 4 monoclonal antibodies) were analyzed for ocular toxicity profiles based on evidence of ocular toxicity. Trials cited by FDA labels were retrieved, and a combination search in Medline, Google Scholar, the Cochrane database, and the NIH Clinical Trials Database was conducted. The majority of ocular toxicities reported were low severity, and the most common were conjunctivitis and “visual disturbances.” However, severe events including incidents of blindness, retinal vascular occlusion, and corneal ulceration occurred. The frequency and severity at which ocular toxicities occur merits a more multidisciplinary approach to managing patients with agents that are known to cause ocular issues. We suggest a standardized methodology for referral and surveillance of patients who are potentially at risk of severe ocular toxicity. PMID:28938590

A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY TOXIC INDUSTRIAL CHEMICALS

EPA Science Inventory

One of the reported effects for exposure to many of the toxic industrial chemicals is DNA damage. The present study describes a simple, rapid and innovative assay to detect DNA damage resulting from exposure of surrogate DNA to toxic industrial chemicals (acrolein, allylamine, ch...

[Chemicals toxic to the olfactory system. Analysis and description].

PubMed

Norès, J M; Biacabe, B; Bonfils, P

2000-10-28

AN IMPORTANT PROBLEM: Occupational exposure to chemical products can have toxic effects on the olfactory system. An important number of patients have experienced olfactory disorders subsequent to the development of the chemical industry and atmospheric pollution. EPIDEMIOLOGY DATA: Straightforward data are difficult to collect because several cofactors other than the toxic product are involved. Two lists of toxic products can be made. The first list includes products for which scientific data is available and the second products for which data is lacking. Olfactory tests also differ between authors and countries. TWO TYPES OF TOXICITY: Acute, accidental toxicity is evidenced by the lesions caused by inhalation of high-doses of strongly toxic agents. Chronic intoxication caused by lower concentrations of these inhaled agents does not produce a trigeminal reflex leading to a modified respiratory rate reducing the airborne aggression. APPROXIMATIONS: Clinical data describing the olfactory toxicity of certain industrial and chemical compounds are very significant but often cannot prove a cause and effect relationship. Data obtained with experimental models in rodents are difficult to extrapolate to humans.

Renal toxicity of anticancer agents targeting HER2 and EGFR.

PubMed

Cosmai, Laura; Gallieni, Maurizio; Porta, Camillo

2015-12-01

EGFR and HER2 are found overexpressed and/or activated in many different human malignancies (e.g. breast and colon cancer), and a number of drugs specifically targeting these two tyrosine kinases have been developed over the years as anticancer agents. In the present review, the renal safety profile of presently available agents targeting either HER2 or EGFR will be discussed, together with the peculiarities related to their clinical use in patients with impaired renal function, or even in dialysis. Indeed, even though renal toxicity is not so common with these agents, it may nevertheless happen, especially when these agents are combined with traditional chemotherapeutic agents. As a whole, kidney impairment or dialysis should not be regarded per se as reasons not to administer or to stop an active anti-HER or anti-EGFR anticancer treatment, especially given the possibility of significantly improving the life expectancy of many cancer patients with the use of these agents.

Toxicity of the Organophosphate Chemical Warfare Agents GA, GB, and VX: Implications for Public Protection.

PubMed Central

Munro, N

1994-01-01

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. Images Figure 2. PMID:9719666

Remote Continuous Wave and Pulsed Laser Raman Detection of Chemical Warfare Agents Simulants and Toxic Industrial Compounds

NASA Astrophysics Data System (ADS)

Ortiz-Rivera, William; Pacheco-Londoño, Leonardo C.; Hernández-Rivera, Samuel P.

2010-09-01

This study describes the design, assembly, testing and comparison of two Remote Raman Spectroscopy (RRS) systems intended for standoff detection of hazardous chemical liquids. Raman spectra of Chemical Warfare Agents Simulants (CWAS) and Toxic Industrial Compounds (TIC) were measured in the laboratory at a 6.6 m source-target distance using continuous wave (CW) laser detection. Standoff distances for pulsed measurements were 35 m for dimethyl methylphosphonate (DMMP) detection and 60, 90 and 140 m for cyclohexane detection. The prototype systems consisted of a Raman spectrometer equipped with a CCD detector (for CW measurements) and an I-CCD camera with time-gated electronics (for pulsed laser measurements), a reflecting telescope, a fiber optic assembly, a single-line CW laser source (514.5, 488.0, 351.1 and 363.8 nm) and a frequency-doubled single frequency Nd:YAG 532 nm laser (5 ns pulses at 10 Hz). The telescope was coupled to the spectrograph using an optical fiber, and filters were used to reject laser radiation and Rayleigh scattering. Two quartz convex lenses were used to collimate the light from the telescope from which the telescope-focusing eyepiece was removed, and direct it to the fiber optic assembly. To test the standoff sensing system, the Raman Telescope was used in the detection of liquid TIC: benzene, chlorobenzene, toluene, carbon tetrachloride, cyclohexane and carbon disulfide. Other compounds studied were CWAS: dimethylmethyl phosphonate, 2-chloroethyl ethyl sulfide and 2-(butylamino)-ethanethiol. Relative Raman scattering cross sections of liquid CWAS were measured using single-line sources at 532.0, 488.0, 363.8 and 351.1 nm. Samples were placed in glass and quartz vials at the standoff distances from the telescope for the Remote Raman measurements. The mass of DMMP present in water solutions was also quantified as part of the system performance tests.

Pharmacological activity and toxicity of some neurotropic agents under conditions of experimental hypodynamia

NASA Technical Reports Server (NTRS)

Kirichek, L. T.

1980-01-01

The indices of pharmacological range, risk coefficients, ED50, LD50, the size of the area of toxic activity, and maximal tolerated and absolute lethal doses were compared in hypodynamic mice. The pharmacological activity of the test neurotropic agents exhibiting a central action underwent change, but their toxicity remained unchanged.

Toxicity of the organophosphate chemical warfare agents GA, GB, and VX: Implications for public protection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Munro, N.B.; Ambrose, K.R.; Watson, A.P.

1994-01-01

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 not evidence that itmore » 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 genotoxicity, the nerve agent exposure is the extraordinarily high acute toxicity of these substances. Futhermore, 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 release, 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. 187 refs., 3 figs., 7 tabs.« less

[Wet oxidation of toxic industrial waste with oxygenated water].

PubMed

Alfieri, M; Colombo, G; Velotti, R

1991-01-01

The industrial toxic waste streams hot treatment technology with hydrogen peroxide and catalysts, developed by the research laboratories of Montefluos in Bollate, allows the abatement of many organic and bio-toxic pollutants. Some treatment examples are here reported. The examples, performed on a laboratory scale, relate to industrial waste streams with a high COD (100000-200000 mg/l) in which it was possible to obtain an abatement over the 90% of pollutants like phenols, formaldehyde, dimethylformamide and phenyl acetate. The application range of this technology is similar to that of oxygen or air wet oxidation, but it has remarkable advantages due to the lower plant, maintenance and energy costs, because the treatment is performed using much more bland conditions (atmospheric pressure and 90-100 degrees C of temperature). The aim of the bio-toxic pollutants abatement and COD reduction (70-80%) is to allow the final bio-digestion waste streams with high organic content, but too diluted to be directly incenerated at a suitable cost.

Psychiatrists' relationships with industry: the principal-agent problem.

PubMed

Appelbaum, Paul S; Gold, Azgad

2010-01-01

Psychiatrists' relationships with the pharmaceutical and device industries have been a growing focus of attention, with questions raised about the impact of those relationships on prescribing practices, diagnostic criteria, practice guidelines, continuing education, conduct and reporting of research, and patients' and public trust. Indeed, these concerns exist for the medical profession as a whole, with various remedial measures proposed. We suggest that such relationships can be understood as giving rise to a "principal-agent problem," which occurs when an agent (here, a physician) is engaged to advance the interests of another party, the principal (typically a patient), but also faces incentives to promote other interests. Studies suggest that at least some relationships--which include attending industry-sponsored presentations, meeting with marketing representatives, and accepting samples--can alter psychiatrists' and other physicians' behavior in ways that can compromise patients' interests, and that industry-funded research may create bias in the medical literature. These effects are difficult to detect in specific cases, however, because of asymmetries of information and may not be apparent even to physicians themselves. Principal-agent analysis suggests that the possible responses to such problems, including appeals to ethical principles, monitoring behavior, and managing risk-inducing situations, should include consideration of aligning agents' incentives with principals' interests. This type of analysis underscores the similarity of the issues raised by physicians' relationships with industry to problems that arise more generally in society, thus reducing physicians' potential affective responses to these issues and efforts to address them. Finally, such analysis directs attention to the benefits and costs of each alternative, thereby encouraging reliance on evidence as a basis for policy.

EVALUATIVE PROCESS FOR ASSESSING HUMAN REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF AGENTS

EPA Science Inventory

Agents that may affect reproductive and developmental toxicity are of great concern to the general public. espite this, both the regulatory and public health arenas have been made somewhat haphazard use of the existing data when interpreting these health effects. ppropriate infor...

A Study on the D. magna and V. fischeri Toxicity Relationship of Industrial Wastewater from Korea

NASA Astrophysics Data System (ADS)

Pyo, S.; Lee, S.; Chun Sang, H.; Park, T. J.; Kim, M. S.

2015-12-01

It is well known that high concentration of TDS (total dissolved solid) in industrial effluent gives rise to the toxicity to the Daphnia magna toxicity test. D. magna is vulnerable to relatively low TDS concentration showing the 24-hr EC50 of Salinity 0.6% (as the sea salt concentration). Recently, standard mandatory toxicity testing using Daphnia magna has been used to monitor industrial effluent toxicity according to Korea standard method (Acute Toxicity Test Method of the Daphnia magna Straus (Cladocera, Crustacea), ES 04704. 1a) under regulation. Since only one acute toxicity testing is applied in the present, we are trying to introduce microbial battery for more complete toxicity assessment. In this study, the acute toxicities between daphnids and microbes were compared. The results of D. magna and Vibrio fischeri toxicity test from 165 industrial wastewater effluents showed high positive correlation. In addition, the possibility of predicting daphnia toxicity from the bacterial toxicity data amounts to 92.6% if we consider salinity effect (>5ppt) together. From this study, we found that the V. fischeri toxicity test is a powerful battery tool to assess the industrial wastewater toxicity. Here, we suggest that luminescent bacteria toxicity test be useful not only for complete toxicity assessment which can't be obtained by daphnia toxicity testing only but also for the reduction cost, time, and labor in the Korean society. Keywords : D. magna, V. fischeri, Industrial waste water, battery test Acknowledgement This research was supported by a grant (15IFIP-B089908-02) from Plant Research Program funded by Ministry of Land, Infrastructure and Transport of Korean government

Lipophilicity affects the pharmacokinetics and toxicity of local anaesthetic agents administered by caudal block.

PubMed

Nava-Ocampo, Alejandro A; Bello-Ramírez, Angélica M

2004-01-01

1. Drugs administered into the epidural space by caudal block are cleared by means of a process potentially affected by the lipophilic character of the compounds. 2. In the present study, we examined the relationship between the octanol-water partition coefficient (log Poct) and the time to reach the maximum plasma drug concentration (tmax) of lignocaine, bupivacaine and ropivacaine administered by caudal block in paediatric patients. We also examined the relationship between log Poct and the toxicity of these local anaesthetic agents in experimental models. The tmax and toxicity data were obtained from the literature. 3. Ropivacaine, with a log Poct of 2.9, exhibited a tmax of 61.6 min. The tmax of lignocaine, with a log Poct of 2.4, and bupivacaine, with a log Poct of with 3.4, were approximately 50% shorter than ropivacaine. At log Poct of approximately 3.0, the toxicity of these local anaesthetic agents was substantially increased. The relationship between log Poct and the convulsive effect in dogs was similar to the relationship between log Poct and the lethal dose in sheep. 4. With local anaesthetic agents, it appears that the relationship between log Poct and drug transfer from the epidural space to the blood stream is parabolic, being the slowest rate of transference at log Poct 3.0. Toxicity, due to plasma availability of these local anaesthetic agents, seems to be increased at log Poct equal or higher than 3.0 secondary to the highest transfer from plasma into the central nervous system.

Some Electrophysiological Methods for Studying the Action of Narcotic Agents in Animals, with special reference to Industrial Solvents: A Review

PubMed Central

Mikisková, Hana; Mikiska, Aloš

1968-01-01

Four electrophysiological methods, two based on stimulation (measurement of spinal reflex excitability and of direct excitability of the cerebral motor cortex) and two based on bioelectric recording (electro-encephalography and electrocardiography), were used in intact guinea-pigs and rabbits for studying the action of narcotic and anaesthetic agents, especially of industrial solvents. The authors' results have been reviewed and compared with those of other investigators in an attempt to work out experimental procedures for routine toxicity testing. PMID:4296739

Toxicity Studies on Antiradiation Agents.

DTIC Science & Technology

1979-03-01

Mice 193-403 WI 2823 Acute Oral and IP Toxicity in Guinea Pigs 193-404 WR 2823 14-Day IV Toxicity in Rats 193-405 WI 2823 Acute IV Toxicity in Dogs ...193-406 W 2823 14-Day Subacute IV Toxicity in Dogs 193-407 WI 2721 28-Day Oral Toxicity in Monkeys 193-408 WI 2529 Acute Oral Toxicity in Mice 193-409... Dogs 193-415 WI 149, 024 Acute IV Toxicity in Monkeys 193-416 WI 149, 024 2-Week IV Toxicity in Dogs 193-417 WI 149, 024 2-Week Toxicity in Monkeys 193

Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases.

PubMed

Bessac, Bret F; Sivula, Michael; von Hehn, Christian A; Caceres, Ana I; Escalera, Jasmine; Jordt, Sven-Eric

2009-04-01

The release of methyl isocyanate in Bhopal, India, caused the worst industrial accident in history. Exposures to industrial isocyanates induce lacrimation, pain, airway irritation, and edema. Similar responses are elicited by chemicals used as tear gases. Despite frequent exposures, the biological targets of isocyanates and tear gases in vivo have not been identified, precluding the development of effective countermeasures. We use Ca(2+) imaging and electrophysiology to show that the noxious effects of isocyanates and those of all major tear gas agents are caused by activation of Ca(2+) influx and membrane currents in mustard oil-sensitive sensory neurons. These responses are mediated by transient receptor potential ankyrin 1 (TRPA1), an ion channel serving as a detector for reactive chemicals. In mice, genetic ablation or pharmacological inhibition of TRPA1 dramatically reduces isocyanate- and tear gas-induced nocifensive behavior after both ocular and cutaneous exposures. We conclude that isocyanates and tear gas agents target the same neuronal receptor, TRPA1. Treatment with TRPA1 antagonists may prevent and alleviate chemical irritation of the eyes, skin, and airways and reduce the adverse health effects of exposures to a wide range of toxic noxious chemicals.

Respirometric biomonitor for the control of industrial effluent toxicity

NASA Astrophysics Data System (ADS)

Campanella, Luigi; Favero, G.; Mastrofini, D.; Tomassetti, M.

1995-10-01

A yeast cell biosystem has been recently developed for the total toxicity testing of a sample that may contain a number of different polluting species. The method uses an amperometric gas diffusion oxygen sensor as indicating electrode and is based on the perturbation of the respiratory activity of the immobilized yeast Saccharomyces cerevisiae; glucose acts as substrate. Several toxic substances were tested: metal ions, phenol and cationic, anionic or nonionic surfactants. Some results of a monitoring program of an industrial wastewater are also reported and discussed.

Clinical experience with drug delivery systems as tools to decrease the toxicity of anticancer chemotherapeutic agents.

PubMed

Maranhão, Raul C; Vital, Carolina G; Tavoni, Thauany M; Graziani, Silvia R

2017-10-01

The toxicity of chemotherapeutic agents, resulting from their low pharmacological index, introduces considerable discomfort and risk to cancer patients. Among several strategies to reduce the toxicity of chemotherapeutic agents, targeted drug delivery is the most promising one. Areas covered: Liposomes, micelles, albumin-based, polymeric, dendritic and lipid core nanoparticles have been used as carriers to concentrate anticancer drugs in neoplastic tissues, and clinical studies of those preparations are reviewed. In most clinical studies, drug delivery systems reduced drug toxicity. Lipid core nanoparticles (LDE) that bind to cell lipoprotein receptors have the ability to concentrate in neoplastic tissues and were the first artificial non-liposomal system shown in in vivo studies to possess targeting properties. The toxicity reduction achieved by LDE as vehicle of carmustine, etoposide and paclitaxel was singularly strong. Expert opinion: The reduced toxicity offered by drug delivery systems has expanded treatment population that may benefit from chemotherapy including feeble, overtreated and elderly patients that would otherwise be offered palliative therapy. Drug delivery systems may either prolong the duration of treatments or allow increases in drug dose.

Collective judicial management of mass toxic tort controversies: lessons and issues from the Agent Orange litigation.

PubMed

Novey, L B

1988-01-01

Viewing the Agent Orange litigation as a case study, this article explores the feasibility and desirability of strengthening the powers of the courts to manage toxic tort controversies en masse. The Agent Orange lawsuit, brought on behalf of potentially millions of Vietnam War veterans and family members, charged that herbicides used for military purposes during the war caused a wide range of health problems. This article first reviews the current national debate over how mass toxic tort controversies should be handled, including key legislative reform options, and describes how attention is increasingly focused on ways that the court system might better cope with mass toxic torts. The principal events of the Agent Orange litigation are then summarized, by which the litigation was consolidated into a massive class action, the class action was settled, and a streamlined plan for distributing the settlement fund was adopted. The article evaluates the outcome of the litigation, and discusses whether the solution there can and should be broadly applied to other mass toxic tort cases. This question depends, in part, on a series of complex legal and practical issues, but the author suggests that the question will also depend on what institutional role we expect the judiciary to play within society.

TIC-Tox: A preliminary discussion on identifying the forcing agents of DBP-mediated toxicity of disinfected water.

PubMed

Plewa, Michael J; Wagner, Elizabeth D; Richardson, Susan D

2017-08-01

The disinfection of drinking water is a major public health achievement; however, an unintended consequence of disinfection is the generation of disinfection by-products (DBPs). Many of the identified DBPs exhibit in vitro and in vivo toxicity, generate a diversity of adverse biological effects, and may be hazards to the public health and the environment. Only a few DBPs are regulated by several national and international agencies and it is not clear if these regulated DBPs are the forcing agents that drive the observed toxicity and their associated health effects. In this study, we combine analytical chemical and biological data to resolve the forcing agents associated with mammalian cell cytotoxicity of drinking water samples from three cities. These data suggest that the trihalomethanes (THMs) and haloacetic acids may be a small component of the overall cytotoxicity of the organic material isolated from disinfected drinking water. Chemical classes of nitrogen-containing DBPs, such as the haloacetonitriles and haloacetamides, appear to be the major forcing agents of toxicity in these samples. These findings may have important implications for the design of epidemiological studies that primarily rely on the levels of THMs to define DBP exposure among populations. The TIC-Tox approach constitutes a beginning step in the process of identifying the forcing agents of toxicity in disinfected water. Copyright © 2017. Published by Elsevier B.V.

VAPOR SAMPLING DEVICE FOR INTERFACE WITH MICROTOX ASSAY FOR SCREENING TOXIC INDUSTRIAL CHEMICALS

EPA Science Inventory

A time-integrated sampling system interfaced with a toxicity-based assay is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethyl sulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor...

Five years audit for presence of toxic agents/drug of abuse at autopsy.

PubMed

Ali, S Muhammad Aijaz; Khalil, Inayatur-ur-Rehman; Saeed, Ahmed; Hussain, Zahid

2003-09-01

To know the frequency of fatal poisoning in Peshawar regarding the toxic agents mostly involved and yearwise percentage. To know the age group and the gender that is most vulnerable to fatal poisoning. Non-interventional (descriptive) type. This study was conducted over a period of five years (1997-2001) at Forensic Medicine Department, Khyber Medical College, Peshawar. The study included 3508 autopsies conducted at Khyber Medical College, Peshawar. Out of these, 52 cases were those caused by fatal poisoning. These were analyzed according to age, gender and the toxic agent involved. t-test was applied as the test of significance. Poisoning was the cause of death in 1.48% of the total autopsies conducted during the five years. Males were more involved than the females, 90.38 %. Suicidal poisoning was present in 17.30% of the total cases and accidental poisoning was found in 80.72% cases, while homicidal cases were 1.29% only. Diacetylmorphine (heroin) was the most commonly involved agent, 65.38 %, of the total cases. The incidence of poisoning was more during the third and fourth decades of life. Diacetylmorphine (heroin) was the main causative agent involved in young males due to accidental over- dosage. Accidental and suicidal deaths should not be considered as inevitable. More elaborative studies are required in this area of recent research to adopt appropriate and adequate measures to save precious lives.

Toxicity Identification and Evaluation for the Effluent from Wastewater Treatment Plant in Industrial Complex using D.magna

NASA Astrophysics Data System (ADS)

Lee, S.; Keum, H.; Chun Sang, H.

2015-12-01

In recent years, the interests on the impacts of industrial wastewater on aquatic ecosystem have increased with concern about ecosystem protection and human health. Whole effluent toxicity tests are used to monitor toxicity by unknown toxic chemicals as well as conventional pollutants from industrial effluent discharges. This study describes the application of TIE (toxicity identification evaluation) procedures to an acutely toxic effluent from a wastewater treatment plant in industrial complex which was toxic to Daphnia magna. In TIE phase I (characterization step), the toxic effects by heavy metals, organic compounds, oxidants, volatile organic compounds, suspended solids and ammonia were screened and revealed that the source of toxicity is far from these toxicants group. Chemical analysis (TIE phase II) on TDS showed that the concentration of chloride ion (6,900 mg/L) was substantially higher than that predicted from EC50 for D. magna. In confirmation step (TIE phase III), chloride ion was demonstrated to be main toxicant in this effluent by the spiking approach, species sensitivity approach and deletion approach. Calcium, potassium, magnesium, sodium, fluorine, sulfate ion concentration (450, 100, 80, 5,300, 0.66, 2,200mg/L) was not shown toxicity from D. magna. Finally, we concluded that chloride was the most contributing toxicant in the waste water treatment plant. Further research activities are needed for technical support of toxicity identification and evaluation on the various types of wastewater treatment plant discharge in Korea. Keywords : TIE, D. magna, Industrial waste water Acknowledgement This research was supported by a grant (15IFIP-B089908-02) from Plant Research Program funded by Ministry of Land, Infrastructure and Transport of Korean government

Diet composition exacerbates or attenuates soman toxicity in rats: implied metabolic control of nerve agent toxicity.

PubMed

Myers, Todd M; Langston, Jeffrey L

2011-06-01

To evaluate the role of diet composition on nerve agent toxicity, rats were fed four distinct diets ad libitum for 28 d prior to challenge with 110 μg/kg (1.0 LD(50), sc) soman. The four diets used were a standard rodent diet, a choline-enriched diet, a glucose-enriched diet, and a ketogenic diet. Body weight was recorded throughout the study. Toxic signs and survival were evaluated at key times for up to 72 h following soman exposure. Additionally, acquisition of discriminated shuttlebox avoidance performance was characterized beginning 24h after soman challenge and across the next 8 d (six behavioral sessions). Prior to exposure, body weight was highest in the standard diet group and lowest in the ketogenic diet group. Upon exposure, differences in soman toxicity as a function of diet became apparent within the first hour, with mortality in the glucose-enriched diet group reaching 80% and exceeding all other groups (in which mortality ranged from 0 to 6%). At 72 h after exposure, mortality was 100% in the glucose-enriched diet group, and survival approximated 50% in the standard and choline-enriched diet groups, but equaled 87% in the ketogenic diet group. Body weight loss was significantly reduced in the ketogenic and choline-enriched diet groups, relative to the standard diet group. At 1 and 4h after exposure, rats in the ketogenic diet group had significantly lower toxic sign scores than all other groups. The ketogenic diet group performed significantly better than the standard diet group on two measures of active avoidance performance. The exacerbated soman toxicity observed in the glucose-enriched diet group coupled with the attenuated soman toxicity observed in the ketogenic diet group implicates glucose availability in the toxic effects of soman. This increased glucose availability may enhance acetylcholine synthesis and/or utilization, thereby exacerbating peripheral and central soman toxicity. Published by Elsevier B.V.

In vitro toxicities of experimental jet fuel system ice-inhibiting agents.

PubMed

Geiss, K T; Frazier, J M

2001-07-02

One research emphasis within the Department of Defense has been to seek the replacement of operational compounds with alternatives that pose less potential risk to human and ecological systems. Alternatives to glycol ethers, such as diethylene glycol monomethyl ether (M-DE), were investigated for use as jet fuel system ice-inhibiting agents (FSIIs). This group of chemicals includes three derivatives of 1,3-dioxolane-4-methanol (M-1, M-2, and M-3) and a 1,3-dioxane (M-27). In addition, M-DE was evaluated as a reference compound. Our approach was to implement an in vitro test battery based on primary rat hepatocyte cultures to perform initial toxicity evaluations. Hepatocytes were exposed to experimental chemicals (0, 0.001, 0.01, 0.1, 1, 10 mM dosages) for periods up to 24 h. Samples were assayed for lactate dehydrogenase (LDH) release, MTT dye reduction activity, glutathione level, and rate of protein synthesis as indicators of toxicity. Of the compounds tested, M-1, especially at the 10-mM dose, appeared to be more potent than the other chemicals, as measured by these toxicity assays. M-DE, the current FSII, elicited little response in the toxicity assays. Although some variations in toxicity were observed at the 10-mM dose, the in vitro toxicities of the chemicals tested (except for M-1) were not considerably greater than that of M-DE.

Assessing the relationship between toxicity and economic cost of oncological target agents: A systematic review of clinical trials

PubMed Central

Tartari, Francesca; Conti, Alessandro

2017-01-01

Target agents are peculiar oncological drugs which differ from the traditional therapies in their ability of recognizing specific molecules expressed by tumor cells and microenvironment. Thus, their toxicity is generally lower than that associated to chemotherapy, and they represent nowadays a new standard of care in a number of tumors. This paper deals with the relationship between economic costs and toxicity of target agents. At this aim, a cluster analysis-based exploration of the main features of a large collection of them is carried out, with a specific focus on the variables leading to the identification of their toxicity and related costs. The analysis of the toxicity is based on the Severe Adverse Events (SAE) and Discontinuation (D) rates of each target agent considering data published on PubMed from 1965 to 2016 in the phase II and III studies that have led to the approval of these drugs for cancer patients by US Food and Drug Administration. The construction of the dataset represents a key step of the research, and is grounded on the critical analysis of a wide set of clinical studies. In order to capture different evaluation strategies of the toxicity, clustering is performed according to three different criteria (including Voronoi tessellation). Our procedure allows us to identify 5 different groups of target agents pooled by similar SAE and D rates and, at the same time, 3 groups based on target agents’ costs for 1 month and for the median whole duration of therapy. Results highlight several specific regularities for toxicity and costs. This study present several limitations, being realized starting from clinical trials and not from individual patients’ data. However, a macroscopic perspective suggests that costs are rather heterogeneous, and they do not clearly follow the clustering based on SAE and D rates. PMID:28829823

Toxicity and medical countermeasure studies on the organophosphorus nerve agents VM and VX

PubMed Central

Rice, Helen; Dalton, Christopher H.; Price, Matthew E.; Graham, Stuart J.; Green, A. Christopher; Jenner, John; Groombridge, Helen J.; Timperley, Christopher M.

2015-01-01

To support the effort to eliminate the Syrian Arab Republic chemical weapons stockpile safely, there was a requirement to provide scientific advice based on experimentally derived information on both toxicity and medical countermeasures (MedCM) in the event of exposure to VM, VX or VM–VX mixtures. Complementary in vitro and in vivo studies were undertaken to inform that advice. The penetration rate of neat VM was not significantly different from that of neat VX, through either guinea pig or pig skin in vitro. The presence of VX did not affect the penetration rate of VM in mixtures of various proportions. A lethal dose of VM was approximately twice that of VX in guinea pigs poisoned via the percutaneous route. There was no interaction in mixed agent solutions which altered the in vivo toxicity of the agents. Percutaneous poisoning by VM responded to treatment with standard MedCM, although complete protection was not achieved. PMID:27547080

Toxicity and medical countermeasure studies on the organophosphorus nerve agents VM and VX.

PubMed

Rice, Helen; Dalton, Christopher H; Price, Matthew E; Graham, Stuart J; Green, A Christopher; Jenner, John; Groombridge, Helen J; Timperley, Christopher M

2015-04-08

To support the effort to eliminate the Syrian Arab Republic chemical weapons stockpile safely, there was a requirement to provide scientific advice based on experimentally derived information on both toxicity and medical countermeasures (MedCM) in the event of exposure to VM, VX or VM-VX mixtures. Complementary in vitro and in vivo studies were undertaken to inform that advice. The penetration rate of neat VM was not significantly different from that of neat VX, through either guinea pig or pig skin in vitro . The presence of VX did not affect the penetration rate of VM in mixtures of various proportions. A lethal dose of VM was approximately twice that of VX in guinea pigs poisoned via the percutaneous route. There was no interaction in mixed agent solutions which altered the in vivo toxicity of the agents. Percutaneous poisoning by VM responded to treatment with standard MedCM, although complete protection was not achieved.

Development of Medical Technology for Contingency Response to Marrow Toxic Agents

DTIC Science & Technology

2014-05-06

Development of Medical Technology for Contingency Response to Marrow Toxic Agents - Final Performance/Technical Report for January 01, 2011 to...Enhancing HLA Data for Selected Donors 44 IIB.1.6 Maintain a Quality Control Program 44 IIB.2.1 Collection of Primary Data 45 IIB.2.2 Validation of...Receptor Donor Selection KORI Korean LD Linkage Disequilibrium LTA Lymphotoxin Alpha MALDI-TOF Matrix-Assisted Laser Desorption/Ionization – Time Of

Intracellular haemolytic agents of Heterocapsa circularisquama exhibit toxic effects on H. circularisquama cells themselves and suppress both cell-mediated haemolytic activity and toxicity to rotifers (Brachionus plicatilis).

PubMed

Nishiguchi, Tomoki; Cho, Kichul; Yasutomi, Masumi; Ueno, Mikinori; Yamaguchi, Kenichi; Basti, Leila; Yamasaki, Yasuhiro; Takeshita, Satoshi; Kim, Daekyung; Oda, Tatsuya

2016-10-01

A harmful dinoflagellate, Heterocapsa circularisquama, is highly toxic to shellfish and the zooplankton rotifer Brachionus plicatilis. A previous study found that H. circularisquama has both light-dependent and -independent haemolytic agents, which might be responsible for its toxicity. Detailed analysis of the haemolytic activity of H. circularisquama suggested that light-independent haemolytic activity was mediated mainly through intact cells, whereas light-dependent haemolytic activity was mediated by intracellular agents which can be discharged from ruptured cells. Because H. circularisquama showed similar toxicity to rotifers regardless of the light conditions, and because ultrasonic ruptured H. circularisquama cells showed no significant toxicity to rotifers, it was suggested that live cell-mediated light-independent haemolytic activity is a major factor responsible for the observed toxicity to rotifers. Interestingly, the ultrasonic-ruptured cells of H. circularisquama suppressed their own lethal effect on the rotifers. Analysis of samples of the cell contents (supernatant) and cell fragments (precipitate) prepared from the ruptured H. circularisquama cells indicated that the cell contents contain inhibitors for the light-independent cell-mediated haemolytic activity, toxins affecting H. circularisquama cells themselves, as well as light-dependent haemolytic agents. Ethanol extract prepared from H. circularisquama, which is supposed to contain a porphyrin derivative that displays photosensitising haemolytic activity, showed potent toxicity to Chattonella marina, Chattonella antiqua, and Karenia mikimotoi, as well as to H. circularisquama at the concentration range at which no significant toxicity to rotifers was observed. Analysis on a column of Sephadex LH-20 revealed that light-dependent haemolytic activity and inhibitory activity on cell-mediated light-independent haemolytic activity existed in two separate fractions (f-2 and f-3), suggesting that both

Monitoring of toxic elements present in sludge of industrial waste using CF-LIBS.

PubMed

Kumar, Rohit; Rai, Awadhesh K; Alamelu, Devanathan; Aggarwal, Suresh K

2013-01-01

Industrial waste is one of the main causes of environmental pollution. Laser-induced breakdown spectroscopy (LIBS) was applied to detect the toxic metals in the sludge of industrial waste water. Sludge on filter paper was obtained after filtering the collected waste water samples from different sections of a water treatment plant situated in an industrial area of Kanpur City. The LIBS spectra of the sludge samples were recorded in the spectral range of 200 to 500 nm by focusing the laser light on sludge. Calibration-free laser-induced breakdown spectroscopy (CF-LIBS) technique was used for the quantitative measurement of toxic elements such as Cr and Pb present in the sample. We also used the traditional calibration curve approach to quantify these elements. The results obtained from CF-LIBS are in good agreement with the results from the calibration curve approach. Thus, our results demonstrate that CF-LIBS is an appropriate technique for quantitative analysis where reference/standard samples are not available to make the calibration curve. The results of the present experiment are alarming to the people living nearby areas of industrial activities, as the concentrations of toxic elements are quite high compared to the admissible limits of these substances.

Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

NASA Astrophysics Data System (ADS)

Nam, I. F.; Zhuk, V. V.

2015-04-01

Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

Regulation of priority carcinogens and reproductive or developmental toxicants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hooper, K.; LaDou, J.; Rosenbaum, J.S.

In California, 370 carcinogens and 112 reproductive/developmental toxicants have been identified as a result of the State's Safe Drinking Water and Toxic Enforcement Act of 1986. They include pesticides, solvents, metals, industrial intermediates, environmental mixtures, and reactive agents. Occupational, environmental, and consumer product exposures that involve these agents are regulated under the Act. At levels of concern, businesses must provide warnings for and limit discharges of those chemicals. The lists of chemicals were compiled following systematic review of published data, including technical reports from the U.S. Public Health Service--National Toxicology Program (NTP), and evaluation of recommendations from authoritative bodies suchmore » as the International Agency for Research on Cancer (IARC) and the U.S. Environmental Protection Agency (USEPA). Given the large number of chemicals that are carcinogens or reproductive/developmental toxicants, regulatory concerns should focus on those that have high potential for human exposure, e.g., widely distributed or easily absorbed solvents, metals, environmental mixtures, or reactive agents. In this paper, we present a list of 33 potential priority carcinogens and reproductive/developmental toxicants, including alcoholic beverages, asbestos, benzene, chlorinated solvents, formaldehyde, glycol ethers, lead, tobacco smoke, and toluene.« less

Regulation of priority carcinogens and reproductive or developmental toxicants.

PubMed

Hooper, K; LaDou, J; Rosenbaum, J S; Book, S A

1992-01-01

In California, 370 carcinogens and 112 reproductive/developmental toxicants have been identified as a result of the State's Safe Drinking Water and Toxic Enforcement Act of 1986. They include pesticides, solvents, metals, industrial intermediates, environmental mixtures, and reactive agents. Occupational, environmental, and consumer product exposures that involve these agents are regulated under the Act. At levels of concern, businesses must provide warnings for and limit discharges of those chemicals. The lists of chemicals were compiled following systematic review of published data, including technical reports from the U.S. Public Health Service--National Toxicology Program (NTP), and evaluation of recommendations from authoritative bodies such as the International Agency for Research on Cancer (IARC) and the U.S. Environmental Protection Agency (USEPA). Given the large number of chemicals that are carcinogens or reproductive/developmental toxicants, regulatory concerns should focus on those that have high potential for human exposure, e.g., widely distributed or easily absorbed solvents, metals, environmental mixtures, or reactive agents. In this paper, we present a list of 33 potential priority carcinogens and reproductive/developmental toxicants, including alcoholic beverages, asbestos, benzene, chlorinated solvents, formaldehyde, glycol ethers, lead, tobacco smoke, and toluene.

On the engineering design for systematic integration of agent-orientation in industrial automation.

PubMed

Yu, Liyong; Schüller, Andreas; Epple, Ulrich

2014-09-01

In today's automation industry, agent-oriented development of system functionalities appears to have a great potential for increasing autonomy and flexibility of complex operations, while lowering the workload of users. In this paper, we present a reference model for the harmonious and systematical integration of agent-orientation in industrial automation. Considering compatibility with existing automation systems and best practice, this model combines advantages of function block technology, service orientation and native description methods from the automation standard IEC 61131-3. This approach can be applied as a guideline for the engineering design of future agent-oriented automation systems. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Stoichiometric and catalytic scavengers as protection against nerve agent toxicity: a mini review.

PubMed

Lenz, David E; Yeung, David; Smith, J Richard; Sweeney, Richard E; Lumley, Lucille A; Cerasoli, Douglas M

2007-04-20

Currently fielded treatments for nerve agent intoxication promote survival, but do not afford complete protection against either nerve agent-induced motor and cognitive deficits or neuronal pathology. The use of human plasma-derived butyrylcholinesterase (HuBuChE) to neutralize the toxic effects of nerve agents in vivo has been shown to both aid survival and protect against decreased cognitive function after nerve agent exposure. Recently, a commercially produced recombinant form of human butyrylcholinesterase (r-HuBuChE; PharmAthene Inc.) expressed in the milk of transgenic goats has become available. This material is biochemically similar to plasma-derived HuBuChE in in vitro assays. The pharmacokinetic characteristics of a polyethylene glycol coated (pegylated) form of r-HuBuChE were determined in guinea pigs; the enzyme was rapidly bioavailable with a half-life (t(1/2)) and pharmacokinetic profile that resembled that of plasma-derived huBuChE. Guinea pigs were injected with 140mg/kg (i.m.) of pegylated r-HuBuChE 18h prior to exposure (sc) to 5.5xLD(50) VX or soman. VX and soman were administered in a series of three injections of 1.5xLD(50), 2.0xLD(50), and 2.0xLD(50), respectively, with injections separated by 2h. Pretreatment with pegylated r-HuBuChE provided 100% survival against multiple lethal doses of VX and soman. Guinea pigs displayed no signs of nerve agent toxicity following exposure. Assessments of motor activity, coordination, and acquisition of spatial memory were performed for 2 weeks following nerve agent exposure. There were no measurable decreases in motor or cognitive function during this period. In contrast, animals receiving 1.5xLD(50) challenges of soman or VX and treated with standard atropine, 2-PAM, and diazepam therapy showed 50 and 100% survival, respectively, but exhibited marked decrements in motor function and, in the case of GD, impaired spatial memory acquisition. The advances in this field have resulted in the decision to select

Preparation and mechanism analysis of an environment-friendly maize seed coating agent.

PubMed

Zeng, Defang; Fan, Zhao; Tian, Xu; Wang, Wenjin; Zhou, Mingchun; Li, Haochuan

2018-06-01

Traditional seed coating agents often contain toxic ingredients, which contaminate the environment and threaten human health. This paper expounds a method of preparing a novel environment-friendly seed coating agent for maize and researches its mechanism of action. The natural polysaccharide polymer, which is the main active ingredient of this environment-friendly seed coating agent, has the characteristics of innocuity and harmlessness, and it can replace the toxic ingredients used in traditional seed coating agents. This environment-friendly seed coating agent for maize was mainly made up of the natural polysaccharide polymer and other additives. The field trials results showed that the control efficacy of Helminthosporium maydis came to 93.72%, the anti-feeding rate of cutworms came to 81.29%, and the maize yield was increased by 17.75%. Besides, the LD 50 value (half the lethal dose in rats) of this seed coating agent was 10 times higher than that of the traditional seed coating agents. This seed coating agent could improve the activity of plant protective enzymes (peroxidase, catalase and superoxidase dismutase) and increase the chlorophyll content. This seed coating agent has four characteristics of disease prevention, desinsectization, increasing yield and safety. Results of mechanism analyses showed that this seed coating agent could enhance disease control effectiveness by improving plant protective enzymes activity and increase maize yield by improving chlorophyll content. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Reactive formulations for a neutralization of toxic industrial chemicals

DOEpatents

Tucker, Mark D [Albuqueruqe, NM; Betty, Rita G [Rio Rancho, NM

2006-10-24

Decontamination formulations for neutralization of toxic industrial chemicals, and methods of making and using same. The formulations are effective for neutralizing malathion, hydrogen cyanide, sodium cyanide, butyl isocyanate, carbon disulfide, phosgene gas, capsaicin in commercial pepper spray, chlorine gas, anhydrous ammonia gas; and may be effective at neutralizing hydrogen sulfide, sulfur dioxide, formaldehyde, ethylene oxide, methyl bromide, boron trichloride, fluorine, tetraethyl pyrophosphate, phosphorous trichloride, arsine, and tungsten hexafluoride.

Decomposition of toxicity emission changes on the demand and supply sides: empirical study of the US industrial sector

NASA Astrophysics Data System (ADS)

Fujii, Hidemichi; Okamoto, Shunsuke; Kagawa, Shigemi; Managi, Shunsuke

2017-12-01

This study investigated the changes in the toxicity of chemical emissions from the US industrial sector over the 1998-2009 period. Specifically, we employed a multiregional input-output analysis framework and integrated a supply-side index decomposition analysis (IDA) with a demand-side structural decomposition analysis (SDA) to clarify the main drivers of changes in the toxicity of production- and consumption-based chemical emissions. The results showed that toxic emissions from the US industrial sector decreased by 83% over the studied period because of pollution abatement efforts adopted by US industries. A variety of pollution abatement efforts were used by different industries, and cleaner production in the mining sector and the use of alternative materials in the manufacture of transportation equipment represented the most important efforts.

Monitoring and Management of Toxicities of Novel B Cell Signaling Agents.

PubMed

Rhodes, Joanna; Mato, Anthony; Sharman, Jeff P

2018-04-11

B cell signaling agents, including ibrutinib, idelalisib, and the BCL-2 inhibitor venetoclax have become an integral part of therapy for patients with non-Hodgkin's lymphomas. The toxicity profiles of these medications is distinct from chemoimmunotherapy. Here, we will review the mechanism of action of these drugs, their efficacy, and toxicity management. Ibrutinib use is associated with increased risk of atrial fibrillation and bleeding which can be managed using dose interruptions and modifications. Patients on idelalisib require close clinical and frequent laboratory monitoring, particularly of liver function tests to ensure there are no serious adverse events. Monitoring for infections is important in patients on both idelalisib and ibrutinib. Venetoclax requires close clinical and laboratory monitoring to prevent significant tumor lysis. Targeted B cell receptor therapies each have unique side effect profiles which require careful clinical monitoring. As we continue to use these therapies, optimal management strategies will continue to be elucidated.

A multi-agent safety response model in the construction industry.

PubMed

Meliá, José L

2015-01-01

The construction industry is one of the sectors with the highest accident rates and the most serious accidents. A multi-agent safety response approach allows a useful diagnostic tool in order to understand factors affecting risk and accidents. The special features of the construction sector can influence the relationships among safety responses along the model of safety influences. The purpose of this paper is to test a model explaining risk and work-related accidents in the construction industry as a result of the safety responses of the organization, the supervisors, the co-workers and the worker. 374 construction employees belonging to 64 small Spanish construction companies working for two main companies participated in the study. Safety responses were measured using a 45-item Likert-type questionnaire. The structure of the measure was analyzed using factor analysis and the model of effects was tested using a structural equation model. Factor analysis clearly identifies the multi-agent safety dimensions hypothesized. The proposed safety response model of work-related accidents, involving construction specific results, showed a good fit. The multi-agent safety response approach to safety climate is a useful framework for the assessment of organizational and behavioral risks in construction.

Evaluate the use of tanning agent in leather industry using material flow analysis, life cycle assessment and fuzzy multi-attribute decision making (FMADM)

NASA Astrophysics Data System (ADS)

Alfarisi, Salman; Sutono, Sugoro Bhakti; Sutopo, Wahyudi

2017-11-01

Tanning industry is one of the companies that produce many pollutants and cause the negative impact on the environment. In the production process of tanning leather, the use of input material need to be evaluated. The problem of waste, not only have a negative impact on the environment, but also human health. In this study, the impact of mimosa as vegetable tanning agent evaluated. This study will provide alternative solutions for improvements to the use of vegetable tanning agent. The alternative solution is change mimosa with indusol, gambier, and dulcotan. This study evaluate the vegetable tanning of some aspects using material flow analysis and life cycle assessment approach. Life cycle assessment (LCA) is used to evaluate the environmental impact of vegetable tanning agent. Alternative solution selection using fuzzy multi-attribute decision making (FMADM) approach. Results obtained by considering the environment, human toxicity, climate change, and marine aquatic ecotoxicity, is to use dulcotan.

Acute and Chronic Toxicity of Soluble Fractions of Industrial Solid Wastes on Daphnia magna and Vibrio fischeri

PubMed Central

Flohr, Letícia; de Castilhos Júnior, Armando Borges; Matias, William Gerson

2012-01-01

Industrial wastes may produce leachates that can contaminate the aquatic ecosystem. Toxicity testing in acute and chronic levels is essential to assess environmental risks from the soluble fractions of these wastes, since only chemical analysis may not be adequate to classify the hazard of an industrial waste. In this study, ten samples of solid wastes from textile, metal-mechanic, and pulp and paper industries were analyzed by acute and chronic toxicity tests with Daphnia magna and Vibrio fischeri. A metal-mechanic waste (sample MM3) induced the highest toxicity level to Daphnia magna(CE50,48 h = 2.21%). A textile waste induced the highest toxicity level to Vibrio fischeri (sample TX2, CE50,30 min = 12.08%). All samples of pulp and paper wastes, and a textile waste (sample TX2) induced chronic effects on reproduction, length, and longevity of Daphnia magna. These results could serve as an alert about the environmental risks of an inadequate waste classification method. PMID:22619632

Acute and chronic toxicity of soluble fractions of industrial solid wastes on Daphnia magna and Vibrio fischeri.

PubMed

Flohr, Letícia; de Castilhos Júnior, Armando Borges; Matias, William Gerson

2012-01-01

Industrial wastes may produce leachates that can contaminate the aquatic ecosystem. Toxicity testing in acute and chronic levels is essential to assess environmental risks from the soluble fractions of these wastes, since only chemical analysis may not be adequate to classify the hazard of an industrial waste. In this study, ten samples of solid wastes from textile, metal-mechanic, and pulp and paper industries were analyzed by acute and chronic toxicity tests with Daphnia magna and Vibrio fischeri. A metal-mechanic waste (sample MM3) induced the highest toxicity level to Daphnia magna(CE(50,48 h) = 2.21%). A textile waste induced the highest toxicity level to Vibrio fischeri (sample TX2, CE(50,30 min) = 12.08%). All samples of pulp and paper wastes, and a textile waste (sample TX2) induced chronic effects on reproduction, length, and longevity of Daphnia magna. These results could serve as an alert about the environmental risks of an inadequate waste classification method.

76 FR 72952 - Guidance for Industry on Nonclinical Evaluation of Late Radiation Toxicity of Therapeutic...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-28

... effects of therapeutic radiopharmaceutical agents. This guidance is not intended to address late radiation... and is often self-limiting and reversible. In contrast, late radiation toxicity (e.g., renal failure...

Assessment of combined toxicity of heavy metals from industrial wastewaters on Photobacterium phosphoreum T3S

NASA Astrophysics Data System (ADS)

Zeb, BibiSaima; Ping, Zheng; Mahmood, Qaisar; Lin, Qiu; Pervez, Arshid; Irshad, Muhammad; Bilal, Muhammad; Bhatti, Zulfiqar Ahmad; Shaheen, Shahida

2017-07-01

This research work is focusing on the toxicities of heavy metals of industrial origin to anaerobic digestion of the industrial wastewater. Photobacterium phosphoreum T3S was used as an indicator organism. The acute toxicities of heavy metals on P. phosphoreum T3S were assessed during 15-min half inhibitory concentration (IC50) as indicator at pH 5.5-6. Toxicity assays involved the assessment of multicomponent mixtures using TU and MTI approaches. The results of individual toxicity indicated that the toxicity of Cd, Cu and Pb on P. phosphoreum increased with increasing concentrations and there was a linear correlation. The 15-min IC50 values of Cd, Cu and Pb were 0.537, 1.905 and 1.231 mg/L, respectively, and their toxic order was Cd > Pb > Cu. The combined effects of Cd, Cu and Pb were assayed by equivalent concentration mixing method. The results showed that the combined effects of Cd + Cu, Cd + Pb, Cu + Pb, Cd + Cu + Pb were antagonistic, antagonistic and partly additive. The combined effect of three heavy metals was partly additive.

Unacceptable "occupational" exposure to toxic agents among children in Ecuador.

PubMed

Harari, R; Forastiere, F; Axelson, O

1997-09-01

To document the problem of child labor as a health issue, we report here three case-studies in Ecuador: exposure to mercury among gold washers, exposure to organophosphates and carbamates in the fruit-growing industry, and exposure to solvents among shoe cleaners. We measured the relevant biological indicators of exposure (mercury in urine, urinary levels of phenols, and acetylcholine esterase in erythrocytes) among selected samples of 10 children for each working place. In all the case studies, the values of the biological indicators showed elevated exposure to well-known toxicants, which are now rare in developed countries, even among adult workers. The findings meld with a previously reported case study of intoxication from inorganic lead among children employed in the manufacture of roof tiles in Ecuador. This study highlights the need to properly evaluate and control the potential health effects due to exposure to toxic substances among children employed in different occupations in several parts of the world.

Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolite.

PubMed

Priyandoko, Didik; Ishii, Tetsuro; Kaul, Sunil C; Wadhwa, Renu

2011-05-04

The present day lifestyle heavily depends on industrial chemicals in the form of agriculture, cosmetics, textiles and medical products. Since the toxicity of the industrial chemicals has been a concern to human health, the need for alternative non-toxic natural products or adjuvants that serve as antidotes are in high demand. We have investigated the effects of Ayurvedic herb Ashwagandha (Withania somnifera) leaf extract on methoxyacetic acid (MAA) induced toxicity. MAA is a major metabolite of ester phthalates that are commonly used in industry as gelling, viscosity and stabilizer reagents. We report that the MAA cause premature senescence of normal human cells by mechanisms that involve ROS generation, DNA and mitochondrial damage. Withanone protects cells from MAA-induced toxicity by suppressing the ROS levels, DNA and mitochondrial damage, and induction of cell defense signaling pathways including Nrf2 and proteasomal degradation. These findings warrant further basic and clinical studies that may promote the use of withanone as a health adjuvant in a variety of consumer products where the toxicity has been a concern because of the use of ester phthalates.

Ashwagandha Leaf Derived Withanone Protects Normal Human Cells Against the Toxicity of Methoxyacetic Acid, a Major Industrial Metabolite

PubMed Central

Priyandoko, Didik; Ishii, Tetsuro; Kaul, Sunil C.; Wadhwa, Renu

2011-01-01

The present day lifestyle heavily depends on industrial chemicals in the form of agriculture, cosmetics, textiles and medical products. Since the toxicity of the industrial chemicals has been a concern to human health, the need for alternative non-toxic natural products or adjuvants that serve as antidotes are in high demand. We have investigated the effects of Ayurvedic herb Ashwagandha (Withania somnifera) leaf extract on methoxyacetic acid (MAA) induced toxicity. MAA is a major metabolite of ester phthalates that are commonly used in industry as gelling, viscosity and stabilizer reagents. We report that the MAA cause premature senescence of normal human cells by mechanisms that involve ROS generation, DNA and mitochondrial damage. Withanone protects cells from MAA-induced toxicity by suppressing the ROS levels, DNA and mitochondrial damage, and induction of cell defense signaling pathways including Nrf2 and proteasomal degradation. These findings warrant further basic and clinical studies that may promote the use of withanone as a health adjuvant in a variety of consumer products where the toxicity has been a concern because of the use of ester phthalates. PMID:21573189

Renal toxicity of anticancer agents targeting vascular endothelial growth factor (VEGF) and its receptors (VEGFRs).

PubMed

Cosmai, Laura; Gallieni, Maurizio; Liguigli, Wanda; Porta, Camillo

2017-04-01

Since angiogenesis plays a key role in tumor growth, progression and metastasization, anti-vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) agents have been developed over the years as anticancer agents, and have changed, for the better, the natural history of a number of cancer types. In the present review, the renal safety profile of presently available agents targeting either VEGF or VEGFRs will be discussed, together with the peculiarities related to their clinical use in patients with impaired renal function, or even in dialysis. Indeed, renal toxicity (especially, but not exclusively, hypertension and proteinuria) are quite commonly observed with these agents, and may be increased by the concomitant use of cytoxic chemotherapeutics. Despite all the above, kidney impairment or dialysis must not be regarded di per se as reasons not to administer or to stop an active anticancer treatment, especially considering the possibility of a significant survival improvement in many cancer patients treated with these agents.

Oxidative toxic stress in workers occupationally exposed to ceramic dust: A study in a ceramic manufacturing industry.

PubMed

Shad, Mehri Keshvari; Barkhordari, Abolfaz; Mehrparvar, Amir Houshang; Dehghani, Ali; Ranjbar, Akram; Moghadam, Rashid Heidari

2016-09-27

Exposure to compounds used in ceramic industries appears to be associated with induction of oxidative toxic stress. This cross sectional study was undertaken to assess the oxidative toxic stress parameters associated with occupational exposure to ceramic dust. Forty ceramic-exposed workers from a ceramic manufacturing industry and 40 unexposed referent subjects were studied. A questionnaire containing information regarding demographic variables, occupational history, history of any chronic disease, antioxidant consumption, and use of therapeutic drugs was administrated to them. Oxidative toxic stress biomarkers including lipid peroxidation (LPO), total antioxidant power (TAP), levels of total Thiol groups (TTG) and catalase (CAT) activity were measured. Significant increments in blood LPO levels, CAT activity and concomitant lower TAP were observed in ceramic exposed workers in comparison to referent group. No statistically significant difference was noted between the means of TTG levels between the groups. Findings of the study indicate that occupational exposure to ceramic dust induces oxidative toxic stress. Supplementation of workers with antioxidants may have beneficial effects on oxidative damages in ceramic industries.

Suicide attempts by exposure to toxic agents registered in a Toxicological Information and Assistance Center in Fortaleza, Ceará, Brazil, 2013.

PubMed

Gondim, Ana Paula Soares; Nogueira, Rachel Rabay; Lima, João Gabriel Barbosa; Lima, Rayra Aguiar Campos; Albuquerque, Polianna Lemos Moura Moreira; Veras, Maria do Socorro Batista; Ferreira, Maria Augusta Drago

2017-01-01

to describe cases of suicide attempts by exposure to toxic agents registered by the Toxicological Information and Assistance Center in Fortaleza, Ceará, Brazil. this is a descriptive study using secondary data of the cases registered in 2013. 410 cases were registered; 56.2% of the individuals were female and 79.7% were between 12 and 39 years old; most of them (86.4%) lived in urban areas and 67.2%, in Fortaleza; in 94.9% of the cases, the exposure took place in the individual's own home; the toxic agents most commonly used were pesticides (42.9%), especially for agricultural use (30.2%), medicines (39.5%) and house cleaning products (3.4%); of 16 suicide attempts that resulted in death, 15 were caused by agricultural pesticides. the study shows that the intake of toxic agents, especially of agricultural pesticides, is a common method used in suicide attempts; the integration between actions of promotion and prevention are essential.

Fast detection of toxic industrial compounds by laser ion mobility spectrometry

NASA Astrophysics Data System (ADS)

Oberhuettinger, Carola; Langmeier, Andreas; Oberpriller, Helmut; Kessler, Matthias; Goebel, Johann; Mueller, Gerhard

2009-05-01

Trace detection of toxic industrial compounds has been investigated with the help of a laser ion mobility spectrometer (LIMS). The LIMS was equipped with a tuneable UV laser source for enabling two-photon ionization of the analyte gases and an ion drift tube for the measurement of the ion mobility. Different aromatic and aliphatic hydrocarbons as well as amines were investigated. We find that the first class of molecules can be well ionized due to the delocalization of their valence electron shells and the second due to the presence of non-bonding electrons in lone-pair orbitals. Selectivity of detection is attained on the basis of molecule-specific photo-ionization and drift time spectra. Ion currents were found to scale linearly with the substance concentration over several orders of magnitude down to the detection limits in the ppt range. As besides toxic industrial compounds, similar electron configurations also occur in illicit drugs, toxins and pharmaceutical substances, LIMS can be applied in a variety of fields ranging from environmental analysis, air pollution monitoring, drug detection and chemical process monitoring.

Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

PubMed

Angelini, Daniel J; Dorsey, Russell M; Willis, Kristen L; Hong, Charles; Moyer, Robert A; Oyler, Jonathan; Jensen, Neil S; Salem, Harry

2013-01-01

Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

Stoichiometric and Catalytic Scavengers as Protection Against Nerve Agent Toxicity: A Mini Review

DTIC Science & Technology

2007-01-01

signs of nerve agent toxicity following exposure . Assessments of motor activity , coordination, and acquisition of spatial memory were performed for 2...serious side occur before endogenous AChE is affected (approxi- effects if administered in the absence of cholinesterase mately 2 min after exposure to an...after guinea pigs of cholinesterase in the blood and the level of protec- were administered 60mg/kg of HuBuChE (-󈧎-fold tion against OP poisoning

Estimating genetic potential of biofuel forest hardwoods to withstand metal toxicity in industrial effluent under dry tropical conditions.

PubMed

Manzoor, S A; Mirza, S N; Zubair, M; Nouman, W; Hussain, S B; Mehmood, S; Irshad, A; Sarwar, N; Ammar, A; Iqbal, M F; Asim, A; Chattha, M U; Chattha, M B; Zafar, A; Abid, R

2015-08-14

Biofuel tree species are recognized as a promising alternative source of fuel to conventional forms. Additionally, these tree species are also effective in accumulating toxic heavy metals present in some industrial effluents. In developing countries such as Pakistan, the use of biofuel tree species is gaining popularity not only for harvesting economical and environmentally friendly biofuel, but also to sequester poisonous heavy metals from industrial wastewater. This study was aimed at evaluating the genetic potential of two biofuel species, namely, Jatropha curcas and Pongamia pinnata, to grow when irrigated with industrial effluent from the Pak-Arab Fertilizer Factory Multan, Southern Punjab, Pakistan. The growth performances of one-year-old seedlings of both species were compared in soil with adverse physiochemical properties. It was found that J. curcas was better able to withstand the toxicity of the heavy metals present in the fertilizer factory effluent. J. curcas showed maximum gain in height, diameter, and biomass production in soil irrigated with 75% concentrated industrial effluent. In contrast, P. pinnata showed a significant reduction in growth in soil irrigated with more than 50% concentrated industrial effluent, indicating that this species is less tolerant to higher toxicity levels of industrial effluent. This study identifies J. curcas as a promising biofuel tree species that can be grown using industrial wastewater.

Provisional Advisory Levels (PALs) for Hazardous Agents ...

EPA Pesticide Factsheets

Technical Brief PROVISIONAL ADVISORY LEVELS. Few health-based guidelines are available to inform decisions regarding the reoccupation of buildings or sites, or the re-use of water resources, following their contamination through the accidental or intentional release of toxic chemicals or chemical warfare agents, or following a large-scale disaster. To address this need, EPA/ORD’s National Homeland Security Research Center (NHSRC) develops health-based Provisional Advisory Levels (PALs) for high priority chemicals including toxic industrial chemicals and chemical warfare agents, for both inhalation and oral exposures. Oral PALs are targeted to drinking water ingestion, but are applicable to other oral exposures such as soil ingestion. This product will be used as a hand-out at professional meetings to promote awareness of NHSRC's Provisional Advisory values. It will be posted on the intra and internet sites describing activities and products of EPA/ORD/NHSRC.

Influence of ozonation and biodegradation on toxicity of industrial textile wastewater.

PubMed

Paździor, Katarzyna; Wrębiak, Julita; Klepacz-Smółka, Anna; Gmurek, Marta; Bilińska, Lucyna; Kos, Lech; Sójka-Ledakowicz, Jadwiga; Ledakowicz, Stanisław

2017-06-15

The textile industry demands huge volumes of high quality water which converts into wastewater contaminated by wide spectrum of chemicals. Estimation of textile wastewater influence on the aquatic systems is a very important issue. Therefore, closing of the water cycle within the factories is a promising method of decreasing its environmental impact as well as operational costs. Taking both reasons into account, the aim of this work was to establish the acute toxicity of the textile wastewater before and after separate chemical, biological as well as combined chemical-biological treatment. For the first time the effects of three different combinations of chemical and biological methods were investigated. The acute toxicity analysis were evaluated using the Microtox ® toxicity test. Ozonation in two reactors of working volume 1 dm 3 (stirred cell) and 20 dm 3 (bubble column) were tested as chemical process, while biodegradation was conducted in two, different systems - Sequence Batch Reactors (SBR; working volume 1.5 dm 3 ) and Horizontal Continuous Flow Bioreactor (HCFB; working volume 12 dm 3 ). The untreated wastewater had the highest toxicity (EC50 value in range: 3-6%). Ozonation caused lower reduction of the toxicity than biodegradation. In the system with SBR the best results were obtained for the biodegradation followed by the ozonation and additional biodegradation - 96% of the toxicity removal. In the second system (with HCFB) two-stage treatment (biodegradation followed by the ozonation) led to the highest toxicity reduction (98%). Copyright © 2016 Elsevier Ltd. All rights reserved.

Application of Toxic Chinese Medicine in Chinese Pharmacopoeia

NASA Astrophysics Data System (ADS)

Zhao, Hui; Feng, Yu; Mao, Mingsan

2018-01-01

Objective: Explore the application characteristics of proprietary Chinese medicine prescriptions containing toxic herbs in pharmacopoeia. Methods: In this paper, according to the clinical application of pharmacopoeia proprietary Chinese medicine is divided into table agent, Qushu agent, diarrhea agent, heat agent, Wen Li agent, cough and asthma agents, resuscitation agent, Gutian agent, Fuzheng agent, Anshen agent, hemostatic agent, The traditional Chinese medicine prescription and the clinical application of the Chinese herbal medicine containing the toxic Chinese medicine were analyzed and sorted out., Summed up the compatibility of toxic herbs and application characteristics. Results: Toxic Chinese herbal medicine in the cure of traditional Chinese medicine to play a long-standing role, through the overall thinking, dialectical thinking, and thinking of toxic Chinese medicine in the analysis of Chinese medicine that [2], toxic Chinese medicine in the application of proprietary Chinese medicine can not lack. Conclusion: Pharmacopoeia included proprietary Chinese medicine not only in the clinical treatment of good, but also the application of its toxic traditional Chinese medicine and its understanding of the enrichment of the toxic characteristics of traditional Chinese medicine and treatment-related disease pathology between the points of contact for patients with clinical applications Based on and theoretical guidance of Chinese medicine [3].

Assessing Physiological Response to Toxic Industrial Chemical Exposure in Megacities

DTIC Science & Technology

2016-03-15

organophosphate pesticides . Toxicology and Industrial Health , 28(1), 90–96. http://doi.org/10.1177/0748233711407243 6. Boudonck, K. J., Rose, D. J., Karoly, E. D...Högberg, J. (2011). Combined Toxic Exposures and Human Health : Biomarkers of Exposure and Effect. International Journal of Environmental Research and...Center for Environmental Health Research REPORT NUMBER 568 Doughten Drive Fort Detrick, MD 2 1702-50 l 0 16-047 9. SPONSORING/MONITORING AGENCY NAME

Differential mobility spectroscopy for chemical agent detection

NASA Astrophysics Data System (ADS)

Griffin, M. Todd

2006-05-01

General Dynamics ATP (GDATP) and Sionex Corporation (Sionex) are carrying out a cooperative development for a handheld chemical agent detector, being called JUNO TM, which will have lower false positives, higher sensitivity, and improved interference rejection compared with presently available detectors. This enhanced performance is made possible by the use of a new principle of ion separation called Differential Mobility Spectrometry (DMS). The enhanced selectivity is provided by the field tunable nature of the Sionex differential mobility technology (microDMxTM) which forms the analytical heart of the JUNO system and enables fingerprinting of molecules by characterization of the ionized molecular behavior under multiple electric field conditions. This enhanced selectivity is valuable in addressing not only the traditional list of chemical warfare agents (CWA) but also the substantial list of Toxic Industrial Compounds (TICs) and Toxic Industrial Materials (TIMs) which may be released in warfare or terrorist situations. Experimental results showing the ability of the microDMx to reject interferences, detect and resolve live agents are presented. An additional breakthrough in the technology was realized by operating the device at a reduced pressure of around 0.5 atmospheres. This reduced pressure operation resulted in roughly doubling the spectrometers resolution over what has previously been reported [1]. Advances have also been made in power consumption and packaging leading to a device suitable for portable, handheld, applications. Experimental results illustrating the performance of the microDMx technology employed in JUNO are highlighted.

Fact Sheet: Final Air Toxics Standards for Area Sources in the Chemical Manufacturing Industry

EPA Pesticide Factsheets

Fact sheet on the national air toxics standards issued October 16, 2009 by the Environmental Protection Agency (EPA) for smaller-emitting sources, known as area sources, in the chemical manufacturing industry.

Deactivating Chemical Agents Using Enzyme-Coated Nanofibers Formed by Electrospinning

DTIC Science & Technology

2016-01-01

7.3mM/mg). Key words Coaxial electrospinning, DFPase, Enzyme, chemical warfare , nanofiber, decontamination . Introduction Chemical warfare ...Krile, R.; Nishioka, M.; Taylor, M.; Riggs, K.; Stone, H. Decontamination of Toxic Industrial Chemicals and Chemical Warfare Agents On Building...298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 MATS COATINGS ELECTROSPINNING CHEMICAL WARFARE

Toxic industrial deposit remediation by ant activity

NASA Astrophysics Data System (ADS)

Jilkova, Veronika; Frouz, Jan

2016-04-01

Toxic industrial deposits are often contaminated by heavy metals and the substrates have low pH values. In such systems, soil development is thus slowed down by high toxicity and acidic conditions which are unfavourable to soil fauna. Ants (Hymenoptera, Formicidae) are considered tolerant to heavy metal pollution and are known to increase organic matter content and microbial activity in their nests. Here, we focused on soil remediation caused by three ant species (Formica sanguinea, Lasius niger, and Tetramorium sp.) in an ore-washery sedimentation basin near Chvaletice (Czech Republic). Soil samples were taken from the centre of ant nests and from the nest surroundings (>3 m from nests). Samples were then analyzed for microbial activity and biomass and contents of organic matter and nutrients. As a result, ant species that most influenced soil properties was F. sanguinea as there were higher microbial activity and total nitrogen and ammonia contents in ant nests than in the surrounding soil. We expected such a result because F. sanguinea builds conspicuous large nests and is a carnivorous species that brings substantial amounts of nitrogen in insect prey to their nests. Effects of the other two ant species might be lower because of smaller nests and different feeding habits as they rely mainly on honeydew from aphids or on plant seeds that do not contain much nutrients.

Defusing the Toxics Threat: Controlling Pesticides and Industrial Waste. Worldwatch Paper 79.

ERIC Educational Resources Information Center

Postel, Sandra

The use of pesticides in agriculture and the discarding of industrial chemical waste into the air, soil, and water constitute two major pathways of human exposure to toxic substances. It is argued that these practices release hundreds of millions of tons of potentially hazardous substances into the environment each year. Speculation continues into…

[Toxicity evaluation of sewage treatment plant effluent of chemical industrial park along the Yangtze River on rat testicular germ cells in vitro].

PubMed

Hu, Guan-Jiu; Wang, Xiao-Yi; Shi, Wei; Bai, Chou-Yong; Wu, Jiang; Liu, Hong-Ling; Yu, Hong-Xia

2009-05-15

By using rat testicular germ cells in vitro toxicity testing method based on original cells culture, the reproduction toxicity of sewage treatment plant effluent of Chemical Industrial Park along the Yangtze River was evaluated, through cells changes in morphologic, activity and viability parameters. The results showed that both of the effluents from new developed Chemical Industrial Park A and provincial Chemical Industrial Park B contain reproductive toxic substances. The toxicity of Park A has more significant undergone changes in cells activity of sertoli cells (p < 0.01), spermatogenic cells (p < 0.05) and leyding cells (p < 0.05), lactate dehydrogenase activity (p < 0.01) and testosterone secretion (p < 0.01) than that of Park B. Sepermatogenic cells are more sensitive in indicating reproduction toxicity for testicular, compared with leyding cells and sertoli cells. This study demonstrated that, as an indispensable and complementary tool for water quality assessment, rat testicular germ cells in vitro toxicity testing based on original cells culture can be used to comprehensively evaluate the reproduction toxicity of sewage treatment plant effluent, and provide prompt and useful discharge quality information.

Joint Chemical Agent Detector (JCAD): the future of chemical agent detection

NASA Astrophysics Data System (ADS)

Laljer, Charles E.; Owen, Jeffery L.

2002-06-01

The Joint Chemical Agent Detector (JCAD) will provide state of the art chemical warfare agent detection capability to ground vehicle operators. Intelligence sources estimate that over twenty counties have active chemical weapons programs. The spread of chemical weapons to third world nations, coupled with the potential for US involvement in these areas in an operational or support capacity, increases the probability that the Joint Services may encounter chemical agents and toxic industrial materials anywhere in the world. Currently, fielded chemical agent detectors are bulky, labor intensive, and subject to false readings. No legacy detector is sensitive enough to provide detection and warning of the low dose hazards associated with miosis contamination. The JCAD will provide a small, lightweight chemical agent detector for vehicle interiors, aircraft, individual personnel, shipboard, and fixed site locations. The system provides a common detection components across multi-service platforms. This common detector system will allow the Joint Services to use the same operational and support concept for more efficient utilization of resources. The JCAD will detect, identify, quantify, and warn of the presence of chemical agents prior to onset of miosis. Upon detection of chemical agents, the detector will provide local and remote audible and visual alarms to the operators. Advance warning will provide the vehicle crew with the time necessary to protect themselves from the lethal effects of chemical agents. The JCAD will also be capable of being upgraded to protect against future chemical agent threats. The JCAD will provide the vehicle operators with the warning necessary to survive and fight in a chemical warfare agent threat environment.

Maintenance service contract model for heavy equipment in mining industry using principal agent theory

NASA Astrophysics Data System (ADS)

Pakpahan, Eka K. A.; Iskandar, Bermawi P.

2015-12-01

Mining industry is characterized by a high operational revenue, and hence high availability of heavy equipment used in mining industry is a critical factor to ensure the revenue target. To maintain high avaliability of the heavy equipment, the equipment's owner hires an agent to perform maintenance action. Contract is then used to control the relationship between the two parties involved. The traditional contracts such as fixed price, cost plus or penalty based contract studied is unable to push agent's performance to exceed target, and this in turn would lead to a sub-optimal result (revenue). This research deals with designing maintenance contract compensation schemes. The scheme should induce agent to select the highest possible maintenance effort level, thereby pushing agent's performance and achieve maximum utility for both parties involved. Principal agent theory is used as a modeling approach due to its ability to simultaneously modeled owner and agent decision making process. Compensation schemes considered in this research includes fixed price, cost sharing and revenue sharing. The optimal decision is obtained using a numerical method. The results show that if both parties are risk neutral, then there are infinite combination of fixed price, cost sharing and revenue sharing produced the same optimal solution. The combination of fixed price and cost sharing contract results in the optimal solution when the agent is risk averse, while the optimal combination of fixed price and revenue sharing contract is obtained when agent is risk averse. When both parties are risk averse, the optimal compensation scheme is a combination of fixed price, cost sharing and revenue sharing.

Biochars made from agro-industrial by-products remove chlorine and lower water toxicity

NASA Astrophysics Data System (ADS)

Tzachristas, Andreas; Xirou, Maria; Manariotis, Ioannis D.; Dailianis, Stefanos; Karapanagioti, Hrissi K.

2016-04-01

Chlorination is the most common disinfection process for water and treated wastewater. For the industrial use of water in food production, chlorine can add undesired taste and odor to the final product. For this reason, dechlorination is desired for food industries that use municipal tap water. For treated wastewater discharge or reuse, chlorine can be toxic to the receiving aqueous systems and to the irrigated plants. In both the above cases, dechlorination is also required. Traditionally activated carbon has been used as the ideal material for the removal of chlorine. The main mechanisms that describe the interaction between activated carbon and HOCl or OCl- are described by the following equations (AWWA, 1990): HOCl + C* → C*O + H+ + Cl- (1), OCl- + C* → C*O + Cl- (2) Where C* and C*O represent the activated carbon surface and a surface oxide, respectively. The present study proposes the use of agro-industrial by-products for the production of biochars that will be used for dechlorination of tap-water used for food-industry production. Different raw materials such as malt spent rootlets, coffee residue, olive and grape seeds, etc. are used for the production of biochar. Various temperatures and air-to-solid ratios are tested for optimizing biochar production. Batch tests as well as a column test are employed to study the dechlorination efficiency and kinetics of the different raw and biochar materials as well as those of commercial activated carbons. As chlorine concentration increases the removal also increases linearily. After 1 and 24 hours of contact the chlorine relative removal efficiencies for the biochar made from olive seeds are 50 and 77 ± 4%, respectively. It seems that the removal kinetics are faster during the first hour; then, removal continues but with a slower rate. Most of the biochars tested (with 3 mg of solid in 20 mL of chlorine solution at initial concentration Co=1.5 mg/L) demonstrated removal efficiencies with an average of 9.4 ± 0

Enhanced formulations for neutralization of chemical, biological and industrial toxants

DOEpatents

Tucker, Mark D [Albuqueque, NM

2008-06-24

An enhanced formulation and method of making that neutralizes the adverse health effects of both chemical and biological compounds, especially chemical warfare (CW) and biological warfare (BW) agents, and toxic industrial chemicals. The enhanced formulation according to the present invention is non-toxic and non-corrosive and can be delivered by a variety of means and in different phases. The formulation provides solubilizing compounds that serve to effectively render the chemical and biological compounds, particularly CW and BW compounds, susceptible to attack, and at least one reactive compound that serves to attack (and detoxify or kill) the compound. The formulation includes at least one solubilizing agent, a reactive compound, a bleaching activator and water.

Application of carbon foam for heavy metal removal from industrial plating wastewater and toxicity evaluation of the adsorbent.

PubMed

Lee, Chang-Gu; Song, Mi-Kyung; Ryu, Jae-Chun; Park, Chanhyuk; Choi, Jae-Woo; Lee, Sang-Hyup

2016-06-01

Electroplating wastewater contains various types of toxic substances, such as heavy metals, solvents, and cleaning agents. Carbon foam was used as an adsorbent for the removal of heavy metals from real industrial plating wastewater. Its sorption capacity was compared with those of a commercial ion-exchange resin (BC258) and a heavy metal adsorbent (CupriSorb™) in a batch system. The experimental carbon foam has a considerably higher sorption capacity for Cr and Cu than commercial adsorbents for acid/alkali wastewater and cyanide wastewater. Additionally, cytotoxicity test showed that the newly developed adsorbent has low cytotoxic effects on three kinds of human cells. In a pilot plant, the carbon foam had higher sorption capacity for Cr (73.64 g kg(-1)) than for Cu (14.86 g kg(-1)) and Ni (7.74 g kg(-1)) during 350 h of operation time. Oxidation pretreatments using UV/hydrogen peroxide enhance heavy metal removal from plating wastewater containing cyanide compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

New ceramics incorporated with industrial by-products as pore formers for sorption of toxic chromium from aqueous media

NASA Astrophysics Data System (ADS)

Domopoulou, Artemi

2015-04-01

The incorporation of secondary resources including various industrial wastes as pore-forming agents into clayey raw material mixtures for the development of tailored porous ceramic microstructures is currently of increasing interest. In the present research, sintered ceramic compacts were developed incorporated with industrial solid by-products as pore formers, and then used as new sorbents for chromium removal from aqueous media. The microstructures obtained were characterized through X-ray diffraction (XRD) analysis as well as scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectrometry (EDX). Sorption potential of chromium from synthetic solutions on the porous ceramics was studied by static adsorption experiments as a function of the pore-former percentage in the ceramic matrix as well as the initial heavy metal (chromium) concentration, solution pH and temperature. Kinetic studies were conducted and adsorption isotherms of chromium were determined using the Langmuir equation. Preliminary experimental results concerning the adsorption characteristics of chromium on the ceramic materials produced appear encouraging for their possible beneficial use as new sorbents for the removal of toxic chromium from aqueous media. Keywords: sorbents, ceramics, industrial solid by-products, pore-former, chromium. Acknowledgements: This research has been co-financed by the European Union (European Social Fund - ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program ARCHIMEDES III: Investing in knowledge society through the European Social Fund.

New ceramics incorporated with industrial by-products as pore formers for sorption of toxic chromium from aqueous media

NASA Astrophysics Data System (ADS)

Domopoulou, Asimina; Spiliotis, Xenofon; Baklavaridis, Apostolos; Papapolymerou, George; Karayannis, Vayos

2015-04-01

The incorporation of secondary resources including various industrial wastes as pore-forming agents into clayey raw material mixtures for the development of tailored porous ceramic microstructures is currently of increasing interest. In the present research, sintered ceramic compacts were developed incorporated with industrial solid by-products as pore formers, and then used as new sorbents for chromium removal from aqueous media. The microstructures obtained were characterized through X-ray diffraction (XRD) analysis as well as scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectrometry (EDX). Sorption potential of chromium from synthetic solutions on the porous ceramics was studied by static adsorption experiments as a function of the pore-former percentage in the ceramic matrix as well as the initial heavy metal (chromium) concentration, solution pH and temperature. Kinetic studies were conducted and adsorption isotherms of chromium were determined using the Langmuir equation. Preliminary experimental results concerning the adsorption characteristics of chromium on the ceramic materials produced appear encouraging for their possible beneficial use as new sorbents for the removal of toxic chromium from aqueous media. Keywords: sorbents, ceramics, industrial solid by-products, pore former, chromium. Acknowledgements: This research has been co-financed by the European Union (European Social Fund - ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) - Research Funding Program ARCHIMEDES III: Investing in knowledge society through the European Social Fund.

Personal care product preservatives: risk assessment and mixture toxicities with an industrial wastewater.

PubMed

Carbajo, Jose B; Perdigón-Melón, Jose A; Petre, Alice L; Rosal, Roberto; Letón, Pedro; García-Calvo, Eloy

2015-04-01

The aquatic toxicity of eight preservatives frequently used in personal care products (PCPs) (iodopropynyl butylcarbamate, bronopol, diazolidinyl urea, benzalkonium chloride, zinc pyrithione, propylparaben, triclosan and a mixture of methylchloroisothiazolinone and methylisothiazolinone) was assessed by means of two different approaches: a battery of bioassays composed of single species tests of bacteria (Vibrio fischeri and Pseudomonas putida) and protozoa (Tetrahymena thermophila), and a whole biological community resazurin-based assay using activated sludge. The tested preservatives showed considerable toxicity in the studied bioassays, but with a marked difference in potency. In fact, all biocides except propylparaben and diazolidinyl urea had EC50 values lower than 1 mg L(-1) in at least one assay. Risk quotients for zinc pyrithione, benzalkonium chloride, iodopropynyl butylcarbamate and triclosan as well as the mixture of the studied preservatives exceeded 1, indicating a potential risk for the process performance and efficiency of municipal sewage treatment plants (STPs). These four single biocides explained more than 95% of the preservative mixture risk in all bioassays. Each individual preservative was also tested in combination with an industrial wastewater (IWW) from a cosmetics manufacturing facility. The toxicity assessment was performed on binary mixtures (preservative + IWW) and carried out using the median-effect principle, which is a special case of the concept of Concentration Addition (CA). Almost 70% of all experiments resulted in EC50 values within a factor of 2 of the values predicted by the median-effect principle (CI values between 0.5 and 2). The rest of the mixtures whose toxicity was mispredicted by CA were assessed with the alternative concept of Independent Action (IA), which showed higher predictive power for the biological community assay. Therefore, the concept used to accurately predict the toxicity of mixtures of a preservative

Fluorescent sensor based models for the detection of environmentally-related toxic heavy metals.

PubMed

Rasheed, Tahir; Bilal, Muhammad; Nabeel, Faran; Iqbal, Hafiz M N; Li, Chuanlong; Zhou, Yongfeng

2018-02-15

The quest for industrial and biotechnological revolution has been contributed in increasing environmental contamination issues, worldwide. The controlled or uncontrolled release of hazardous pollutants from various industrial sectors is one of the key problems facing humanity. Among them, adverse influences of lead, cadmium, and mercury on human health are well known to cause many disorders like reproductive, neurological, endocrine system, and cardiovascular, etc. Besides their presence at lower concentrations, most of these toxic heavy metals are posing noteworthy toxicological concerns. In this context, notable efforts from various regulatory authorities, the increase in the concentration of these toxic heavy metals in the environment is of serious concern, so real-time monitoring is urgently required. This necessitates the exploration for novel and efficient probes for recognition of these toxic agents. Among various methodologies adopted for tailoring such probes, generally the methodologies, in which changes associated with spectral properties, are preferred for the deceptive ease in the recognition process. Accordingly, a promising modality has emerged in the form of radiometric and colorimetric monitoring of these toxic agents. Herein, we review fluorescent sensor based models and their potentialities to address the detection fate of hazardous pollutants for a cleaner environment. Second, recent advances regarding small molecule and rhodamine-based fluorescent sensors, radiometric and colorimetric probes are discussed. The information is also given on the photoinduced electron transfer (PET) mechanism, chelation enhancement fluorescence (CHEF) effect and spirocyclic ring opening mechanism. Copyright © 2017 Elsevier B.V. All rights reserved.

Toxicity assessment of industrial chemicals and airborne contaminants: transition from in vivo to in vitro test methods: a review.

PubMed

Bakand, S; Winder, C; Khalil, C; Hayes, A

2005-12-01

Exposure to occupational and environmental contaminants is a major contributor to human health problems. Inhalation of gases, vapors, aerosols, and mixtures of these can cause a wide range of adverse health effects, ranging from simple irritation to systemic diseases. Despite significant achievements in the risk assessment of chemicals, the toxicological database, particularly for industrial chemicals, remains limited. Considering there are approximately 80,000 chemicals in commerce, and an extremely large number of chemical mixtures, in vivo testing of this large number is unachievable from both economical and practical perspectives. While in vitro methods are capable of rapidly providing toxicity information, regulatory agencies in general are still cautious about the replacement of whole-animal methods with new in vitro techniques. Although studying the toxic effects of inhaled chemicals is a complex subject, recent studies demonstrate that in vitro methods may have significant potential for assessing the toxicity of airborne contaminants. In this review, current toxicity test methods for risk evaluation of industrial chemicals and airborne contaminants are presented. To evaluate the potential applications of in vitro methods for studying respiratory toxicity, more recent models developed for toxicity testing of airborne contaminants are discussed.

Fate of sessile droplet chemical agents in environmental substrates in the presence of physiochemical processes

NASA Astrophysics Data System (ADS)

Navaz, H. K.; Dang, A. L.; Atkinson, T.; Zand, A.; Nowakowski, A.; Kamensky, K.

2014-05-01

A general-purpose multi-phase and multi-component computer model capable of solving the complex problems encountered in the agent substrate interaction is developed. The model solves the transient and time-accurate mass and momentum governing equations in a three dimensional space. The provisions for considering all the inter-phase activities (solidification, evaporation, condensation, etc.) are included in the model. The chemical reactions among all phases are allowed and the products of the existing chemical reactions in all three phases are possible. The impact of chemical reaction products on the transport properties in porous media such as porosity, capillary pressure, and permeability is considered. Numerous validations for simulants, agents, and pesticides with laboratory and open air data are presented. Results for chemical reactions in the presence of pre-existing water in porous materials such as moisture, or separated agent and water droplets on porous substrates are presented. The model will greatly enhance the capabilities in predicting the level of threat after any chemical such as Toxic Industrial Chemicals (TICs) and Toxic Industrial Materials (TIMs) release on environmental substrates. The model's generality makes it suitable for both defense and pharmaceutical applications.

Elemental selenium at nano size (Nano-Se) as a potential chemopreventive agent with reduced risk of selenium toxicity: comparison with se-methylselenocysteine in mice.

PubMed

Zhang, Jinsong; Wang, Xufang; Xu, Tongwen

2008-01-01

Selenium (Se) is an essential trace element with a narrow margin between beneficial and toxic effects. As a promising chemopreventive agent, its use requires consumption over the long term, so the toxicity of Se is always a crucial concern. Based on clinical findings and recent studies in selenoprotein gene-modified mice, it is likely that the antioxidant function of one or more selenoproteins is responsible for the chemopreventive effect of Se. Furthermore, upregulation of phase 2 enzymes by Se has been implicated as a possible chemopreventive mechanism at supranutritional dietary levels. Se-methylselenocysteine (SeMSC), a naturally occurring organic Se product, is considered as one of the most effective chemopreventive selenocompounds. The present study revealed that, as compared with SeMSC, elemental Se at nano size (Nano-Se) possessed equal efficacy in increasing the activities of glutathione peroxidase, thioredoxin reductase, and glutathione S-transferase, but had much lower toxicity as indicated by median lethal dose, acute liver injury, survival rate, and short-term toxicity. Our results suggest that Nano-Se can serve as a potential chemopreventive agent with reduced risk of Se toxicity.

Evaluation of aquatic toxicities of chromium and chromium-containing effluents in reference to chromium electroplating industries.

PubMed

Baral, A; Engelken, R; Stephens, W; Farris, J; Hannigan, R

2006-05-01

This study evaluated aquatic toxicities of chromium and chromium-containing laboratory samples representative of effluents from chromium electroplating industries, and compared the aquatic environmental risks of hexavalent and trivalent chromium electroplating operations. Trivalent chromium electroplating has emerged as an acceptable alternative to hazardous hexavalent chromium electroplating. This process substitution has reduced the human health impact in the workplace and minimized the production of hazardous sludge regulated under the Resource Conservation and Recovery Act (RCRA). The thrust behind this research was to investigate whether trivalent chromium electroplating operations have lower adverse impacts on standardized toxicity test organisms. Ceriodaphnia dubia and Pimephales promelas were used to investigate toxicities of trivalent chromium (Cr (III)), hexavalent chromium (Cr (VI)), and industrial effluents. In agreement with previous studies, Cr (III) was found to be less toxic than Cr (VI). Despite having several organic and inorganic constituents in the effluents obtained from trivalent chromium plating baths, they exhibited less adverse effects to C. dubia than effluents obtained from hexavalent chromium electroplating baths. Thus, transition from hexavalent to trivalent chromium electroplating processes may be justified. However, because of the presence of organic constituents such as formate, oxalate, and triethylene glycol in effluents, trivalent chromium electroplating operations may face additional regulatory requirements for removal of total organic carbon.

76 FR 59142 - Guidance for Industry on Reproductive and Developmental Toxicities-Integrating Study Results To...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

...--Integrating Study Results To Assess Concerns; Availability AGENCY: Food and Drug Administration, HHS. ACTION... industry entitled ``Reproductive and Developmental Toxicities--Integrating Study Results to Assess Concerns.'' This guidance describes an approach to estimating possible human developmental or reproductive risks...

Gadolinium-based contrast agent toxicity: a review of known and proposed mechanisms.

PubMed

Rogosnitzky, Moshe; Branch, Stacy

2016-06-01

Gadolinium chelates are widely used as contrast media for magnetic resonance imaging. The approved gadolinium-based contrast agents (GBCAs) have historically been considered safe and well tolerated when used at recommended dosing levels. However, for nearly a decade, an association between GBCA administration and the development of nephrogenic systemic fibrosis (NSF) has been recognized in patients with severe renal impairment. This has led to modifications in clinical practices aimed at reducing the potential and incidence of NSF development. Newer reports have emerged regarding the accumulation of gadolinium in various tissues of patients who do not have renal impairment, including bone, brain, and kidneys. Despite the observations of gadolinium accumulation in tissues regardless of renal function, very limited clinical data regarding the potential for and mechanisms of toxicity is available. This significant gap in knowledge warrants retrospective cohort study efforts, as well as prospective studies that involve gadolinium ion (Gd(3+)) testing in patients exposed to GBCA. This review examines the potential biochemical and molecular basis of gadolinium toxicity, possible clinical significance of gadolinium tissue retention and accumulation, and methods that can limit gadolinium body burden.

Grey-scale ultrasonography for monitoring industrial exposure to hepatotoxic agents.

PubMed

Taylor, K J; Williams, D M; Smith, P M; Duck, B W

1975-05-31

Industrial exposure to several potentially hepatotoxic agents, such as vinyl-chloride monomer may occur, and there is a need for non-vasive, diagnostic techniques to detect and monitor progressive pathological processes in liver or spleen. Grey-scale ultrasonography permits display of detailed anatomy and pathology in the liver, portal veins, and spleen. The combination of fine resolution, non-invasiveness, absence of ionising radiation hazard, and portable equipment makes the technique ideal for screening populations at risk.

Priorities in the investigation of human health hazards in the plastics and synthetic rubber industries

PubMed Central

Selikoff, Irving J.

1976-01-01

Experiences in the past decade provide guidance in selecting priorities for investigation of health hazards in chemical industries. Pride of place should be given to the experience of large industrial populations, in part simply because large numbers of people are at risk and in part because such studies are more likely to give reliable answers. This recommendation has further strength when there is community exposure as well. Parenthetically, large populations provide opportunity to study multiple factor interaction; without this, toxic potential of a single agent may be obscured. Second, investigations should be mounted when there is reason for suspicion, as with particular chemical configurations, observed organ toxicity, animal carcinogenicity, unusual clinical experience (“signal” tumors). It may be added that when agents have already been used several decades, evaluation of human experience with them is now in order, if only to document absence of toxicity. The same recommendations hold for planned introduction of new agents or widened distribution of existing ones, until we have better information concerning validity of “pretesting” programs. Major advances have been made in epidemiological methods for these investigations. These now allow us to successfully focus on small defined groups as well as to manage large populations. PMID:1026418

Saffron as an antidote or a protective agent against natural or chemical toxicities.

PubMed

Razavi, Bibi Marjan; Hosseinzadeh, Hossein

2015-05-01

Saffron (Crocus sativus) is an extensively used food additive for its color and taste. Since ancient times this plant has been introduced as a marvelous medicine throughout the world. The wide spectrum of saffron pharmacological activities is related to its major constituents including crocin, crocetin and safranal. Based on several studies, saffron and its active ingredients have been used as an antioxidant, antiinflammatory and antinociceptive, antidepressant, antitussive, anticonvulsant, memory enhancer, hypotensive and anticancer. According to the literatures, saffron has remarkable therapeutic effects. The protective effects of saffron and its main constituents in different tissues including brain, heart, liver, kidney and lung have been reported against some toxic materials either natural or chemical toxins in animal studies.In this review article, we have summarized different in vitro and animal studies in scientific databases which investigate the antidotal and protective effects of saffron and its major components against natural toxins and chemical-induced toxicities. Due to the lake of human studies, further investigations are required to ascertain the efficacy of saffron as an antidote or a protective agent in human intoxication.

Long-term evaluation of lethal and sublethal toxicity of industrial effluents using Daphnia magna and Moina macrocopa.

PubMed

Yi, Xianliang; Kang, Sung-Wook; Jung, Jinho

2010-06-15

Acute toxicity and feeding rate inhibition of effluent from a wastewater treatment plant and its adjacent stream water on Daphnia magna and Moina macrocopa were comparatively studied. The acute toxicity of the final effluent (FE) fluctuated greatly over the sampling period from January to August 2009. Toxicity identification results of the FE in July 2009 showed that Cu originating from the Fenton's reagent was likely a key toxicant. In addition, the feeding rate of both species was still inhibited by the FEs in which acute toxicity was not observed. These findings indicate that the feeding response would be a useful tool for monitoring sublethal effects of industrial effluents. For the acute toxicity test, M. macrocopa was more sensitive than D. magna, but the opposite result was true in the case of the feeding rate inhibition. These suggest that different species have different sensitivities to toxic chemicals and to the test methods. Copyright 2010 Elsevier B.V. All rights reserved.

Aquatic toxicity of petroleum products and dispersant agents ...

EPA Pesticide Factsheets

The U.S. EPA Office of Research and Development has developed baseline data on the ecotoxicity of selected petroleum products and several chemical dispersants as part of its oil spills research program. Two diluted bitumens (dilbits) from the Alberta Tar Sands were tested for acute and chronic toxicity to standard freshwater and marine organisms given their spill potential during shipment within the United States. Separately, two reference crude oils representing a range of characteristics, and their mixtures with four representative dispersants, were tested to evaluate acute and chronic toxicity to marine organisms in support of Subpart J of the U.S. National Contingency Plan. Water accommodated fractions (WAF) of oil were prepared using traditional slow-stir methods and toxicity tests generally followed U.S. EPA standard effluent testing guidelines. WAFs were characterized for petroleum hydrocarbons including alkyl PAH homologs. The results of these studies will assist the U.S. EPA to assess toxicity data for unconventional oils (dilbits), and establish baseline toxicity data for selected crude oils and dispersant in support of planning and response activities. Abstract reporting the results of EPA's oil and dispersant toxicity testing program

A general mechanism for intracellular toxicity of metal-containing nanoparticles

NASA Astrophysics Data System (ADS)

Sabella, Stefania; Carney, Randy P.; Brunetti, Virgilio; Malvindi, Maria Ada; Al-Juffali, Noura; Vecchio, Giuseppe; Janes, Sam M.; Bakr, Osman M.; Cingolani, Roberto; Stellacci, Francesco; Pompa, Pier Paolo

2014-05-01

The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment - where particles are abundantly internalized - is responsible for the cascading events associated with nanoparticles-induced intracellular toxicity. We call this mechanism a ``lysosome-enhanced Trojan horse effect'' since, in the case of nanoparticles, the protective cellular machinery designed to degrade foreign objects is actually responsible for their toxicity. To test our hypothesis, we compare the toxicity of similar gold particles whose main difference is in the internalization pathways. We show that particles known to pass directly through cell membranes become more toxic when modified so as to be mostly internalized by endocytosis. Furthermore, using experiments with chelating and lysosomotropic agents, we found that the toxicity mechanism for different metal containing NPs (such as metallic, metal oxide, and semiconductor NPs) is mainly associated with the release of the corresponding toxic ions. Finally, we show that particles unable to release toxic ions (such as stably coated NPs, or diamond and silica NPs) are not harmful to intracellular environments.The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment - where

Mustard vesicating agent-induced toxicity in the skin tissue and silibinin as a potential countermeasure.

PubMed

Tewari-Singh, Neera; Agarwal, Rajesh

2016-06-01

Exposure to the vesicating agents sulfur mustard (SM) and nitrogen mustard (NM) causes severe skin injury with delayed blistering. Depending upon the dose and time of their exposure, edema and erythema develop into blisters, ulceration, necrosis, desquamation, and pigmentation changes, which persist weeks and even years after exposure. Research advances have generated data that have started to explain the probable mechanism of action of vesicant-induced skin toxicity; however, despite these advances, effective and targeted therapies are still deficient. This review highlights studies on two SM analogs, 2-chloroethyl ethyl sulfide (CEES) and NM, and CEES- and NM-induced skin injury mouse models that have substantially added to the knowledge on the complex pathways involved in mustard vesicating agent-induced skin injury. Furthermore, employing these mouse models, studies under the National Institutes of Health Countermeasures Against Chemical Threats program have identified the flavanone silibinin as a novel therapeutic intervention with the potential to be developed as an effective countermeasure against skin injury following exposure to mustard vesicating agents. © 2016 New York Academy of Sciences.

Environmental sentinel biomonitors: integrated response systems for monitoring toxic chemicals

NASA Astrophysics Data System (ADS)

van der Schalie, William H.; Reuter, Roy; Shedd, Tommy R.; Knechtges, Paul L.

2002-02-01

Operational environments for military forces are becoming potentially more dangerous due to the increased number, use, and misuse of toxic chemicals across the entire range of military missions. Defense personnel may be exposed to harmful chemicals as a result of industrial accidents or intentional or unintentional action of enemy, friendly forces, or indigenous populations. While there has been a significant military effort to enable forces to operate safely and survive and sustain operations in nuclear, biological, chemical warfare agent environments, until recently there has not been a concomitant effort associated with potential adverse health effects from exposures of deployed personnel to toxic industrial chemicals. To provide continuous real-time toxicity assessments across a broad spectrum of individual chemicals or chemical mixtures, an Environmental Sentinel Biomonitor (ESB) system concept is proposed. An ESB system will integrate data from one or more platforms of biologically-based systems and chemical detectors placed in the environment to sense developing toxic conditions and transmit time-relevant data for use in risk assessment, mitigation, and/or management. Issues, challenges, and next steps for the ESB system concept are described, based in part on discussions at a September 2001 workshop sponsored by the U.S. Army Center for Environmental Health Research.

Toxic oil syndrome: the perspective after 20 years.

PubMed

Posada de la Paz, M; Philen, R M; Borda, A I

2001-01-01

Toxic oil syndrome burst upon the scene in Spain in May of 1981, draining the resources of a newly evolving political and social medicine system. The vehicle of the causative toxic agent was identified as an illicit oil that had been diverted from industrial use and refined in order to remove the aniline denaturant, and that was sold in unlabeled 5-liter containers by itinerant salesmen. Over 20,000 people were ultimately affected, and over 1,200 deaths from all causes have been recorded in the affected cohort. The epidemiologic investigation of toxic oil syndrome involved all facets of investigative and analytical work; from visits to factories and interviewing workers, to sophisticated chemical and statistical analytical techniques. This investigation serves as a further illustration that data and information of all types, and from a wide range of fields, need to be systematically collected and evaluated in order to best resolve an epidemiologic mystery. Astute clinical observation of the patients, however, led to the hypothesis that toxic oil syndrome was a result of a toxic exposure. In this and other epidemics of unknown etiology, clinical observation and the intense scrutiny of patients' histories, signs, and symptoms by treating clinicians have often led to hypotheses that could be tested epidemiologically. When there are medical unknowns, the role of the astute clinician continues to be crucial. The toxic oil syndrome epidemic is an example of how even a developed country can be affected by a massive epidemic of environmental origin if failures occur in the systems that control and regulate the food supply or other consumer products. However, such failures could occur anywhere that large commercial networks operate on the regulatory edge, and if these business lack an in depth knowledge of the consequences of alterations in manufacturing conditions. Such was the case with eosinophilia-myalgia syndrome as well, when apparently minor alterations in

In silico analysis of Pycnoporus cinnabarinus laccase active site with toxic industrial dyes.

PubMed

Prasad, Nirmal K; Vindal, Vaibhav; Narayana, Siva Lakshmi; Ramakrishna, V; Kunal, Swaraj Priyaranjan; Srinivas, M

2012-05-01

Laccases belong to multicopper oxidases, a widespread class of enzymes implicated in many oxidative functions in various industrial oxidative processes like production of fine chemicals to bioremediation of contaminated soil and water. In order to understand the mechanisms of substrate binding and interaction between substrates and Pycnoporus cinnabarinus laccase, a homology model was generated. The resulted model was further validated and used for docking studies with toxic industrial dyes- acid blue 74, reactive black 5 and reactive blue 19. Interactions of chemical mediators with the laccase was also examined. The docking analysis showed that the active site always cannot accommodate the dye molecules, due to constricted nature of the active site pocket and steric hindrance of the residues whereas mediators are relatively small and can easily be accommodated into the active site pocket, which, thereafter leads to the productive binding. The binding properties of these compounds along with identification of critical active site residues can be used for further site-directed mutagenesis experiments in order to identify their role in activity and substrate specificity, ultimately leading to improved mutants for degradation of these toxic compounds.

Textile industry and occupational cancer.

PubMed

Singh, Zorawar; Chadha, Pooja

2016-01-01

Thousands of workers are engaged in textile industry worldwide. Textile industry involves the use of different kinds of dyes which are known to possess carcinogenic properties. Solvents used in these industries are also associated with different health related hazards including cancer. In previous studies on textile and iron industries, the authors have reported genotoxicity among them and observed occurrence of cancer deaths among textile industry workers. Thus, an attempt has been made to compile the studies on the prevalence of different types of cancers among textile industry workers. A wide literature search has been done for compiling the present paper. Papers on cancer occurrence among textile industry workers have been taken from 1976 to 2015. A variety of textile dyes and solvents, many of them being carcinogenic, are being used worldwide in the textile industry. The textile industry workers are therefore, in continuous exposure to these dyes, solvents, fibre dusts and various other toxic chemicals. The present study evaluates the potential of different chemicals and physical factors to be carcinogenic agents among occupationally exposed workers by going through various available reports and researches. Papers were collected using different databases and a number of studies report the association of textile industry and different types of cancer including lung, bladder, colorectal and breast cancer. After going through the available reports, it can be concluded that workers under varied job categories in textile industries are at a higher risk of developing cancer as various chemicals used in the textile industry are toxic and can act as potential health risk in inducing cancer among them. Assessing the cancer risk at different job levels in textile industries may be found useful in assessing the overall risk to the workers and formulating the future cancer preventive strategies.

An in silico algal toxicity model with a wide applicability potential for industrial chemicals and pharmaceuticals.

PubMed

Önlü, Serli; Saçan, Melek Türker

2017-04-01

The authors modeled the 72-h algal toxicity data of hundreds of chemicals with different modes of action as a function of chemical structures. They developed mode of action-based local quantitative structure-toxicity relationship (QSTR) models for nonpolar and polar narcotics as well as a global QSTR model with a wide applicability potential for industrial chemicals and pharmaceuticals. The present study rigorously evaluated the generated models, meeting the Organisation for Economic Co-operation and Development principles of robustness, validity, and transparency. The proposed global model had a broad structural coverage for the toxicity prediction of diverse chemicals (some of which are high-production volume chemicals) with no experimental toxicity data. The global model is potentially useful for endpoint predictions, the evaluation of algal toxicity screening, and the prioritization of chemicals, as well as for the decision of further testing and the development of risk-management measures in a scientific and regulatory frame. Environ Toxicol Chem 2017;36:1012-1019. © 2016 SETAC. © 2016 SETAC.

Plant seeds as sources of potential industrial chemicals, pharmaceuticals, and pest control agents.

PubMed

Powell, Richard G

2009-03-27

Investigations of natural products isolated from seeds have resulted in a remarkable variety of compounds having unusual structures. Seeds of many plant species contain uncommon fatty acids and lipids, some of which have found uses in the cosmetic industry or as renewable (non-petroleum based) industrial raw materials. In addition to proteins and energy storage substances such as carbohydrates and lipids, seeds generally contain, or have the ability to produce, protective compounds that are active as plant growth regulators, fungicides, insecticides, and repellents of herbivores; seeds occasionally contain compounds that are toxic to most other organisms. These compounds may also be present in other plant parts, but often are found at higher concentrations in seeds. Other compounds of interest have been associated with plant-endophyte interactions that are of mutual benefit to both organisms. Tests of seed extracts for cytotoxic and antitumor activity, toxicity to insects, and relationships to several animal disease syndromes have been revealing. Examples of compounds isolated from plant seeds that have served as lead compounds for additional research, or that continue to be of interest to researchers in multiple areas, are reviewed.

The use of sugar and alcohol industry waste in the adsorption of potentially toxic metals.

PubMed

Santos, Oseas Silva; Mendonça, André Gustavo Ribeiro; Santos, Josué Carinhanha Caldas; Silva, Amanda Paulina Bezerra; Costa, Silvanio Silverio Lopes; Oliveira, Luciana Camargo; Carmo, Janaina Braga; Botero, Wander Gustavo

2016-01-01

One of the waste products of the industrial process of the sugar and alcohol agribusiness is filter cake (FC). This waste product has high levels of organic matter, mainly proteins and lipids, and is rich in calcium, nitrogen, potassium and phosphorous. In this work we characterized samples of FC from sugar and alcohol industries located in sugarcane-producing regions in Brazil and assessed the adsorption of potentially toxic metals (Cu(II), Cd(II), Pb(II), Ni(II) and Cr(III)) by this waste in mono- and multi-elemental systems, seeking to use FC as an adsorbent in contaminated environments. The characterization of FCs showed significant differences between the samples and the adsorption studies showed retention of over 90% of potentially toxic metals. In a competitive environment (multi-metallic solution), the FC was effective in adsorbing all metals except lead, but less effective compared to the mono-metallic solution. These results show the potential for use of this residue as an adsorbent in contaminated environments.

Dermostyx (IB1) - High efficacy and safe topical skin protectant against percutaneous toxic agents.

PubMed

Dachir, Shlomit; Barness, Izhak; Fishbine, Eliezer; Meshulam, Jacob; Sahar, Rita; Eisenkraft, Arik; Amir, Adina; Kadar, Tamar

2017-04-01

Prevention of the penetration of toxic agents through the skin is crucial for both military troops and civilian populations. We have developed a novel topical skin protectant (TSP), coded as IB1 and commercially available as Dermostyx protective solution (Rekah Pharm, Israel). The formulation afforded significant protection against chemical warfare agents such as sulfur mustard (SM) and VX (2LD50), pesticides such as parathion and irritants such as acrolein. The efficacy of the protectant was evaluated in the pig model using clinical, histological and biochemical monitoring. A single topical application prior to exposure to the toxic agents reduced significantly the size and severity of skin lesions and ameliorated or prevented systemic clinical symptoms. The barrier properties of IB1 are immediate upon application and remain effective for at least 12 h. It is absorbed into the stratum corneum of the skin and remains there until rinsing with water, yet the ingredients are not absorbed into the body. The formulation is a hydrophilic water-based solution, composed of magnesium sulfate and glycerin that are widely used in cosmetic and medicine, and was shown to be safe in preclinical and in Phase I clinical studies. The suggested mode of action is based on the unique interaction of glycerin with the stratum corneum, changing its properties to hydrophilic and on the "salting out" effect of magnesium sulfate. The expected use of the TSP is by application on exposed skin areas and sensitive skin sites (e.g. armpits, groin, waist), when necessary. A quantity of 10 ml is sufficient for one application covering approximately 20% of the body surface area. The formulation was approved for human use by the Israel Ministry of Health and a CE mark certificate in Europe has been recently issued (Class I). Dermostyx has been adopted by the IDF and first responders as a skin protectant for special needs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical Compounds Toxic to Invertebrates Isolated from Marine Cyanobacteria of Potential Relevance to the Agricultural Industry

PubMed Central

Essack, Magbubah; Alzubaidy, Hanin S.; Bajic, Vladimir B.; Archer, John A. C.

2014-01-01

In spite of advances in invertebrate pest management, the agricultural industry is suffering from impeded pest control exacerbated by global climate changes that have altered rain patterns to favour opportunistic breeding. Thus, novel naturally derived chemical compounds toxic to both terrestrial and aquatic invertebrates are of interest, as potential pesticides. In this regard, marine cyanobacterium-derived metabolites that are toxic to both terrestrial and aquatic invertebrates continue to be a promising, but neglected, source of potential pesticides. A PubMed query combined with hand-curation of the information from retrieved articles allowed for the identification of 36 cyanobacteria-derived chemical compounds experimentally confirmed as being toxic to invertebrates. These compounds are discussed in this review. PMID:25356733

Chemical compounds toxic to invertebrates isolated from marine cyanobacteria of potential relevance to the agricultural industry.

PubMed

Essack, Magbubah; Alzubaidy, Hanin S; Bajic, Vladimir B; Archer, John A C

2014-10-29

In spite of advances in invertebrate pest management, the agricultural industry is suffering from impeded pest control exacerbated by global climate changes that have altered rain patterns to favour opportunistic breeding. Thus, novel naturally derived chemical compounds toxic to both terrestrial and aquatic invertebrates are of interest, as potential pesticides. In this regard, marine cyanobacterium-derived metabolites that are toxic to both terrestrial and aquatic invertebrates continue to be a promising, but neglected, source of potential pesticides. A PubMed query combined with hand-curation of the information from retrieved articles allowed for the identification of 36 cyanobacteria-derived chemical compounds experimentally confirmed as being toxic to invertebrates. These compounds are discussed in this review.

Determination of toxic inorganic elements pollution in ground waters of Kahuta Industrial Triangle Islamabad, Pakistan using inductively coupled plasma mass spectrometry.

PubMed

Kausar, Rubina; Ahmad, Zulfiqar

2009-10-01

The present study deals with the ground water quality assessment in Kahuta Industrial Triangle Islamabad, Pakistan. The objective of the study was to assess ground water quality against the drinking water standards for various toxic inorganic elements. Representative groundwater samples were collected and analyzed in the Water Quality Laboratory of Pakistan Council of Research in Water Resources (PCRWR) at Islamabad, Pakistan. The samples were run on ICP-MS (Inductively coupled plasma mass spectrometry), which has the capability to separate and quantify 70 elements at a time. One of the finding of study is that ICP-MS is a very good tool to analyze broad range of toxic inorganic elements to the level of parts per billion (ppb). World Health Organization drinking water standards shows that these toxic inorganic elements such as heavy metals even at this concentration level (ppb) are injurious to human health. This analysis indicated pollution of various toxic elements including Selenium. Vertical leachate through industrial waste septic tanks is identified as major cause of groundwater pollution in the Industrial Triangle. Monitoring of the septic tanks and groundwater quality in study area is suggested along with remedial measures.

Environmental levels, toxicity and human exposure to tributyltin (TBT)-contaminated marine environment. a review. b_antizar@hotmail.com.

PubMed

Antizar-Ladislao, Blanca

2008-02-01

Tributyltin (TBT) is a toxic chemical used for various industrial purposes such as slime control in paper mills, disinfection of circulating industrial cooling waters, antifouling agents, and the preservation of wood. Due to its widespread use as an antifouling agent in boat paints, TBT is a common contaminant of marine and freshwater ecosystems exceeding acute and chronic toxicity levels. TBT is the most significant pesticide in marine and freshwaters in Europe and consequently its environmental level, fate, toxicity and human exposure are of current concern. Thus, the European Union has decided to specifically include TBT compounds in its list of priority compounds in water in order to control its fate in natural systems, due to their toxic, persistent, bioaccumulative and endocrine disruptive characteristics. Additionally, the International Maritime Organization has called for a global treaty that bans the application of TBT-based paints starting 1 of January 2003, and total prohibition by 1 of January 2008. This paper reviews the state of the science regarding TBT, with special attention paid to the environmental levels, toxicity, and human exposure. TBT compounds have been detected in a number of environmental samples. In humans, organotin compounds have been detected in blood and in the liver. As for other persistent organic pollutants, dietary intake is most probably the main route of exposure to TBT compounds for the general population. However, data concerning TBT levels in foodstuffs are scarce. It is concluded that investigations on experimental toxicity, dietary intake, potential human health effects and development of new sustainable technologies to remove TBT compounds are clearly necessary.

Immobilized materials for removal of toxic metal ions from surface/groundwaters and aqueous waste streams.

PubMed

Zawierucha, Iwona; Kozlowski, Cezary; Malina, Grzegorz

2016-04-01

Heavy metals from industrial processes are of special concern because they produce chronic poisoning in the aquatic environment. More strict environmental regulations on the discharge of toxic metals require the development of various technologies for their removal from polluted streams (i.e. industrial wastewater, mine waters, landfill leachate, and groundwater). The separation of toxic metal ions using immobilized materials (novel sorbents and membranes with doped ligands), due to their high selectivity and removal efficiency, increased stability, and low energy requirements, is promising for improving the environmental quality. This critical review is aimed at studying immobilized materials as potential remediation agents for the elimination of numerous toxic metal (e.g. Pb, Cd, Hg, and As) ions from polluted streams. This study covers the general characteristics of immobilized materials and separation processes, understanding of the metal ion removal mechanisms, a review of the application of immobilized materials for the removal of toxic metal ions, as well as the impacts of various parameters on the removal efficiency. In addition, emerging trends and opportunities in the field of remediation technologies using these materials are addressed.

Secret science: tobacco industry research on smoking behaviour and cigarette toxicity.

PubMed

Hammond, David; Collishaw, Neil E; Callard, Cynthia

2006-03-04

A lack of scientific data remains the principal obstacle to regulating cigarette toxicity. In particular, there is an immediate need to improve our understanding of the interaction between smoking behaviour and product design, and its influence on cigarette deliveries. This article reviews internal tobacco industry documents on smoking behaviour research undertaken by Imperial Tobacco Limited (ITL) and British-American Tobacco (BAT). BAT documents indicate that smokers vary their puffing behaviour to regulate nicotine levels and compensate for low-yield cigarettes by smoking them more intensely. BAT research also shows that the tar and nicotine delivered to smokers is substantially greater than the machine-smoked yields reported to consumers and regulators. Internal documents describe a strategy to maximise this discrepancy through product design. In particular, BAT developed elastic cigarettes that produced low yields under standard testing protocols, whereas in consumers' hands they elicited more intensive smoking and provided higher concentrations of tar and nicotine to smokers. Documents also show that BAT pursued this product strategy despite the health risks to consumers and ethical concerns raised by senior scientists, and paired it with an equally successful marketing campaign that promoted these cigarettes as low-tar alternatives for health-concerned smokers. Overall, the documents seem to reveal a product strategy intended to exploit the limitations of the testing protocols and to intentionally conceal from consumers and regulators the potential toxicity of BAT products revealed by BAT's own research. Tobacco industry research underscores the serious limitations of the current cigarette testing protocols and the documents describe deceptive business practices that remain in place.

Laboratory scale studies on removal of chromium from industrial wastes.

PubMed

Baig, M A; Mir, Mohsin; Murtaza, Shazad; Bhatti, Zafar I

2003-05-01

Chromium being one of the major toxic pollutants is discharged from electroplating and chrome tanning processes and is also found in the effluents of dyes, paint pigments, manufacturing units etc. Chromium exists in aqueous systems in both trivalent (Cr(3+)) and hexavalent (Cr(6+)) forms. The hexavalent form is carcinogenic and toxic to aquatic life, whereas Cr(3+) is however comparatively less toxic. This study was undertaken to investigate the total chromium removal from industrial effluents by chemical means in order to achieve the Pakistan NEQS level of 1 mg/L by the methods of reduction and precipitation. The study was conducted in four phases. In phase I, the optimum pH and cost effective reducing agent among the four popular commercial chemicals was selected. As a result, pH of 2 was found to be most suitable and sodium meta bisulfate was found to be the most cost effective reducing agent respectively. Phase II showed that lower dose of sodium meta bisulfate was sufficient to obtain 100% efficiency in reducing Cr(6+) to Cr(3+), and it was noted that reaction time had no significance in the whole process. A design curve for reduction process was established which can act as a tool for treatment of industrial effluents. Phase III studies indicated the best pH was 8.5 for precipitation of Cr(3+) to chromium hydroxide by using lime. An efficiency of 100% was achievable and a settling time of 30 minutes produced clear effluent. Finally in Phase IV actual waste samples from chrome tanning and electroplating industries, when precipitated at pH of 12 gave 100% efficiency at a settling time of 30 minutes and confined that chemical means of reduction and precipitation is a feasible and viable solution for treating chromium wastes from industries.

Effect of Pachybasin on General Toxicity and Developmental Toxicity in Vivo.

PubMed

Lin, Yi-Ruu; Peng, Kou-Cheng; Chan, Ming-Huan; Peng, Huan-Lin; Liu, Shu-Ying

2017-12-06

To document the safety of pachybasin, a secondary metabolite of Trichoderma harzianum, for use as a bioagricultural agent, it was subjected to general toxicological testing in mice and developmental toxicity in zebrafish. With either 5 or 20 mg kg -1 pachybasin i.p. injection, mice behavioral responses such as motor coordination, spontaneous locomotor activity, or nociceptive pain were not influenced. In long-term effect (daily injection for 14 days), the physiological, hematological, liver, and kidney functions were not altered either. Evidence for the developmental toxicity of pachybasin (10-100 μM) in 72-h exposure period was shown in zebrafish larvae, based on developmental retardation, impairment of chorion, and increase of mortality. In summary, there are no significant general toxicities presented in the pachybasin-treated adult male mice. However, the embryo-toxicity in aquatic biota should be taken into consideration during bioagricultural agent application.

Biotechnological and industrial significance of cyanobacterial secondary metabolites.

PubMed

Rastogi, Rajesh P; Sinha, Rajeshwar P

2009-01-01

Cyanobacteria are considered to be a rich source of novel metabolites of a great importance from a biotechnological and industrial point of view. Some cyanobacterial secondary metabolites (CSMs), exhibit toxic effects on living organisms. A diverse range of these cyanotoxins may have ecological roles as allelochemicals, and could be employed for the commercial development of compounds with applications such as algaecides, herbicides and insecticides. Recently, cyanobacteria have become an attractive source of innovative classes of pharmacologically active compounds showing interesting and exciting biological activities ranging from antibiotics, immunosuppressant, and anticancer, antiviral, antiinflammatory to proteinase-inhibiting agents. A different but not less interesting property of these microorganisms is their capacity of overcoming the toxicity of ultraviolet radiation (UVR) by means of UV-absorbing/screening compounds, such as mycosporine-like amino acids (MAAs) and scytonemin. These last two compounds are true 'multipurpose' secondary metabolites and considered to be natural photoprotectants. In this sense, they may be biotechnologically exploited by the cosmetic industry. Overall CSMs are striking targets in biotechnology and biomedical research, because of their potential applications in agriculture, industry, and especially in pharmaceuticals.

Understanding the tolerance of the industrial yeast Saccharomyces cerevisiae against a major class of toxic aldehyde compounds.

PubMed

Liu, ZongLin Lewis

2018-07-01

Development of the next-generation biocatalyst is vital for fermentation-based industrial applications and a sustainable bio-based economy. Overcoming the major class of toxic compounds associated with lignocellulose-to-biofuels conversion is one of the significant challenges for new strain development. A significant number of investigations have been made to understand mechanisms of the tolerance for industrial yeast. It is humbling to learn how complicated the cell's response to the toxic chemicals is and how little we have known about yeast tolerance in the universe of the living cell. This study updates our current knowledge on the tolerance of industrial yeast against aldehyde inhibitory compounds at cellular, molecular and the genomic levels. It is comprehensive yet specific based on reproducible evidence and cross confirmed findings from different investigations using varied experimental approaches. This research approaches a rational foundation toward a more comprehensive understanding on the yeast tolerance. Discussions and perspectives are also proposed for continued exploring the puzzle of the yeast tolerance to aid the next-generation biocatalyst development.

Chemical warfare agent simulants for human volunteer trials of emergency decontamination: A systematic review

PubMed Central

Wyke, Stacey; Marczylo, Tim; Collins, Samuel; Gaulton, Tom; Foxall, Kerry; Amlôt, Richard; Duarte‐Davidson, Raquel

2017-01-01

Abstract Incidents involving the release of chemical agents can pose significant risks to public health. In such an event, emergency decontamination of affected casualties may need to be undertaken to reduce injury and possible loss of life. To ensure these methods are effective, human volunteer trials (HVTs) of decontamination protocols, using simulant contaminants, have been conducted. Simulants must be used to mimic the physicochemical properties of more harmful chemicals, while remaining non‐toxic at the dose applied. This review focuses on studies that employed chemical warfare agent simulants in decontamination contexts, to identify those simulants most suitable for use in HVTs of emergency decontamination. Twenty‐two simulants were identified, of which 17 were determined unsuitable for use in HVTs. The remaining simulants (n = 5) were further scrutinized for potential suitability according to toxicity, physicochemical properties and similarities to their equivalent toxic counterparts. Three suitable simulants, for use in HVTs were identified; methyl salicylate (simulant for sulphur mustard), diethyl malonate (simulant for soman) and malathion (simulant for VX or toxic industrial chemicals). All have been safely used in previous HVTs, and have a range of physicochemical properties that would allow useful inference to more toxic chemicals when employed in future studies of emergency decontamination systems. PMID:28990191

Toxicity induced by chemical warfare agents: insights on the protective role of melatonin.

PubMed

Pita, René; Marco-Contelles, José; Ramos, Eva; Del Pino, Javier; Romero, Alejandro

2013-11-25

Chemical Warfare Agents (CWAs) are substances that can be used to kill, injure or incapacitate an enemy in warfare, but also against civilian population in terrorist attacks. Many chemical agents are able to generate free radicals and derived reactants, excitotoxicity process, or inflammation, and as consequence they can cause neurological symptoms and damage in different organs. Nowadays, taking into account that total immediate decontamination after exposure is difficult to achieve and there are not completely effective antidotes and treatments against all CWAs, we advance and propose that medical countermeasures against CWAs poisoning would benefit from a broad-spectrum multipotent molecule. Melatonin, a versatile and ubiquitous antioxidant molecule, originally discovered as a hormone synthesized mainly in the pineal gland, has low toxicity and high efficacy in reducing oxidative damage, anti-inflammatory effects by regulation of multiple cellular pathways and properties to prevent excitotoxicity, among others. The purpose of this review is to show the multiple and diverse properties of melatonin, as a pleiotropic indole derivative, and its marked potential for improving human health against the most widely used chemical weapons. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Pharmacological action of Panax ginseng on the behavioral toxicities induced by psychotropic agents.

PubMed

Kim, Hyoung-Chun; Shin, Eun-Joo; Jang, Choon-Gon; Lee, Myung-Koo; Eun, Jae-Soon; Hong, Jin-Tae; Oh, Ki-Wan

2005-09-01

Morphine-induced analgesia has been shown to be antagonized by ginseng total saponins (GTS), which also inhibit the development of analgesic tolerance to and physical dependence on morphine. GTS is involved in both of these processes by inhibiting morphine-6-dehydrogenase, which catalyzes the synthesis of morphinone from morphine, and by increasing the level of hepatic glutathione, which participates in the toxicity response. Thus, the dual actions of ginseng are associated with the detoxification of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contractions in guinea pig ileum (mu-receptors) and mouse vas deferens (delta-receptors) are not mediated through opioid receptors, suggesting the involvement of non-opioid mechanisms. GTS also attenuates hyperactivity, reverse tolerance (behavioral sensitization), and conditioned place preference induced by psychotropic agents, such as methamphetamine, cocaine, and morphine. These effects of GTS may be attributed to complex pharmacological actions between dopamine receptors and a serotonergic/adenosine A2A/ delta-opioid receptor complex. Ginsenosides also attenuate the morphine-induced cAMP signaling pathway. Together, the results suggest that GTS may be useful in the prevention and therapy of the behavioral side effects induced by psychotropic agents.

Tavaborole, a Novel Boron-Containing Small Molecule Pharmaceutical Agent for Topical Treatment of Onychomycosis: I. Reproductive and Developmental Toxicity Studies.

PubMed

Ciaravino, Vic; Coronado, Dina; Lanphear, Cheryl; Hoberman, Alan; Chanda, Sanjay

2016-09-01

Tavaborole is a topical antifungal agent approved by the US Food and Drug Administration for the treatment of toenail onychomycosis. As part of the nonclinical development program, reproductive and developmental toxicity studies were conducted (rat oral fertility and early embryonic development, rat (oral) and rabbit (dermal) embryo-fetal development). There were no effects on fertility or reproductive performance at doses up to 300 mg/kg/d (107 times the maximum recommended human dose [MRHD] based on mean area under the plasma concentration-time curve comparisons). In the rat embryo-fetal development toxicity studies, teratogenicity was not observed at doses up to 100 mg/kg/d (29 times the MRHD). However, several treatment-related skeletal malformations and variations were observed at 300 mg/kg/d (570 times the MRHD). In rabbit embryo-fetal development toxicity studies dosed via oral or dermal administration, the no observable adverse effect level for maternal toxicity and embryo-fetal toxicity was 50 mg/kg/d (16 times the MRHD) and 5% (26 times the MRHD), respectively. © The Author(s) 2016.

Valorization of titanium metal wastes as tanning agent used in leather industry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crudu, Marian, E-mail: mariancrudu@yahoo.com; Deselnicu, Viorica, E-mail: viorica.deselnicu@icpi.ro; Deselnicu, Dana Corina, E-mail: d_deselnicu@yahoo.com

2014-10-15

Highlights: • Valorization of titanium wastes which cannot be recycled in metallurgical industry. • Transferring Ti waste into raw materials for obtaining Ti based tanning agent. • Characterization of new Ti based tanning agents and leather tanned with them. • Characterization of sewage waste water and sludge resulted from leather manufacture. • Analysis of the impact of main metal component of Ti waste. - Abstract: The development of new tanning agents and new technologies in the leather sector is required to cope with the increasingly higher environmental pressure on the current tanning materials and processes such as tanning with chromiummore » salts. In this paper, the use of titanium wastes (cuttings) resulting from the process of obtaining highly pure titanium (ingots), for the synthesis of new tanning agent and tanning bovine hides with new tanning agent, as alternative to tanning with chromium salts are investigated. For this purpose, Ti waste and Ti-based tanning agent were characterized for metal content by inductively coupled plasma mass spectrometry (ICP-MS) and chemical analysis; the tanned leather (wet white leather) was characterized by Scanning Electron Microscope/Energy Dispersive Using X-ray (Analysis). SEM/EDX analysis for metal content; Differential scanning calorimetric (DSC), Micro-Hot-Table and standard shrinkage temperature showing a hydrothermal stability (ranged from 75.3 to 77 °C) and chemical analysis showing the leather is tanned and can be processed through the subsequent mechanical operations (splitting, shaving). On the other hand, an analysis of major minor trace substances from Ti-end waste (especially vanadium content) in new tanning agent and wet white leather (not detected) and residue stream was performed and showed that leachability of vanadium is acceptable. The results obtained show that new tanning agent obtained from Ti end waste can be used for tanning bovine hides, as eco-friendly alternative for chrome

Sensing and capture of toxic and hazardous gases and vapors by metal-organic frameworks.

PubMed

Wang, Hao; Lustig, William P; Li, Jing

2018-03-13

Toxic and hazardous chemical species are ubiquitous, predominantly emitted by anthropogenic activities, and pose serious risks to human health and the environment. Thus, the sensing and subsequent capture of these chemicals, especially in the gas or vapor phase, are of extreme importance. To this end, metal-organic frameworks have attracted significant interest, as their high porosity and wide tunability make them ideal for both applications. These tailorable framework materials are particularly promising for the specific sensing and capture of targeted chemicals, as they can be designed to fit a diverse range of required conditions. This review will discuss the advantages of metal-organic frameworks in the sensing and capture of harmful gases and vapors, as well as principles and strategies guiding the design of these materials. Recent progress in the luminescent detection of aromatic and aliphatic volatile organic compounds, toxic gases, and chemical warfare agents will be summarized, and the adsorptive removal of fluorocarbons/chlorofluorocarbons, volatile radioactive species, toxic industrial gases and chemical warfare agents will be discussed.

Acute and early life stage toxicity of industrial effluent on Japanese medaka (Oryzias latipes).

PubMed

Zha, Jinmiao; Wang, Zijian

2006-03-15

To develop the whole effluent toxicity testing methods (WET), embryo larval stage toxicity test using Japanese medaka (Oryzias latipes) was conducted to evaluate an effluent from a banknote printing plant (BPP). The method is based on acute toxicity using endpoint of 96-h larval morality and on chronic toxicity using endpoints such as the time to hatch, hatching success, deformity, growth rate, swim-up failure, accumulative mortality and sexual ratio. In test for 96-h larval mortality, LC50 (the concentration was lethal to 50% of newly hatching medaka larvae) was 72.9%. In chronic toxicity test, newly fertilized embryos (<5-h old) were exposed to 1%, 6.25%, 12.5%, 25%, 50% effluent concentrations and to 200 mug/l BPA in a 24-h static renewal system at 25+/-1 degrees C until 15 day post-hatch. The results showed that all chronic endpoints were significantly different from the control at 50% dilution (p < 0.01). Embryos began to show lesions on 4th day at higher concentrations (12.5%, 25%, 50% BPP effluent concentrations). Treatment group of 25% dilution showed delayed time to hatch. A reduction in body weight was observed at 25% dilutions for males and females, respectively. Deformities were observed in newly hatched larvae at 25% and 50% BPP effluent concentrations. At 25% dilution, sex ratio of larvae was alternated and there was feminization phenomenon. We conclude that embryo larval stage test using medaka is feasible to evaluate both acute and chronic toxicities and potential endocrine disrupting activity of industrial effluents.

Maternally Mediated Developmental Toxicity

EPA Science Inventory

The current practice for the assessment of an agent’s potential effects on the developing embryo/fetus includes administration of high, maternally toxic doses to pregnant laboratory animals. For most agents evaluated, developmental effects occur concomitant with maternal toxicity...

Scientific and industrial challenges of developing nanoparticle-based theranostics and multiple-modality contrast agents for clinical application

NASA Astrophysics Data System (ADS)

Wáng, Yì Xiáng J.; Idée, Jean-Marc; Corot, Claire

2015-10-01

Designing of theranostics and dual or multi-modality contrast agents are currently two of the hottest topics in biotechnology and biomaterials science. However, for single entity theranostics, a right ratio of their diagnostic component and their therapeutic component may not always be realized in a composite suitable for clinical application. For dual/multiple modality molecular imaging agents, after in vivo administration, there is an optimal time window for imaging, when an agent is imaged by one modality, the pharmacokinetics of this agent may not allow imaging by another modality. Due to reticuloendothelial system clearance, efficient in vivo delivery of nanoparticles to the lesion site is sometimes difficult. The toxicity of these entities also remains poorly understood. While the medical need of theranostics is admitted, the business model remains to be established. There is an urgent need for a global and internationally harmonized re-evaluation of the approval and marketing processes of theranostics. However, a reasonable expectation exists that, in the near future, the current obstacles will be removed, thus allowing the wide use of these very promising agents.

Emergency planning and preparedness for the deliberate release of toxic industrial chemicals.

PubMed

Russell, David; Simpson, John

2010-03-01

Society in developed and developing countries is hugely dependent upon chemicals for health, wealth, and economic prosperity, with the chemical industry contributing significantly to the global economy. Many chemicals are synthesized, stored, and transported in vast quantities and classified as high production volume chemicals; some are recognized as being toxic industrial chemicals (TICs). Chemical accidents involving chemical installations and transportation are well recognized. Such chemical accidents occur with relative frequency and may result in large numbers of casualties with acute and chronic health effects as well as fatalities. The large-scale production of TICs, the potential for widespread exposure and significant public health impact, together with their relative ease of acquisition, makes deliberate release an area of potential concern. The large numbers of chemicals, together with the large number of potential release scenarios means that the number of possible forms of chemical incident are almost infinite. Therefore, prior to undertaking emergency planning and preparedness, it is necessary to prioritize risk and subsequently mitigate. This is a multi-faceted process, including implementation of industrial protection layers, substitution of hazardous chemicals, and relocation away from communities. Residual risk provides the basis for subsequent planning. Risk-prioritized emergency planning is a tool for identifying gaps, enhancing communication and collaboration, and for policy development. It also serves to enhance preparedness, a necessary prelude to preventing or mitigating the public health risk to deliberate release. Planning is an iterative and on-going process that requires multi-disciplinary agency input, culminating in the formation of a chemical incident plan complimentary to major incident planning. Preparedness is closely related and reflects a state of readiness. It is comprised of several components, including training and exercising

Understanding the tolerance of the industrial yeast Saccharomyces cerevisiae against a major class of toxic aldehyde compounds

USDA-ARS?s Scientific Manuscript database

Development of the next-generation biocatalyst is vital for fermentation-based industrial applications and a sustainable bio-based economy. Overcoming the major class of toxic compounds associated with lignocellulose-to-biofuels conversion is one of the significant challenges for new strain developm...

Identification of acute toxicants in New Bedford Harbor sediments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ho, K.T.; McKinney, R.A.; Kuhn, A.

1997-03-01

New Bedford Harbor (NBH) is a marine Superfund site contaminated with high concentrations of polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs) and metals. Experiments were conducted to determine the causal toxic agent(s) in pore waters from New Bedford Harbor sediments to amphipods and mysid shrimp. Chemical manipulations to characterize toxicity revealed that pore-water toxicity was organic in nature. Fractionation and subsequent mass spectral identification of peaks in the toxic fraction indicated that PCBs. PAHs, and unknown compounds were present. Comparisons of PAH LC50s and PAH concentrations in this fraction indicated that the toxicity was not due to PAHs because themore » PAH concentrations were much lower than the reported PAH LC50s. One unknown peak was positively identified as bis(2-ethylhexyl) phthalate, and the other tentatively identified as pyrazole. Toxicity tests and comparison of toxicity in the blank and toxic fractions eliminated the two unknowns as toxic causal agents. The authors determined the range of PCB LC50s to fall between 10 and 110 ppb for Mysidopsis bahia and Ampelisca abdita. Concentrations of PCBs for the toxic fractions ranged from 12 to 27 ppb. This range falls within the observed PCB LC50s for M. bahia and A. abdita. Based upon these PCB concentrations, they concluded that PCBs were the acute toxic agents in NBH pore waters. Other compounds in the toxic fractions, or compounds that coeluted and were undistinguished from PCBs had minor contributions to the measured toxicity.« less

Toxicity following laundry detergent pod ingestion.

PubMed

Schneir, Aaron B; Rentmeester, Landen; Clark, Richard F; Cantrell, F Lee

2013-06-01

Laundry detergent pods (LDPs) have only recently become available in the United States, and there has been increasing concern regarding pediatric ingestions of them. We describe a 15-month-old female infant who ingested an LDP and had a depressed level of consciousness, metabolic acidosis, pulmonary toxicity, and swallowing difficulties. It is currently unclear what the exact etiologic agent(s) is responsible for the toxicity associated with LDPs. The case demonstrates the potential for significant toxicity following the ingestion of an LDP. Clearly, measures should be taken to avoid ingestions of these products.

Lethal toxicity of industrial chemicals to early life stages of Tilapia guineensis.

PubMed

Ezemonye, L I N; Ogeleka, D F; Okieimen, F E

2008-08-30

The toxic effects of industrial chemicals on three early life stages of an economically important fish, Tilapia guineensis were investigated using the Organisation for Economic Cooperation and Development (OECD) # 203 recommended semi-static renewal bioassay. The assessment was necessary for the uncontrollable disposal of Neatex (liquid detergent) and Norust CR 486 (corrosion inhibitor) into the Niger Delta environment of Nigeria. The estimated 96-h LC(50) for 7-, 14- and 28-day-old fish in Norust CR 486 exposure was considered "more toxic" than Neatex in all life stages and was dependent on species age, exposure duration and environment. In the fresh water test, for Neatex and Norust CR 486 exposures for day 7, 14 and 28, the 96-h LC50 were 8.79, 17.10 and 82.42 mg/l and 5.55, 13.58 and 20.21 mg/l, respectively. In the brackish test, 15.42 and 46.52 mg/l, not determined (ND) and 7.35, 13.95 and 24.50mg/l were obtained. Differential toxicity was observed in the fresh and brackish water fish for the two chemicals and controls at p<0.05. The high sensitivity of the 7-day-old test organisms to both chemicals provides a rationale for regulatory surveillance and monitoring of both chemicals in the fragile Niger Delta environment.

Crataegus monogyna fruit aqueous extract as a protective agent against doxorubicin-induced reproductive toxicity in male rats

PubMed Central

Shalizar Jalali, Ali; Hasanzadeh, Shapour

2013-01-01

Objective: Doxorubicin (DOX) is a broad spectrum chemotherapeutic agent used in the treatment of several malignancies. The use of DOX in clinical chemotherapy has been restricted due to its diverse toxicities, including reproductive toxicity. Crataegus monogyna (C. monogyna) is one of the oldest medicinal plants that have been shown to be cytoprotective because of scavenging free radicals. The present study was undertaken to determine whether C. monogyna fruits aqueous extract could serve as a protective agent against reproductive toxicity during DOX treatment in a rat model through antioxidant-mediated mechanisms. Materials and Methods: Male Wistar rats were allocated to four groups. Two groups of rats were treated with DOX at a dose of 4 mg/kg intraperitoneally on days 1, 7, 14, 21, and 28 (accumulated dose of 20 mg/kg). One of the groups received C. monogyna fruits aqueous extract at a dose of 20 mg/kg per day orally for 28 days along with DOX. A vehicle-treated control group and a C. monogyna control group were also included. Results: The DOX-treated group showed significant decreases in the body and organ weights and spermatogenic activities as well as many histological alterations. DOX treatment also caused a significant decrease in sperm count and motility with an increase in dead and abnormal sperms. Moreover, significant decrease in serum levels of testosterone and increased serum concentrations of FSH, LH, LDH, CPK, and SGOT were observed in DOX-treated rats. Notably, Crataegus co-administration caused a partial recovery in above-mentioned parameters. Conclusion: These findings indicated that doxorubicin can adversely damage the testicular tissue, while Crataegus co-administration could effectively prevent these adverse effects by effective inhibiting oxidative processes and restoration of antioxidant defense system. PMID:25050270

Perspective of surface active agents in baking industry: an overview.

PubMed

Ahmad, Asif; Arshad, Nazish; Ahmed, Zaheer; Bhatti, Muhammad Shahbaz; Zahoor, Tahir; Anjum, Nomana; Ahmad, Hajra; Afreen, Asma

2014-01-01

Different researchers have previously used surfactants for improving bread qualities and revealed that these compounds result in improving the quality of dough and bread by influencing dough strength, tolerance, uniform crumb cell size, and improve slicing characteristics and gas retention. The objective of this review is to highlight the areas where surfactants are most widely used particularly in the bread industries, their role and mechanism of interaction and their contribution to the quality characteristics of the dough and bread. This review reveals some aspects of surface-active agents regarding its role physiochemical properties of dough that in turn affect the bread characteristics by improving its sensory quality and storage stability.

Impact of gender on efficacy and acute toxicity of alkylating agent -based chemotherapy in Ewing sarcoma: secondary analysis of the Euro-Ewing99-R1 trial.

PubMed

van den Berg, Henk; Paulussen, Michael; Le Teuff, Gwénaël; Judson, Ian; Gelderblom, Hans; Dirksen, Uta; Brennan, Bernadette; Whelan, Jeremy; Ladenstein, Ruth Lydia; Marec-Berard, Perrine; Kruseova, Jarmila; Hjorth, Lars; Kühne, Thomas; Brichard, Benedicte; Wheatley, Keith; Craft, Alan; Juergens, Heribert; Gaspar, Nathalie; Le Deley, Marie-Cécile

2015-11-01

Based on the randomised Euro-EWING99-R1 trial, vincristine, adriamycin, cyclophosphamide (VAC) may be able to replace vincristine, adriamycin, ifosfamide (VAI) in the treatment of standard-risk Ewing sarcoma. However some heterogeneity of treatment effect by gender was observed. The current exploratory study aimed at investigating the influence of gender on treatment efficacy and acute toxicity. Impact of gender on event-free survival (EFS), acute toxicity by course, switches between treatment arms and cumulative dose of alkylating agents was evaluated in multivariable models adjusted for age including terms to test for heterogeneity of treatment effect by gender. The analysis of the EFS was performed on the intention-to-treat population. EFS did not significantly differ between the 509 males and 347 females (p=0.33), but an interaction in terms of efficacy was suspected between treatment and gender (p=0.058): VAC was associated with poorer EFS than VAI in males, hazard ratio (HR) (VAC/VAI)=1.37 [95% confidence interval (CI), 0.98-1.90], contrasting with HR=0.81 [95%CI, 0.53-1.24] in females. Severe toxicity was more frequent in females, whatever the toxicity type. Thirty patients switched from VAI to VAC (9/251 males, 4%, and 21/174 females, 12%) mostly due to renal toxicity, and three from VAC to VAI (2/258 males, 0.8%, and 1/173 females, 0.6%). A reduction of alkylating agent cumulative dose >20% was more frequent in females (15% versus 9%, p=0.005), with no major difference between VAC and VAI (10% versus 13%, p=0.15). Differences of acute toxicity rate and cumulative doses of alkylating agents could not explain the marginal interaction observed in the Euro-EWING99-R1 trial data. Effects of gender-dependent polymorphism/activity of metabolic enzymes (e.g. known for CYP2B6) of ifosfamide versus cyclophosphamide should be explored. External data are required to further evaluate whether there is heterogeneity of alkylating agent effect by gender. NCT00987636 and

Frequency and impact of grade three or four toxicities of novel agents on outcomes of older patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma (alliance A151611).

PubMed

Tallarico, Michael; Foster, Jared C; Seisler, Drew; Lafky, Jacqueline M; Hurria, Arti; Jatoi, Aminah; Cohen, Harvey J; Muss, Hyman B; Bartlett, Nancy; Cheson, Bruce D; Jung, Sin-Ho; Leonard, John P; Byrd, John C; Nabhan, Chadi

2018-07-01

Older patients with cancer suffer from chemotherapy-related toxicities more frequently than younger patients. As novel agents are being used more commonly in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), toxicities of these agents in older patients have not been well studied. Further, impact of these toxicities on outcomes in the elderly is unknown. This study aimed to answer both questions. We reviewed 14 Alliance for Clinical Trials in Oncology trials that enrolled CLL and/or NHL patients between 2004-2014. Toxicity was assessed per the NCI-CTCAE (version 3-5). Probabilities of experiencing grade three or four hematologic and non-hematologic toxicities were modeled as a function of clinical and disease-related factors using logistic regression. 1199 patients (409 age ≥ 65; 790 age < 65) were analyzed; 438 received only biologic therapy (145 age ≥ 65; 293 age < 65), and 761 received biologic + chemotherapy (264 age ≥ 65; 497 age < 65). The odds of grade three or four hematologic [odds ratio (OR) 1.70; p = 0.009: 95% CI (1.57-1.84)] and non-hematologic toxicities [OR 1.47; p = 0.022; 95% CI (1.39-1.55)] were increased in older patients with CLL, as well as odds of grade three or four non-hematologic toxicities [OR 1.89; p = 0.017; 95% CI (1.64-2.17)] in older patients with NHL. Grade three or four hematologic toxicities were associated with inferior OS and PFS in older patients with NHL [HR 3.14; p = 0.006; 95% CI (2.25-4.39) for OS and 3.06; p = 0.011; 95% CI (2.10-4.45) for PFS], though not in CLL. A prognostic model predicting grade three or four toxicities was also developed. CLL and NHL patients ≥ 65 year encounter more toxicities than younger patients even when treated with novel biologic agents. Development of grade three or four hematologic toxicities lead to inferior PFS and OS in NHL but not in CLL. Copyright © 2018 Elsevier Ltd. All rights reserved.

Basalt fiber insulating material with a mineral binding agent for industrial use

NASA Astrophysics Data System (ADS)

Drozdyuk, T.; Aizenshtadt, A.; Tutygin, A.; Frolova, M.

2016-04-01

The paper considers a possibility of using mining industry waste as a binding agent for heat insulating material on the basis of basalt fiber. The main objective of the research is to produce a heat-insulating material to be applied in machine building in high-temperature environments. After synthetic binder having been replaced by a mineral one, an environmentally sound thermal insulating material having desirable heat-protecting ability and not failing when exposed to high temperatures was obtained.

Predicting the Future: Opportunities and Challenges for the Chemical Industry to Apply 21st-Century Toxicity Testing

PubMed Central

Settivari, Raja S; Ball, Nicholas; Murphy, Lynea; Rasoulpour, Reza; Boverhof, Darrell R; Carney, Edward W

2015-01-01

Interest in applying 21st-century toxicity testing tools for safety assessment of industrial chemicals is growing. Whereas conventional toxicology uses mainly animal-based, descriptive methods, a paradigm shift is emerging in which computational approaches, systems biology, high-throughput in vitro toxicity assays, and high-throughput exposure assessments are beginning to be applied to mechanism-based risk assessments in a time- and resource-efficient fashion. Here we describe recent advances in predictive safety assessment, with a focus on their strategic application to meet the changing demands of the chemical industry and its stakeholders. The opportunities to apply these new approaches is extensive and include screening of new chemicals, informing the design of safer and more sustainable chemical alternatives, filling information gaps on data-poor chemicals already in commerce, strengthening read-across methodology for categories of chemicals sharing similar modes of action, and optimizing the design of reduced-risk product formulations. Finally, we discuss how these predictive approaches dovetail with in vivo integrated testing strategies within repeated-dose regulatory toxicity studies, which are in line with 3Rs principles to refine, reduce, and replace animal testing. Strategic application of these tools is the foundation for informed and efficient safety assessment testing strategies that can be applied at all stages of the product-development process. PMID:25836969

Predicting the future: opportunities and challenges for the chemical industry to apply 21st-century toxicity testing.

PubMed

Settivari, Raja S; Ball, Nicholas; Murphy, Lynea; Rasoulpour, Reza; Boverhof, Darrell R; Carney, Edward W

2015-03-01

Interest in applying 21st-century toxicity testing tools for safety assessment of industrial chemicals is growing. Whereas conventional toxicology uses mainly animal-based, descriptive methods, a paradigm shift is emerging in which computational approaches, systems biology, high-throughput in vitro toxicity assays, and high-throughput exposure assessments are beginning to be applied to mechanism-based risk assessments in a time- and resource-efficient fashion. Here we describe recent advances in predictive safety assessment, with a focus on their strategic application to meet the changing demands of the chemical industry and its stakeholders. The opportunities to apply these new approaches is extensive and include screening of new chemicals, informing the design of safer and more sustainable chemical alternatives, filling information gaps on data-poor chemicals already in commerce, strengthening read-across methodology for categories of chemicals sharing similar modes of action, and optimizing the design of reduced-risk product formulations. Finally, we discuss how these predictive approaches dovetail with in vivo integrated testing strategies within repeated-dose regulatory toxicity studies, which are in line with 3Rs principles to refine, reduce, and replace animal testing. Strategic application of these tools is the foundation for informed and efficient safety assessment testing strategies that can be applied at all stages of the product-development process.

Chemical warfare agent simulants for human volunteer trials of emergency decontamination: A systematic review.

PubMed

James, Thomas; Wyke, Stacey; Marczylo, Tim; Collins, Samuel; Gaulton, Tom; Foxall, Kerry; Amlôt, Richard; Duarte-Davidson, Raquel

2018-01-01

Incidents involving the release of chemical agents can pose significant risks to public health. In such an event, emergency decontamination of affected casualties may need to be undertaken to reduce injury and possible loss of life. To ensure these methods are effective, human volunteer trials (HVTs) of decontamination protocols, using simulant contaminants, have been conducted. Simulants must be used to mimic the physicochemical properties of more harmful chemicals, while remaining non-toxic at the dose applied. This review focuses on studies that employed chemical warfare agent simulants in decontamination contexts, to identify those simulants most suitable for use in HVTs of emergency decontamination. Twenty-two simulants were identified, of which 17 were determined unsuitable for use in HVTs. The remaining simulants (n = 5) were further scrutinized for potential suitability according to toxicity, physicochemical properties and similarities to their equivalent toxic counterparts. Three suitable simulants, for use in HVTs were identified; methyl salicylate (simulant for sulphur mustard), diethyl malonate (simulant for soman) and malathion (simulant for VX or toxic industrial chemicals). All have been safely used in previous HVTs, and have a range of physicochemical properties that would allow useful inference to more toxic chemicals when employed in future studies of emergency decontamination systems. © 2017 Crown Copyright. Journal of Applied Toxicology published by John Wiley & Sons, Ltd.

Toxic-Waste Disposal by Combustion in Containers

NASA Technical Reports Server (NTRS)

Houseman, J.; Stephens, J. B.; Moynihan, P. I.; Compton, L. E.; Kalvinskas, J. J.

1986-01-01

Chemical wastes burned with minimal handling in storage containers. Technique for disposing of chemical munitions by burning them inside shells applies to disposal of toxic materials stored in drums. Fast, economical procedure overcomes heat-transfer limitations of conventional furnace designs by providing direct contact of oxygenrich combustion gases with toxic agent. No need to handle waste material, and container also decontaminated in process. Oxygen-rich torch flame cuts burster well and causes vaporization and combustion of toxic agent contained in shell.

Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nambiar, Madhusoodana P.; Gordon, Richard K.; Rezk, Peter E.

2007-03-15

To develop therapeutics against lung injury and respiratory toxicity following nerve agent VX exposure, we evaluated the protective efficacy of a number of potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m{sup 3} of VX or saline using a microinstillation inhalation exposure technique for 4 min and then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h survival rate of 52%. There was a significant increase in bronchoalveolar lavage (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti-sense syk oligonucleotides 2 min post-exposure didmore » not significantly increase the survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway, and bronchioles, VX-induced viscous mucous secretions were exacerbated by these aerosolized treatments. To overcome these events, we developed a strategy to protect the animals by treatment with atropine. Atropine inhibits muscarinic stimulation and markedly reduces the copious airway secretion following nerve agent exposure. Indeed, post-exposure treatment with atropine methyl bromide, which does not cross the blood-brain barrier, resulted in 100% survival of VX-exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated animals exhibited lower protein levels, cell number, and cell death compared to VX-exposed controls, indicating less lung injury. When pulmonary therapeutics were combined with atropine, significant protection to VX-exposure was observed. These results indicate that combinations of pulmonary therapeutics with atropine or drugs that inhibit mucous secretion are important for the treatment of respiratory toxicity and lung injury following VX exposure.« less

Organochlorine pesticides, their toxic effects on living organisms and their fate in the environment

PubMed Central

Megha, Pankajshan; Sreedev, Puthur

2016-01-01

Organochlorine (OC) pesticides are synthetic pesticides widely used all over the world. They belong to the group of chlorinated hydrocarbon derivatives, which have vast application in the chemical industry and in agriculture. These compounds are known for their high toxicity, slow degradation and bioaccumulation. Even though many of the compounds which belong to OC were banned in developed countries, the use of these agents has been rising. This concerns particularly abuse of these chemicals which is in practice across the continents. Though pesticides have been developed with the concept of target organism toxicity, often non-target species are affected badly by their application. The purpose of this review is to list the major classes of pesticides, to understand organochlorine pesticides based on their activity and persistence, and also to understand their biochemical toxicity. PMID:28652852

Determination of the toxic variability of lipophilic biotoxins in marine bivalve and gastropod tissues treated with an industrial canning process.

PubMed

García, Carlos; Oyaneder-Terrazas, Javiera; Contreras, Cristóbal; Del Campo, Miguel; Torres, Rafael; Contreras, Héctor R

2016-11-01

Contamination of shellfish with lipophilic marine biotoxins (LMB), pectenotoxins (PTXs), yessotoxins (YTXs) and okadaic acid (OA) toxin groups in southern Chile is a constant challenge for the development of miticulture considering the high incidence of toxic episodes that tend to occur. This research is focused on using methodologies for assessing the decrease in toxins of natural resources in Chile with high value, without altering the organoleptic properties of the shellfish. The species were processed through steaming (1 min at 121°C) and subsequent canning (5 min at 121°C). Changes in the profiles of toxins and total toxicity levels of LMB in endemic bivalves and gastropods were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The total reduction of toxicity (≈ 15%) was not related to the destruction of the toxin, but rather to the loss of LMB on removing the shells and packing media of canned products (***p < 0.001). Industrial processing of shellfish reduces LMB contents by up to 15% of the total initial contents, concomitant only with the interconversion of PTX-group toxins into PTX-2sa. In soft bottom-dwelling species with toxicities beyond the standard for safe human consumption (≥ 160 μg OA-eq kg - 1 ), toxicity can be reduced to safe levels through industrial preparation procedures.

Influence of anionic surface-active agents on the uptake of heavy metals by water hyacinth (Eichhornia crassipes)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muramoto, S.; Oki, Y.

1984-10-01

In a previous paper, the ability of water hyacinth to remove toxic heavy metals, cadmium, lead, and mercury, from a metal-containing solution was reported. However, information on the effects of surface-active agents on the metal uptake from waste water by water hyacinth is insufficient. Surface-active agents including anionic detergents have been found in lake, ponds, and rivers polluted by waste from industry and municipal sewage treatment plants. The present study examines the uptake of cadmium or nickel in the presence of the anionic detergent sodium dedecyl sulfate.

Chemical warfare agents. Classes and targets.

PubMed

Schwenk, Michael

2018-09-01

Synthetic toxic chemicals (toxicants) and biological poisons (toxins) have been developed as chemical warfare agents in the last century. At the time of their initial consideration as chemical weapon, only restricted knowledge existed about their mechanisms of action. There exist two different types of acute toxic action: nonspecific cytotoxic mechanisms with multiple chemo-biological interactions versus specific mechanisms that tend to have just a single or a few target biomolecules. TRPV1- and TRPA-receptors are often involved as chemosensors that induce neurogenic inflammation. The present work briefly surveys classes and toxicologically relevant features of chemical warfare agents and describes mechanisms of toxic action. Copyright © 2017 Elsevier B.V. All rights reserved.

Priority screening of toxic chemicals and industry sectors in the U.S. toxics release inventory: a comparison of the life cycle impact-based and risk-based assessment tools developed by U.S. EPA.

PubMed

Lim, Seong-Rin; Lam, Carl W; Schoenung, Julie M

2011-09-01

Life Cycle Impact Assessment (LCIA) and Risk Assessment (RA) employ different approaches to evaluate toxic impact potential for their own general applications. LCIA is often used to evaluate toxicity potentials for corporate environmental management and RA is often used to evaluate a risk score for environmental policy in government. This study evaluates the cancer, non-cancer, and ecotoxicity potentials and risk scores of chemicals and industry sectors in the United States on the basis of the LCIA- and RA-based tools developed by U.S. EPA, and compares the priority screening of toxic chemicals and industry sectors identified with each method to examine whether the LCIA- and RA-based results lead to the same prioritization schemes. The Tool for the Reduction and Assessment of Chemical and other environmental Impacts (TRACI) is applied as an LCIA-based screening approach with a focus on air and water emissions, and the Risk-Screening Environmental Indicator (RSEI) is applied in equivalent fashion as an RA-based screening approach. The U.S. Toxic Release Inventory is used as the dataset for this analysis, because of its general applicability to a comprehensive list of chemical substances and industry sectors. Overall, the TRACI and RSEI results do not agree with each other in part due to the unavailability of characterization factors and toxic scores for select substances, but primarily because of their different evaluation approaches. Therefore, TRACI and RSEI should be used together both to support a more comprehensive and robust approach to screening of chemicals for environmental management and policy and to highlight substances that are found to be of concern from both perspectives. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reactive skin decontamination lotion (RSDL) for the decontamination of chemical warfare agent (CWA) dermal exposure.

PubMed

Schwartz, M D; Hurst, C G; Kirk, M A; Reedy, S J D; Braue, E H

2012-08-01

Rapid decontamination of the skin is the single most important action to prevent dermal absorption of chemical contaminants in persons exposed to chemical warfare agents (CWA) and toxic industrial chemicals (TICs) as a result of accidental or intentional release. Chemicals on the skin may be removed by mechanical means through the use of dry sorbents or water. Recent interest in decontamination systems which both partition contaminants away from the skin and actively neutralize the chemical has led to the development of several reactive decontamination solutions. This article will review the recently FDA-approved Reactive Skin Decontamination Lotion (RSDL) and will summarize the toxicity and efficacy studies conducted to date. Evidence of RSDL's superior performance against vesicant and organophosphorus chemical warfare agents compared to water, bleach, and dry sorbents, suggests that RSDL may have a role in mass human exposure chemical decontamination in both the military and civilian arenas.

Plant-Derived Agents for Counteracting Cisplatin-Induced Nephrotoxicity.

PubMed

Ojha, Shreesh; Venkataraman, Balaji; Kurdi, Amani; Mahgoub, Eglal; Sadek, Bassem; Rajesh, Mohanraj

2016-01-01

Cisplatin (CSP) is a chemotherapeutic agent commonly used to treat a variety of malignancies. The major setback with CSP treatment is that its clinical efficacy is compromised by its induction of organ toxicity, particular to the kidneys and ears. Despite the significant strides that have been made in understanding the mechanisms underlying CSP-induced renal toxicity, advances in developing renoprotective strategies are still lacking. In addition, the renoprotective approaches described in the literature reveal partial amelioration of CSP-induced renal toxicity, stressing the need to develop potent combinatorial/synergistic agents for the mitigation of renal toxicity. However, the ideal renoprotective adjuvant should not interfere with the anticancer efficacy of CSP. In this review, we have discussed the progress made in utilizing plant-derived agents (phytochemicals) to combat CSP-induced nephrotoxicity in preclinical studies. Furthermore, we have also presented strategies to utilize phytochemicals as prototypes for the development of novel renoprotective agents for counteracting chemotherapy-induced renal damage.

Plant-Derived Agents for Counteracting Cisplatin-Induced Nephrotoxicity

PubMed Central

Venkataraman, Balaji; Kurdi, Amani; Mahgoub, Eglal; Sadek, Bassem

2016-01-01

Cisplatin (CSP) is a chemotherapeutic agent commonly used to treat a variety of malignancies. The major setback with CSP treatment is that its clinical efficacy is compromised by its induction of organ toxicity, particular to the kidneys and ears. Despite the significant strides that have been made in understanding the mechanisms underlying CSP-induced renal toxicity, advances in developing renoprotective strategies are still lacking. In addition, the renoprotective approaches described in the literature reveal partial amelioration of CSP-induced renal toxicity, stressing the need to develop potent combinatorial/synergistic agents for the mitigation of renal toxicity. However, the ideal renoprotective adjuvant should not interfere with the anticancer efficacy of CSP. In this review, we have discussed the progress made in utilizing plant-derived agents (phytochemicals) to combat CSP-induced nephrotoxicity in preclinical studies. Furthermore, we have also presented strategies to utilize phytochemicals as prototypes for the development of novel renoprotective agents for counteracting chemotherapy-induced renal damage. PMID:27774117

Bioassay directed identification of toxicants in sludge and related reused materials from industrial wastewater treatment plants in the Yangtze River Delta.

PubMed

Fang, Binbin; Guo, Jing; Li, Fuxing; Giesy, John P; Wang, Lianjun; Shi, Wei

2017-02-01

Industrialized development of the Yangtze River Delta, China, has resulted in larger amounts of wastes, including sludges from treatment of these wastes. Methods to manage and dispose, including reuse were urgently needed. Sludge and reused products were collected from two largest factories, KEYUAN and HENGJIA where treated sludges were turned into bricks or sludge cake to be placed in landfills, respectively. Metals and organic compounds were quantified in sludges and leachates assessed by use of toxicity characterized leaching procedure (TCLP) while acute toxicity was determined by Daphnia magna. Nine metals were detected in all raw sludges with concentrations of Cr and Ni exceeding Chinese standards. For sludge leachate, concentrations of metals were all less than Chinese standards, which changed little after being made into cake by HENGJIA, but were significantly less after being made into brick by KEYUAN. Toxicity units (TU) for all samples are greater than 1.0 indicating that they are potentially toxic to aquatic organisms. TUs changed little after being made into filter cake, but were 10-fold less after being made into bricks. Cr and Ni contributed most to the total toxicity followed by Zn and Cu. Making of sludges into K-brick 1 resulted in better inactivation of contaminants, which resulted in less toxic potencies. So that is the recommended method for handling of industrial sludges. To further assure their safe reuse, additional research on identification of key toxicants and potential hazards, based on additional endpoints, by combining bio-tests and chemical analysis should be done for reused sludges. Copyright © 2016 Elsevier Ltd. All rights reserved.

Toxicity studies on agent GA (Phase 2): 90 day subchronic study of GA (Tabun) in cd rats. Appendices. Final report, July 1985-August 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-03-01

The purpose of the report is to provide essential toxicologic information on Tabun administration over a 90 day period. This toxicologic information may be used to adjust the maximum-tolerated dose for subsequent dominant-lethal and two-generation reproduction studies. The objectives were to determine the toxic effects of nerve agent exposure (e.g., target organs); and to determine the effects of nerve agent GA on sperm morphology and motility and vaginal cytology.

Nail toxicity induced by cancer chemotherapy.

PubMed

Gilbar, Peter; Hain, Alice; Peereboom, Veta-Marie

2009-09-01

To provide a comprehensive literature review of chemotherapy-induced nail toxicity, including clinical presentation, implicated drugs and approaches for prevention and management. A search of MEDLINE and EMBASE (1966-2008) databases was conducted using the terms (and variations of the terms) antineoplastic agents, nails, nail toxicity, onycholysis, and paronychia. Bibliographies from selected articles were reviewed for appropriate references. The retrieved literature was reviewed to include all articles relevant to the clinical presentation, diagnosis, incidence, prevention, and treatment of chemotherapy-induced nail toxicity. Nail toxicity is a relatively uncommon adverse effect linked to a number of chemotherapeutic agents. Clinical presentation varies, depending on which nail structure is affected and the severity of the insult. Nail changes may involve all or some nails. Toxicity may be asymptomatic and limited to cosmetic concerns, however, more severe effects, involving pain and discomfort can occur. Taxanes and anthracyclines are the antineoplastic drug groups most commonly implicated. It is suggested that the administration schedule may influence the incidence of nail abnormalities, for example reported cases linked to the weekly administration of paclitaxel.Before instituting chemotherapy, patients should be educated regarding potential nail toxicities and strategies for prevention implemented. Management includes appropriate nail cutting, avoiding potential irritants, topical, or oral antimicrobials, and possibly cessation or dose reduction of the offending agent. Cryotherapy, through the application of frozen gloves or socks, has been beneficial in reducing docetaxel-induced nail toxicity and may be effective for other drugs.

Microbial biosurfactants as additives for food industries.

PubMed

Campos, Jenyffer Medeiros; Stamford, Tânia Lúcia Montenegro; Sarubbo, Leonie Asfora; de Luna, Juliana Moura; Rufino, Raquel Diniz; Banat, Ibrahim M

2013-01-01

Microbial biosurfactants with high ability to reduce surface and interfacial surface tension and conferring important properties such as emulsification, detergency, solubilization, lubrication and phase dispersion have a wide range of potential applications in many industries. Significant interest in these compounds has been demonstrated by environmental, bioremediation, oil, petroleum, food, beverage, cosmetic and pharmaceutical industries attracted by their low toxicity, biodegradability and sustainable production technologies. Despite having significant potentials associated with emulsion formation, stabilization, antiadhesive and antimicrobial activities, significantly less output and applications have been reported in food industry. This has been exacerbated by uneconomical or uncompetitive costing issues for their production when compared to plant or chemical counterparts. In this review, biosurfactants properties, present uses and potential future applications as food additives acting as thickening, emulsifying, dispersing or stabilising agents in addition to the use of sustainable economic processes utilising agro-industrial wastes as alternative substrates for their production are discussed. © 2013 American Institute of Chemical Engineers.

Guidelines for Reproductive Toxicity Risk Assessment

EPA Pesticide Factsheets

These guidelines discuss the scientific basis for concern about exposure to agents that cause reproductive toxicity and describe the principles and procedures to be followed in conducting risk assessments for reproductive toxicity.

Industrial antifoam agents impair ethanol fermentation and induce stress responses in yeast cells.

PubMed

Nielsen, Jens Christian; Senne de Oliveira Lino, Felipe; Rasmussen, Thomas Gundelund; Thykær, Jette; Workman, Christopher T; Basso, Thiago Olitta

2017-11-01

The Brazilian sugarcane industry constitutes one of the biggest and most efficient ethanol production processes in the world. Brazilian ethanol production utilizes a unique process, which includes cell recycling, acid wash, and non-aseptic conditions. Process characteristics, such as extensive CO 2 generation, poor quality of raw materials, and frequent contaminations, all lead to excessive foam formation during fermentations, which is treated with antifoam agents (AFA). In this study, we have investigated the impact of industrial AFA treatments on the physiology and transcriptome of the industrial ethanol strain Saccharomyces cerevisiae CAT-1. The investigated AFA included industrially used AFA acquired from Brazilian ethanol plants and commercially available AFA commonly used in the fermentation literature. In batch fermentations, it was shown that industrial AFA compromised growth rates and glucose uptake rates, while commercial AFA had no effect in concentrations relevant for defoaming purposes. Industrial AFA were further tested in laboratory scale simulations of the Brazilian ethanol production process and proved to decrease cell viability compared to the control, and the effects were intensified with increasing AFA concentrations and exposure time. Transcriptome analysis showed that AFA treatments induced additional stress responses in yeast cells compared to the control, shown by an up-regulation of stress-specific genes and a down-regulation of lipid biosynthesis, especially ergosterol. By documenting the detrimental effects associated with chemical AFA, we highlight the importance of developing innocuous systems for foam control in industrial fermentation processes.

Natural chelating agents for radionuclide decorporation

DOEpatents

Premuzic, E.T.

1985-06-11

This invention relates to the production of metal-binding compounds useful for the therapy of heavy metal poisoning, for biological mining and for decorporation of radionuclides. The present invention deals with an orderly and effective method of producing new therapeutically effective chelating agents. This method uses challenge biosynthesis for the production of chelating agents that are specific for a particular metal. In this approach, the desired chelating agents are prepared from microorganisms challenged by the metal that the chelating agent is designed to detoxify. This challenge induces the formation of specific or highly selective chelating agents. The present invention involves the use of the challenge biosynthetic method to produce new complexing/chelating agents that are therapeutically useful to detoxify uranium, plutonium, thorium and other toxic metals. The Pseudomonas aeruginosa family of organisms is the referred family of microorganisms to be used in the present invention to produce the new chelating agent because this family is known to elaborate strains resistant to toxic metals.

Initial formal toxicity evaluation of APC-2, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate in preparation for a first-in-man clinical trial

NASA Astrophysics Data System (ADS)

Bugaj, Joseph E.; Dorshow, Richard B.

2014-03-01

The fluorescent tracer agent 2,5-bis[N-(1-carboxy-2-hydroxy)]carbamoyl-3,6-diaminopyrazine, designated APC-2, has been developed with properties and attributes necessary for use as a direct measure of glomerular filtration rate (GFR). Comparison to known standard exogenous GFR agents in animal models has demonstrated an excellent correlation. A clinical trial to demonstrate this same correlation in humans is in preparation. A battery of formal toxicity tests necessary for regulatory clearance to proceed with a clinical trial has been recently completed on this new fluorescent tracer agent. These include single dose toxicity studies in rats and dogs to determine overall toxicity and toxicokinetics of the compound. Blood compatibility, mutation assay, chromosomal aberration assay, and several other assays were also completed. Toxicity assessments were based on mortality, clinical signs, body weight, food consumption and anatomical pathology. Blood samples were collected to assess pharmacokinetic parameters including half-life, area under the curve, and clearance. Urine samples were collected to assess distribution. Doses of up to 200-300 times the estimated human dose were administered. No test-article related effects were noted on body weight, food consumption, ophthalmic observations and no abnormal pathology was seen in either macroscopic or microscopic evaluations of any organs or tissues. All animals survived to scheduled sacrifice. Transient discoloration of skin and urine was noted at the higher dose levels in both species as expected from a highly fluorescent compound and was not considered pathological. Thus initial toxicology studies of this new fluorescent tracer agent APC-2 have resulted in no demonstrable pathological test article concerns.

Toxic Element Contamination of Natural Health Products and Pharmaceutical Preparations

PubMed Central

Genuis, Stephen J.; Schwalfenberg, Gerry; Siy, Anna-Kristen J.; Rodushkin, Ilya

2012-01-01

Background Concern has recently emerged regarding the safety of natural health products (NHPs)–therapies that are increasingly recommended by various health providers, including conventional physicians. Recognizing that most individuals in the Western world now consume vitamins and many take herbal agents, this study endeavored to determine levels of toxic element contamination within a range of NHPs. Methods Toxic element testing was performed on 121 NHPs (including Ayurvedic, traditional Chinese, and various marine-source products) as well as 49 routinely prescribed pharmaceutical preparations. Testing was also performed on several batches of one prenatal supplement, with multiple samples tested within each batch. Results were compared to existing toxicant regulatory limits. Results Toxic element contamination was found in many supplements and pharmaceuticals; levels exceeding established limits were only found in a small percentage of the NHPs tested and none of the drugs tested. Some NHPs demonstrated contamination levels above preferred daily endpoints for mercury, cadmium, lead, arsenic or aluminum. NHPs manufactured in China generally had higher levels of mercury and aluminum. Conclusions Exposure to toxic elements is occurring regularly as a result of some contaminated NHPs. Best practices for quality control–developed and implemented by the NHP industry with government oversight–is recommended to guard the safety of unsuspecting consumers. PMID:23185404

Skin diseases associated with Agent Orange and other organochlorine exposures.

PubMed

Patterson, Andrew T; Kaffenberger, Benjamin H; Keller, Richard A; Elston, Dirk M

2016-01-01

Organochlorine exposure is an important cause of cutaneous and systemic toxicity. Exposure has been associated with industrial accidents, intentional poisoning, and the use of defoliants, such as Agent Orange in the Vietnam War. Although long-term health effects are systematically reviewed by the Institute of Medicine, skin diseases are not comprehensively assessed. This represents an important practice gap as patients can present with cutaneous findings. This article provides a systematic review of the cutaneous manifestations of known mass organochlorine exposures in military and industrial settings with the goal of providing clinically useful recommendations for dermatologists seeing patients inquiring about organochlorine effects. Patients with a new diagnosis of chloracne, porphyria cutanea tarda, cutaneous lymphomas (non-Hodgkin lymphoma), and soft-tissue sarcomas including dermatofibrosarcoma protuberans and leiomyosarcomas should be screened for a history of Vietnam service or industrial exposure. Inconclusive evidence exists for an increased risk of other skin diseases in Vietnam veterans exposed to Agent Orange including benign fatty tumors, melanomas, nonmelanoma skin cancers, milia, eczema, dyschromias, disturbance of skin sensation, and rashes not otherwise specified. Affected veterans should be informed of the uncertain data in those cases. Referral to Department of Veterans Affairs for disability assessment is indicated for conditions with established associations. Copyright © 2015 American Academy of Dermatology, Inc. All rights reserved.

General aspects of metal toxicity.

PubMed

Kozlowski, H; Kolkowska, P; Watly, J; Krzywoszynska, K; Potocki, S

2014-01-01

This review is focused on the general mechanisms of metal toxicity in humans. The possible and mainly confirmed mechanisms of their action are discussed. The metals are divided into four groups due to their toxic effects. First group comprises of metal ions acting as Fenton reaction catalyst mainly iron and copper. These types of metal ions participate in generation of the reactive oxygen species. Metals such as nickel, cadmium and chromium are considered as carcinogenic agents. Aluminum, lead and tin are involved in neurotoxicity. The representative of the last group is mercury, which may be considered as a generally toxic metal. Fenton reaction is a naturally occurring process producing most active oxygen species, hydroxyl radical: Fe(2+) + He2O2 ↔ Fe(3+) + OH(-) + OH(•) It is able to oxidize most of the biomolecules including DNA, proteins, lipids etc. The effect of toxicity depends on the damage of molecules i.e. production site of the hydroxyl radical. Chromium toxicity depends critically on its oxidation state. The most hazardous seems to be Cr(6+) (chromates) which are one of the strongest inorganic carcinogenic agents. Cr(6+) species act also as oxidative agents damaging among other nucleic acids. Redox inactive Al(3+), Cd(2+) or Hg(2+) may interfere with biology of other metal ions e.g. by occupying metal binding sites in biomolecules. All these aspects will be discussed in the review.

Toxicity evaluation of process water from hydrothermal carbonization of sugarcane industry by-products.

PubMed

Fregolente, Laís Gomes; Miguel, Thaiz Batista Azevedo Rangel; de Castro Miguel, Emilio; de Almeida Melo, Camila; Moreira, Altair Benedito; Ferreira, Odair Pastor; Bisinoti, Márcia Cristina

2018-03-29

Hydrothermal carbonization (HTC) is a thermochemical process carried out in an aqueous medium. It is capable of converting biomass into a solid, carbon-rich material (hydrochar), and producing a liquid phase (process water) which contains the unreactive feedstock and/or chemical intermediates from the carbonization reaction. The aim of this study was to evaluate the characteristics of process water generated by HTC from vinasse and sugarcane bagasse produced by sugarcane industry and to evaluate its toxicity to both marine (using Artemia salina as a model organism) and the terrestrial environment (through seed germination studies of maize, lettuce, and tomato). The experiments showed that concentrated process water completely inhibited germination of maize, lettuce, and tomato seeds. On the other hand, diluted process water was able to stimulate seedlings of maize and tomato and enhance root and shoot growth. For Artemia, the LC 50 indicated that the process water is practically non-toxic; however, morphological changes, especially damages to the digestive tube and antennas of Artemia, were observed for the concentration of 1000 mg C L -1 .

Mechanistic Understanding of Toxicity from Nanocatalysts

PubMed Central

Jiang, Cuijuan; Jia, Jianbo; Zhai, Shumei

2014-01-01

Nanoparticle-based catalysts, or nanocatalysts, have been applied in various industrial sectors, including refineries, petrochemical plants, the pharmaceutical industry, the chemical industry, food processing, and environmental remediation. As a result, there is an increasing risk of human exposure to nanocatalysts. This review evaluates the toxicity of popular nanocatalysts applied in industrial processes in cell and animal models. The molecular mechanisms associated with such nanotoxicity are emphasized to reveal common toxicity-inducing pathways from various nanocatalysts and the uniqueness of each specific nanocatalyst. PMID:25119861

Occurrence and Concentrations of Toxic VOCs in the Ambient Air of Gumi, an Electronics-Industrial City in Korea.

PubMed

Baek, Sung-Ok; Suvarapu, Lakshmi Narayana; Seo, Young-Kyo

2015-08-05

This study was carried out to characterize the occurrence and concentrations of a variety of volatile organic compounds (VOCs) including aliphatic, aromatic, halogenated, nitrogenous, and carbonyl compounds, in the ambient air of Gumi City, where a large number of electronics industries are found. Two field monitoring campaigns were conducted for a one year period in 2003/2004 and 2010/2011 at several sampling sites in the city, representing industrial, residential and commercial areas. More than 80 individual compounds were determined in this study, and important compounds were then identified according to their abundance, ubiquity and toxicity. The monitoring data revealed toluene, trichloroethylene and acetaldehyde to be the most significant air toxics in the city, and their major sources were mainly industrial activities. On the other hand, there was no clear evidence of an industrial impact on the concentrations of benzene and formaldehyde in the ambient air of the city. Overall, seasonal variations were not as distinct as locational variations in the VOCs concentrations, whereas the within-day variations showed a typical pattern of urban air pollution, i.e., increase in the morning, decrease in the afternoon, and an increase again in the evening. Considerable decreases in the concentrations of VOCs from 2003 to 2011 were observed. The reductions in the ambient concentrations were confirmed further by the Korean PRTR data in industrial emissions within the city. Significant decreases in the concentrations of benzene and acetaldehyde were also noted, whereas formaldehyde appeared to be almost constant between the both campaigns. The decreased trends in the ambient levels were attributed not only to the stricter regulations for VOCs in Korea, but also to the voluntary agreement of major companies to reduce the use of organic solvents. In addition, a site planning project for an eco-friendly industrial complex is believed to play a contributory role in improving

Safety and feasibility of targeted agent combinations in solid tumours.

PubMed

Park, Sook Ryun; Davis, Myrtle; Doroshow, James H; Kummar, Shivaani

2013-03-01

The plethora of novel molecular-targeted agents (MTAs) has provided an opportunity to selectively target pathways involved in carcinogenesis and tumour progression. Combination strategies of MTAs are being used to inhibit multiple aberrant pathways in the hope of optimizing antitumour efficacy and to prevent development of resistance. While the selection of specific agents in a given combination has been based on biological considerations (including the role of the putative targets in cancer) and the interactions of the agents used in combination, there has been little exploration of the possible enhanced toxicity of combinations resulting from alterations in multiple signalling pathways in normal cell biology. Owing to the complex networks and crosstalk that govern normal and tumour cell proliferation, inhibiting multiple pathways with MTA combinations can result in unpredictable disturbances in normal physiology. This Review focuses on the main toxicities and the lack of tolerability of some common MTA combinations, particularly where evidence of enhanced toxicity compared to either agent alone is documented or there is development of unexpected toxicity. Toxicities caused by MTA combinations highlight the need to introduce new preclinical testing paradigms early in the drug development process for the assessment of chronic toxicities resulting from such combinations.

In silico prediction of Tetrahymena pyriformis toxicity for diverse industrial chemicals with substructure pattern recognition and machine learning methods.

PubMed

Cheng, Feixiong; Shen, Jie; Yu, Yue; Li, Weihua; Liu, Guixia; Lee, Philip W; Tang, Yun

2011-03-01

There is an increasing need for the rapid safety assessment of chemicals by both industries and regulatory agencies throughout the world. In silico techniques are practical alternatives in the environmental hazard assessment. It is especially true to address the persistence, bioaccumulative and toxicity potentials of organic chemicals. Tetrahymena pyriformis toxicity is often used as a toxic endpoint. In this study, 1571 diverse unique chemicals were collected from the literature and composed of the largest diverse data set for T. pyriformis toxicity. Classification predictive models of T. pyriformis toxicity were developed by substructure pattern recognition and different machine learning methods, including support vector machine (SVM), C4.5 decision tree, k-nearest neighbors and random forest. The results of a 5-fold cross-validation showed that the SVM method performed better than other algorithms. The overall predictive accuracies of the SVM classification model with radial basis functions kernel was 92.2% for the 5-fold cross-validation and 92.6% for the external validation set, respectively. Furthermore, several representative substructure patterns for characterizing T. pyriformis toxicity were also identified via the information gain analysis methods. Copyright © 2010 Elsevier Ltd. All rights reserved.

Acute pulmonary toxicity following occupational exposure to a floor stain protector in the building industry in Switzerland.

PubMed

Lazor-Blanchet, Catherine; Rusca, Sophie; Vernez, David; Berry, Raymond; Albrecht, Eric; Droz, Pierre-Olivier; Boillat, Marcel-André

2004-05-01

Waterproofing agents are widely applied to leather and textile garments; they are also used as floor stain protectors by professionals. Acute respiratory injury is described in three cases of young healthy adults following occupational inhalation of a new waterproofing formulation containing an acrylate fluoropolymer. Within 1 or 2 h after exposure they developed a rapidly progressive dyspnoea; two of them had hypoxaemia and flu-like reactions. All patients improved with supportive treatment in a few days. The mechanism of toxicity is still under investigation, but experimental data suggest the role of this new acrylate fluoropolymer. Tilers should be warned against spraying floor stain repellents; there is also a need to make consumers aware that the spraying of waterproofing agents in a closed environment and concomitant smoking should be avoided.

Effects of Humic and Fulvic Acids on Silver Nanoparticle Stability, Dissolution, and Toxicity

PubMed Central

Gunsolus, Ian L.; Mousavi, Maral P. S.; Hussein, Kadir; Bühlmann, Philippe; Haynes, Christy L.

2015-01-01

The colloidal stability of silver nanoparticles (AgNPs) in natural aquatic environments influences their transport and environmental persistence, while their dissolution to Ag+ influences their toxicity to organisms. Here, we characterize the colloidal stability, dissolution behavior, and toxicity of two industrially relevant classes of AgNPs (i.e., AgNPs stabilized by citrate or polyvinylpyrrolidone) after exposure to natural organic matter (NOM, i.e., Suwannee River Humic and Fulvic Acid Standards and Pony Lake Fulvic Acid Reference). We show that NOM interaction with the nanoparticle surface depends on (i) the NOM’s chemical composition, where sulfur- and nitrogen-rich NOM more significantly increases colloidal stability, and (ii) the affinity of the capping agent for the AgNP surface, where nanoparticles with loosely bound capping agents are more effectively stabilized by NOM. Adsorption of NOM is shown to have little effect on AgNP dissolution under most experimental conditions, the exception being when the NOM is rich in sulfur and nitrogen. Similarly, the toxicity of AgNPs to a bacterial model (Shewanella oneidensis MR-1) decreases most significantly in the presence of sulfur- and nitrogen-rich NOM. Our data suggest that the rate of AgNP aggregation and dissolution in aquatic environments containing NOM will depend on the chemical composition of the NOM, and that the toxicity of AgNPs to aquatic microorganisms is controlled primarily by the extent of nanoparticle dissolution. PMID:26047330

The toxic release inventory: fact or fiction? A case study of the primary aluminum industry.

PubMed

Koehler, Dinah A; Spengler, John D

2007-10-01

Since 1989 manufacturing facilities across the USA must report toxic chemical emissions to the EPA's toxic release inventory (TRI). Public release of this information and increased public scrutiny are believed to significantly contribute to the over 45% reduction in toxic chemical releases since inception of the program and to growing support for this type of informational regulation instead of traditional command-and-control. However, prior research indicates a tendency to under-report emissions. We find specific evidence of under-reporting of polycyclic aromatic hydrocarbons (PAH) to the TRI by primary aluminum facilities after promulgation of the industry's maximum available control technology (MACT) standard in 1997. We also find evidence of dislocation of emission overseas due to these regulatory requirements. Additionally, changes in energy prices affected aluminum production and further distort reported PAH emissions levels. This suggests the possibility of more widespread under-reporting that is modulated by various factors, including market conditions and new regulations, and which may partially explain the downward trend in TRI emissions. It also suggests that the quality of TRI data may improve once facilities are subject to monitoring of emissions of a TRI listed pollutant due to command-and-control regulation.

Pharmacology and pharmacogenetics of chemotherapeutic agents.

PubMed

Dawood, Shaheenah; Leyland-Jones, Brian

2009-06-01

The last decade the field of oncology has seen the introduction of several efficacious chemotherapeutic agents. However the benefits achieved have been modest at best. The choice of chemotherapeutic agent is often empirical and geared to fit the average patient with the result that approximately 40% of patients may be receiving the wrong drug. With greater understanding of the mechanisms behind the heterogeneity observed across patient populations, both in terms of efficacy and toxicity of a variety of therapeutic agents, research has now focused on individualizing treatment strategies by incorporating a combination of physiological variables, genetic characteristics and environmental factors together with the traditional tumor characteristics that currently drives clinical decision making. This review focuses on defining some of the principle components of personalized medicine. In addition we will review the pharmacological and pharmacogenetic predictors of toxic effects of chemotherapeutic agents drawing on examples of commonly used agents in oncology.

Toxic releases and risk disparity: a spatiotemporal model of industrial ecology and social empowerment.

PubMed

Aoyagi, Hannah; Ogunseitan, Oladele A

2015-06-02

Information-based regulations (IBRs) are founded on the theoretical premise that public participation in accomplishing policy goals is empowered by open access to information. Since its inception in 1988, the Toxics Release Inventory (TRI) has provided the framework and regulatory impetus for the compilation and distribution of data on toxic releases associated with industrial development, following the tenets of IBR. As TRI emissions are reputed to disproportionately affect low-income communities, we investigated how demographic characteristics are related to change in TRI emissions and toxicity risks between 1989 and 2002, and we sought to identify factors that predict these changes. We used local indicators of spatial association (LISA) maps and spatial regression techniques to study risk disparity in the Los Angeles urban area. We also surveyed 203 individuals in eight communities in the same region to measure the levels of awareness of TRI, attitudes towards air pollution, and general environmental risk. We discovered, through spatial lag models, that changes in gross and toxic emissions are related to community ethnic composition, poverty level, home ownership, and base 1989 emissions (R-square=0.034-0.083). We generated a structural equation model to explain the determinants of social empowerment to act on the basis of environmental information. Hierarchical confirmatory factor analysis (HCFA) supports the theoretical model that individual empowerment is predicted by risk perception, worry, and awareness (Chi-square=63.315, p=0.022, df=42). This study provides strong evidence that spatiotemporal changes in regional-scale environmental risks are influenced by individual-scale empowerment mediated by IBRs.

Toxic Releases and Risk Disparity: A Spatiotemporal Model of Industrial Ecology and Social Empowerment

PubMed Central

Aoyagi, Hannah; Ogunseitan, Oladele A.

2015-01-01

Information-based regulations (IBRs) are founded on the theoretical premise that public participation in accomplishing policy goals is empowered by open access to information. Since its inception in 1988, the Toxics Release Inventory (TRI) has provided the framework and regulatory impetus for the compilation and distribution of data on toxic releases associated with industrial development, following the tenets of IBR. As TRI emissions are reputed to disproportionately affect low-income communities, we investigated how demographic characteristics are related to change in TRI emissions and toxicity risks between 1989 and 2002, and we sought to identify factors that predict these changes. We used local indicators of spatial association (LISA) maps and spatial regression techniques to study risk disparity in the Los Angeles urban area. We also surveyed 203 individuals in eight communities in the same region to measure the levels of awareness of TRI, attitudes towards air pollution, and general environmental risk. We discovered, through spatial lag models, that changes in gross and toxic emissions are related to community ethnic composition, poverty level, home ownership, and base 1989 emissions (R-square = 0.034–0.083). We generated a structural equation model to explain the determinants of social empowerment to act on the basis of environmental information. Hierarchical confirmatory factor analysis (HCFA) supports the theoretical model that individual empowerment is predicted by risk perception, worry, and awareness (Chi-square = 63.315, p = 0.022, df = 42). This study provides strong evidence that spatiotemporal changes in regional-scale environmental risks are influenced by individual-scale empowerment mediated by IBRs. PMID:26042368

Black Seed (Nigella Sativa) and its Constituent Thymoquinone as an Antidote or a Protective Agent Against Natural or Chemical Toxicities

PubMed Central

Tavakkoli, Alireza; Ahmadi, Ali; Razavi, Bibi Marjan; Hosseinzadeh, Hossein

2017-01-01

Nigella sativa (N. sativa), which belongs to the botanical family of Ranunculaceae, is a widely used medicinal plant all over the world. N. sativa seeds and oil have been used in the treatment of different diseases. Various studies on N. sativa have been carried out and a broad spectrum of its pharmacological actions have been established which include antioxidant, antidiabetic, anticancer, antitussive, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, and bronchodilator. This is also indicated that the majority of the therapeutic effects of N. sativa are due to the presence of thymoquinone (TQ) that is the main bioactive constituent of the essential oil. According to several lines of evidence, the protective effects of this plant and its main constituent in different tissues including brain, heart, liver, kidney, and lung have been proved against some toxic agents either natural or chemical toxins in animal studies. In this review article, several in-vitro and animal studies in scientific databases which investigate the antidotal and protective effects of N. sativa and its main constituents against natural and chemical induced toxicities are introduced. Because human reports are rare, further studies are required to determine the efficacy of this plant as an antidote or protective agent in human intoxication. PMID:29844772

Incorporating GIS data into an agent-based model to support planning policy making for the development of creative industries

NASA Astrophysics Data System (ADS)

Liu, Helin; Silva, Elisabete A.; Wang, Qian

2016-07-01

This paper presents an extension to the agent-based model "Creative Industries Development-Urban Spatial Structure Transformation" by incorporating GIS data. Three agent classes, creative firms, creative workers and urban government, are considered in the model, and the spatial environment represents a set of GIS data layers (i.e. road network, key housing areas, land use). With the goal to facilitate urban policy makers to draw up policies locally and optimise the land use assignment in order to support the development of creative industries, the improved model exhibited its capacity to assist the policy makers conducting experiments and simulating different policy scenarios to see the corresponding dynamics of the spatial distributions of creative firms and creative workers across time within a city/district. The spatiotemporal graphs and maps record the simulation results and can be used as a reference by the policy makers to adjust land use plans adaptively at different stages of the creative industries' development process.

Removal of toxic Cr(VI) ions from tannery industrial wastewater using a newly designed three-phase three-dimensional electrode reactor

NASA Astrophysics Data System (ADS)

Grace Pavithra, K.; Senthil Kumar, P.; Carolin Christopher, Femina; Saravanan, A.

2017-11-01

In this research, the wastewater samples were collected from leather tanning industry at different time intervals. The parameters like pH, electrical conductivity, temperature, turbidity, chromium and chemical oxygen demand (COD) of the samples were analyzed. A three-phase three-dimensional fluidized type electrode reactor (FTER) was newly designed for the effective removal of toxic pollutants from wastewater. The influencing parameters were optimized for the maximum removal of toxic pollutants from wastewater. The optimum condition for the present system was calculated as: contact time of 30 min, applied voltage of 3 V and the particle electrodes of 15 g. The particle electrode was characterized by using FT-IR analysis. Langmuir-Hinshelwood and pseudo-second order kinetic models were fits well with the experimental data. The results showed that the FTER can be successfully employed for the treatment of industrial wastewater.

NON-TOXIC MELANOMA THERAPY BY A NOVEL TUBULIN-BINDING AGENT

PubMed Central

Aneja, Ritu; Asress, Seneshaw; Dhiman, Neerupma; Awasthi, Anshumali; Rida, Padmashree C.G.; Arora, Sudarshan K.; Zhou, Jun; Glass, Jonathan D.; Joshi, Harish C.

2009-01-01

(S)-3-((R)-9-bromo-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquino-lin-5-yl)-6,7-dimethoxyisobenzofuran-1(3H)-one (EM011) is a tubulin-binding agent with significant anticancer activity. Here we show that EM011 modulates microtubule dynamics at concentrations that do not alter the total polymer mass of tubulin. In particular, EM011 decreases the transition frequencies between growth and shortening phases and increases the duration microtubules spend in an idle ‘pause’ state. Using B16LS9 murine melanoma cells, we show that EM011 briefly arrests cell-cycle progression at the G2/M phase by formation of multiple aster spindles. An aberrant mitotic exit without cytokinesis then occurs, leading to the accumulation of abnormal multinucleated cells prior to apoptosis. Our pharmacokinetic studies conformed to a linear dose-response relationship upto 150 mg/kg. However, non-linearity was observed at 300 mg/kg. In a syngeneic murine model of subcutaneous melanoma, better antitumor responses were seen at 150 mg/kg compared to 300 mg/kg of EM011. Unlike currently available chemotherapeutics, EM011 is non-toxic to normal tissues and most importantly, does not cause any immunosuppression and neurotoxicity. Our data thus warrant a clinical evaluation of EM011 for melanoma therapy. PMID:19626589

Natural Pathogen Control Chemistry to Replace Toxic Treatment of Microbes and Biofilm in Cooling Towers

PubMed Central

Brouse, Lon; Brouse, Richard; Brouse, Daniel

2017-01-01

Application of toxic antibacterial agents is considered necessary to control prevalent fresh water microorganisms that grow in evaporative cooling water systems, but can adversely affect the environment and human health. However, natural antibacterial water chemistry has been applied in industrial cooling water systems for over 10 years to inhibit microorganisms with excellent results. The water chemistry method concentrates natural minerals in highly-softened water to produce elevated pH and dissolved solids, while maintaining low calcium and magnesium content. The method provides further benefits in water conservation, and generates a small volume of non-toxic natural salt concentrate for cost efficient separation and disposal if required. This report describes the antimicrobial effects of these chemistry modifications in the cooling water environment and the resultant collective inhibition of microbes, biofilm, and pathogen growth. This article also presents a novel perspective of parasitic microbiome functional relationships, including “Trojan Protozoans” and biofilms, and the function of polyvalent metal ions in the formation and inhibition of biofilms. Reducing global dependence on toxic antibacterial agents discharged to the environment is an emerging concern due to their impact on the natural microbiome, plants, animals and humans. Concurrently, scientists have concluded that discharge of antibacterial agents plays a key role in development of pathogen resistance to antimicrobials as well as antibiotics. Use of natural antibacterial chemistry can play a key role in managing the cooling water environment in a more ecologically sustainable manner. PMID:28420074

Chelate assisted phytoextraction of heavy metals from soil. Effect, mechanism, toxicity, and fate of chelating agents.

PubMed

Evangelou, Michael W H; Ebel, Mathias; Schaeffer, Andreas

2007-06-01

The low-cost, plant-based phytoextraction technique has often been described as a promising technique to remediate heavy metal contaminated agricultural land. The application of chelating agents has shown positive effects in increasing the solubility of heavy metals in soil and therefore in enhancing phytoextraction. This paper gives an overview of the chelating agents applied in recent studies. Various synthetic aminopolycarboxylic acids, such as ethylene diamine tetraacetic acid, and natural ones such as, ethylene diamine disuccinate and nitrilotriacetic acid, are described. Additionally, results of the application of natural low molecular weight organic acids, such as citric and tartaric acid are given. The effectiveness of these different chelating agents varies according to the plant and the heavy metals used. Furthermore, a focus is laid on the chelating agents fate after application and on its toxicity to plants and soil microorganisms, as well as it degradation. The rate of degradation is of great importance for the future of chelate assisted phytoextraction as it has a direct impact on the leaching probability. An effective prevention of leaching will be crucial for the acceptance and the economic breakthrough of enhanced phytoextraction, but a satisfactory solution to this key issue has so far not been found. Possibly further experiments in the field of enhanced phytoextraction will be able to solve this major problem, but over decades various greenhouse experiments and recently field experiments have resulted in different observations. Therefore, it is questionable if further research in this direction will lead to a promising solution. Phytoextraction has possibly reached a turning point in which it should distance itself from chelate assisted phytoextraction and focus on alternative options.

Profiling the reproductive toxicity of chemicals from multigeneration studies in the toxicity reference database

EPA Science Inventory

Multigeneration reproduction studies are used to characterize parental and offspring systemic toxicity, as well as reproductive toxicity of pesticides, industrial chemicals and pharmaceuticals. Results from 329 multigeneration studies on 316 chemicals have been digitized into sta...

Colorimetric sensor array for determination and identification of toxic industrial chemicals.

PubMed

Feng, Liang; Musto, Christopher J; Kemling, Jonathan W; Lim, Sung H; Zhong, Wenxuan; Suslick, Kenneth S

2010-11-15

A low-cost yet highly sensitive colorimetric sensor array for the detection and identification of toxic industrial chemicals (TICs) has been developed. The sensor consists of a disposable array of cross-responsive nanoporous pigments whose colors are changed by diverse chemical interactions with analytes. Clear differentiation among 20 different TICs has been easily achieved at both their IDLH (immediately dangerous to life or health) concentration within 2 min of exposure and PEL (permissible exposure limit) concentration within 5 min of exposure with no errors or misclassifications. Detection limits are generally well below the PEL (in most cases below 5% of PEL) and are typically in the low ppb range. The colorimetric sensor array is not responsive to changes in humidity or temperature over a substantial range. The printed arrays show excellent batch to batch reproducibility and long shelf life (greater than 3 months).

Innovation Agents: Vocational Education and Training Skills and Innovation in Australian Industries and Firms. Volume 2

ERIC Educational Resources Information Center

Toner, Phillip; Marceau, Jane; Hall, Richard; Considine, Gillian

2004-01-01

This volume is a companion to "Innovation Agents: VET Skills and Innovation in Australian Industries and Firms. Volume 1". The detailed report of the project is contained in Volume 1 while Volume 2 contains the appendices: (1) Data tables for construction of the composite index of innovation; (2) Case study interview schedule; and (3)…

40 CFR 125.66 - Toxics control program.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... (1) An applicant that has known or suspected industrial sources of toxic pollutants shall have an... any applicant which has no known or suspected industrial sources of toxic pollutants or pesticides and.... (a) Chemical analysis. (1) The applicant shall submit at the time of application a chemical analysis...

Homogeneous sonophotolysis of food processing industry wastewater: Study of synergistic effects, mineralization and toxicity removal.

PubMed

Durán, A; Monteagudo, J M; Sanmartín, I; Gómez, P

2013-03-01

The mineralization of industrial wastewater coming from food industry using an emerging homogeneous sonophotolytic oxidation process was evaluated as an alternative to or a rapid pretreatment step for conventional anaerobic digestion with the aim of considerably reducing the total treatment time. At the selected operation conditions ([H(2)O(2)]=11,750ppm, pH=8, amplitude=50%, pulse length (cycles)=1), 60% of TOC is removed after 60min and 98% after 180min when treating an industrial effluent with 2114ppm of total organic carbon (TOC). This process removed completely the toxicity generated during storing or due to intermediate compounds. An important synergistic effect between sonolysis and photolysis (H(2)O(2)/UV) was observed. Thus the sonophotolysis (ultrasound/H(2)O(2)/UV) technique significantly increases TOC removal when compared with each individual process. Finally, a preliminary economical analysis confirms that the sono-photolysis with H(2)O(2) and pretreated water is a profitable system when compared with the same process without using ultrasound waves and with no pretreatment. Copyright © 2012 Elsevier B.V. All rights reserved.

Industrial toxicants and Parkinson’s disease

PubMed Central

Caudle, W. Michael; Guillot, Thomas S.; Lazo, Carlos R.; Miller, Gary W.

2012-01-01

The exposure of the human population to environmental contaminants is recognized as a significant contributing factor for the development of Parkinson’s disease (PD) and other forms of parkinsonism. While pesticides have repeatedly been identified as risk factors for PD, these compounds represent only a subset of environmental toxicants that we are exposed to on a regular basis. Thus, non-pesticide contaminants, such as metals, solvents, and other organohalogen compounds have also been implicated in the clinical and pathological manifestations of these movement disorders and it is these non-pesticide compounds that are the subject of this review. As toxic exposures to these classes of compounds can result in a spectrum of PD or PD-related disorders, it is imperative to appreciate shared clinico-pathological characteristics or mechanisms of action of these compounds in order to further delineate the resultant disorders as well as identify improved preventive strategies or therapeutic interventions. PMID:22309908

Liposome encapsulation of chelating agents

DOEpatents

Rahman, Yueh Erh

1976-01-13

A method for transferring a chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes and carrying the liposome-encapsulated chelating agent to the cellular membrane where the liposomes containing the chelating agent will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. A chelating agent can be introduced into the interior of a cell of a living organism wherein the liposomes will be decomposed, releasing the chelating agent to the interior of the cell. The released chelating agent will complex intracellularly deposited toxic heavy metals, permitting the more soluble metal complex to transfer across the cellular membrane from the cell and subsequently be removed from the living organism.

Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pollom, Erqi L.; Deng, Lei; Pai, Reetesh K.

2015-07-01

Combining the latest targeted biologic agents with the most advanced radiation technologies has been an exciting development in the treatment of cancer patients. Stereotactic body radiation therapy (SBRT) is an ablative radiation approach that has become established for the treatment of a variety of malignancies, and it has been increasingly used in combination with biologic agents, including those targeting angiogenesis-specific pathways. Multiple reports have emerged describing unanticipated toxicities arising from the combination of SBRT and angiogenesis-targeting agents, particularly of late luminal gastrointestinal toxicities. In this review, we summarize the literature describing these toxicities, explore the biological mechanism of action ofmore » toxicity with the combined use of antiangiogenic therapies, and discuss areas of future research, so that this combination of treatment modalities can continue to be used in broader clinical contexts.« less

A Bayesian Dose-finding Design for Oncology Clinical Trials of Combinational Biological Agents

PubMed Central

Cai, Chunyan; Yuan, Ying; Ji, Yuan

2013-01-01

Treating patients with novel biological agents is becoming a leading trend in oncology. Unlike cytotoxic agents, for which efficacy and toxicity monotonically increase with dose, biological agents may exhibit non-monotonic patterns in their dose-response relationships. Using a trial with two biological agents as an example, we propose a dose-finding design to identify the biologically optimal dose combination (BODC), which is defined as the dose combination of the two agents with the highest efficacy and tolerable toxicity. A change-point model is used to reflect the fact that the dose-toxicity surface of the combinational agents may plateau at higher dose levels, and a flexible logistic model is proposed to accommodate the possible non-monotonic pattern for the dose-efficacy relationship. During the trial, we continuously update the posterior estimates of toxicity and efficacy and assign patients to the most appropriate dose combination. We propose a novel dose-finding algorithm to encourage sufficient exploration of untried dose combinations in the two-dimensional space. Extensive simulation studies show that the proposed design has desirable operating characteristics in identifying the BODC under various patterns of dose-toxicity and dose-efficacy relationships. PMID:24511160

Method and apparatus for enhanced detection of toxic agents

DOEpatents

Greenbaum, Elias; Rodriguez, Jr., Miguel; Wu, Jie Jayne; Qi, Hairong

2013-10-01

A biosensor based detection of toxins includes enhancing a fluorescence signal by concentrating a plurality of photosynthetic organisms in a fluid into a concentrated region using biased AC electro-osmosis. A measured photosynthetic activity of the photosynthetic organisms is obtained in the concentrated region, where chemical, biological or radiological agents reduce a nominal photosynthetic activity of the photosynthetic organisms. A presence of the chemical, biological and/or radiological agents or precursors thereof, is determined in the fluid based on the measured photosynthetic activity of the concentrated plurality of photosynthetic organisms. A lab-on-a-chip system is used for the concentrating step. The presence of agents is determined from feature vectors, obtained from processing a time dependent signal using amplitude statistics and/or time-frequency analysis, relative to a control signal. A linear discriminant method including support vector machine classification (SVM) is used to identify the agents.

The Toxicity of Soman in the African Green Monkey (Chlorocebus aethiops)

DTIC Science & Technology

2007-01-01

M., and Mestries, 1. C. 1998. Nerve agent poisoning in primates: antilethal, anti -epileptic and neuroprotective effects of GK-11. Arch. Toxico/. 72...toxicity in African green monkeys (Chlorocebus aethiops) and is the first step in exploring the suitability of this species as a model for nerve agent ...rhesus monkey (Macaca mulatta) has traditionally served as the NHP research species of choice to assess nerve agent toxicity and the effectiveness of

Development of a microinstillation model of inhalation exposure to assess lung injury following exposure to toxic chemicals and nerve agents in Guinea pigs.

PubMed

Nambiar, Madhusoodana P; Wright, Benjamin S; Rezk, Peter E; Smith, Kelvin B; Gordon, Richard K; Moran, Theodore S; Richards, Shannon M; Sciuto, Alfred M

2006-01-01

Respiratory disturbances due to chemical warfare nerve agents (CWNAs) are the starting point of mass casualty and the primary cause of death by these weapons of terror and mass destruction. However, very few studies have been implemented to assess respiratory toxicity and exacerbation induced by CWNAs, especially methylphosphonothioic acid S-(2-(bis(1-methylethyl)amino)ethyl)O-ethyl ester (VX). In this study, we developed a microinstillation technique of inhalation exposure to assess lung injury following exposure to CWNAs and toxic chemicals. Guinea pigs were gently intubated by placing a microcatheter into the trachea 1.5 to 2.0 cm centrally above the bifurcation. This location is crucial to deliver aerosolized agents uniformly to the lung's lobes. The placement of the tube is calculated by measuring the distance from the upper front teeth to the tracheal bifurcation, which is typically 8.5 cm for guinea pigs of equivalent size and a weight range of 250 g to 300 g. The catheter is capable of withstanding 100 psi pressure; the terminus has five peripheral holes to pump air that aerosolizes the nerve agent that is delivered in the central hole. The microcatheter is regulated by a central control system to deliver the aerosolized agent in a volume lower than the tidal volume of the guinea pigs. The average particle size of the nerve agent delivered was 1.48 +/- 0.07 micrometer. The microinstillation technology has been validated by exposing the animals to Coomassie brilliant blue, which showed a uniform distribution of the dye in different lung lobes. In addition, the concentration of the dye in the lungs correlated with the dose/time of exposure. Furthermore, histopathological analysis confirmed the absence of barotraumas following micoinstillation. This novel technique delivers the agent safely, requires less amount of agent, avoids exposure to skin, pelt, and eye, and circumvents the concern of deposition of the particles in the nasal and palette due to the

Toxic and carcinogenic agents in dry and moist snuff.

PubMed

Hoffmann, D; Adams, J D; Lisk, D; Fisenne, I; Brunnemann, K D

1987-12-01

The oral use of snuff is causatively associated with cancer of the oral cavity. Since most epidemiologic studies to date relate to the long-term use of dry snuff, which has dominated the U.S. smokeless tobacco market in the past, the concentrations of several toxic and carcinogenic agents in the three most popular dry snuff brands have been compared with those in the five most popular moist snuff brands sold in the United States. All eight samples were analyzed for nitrate, alkaloids, polyphenols, volatile carbonyl compounds, lead, cadmium, selenium, and the carcinogenic compounds benzo[a]pyrene (CAS: 50-32-8), polonium-210 (CAS: 13981-52-7), volatile N-nitrosamines (VNAs), N-nitrosodiethanolamine (CAS: 1116-54-7), and the tobacco-specific N-nitrosamines (TSNAs). Most of the snuff brands were rich in nitrate (greater than or equal to 1.5%), total polyphenols (greater than 2%), and in nicotine (greater than or equal to 1.5%), which is the habituating factor in tobacco use. Concentrations of the VNAs were significantly above the permissible limits set for some food products; the concentrations of the TSNAs in both snuff types exceeded the levels of nitrosamines in other consumer products by at least two to three orders of magnitude. The extremely high levels of the TSNAs in snuff have remained unchanged during the last decade and present the major carcinogenic risk factor for the oral use of snuff. Polonium-210 contributes further to the carcinogenic risk associated with snuff. The chemical-analytical data presented in this study do not indicate marked differences in the carcinogenic potential of moist snuff compared to dry snuff.

Occurrence and Concentrations of Toxic VOCs in the Ambient Air of Gumi, an Electronics-Industrial City in Korea

PubMed Central

Baek, Sung-Ok; Suvarapu, Lakshmi Narayana; Seo, Young-Kyo

2015-01-01

This study was carried out to characterize the occurrence and concentrations of a variety of volatile organic compounds (VOCs) including aliphatic, aromatic, halogenated, nitrogenous, and carbonyl compounds, in the ambient air of Gumi City, where a large number of electronics industries are found. Two field monitoring campaigns were conducted for a one year period in 2003/2004 and 2010/2011 at several sampling sites in the city, representing industrial, residential and commercial areas. More than 80 individual compounds were determined in this study, and important compounds were then identified according to their abundance, ubiquity and toxicity. The monitoring data revealed toluene, trichloroethylene and acetaldehyde to be the most significant air toxics in the city, and their major sources were mainly industrial activities. On the other hand, there was no clear evidence of an industrial impact on the concentrations of benzene and formaldehyde in the ambient air of the city. Overall, seasonal variations were not as distinct as locational variations in the VOCs concentrations, whereas the within-day variations showed a typical pattern of urban air pollution, i.e., increase in the morning, decrease in the afternoon, and an increase again in the evening. Considerable decreases in the concentrations of VOCs from 2003 to 2011 were observed. The reductions in the ambient concentrations were confirmed further by the Korean PRTR data in industrial emissions within the city. Significant decreases in the concentrations of benzene and acetaldehyde were also noted, whereas formaldehyde appeared to be almost constant between the both campaigns. The decreased trends in the ambient levels were attributed not only to the stricter regulations for VOCs in Korea, but also to the voluntary agreement of major companies to reduce the use of organic solvents. In addition, a site planning project for an eco-friendly industrial complex is believed to play a contributory role in improving

Evaluation of antimicrobial activity of glycerol monolaurate nanocapsules against American foulbrood disease agent and toxicity on bees.

PubMed

Lopes, Leonardo Q S; Santos, Cayane G; de Almeida Vaucher, Rodrigo; Gende, Liesel; Raffin, Renata P; Santos, Roberto C V

2016-08-01

The American Foulbrood Disease (AFB) is a fatal larval bee infection. The etiologic agent is the bacterium Paenibacillus larvae. The treatment involves incineration of all contaminated materials, leading to high losses. The Glycerol Monolaurate (GML) is a known antimicrobial potential compound, however its use is reduced due to its low solubility in water and high melting point. The nanoencapsulation of some drugs offers several advantages like improved stability and solubility in water. The present study aimed to evaluate the antimicrobial activity against P. larvae and the toxicity in bees of GML nanoparticles. The nanocapsules were produced and presented mean diameter of 210 nm, polydispersity index of 0.044, and zeta potential of -23.4 mV demonstrating the acceptable values to predict a stable system. The microdilution assay showed that it is necessary 142 and 285 μg/mL of GML nanocapsules to obtain a bacteriostatic and bactericidal effect respectively. The time-kill curve showed the controlled release of compound, exterminating the microorganism after 24 h. The GML nanocapsules were able to kill the spore form of Paenibacillus larvae while the GML do not cause any effect. The assay in bees showed that the GML has a high toxicity while the GML nanoparticles showed a decrease on toxic effects. Concluding, the formulation shows positive results in the action to combat AFB besides not causing damage to bees. Copyright © 2016 Elsevier Ltd. All rights reserved.

Kinetic study of treatment of wastewater contains food preservative agent by anaerobic baffled reactor : An overview

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sumantri, Indro; Purwanto,; Budiyono

The characteristic of wastewater of food industries with preservative substances is high content of organic substances, degradable and high total suspended solid. High organic content in this waste forced the treatment is biologically and pointed out to anaerobic treatment. Anaerobic showed the better performance of degradation than aerobic for high content organic and also for toxic materials. During that day the treatment of food wastewater is aerobically which is high consume of energy required and high volume of sludge produced. The advantage of anaerobic is save high energy, less product of sludge, less requirement of nutrients of microorganism and highmore » efficiency reduction of organic load. The high efficiency of reduction will reduce the load of further treatment, so that, the threshold limit based on the regulation would be easy to achieve. Research of treatment of wastewater of food industries would be utilized by both big scale industries and small industries using addition of preservative substances. The type reactor of anaerobic process is anaerobic baffled reactor that will give better contact between wastewater and microorganism in the sludge. The variables conducted in this research are the baffled configuration, sludge height, preservative agent contents, hydralic retention time and influence of micro nutrients. The respons of this research are the COD effluent, remaining preservative agent, pH, formation of volatile fatty acid and total suspended solid. The result of this research is kinetic model of the anaerobic baffled reactor, reaction kinetic of preservative agent degradation and technology of treatment wastewater contains preservative agent. The benefit of this research is to solve the treatment of wastewater of food industries with preservative substance in order to achieve wastewater limit regulation and also to prevent the environmental deterioration.« less

Kinetic study of treatment of wastewater contains food preservative agent by anaerobic baffled reactor : An overview

NASA Astrophysics Data System (ADS)

Sumantri, Indro; Purwanto, Budiyono

2015-12-01

The characteristic of wastewater of food industries with preservative substances is high content of organic substances, degradable and high total suspended solid. High organic content in this waste forced the treatment is biologically and pointed out to anaerobic treatment. Anaerobic showed the better performance of degradation than aerobic for high content organic and also for toxic materials. During that day the treatment of food wastewater is aerobically which is high consume of energy required and high volume of sludge produced. The advantage of anaerobic is save high energy, less product of sludge, less requirement of nutrients of microorganism and high efficiency reduction of organic load. The high efficiency of reduction will reduce the load of further treatment, so that, the threshold limit based on the regulation would be easy to achieve. Research of treatment of wastewater of food industries would be utilized by both big scale industries and small industries using addition of preservative substances. The type reactor of anaerobic process is anaerobic baffled reactor that will give better contact between wastewater and microorganism in the sludge. The variables conducted in this research are the baffled configuration, sludge height, preservative agent contents, hydralic retention time and influence of micro nutrients. The respons of this research are the COD effluent, remaining preservative agent, pH, formation of volatile fatty acid and total suspended solid. The result of this research is kinetic model of the anaerobic baffled reactor, reaction kinetic of preservative agent degradation and technology of treatment wastewater contains preservative agent. The benefit of this research is to solve the treatment of wastewater of food industries with preservative substance in order to achieve wastewater limit regulation and also to prevent the environmental deterioration.

Nature and prevalence of non-additive toxic effects in industrially relevant mixtures of organic chemicals.

PubMed

Parvez, Shahid; Venkataraman, Chandra; Mukherji, Suparna

2009-06-01

The concentration addition (CA) and the independent action (IA) models are widely used for predicting mixture toxicity based on its composition and individual component dose-response profiles. However, the prediction based on these models may be inaccurate due to interaction among mixture components. In this work, the nature and prevalence of non-additive effects were explored for binary, ternary and quaternary mixtures composed of hydrophobic organic compounds (HOCs). The toxicity of each individual component and mixture was determined using the Vibrio fischeri bioluminescence inhibition assay. For each combination of chemicals specified by the 2(n) factorial design, the percent deviation of the predicted toxic effect from the measured value was used to characterize mixtures as synergistic (positive deviation) and antagonistic (negative deviation). An arbitrary classification scheme was proposed based on the magnitude of deviation (d) as: additive (< or =10%, class-I) and moderately (10< d < or =30 %, class-II), highly (30< d < or =50%, class-III) and very highly (>50%, class-IV) antagonistic/synergistic. Naphthalene, n-butanol, o-xylene, catechol and p-cresol led to synergism in mixtures while 1, 2, 4-trimethylbenzene and 1, 3-dimethylnaphthalene contributed to antagonism. Most of the mixtures depicted additive or antagonistic effect. Synergism was prominent in some of the mixtures, such as, pulp and paper, textile dyes, and a mixture composed of polynuclear aromatic hydrocarbons. The organic chemical industry mixture depicted the highest abundance of antagonism and least synergism. Mixture toxicity was found to depend on partition coefficient, molecular connectivity index and relative concentration of the components.

The Removal of Cu (II) from Aqueous Solution using Sodium Borohydride as a Reducing Agent

NASA Astrophysics Data System (ADS)

Sithole, N. T.; Ntuli, F.; Mashifana, T.

2018-03-01

The removal and recovery of metals from wastewater has been a subject of significant importance due the negative impact these toxic metals have on human health and the environment as a result of water and soil pollution. Increased use of the metals and chemicals in the process industries has resulted in generation of large quantity of effluents that contains high level of toxic metals and other pollutants. The objective of this work was to recover of Cu in its elemental form as metallic powder from aqueous solution using NaBH4 as a reducing agent. Reductive precipitation was achieved in a batch reactor at 65°C using Cu powder as a seeding material. This study also investigated the effect of concentration of sodium borohydride (NaBH4) as a reducing agent. The amount of NaBH4 was varied based on mole ratios which are 1:1, 1:0.25 and 1:0.1 to recover Cu from synthetic wastewater. The results obtained showed that sodium borohydride is an effective reducing agent to recover Cu from wastewater. The optimum concentration of NaBH4 that gives the best results the 1:1 molar ratio with over 99% Cu removal.

Priorities for toxic wastewater management in Pakistan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rahman, A.

1996-12-31

This study assesses the number of industries in Pakistan, the total discharge of wastewater, the biological oxygen demand (BOD) load, and the toxicity of the wastewater. The industrial sector is a major contributor to water pollution, with high levels of BOD, heavy metals, and toxic compounds. Only 30 industries have installed water pollution control equipment, and most are working at a very low operational level. Priority industrial sectors for pollution control are medium- to large-scale textile industries and small-scale tanneries and electroplating industries. Each day the textile industries discharge about 85,000 m{sup 3} of wastewater with a high BOD, whilemore » the electroplating industries discharge about 23,000 m{sup 3} of highly toxic and hazardous wastewater. Various in-plant modifications can reduce wastewater discharges. Economic incentives, like tax rebates, subsidies, and soft loans, could be an option for motivating medium- to large-scale industries to control water pollution. Central treatment plants may be constructed for treating wastewater generated by small-scale industries. The estimated costs for the treatment of textile and electroplating wastewater are given. The legislative structure in Pakistan is insufficient for control of industrial pollution; not only do existing laws need revision, but more laws and regulations are needed to improve the state of affairs, and enforcement agencies need to be strengthened. 15 refs., 1 fig., 9 tabs.« less

Toxicity effects of nickel electroplating effluents treated by photoelectrooxidation in the industries of the Sinos River Basin.

PubMed

Benvenuti, T; Rodrigues, Mas; Arenzon, A; Bernardes, A M; Zoppas-Ferreira, J

2015-05-01

The Sinos river Basin is an industrial region with many tanneries and electroplating plants in southern Brazil. The wastewater generated by electroplating contains high loads of salts and metals that have to be treated before discharge. After conventional treatment, this study applied an advanced oxidative process to degrade organic additives in the electroplating bright nickel baths effluent. Synthetic rinsing water was submitted to physical-chemical coagulation for nickel removal. The sample was submitted to ecotoxicity tests, and the effluent was treated by photoelectrooxidation (PEO). The effects of current density and treatment time were evaluated. The concentration of total organic carbon (TOC) was 38% lower. The toxicity tests of the effluent treated using PEO revealed that the organic additives were partially degraded and the concentration that is toxic for test organisms was reduced.

Gadolinium-Based Contrast Agents for MR Cancer Imaging

PubMed Central

Zhou, Zhuxian; Lu, Zheng-Rong

2013-01-01

Magnetic resonance imaging (MRI) is a clinical imaging modality effective for anatomical and functional imaging of diseased soft tissues, including solid tumors. MRI contrast agents have been routinely used for detecting tumor at an early stage. Gadolinium based contrast agents are the most commonly used contrast agents in clinical MRI. There have been significant efforts to design and develop novel Gd(III) contrast agents with high relaxivity, low toxicity and specific tumor binding. The relaxivity of the Gd(III) contrast agents can be increased by proper chemical modification. The toxicity of Gd(III) contrast agents can be reduced by increasing the agents’ thermodynamic and kinetic stability, as well as optimizing their pharmacokinetic properties. The increasing knowledge in the field of cancer genomics and biology provides an opportunity for designing tumor-specific contrast agents. Various new Gd(III) chelates have been designed and evaluated in animal models for more effective cancer MRI. This review outlines the design and development, physicochemical properties, and in vivo properties of several classes of Gd(III)-based MR contrast agents for tumor imaging. PMID:23047730

Evaluation of toxic agent effects on lung cells by fiber evanescent wave spectroscopy.

PubMed

Lucas, Pierre; Le Coq, David; Juncker, Christophe; Collier, Jayne; Boesewetter, Dianne E; Boussard-Plédel, Catherine; Bureau, Bruno; Riley, Mark R

2005-01-01

Biochemical changes in living cells are detected using a fiber probe system composed of a single chalcogenide fiber acting as both the sensor and transmission line for infrared optical signals. The signal is collected via evanescent wave absorption along the tapered sensing zone of the fiber. We spectroscopically monitored the effects of the surfactant Triton X-100, which serves as a toxic agent simulant on a transformed human lung carcinoma type II epithelial cell line (A549). We observe spectral changes between 2800-3000 cm(-1) in four absorptions bands, which are assigned to hydrocarbon vibrations of methylene and methyl groups in membrane lipids. Comparison of fiber and transmission spectra shows that the present technique allows one to locally probe the cell plasma membrane in the lipid spectral region. These optical responses are correlated with cellular metabolic activity measurements and LDH (lactate dehydrogenase) release assays that indicate a loss of cellular function and membrane integrity as would be expected in response to the membrane solubilizing Triton. The spectroscopic technique shows a significantly greater detection resolution in time and concentration.

In vitro toxicity and interactions of environmental contaminants (Arochlor 1254 and mercury) and immunomodulatory agents (lipopolysaccharide and cortisol) on thymocytes from lake trout (Salvelinus namaycush)

USGS Publications Warehouse

Miller, Gregory G.; Sweet, Leonard I.; Adams, Jean V.; Omann, Geneva M.; Passino-Reader, Dora R.; Meier, Peter G.

2002-01-01

The immunotoxicity of chemical combinations commonly encountered by the lake trout (Salvelinus namaycush) immune system was the focus of this study. It was hypothesised that combinations of an environmental contaminant (mercuric chloride or Aroclor 1254) and an immunomodulatory agent (bacterial endotoxin or cortisol) might interact to produce a greater toxicity than that of the environmental contaminant alone at concentrations typically encountered in piscine blood and other tissues. Thus lake trout thymocytes were isolated and treated with mercuric chloride or Aroclor 1254 in the presence and absence of cortisol or lipopolysaccharide. Incubations were performed for 6 or 20 h at 4° C or 10° C. Lipopolysaccharide did not affect the toxicity of either contaminant. In contrast, cortisol enhanced the toxicity of both environmental contaminants. Hence, stressors that lead to increased cortisol production, but not lipopolysaccharide directly, may increase the toxicity of mercury and Aroclor 1254 to lake trout thymocytes.

Diet Composition Exacerbrates or Attenuates Soman Toxicity in Rats: Implied Metabolic Control of Nerve Agent Toxicity

DTIC Science & Technology

2011-01-01

elevated sugar intake (glucose or high fructose corn syrup in drinking water) exacerbates the toxicity of parathion poisoning, an organophos- phorus...OP) insecticide (Liu et al., 2005, 2007; Olivier et al., 2001). In Liu et al. (2005), adult rats that had consumed high fructose corn syrup in...exacerbated toxicity of the OP pesticide parathion in rats given drinking water with high fructose corn syrup or glucose added. Furthermore, deldrin

Mitochondrial toxicity in human pregnancy: an update on clinical and experimental approaches in the last 10 years.

PubMed

Morén, Constanza; Hernández, Sandra; Guitart-Mampel, Mariona; Garrabou, Glòria

2014-09-22

Mitochondrial toxicity can be one of the most dreadful consequences of exposure to a wide range of external agents including pathogens, therapeutic agents, abuse drugs, toxic gases and other harmful chemical substances. However, little is known about the effects of mitochondrial toxicity on pregnant women exposed to these agents that may exert transplacental activity and condition fetal remodeling. It has been hypothesized that mitochondrial toxicity may be involved in some adverse obstetric outcomes. In the present study, we investigated the association between exposure to mitochondrial toxic agents and pathologic conditions ranging from fertility defects, detrimental fetal development and impaired newborn health due to intra-uterine exposure. We have reviewed data from studies in human subjects to propose mechanisms of mitochondrial toxicity that could be associated with the symptoms present in both exposed pregnant and fetal patients. Since some therapeutic interventions or accidental exposure cannot be avoided, further research is needed to gain insight into the molecular pathways leading to mitochondrial toxicity during pregnancy. The ultimate objective of these studies should be to reduce the mitochondrial toxicity of these agents and establish biomarkers for gestational monitoring of harmful effects.

RESPONSE OF THE THERMOREGULATORY SYSTEM TO TOXIC CHEMICALS

EPA Science Inventory

The thermoregulatory system plays a crucial role in the physiological response to pesticides, airborne pollutants, and other toxic agents. The exposure to toxicants via inhalation, cutaneous absorption, or ingestion, their clearance from the body, the physiological responses, del...

Response of the Thermoregulatory System to Toxic Chemicals

EPA Science Inventory

The thermoregulatory system plays a crucial role in the physiological response to pesticides, airborne pollutants, and other toxic agents. The exposure to toxicants via inhalation, cutaneous absorption, or ingestion, their clearance from the body, the physiological responses, del...

The Respiratory Toxicity of Chemical Warefare Agents

EPA Science Inventory

Inhalation is one of the most important routes of exposure for chemical warfare agents (CWAs) and thus, the lung remains a critical target of injury. Depending on the mode of action by which the CWAs cause injury, the nature of injury, the location being impacted within the respi...

Comparative toxicity of mono- and bifunctional alkylating homologues of sulphur mustard in human skin keratinocytes.

PubMed

Sawyer, Thomas W; McNeely, Karin; Louis, Kristen; Lecavalier, Pierre; Song, Yanfeng; Villanueva, Mercy; Clewley, Robin

2017-05-01

Sulphur mustard (bis(2-chloroethyl) sulphide; agent H) is a vesicant chemical warfare (CW) agent whose mechanism of action is not known with any certainty and for which there are no effective antidotes. It has a pronounced latent period before signs and symptoms of poisoning appear which it shares with the nitrogen mustards, and that differentiates it from other classes of vesicant agents. Sulphur mustard, the sulphur mustard CW agents Q (1,2-bis(2-chloroethylthio) ethane) and T (1,1 bis(2-chloroethylthioethyl) ether), the H partial hydrolysis product hemi-sulphur mustard (2-chloroethyl 2-hydroxyethyl sulphide; HSM), and the commercially available 2-chloroethyl ethyl sulphide (CEES) were characterized with respect to their toxicity in first passage cultures of proliferating human skin keratinocytes, the target cell of H-induced skin vesication. Agents H and T were equitoxic and half as toxic as agent Q. Hemi-sulphur mustard and CEES were approximately six times and seventeen times, respectively less cytotoxic than H. 2-Chloroethyl ethyl sulphide was only slightly less toxic in confluent cultures compared to actively proliferating cells. In contrast, the toxicity of H, Q, T and HSM significantly decreased as the cultures became confluent, paralleling the decreasing sensitivity of skin keratinocytes to H as they leave the basement membrane of the skin. The toxicity of CEES was maximal by 24h. In contrast, the maximal toxicity of the other four agents occurred at 48h, mirroring the latent period observed for these agents in vivo. The markedly different characteristics of toxicity between CEES and the other four test compounds indicate that it is likely that different mechanisms of action are operative between them. Caution should therefore be taken when interpreting the results of studies utilizing CEES as a simulant for the mechanistic study of H, or in the elucidation of medical countermeasures against this CW agent. It is also notable that the toxicity

Toxic Substances in the Environment.

ERIC Educational Resources Information Center

Clearing: Nature and Learning in the Pacific Northwest, 1984

1984-01-01

Discusses the nature of toxic substances, examining pesticides and herbicides, heavy metals, industrial chemicals, and household substances. Includes a list of major toxic substances (indicating what they are, where they are found, and health concerns) and a student activity on how pesticides enter the food chain. (JN)

Maternally Mediated Developmental Toxicity

EPA Science Inventory

The current practice for the assessment of an agent’s potential effects on the developing embryo/fetus includes administration of high, maternally toxic doses to pregnant laboratory animals. For most agents evaluated, developmental effects occur concomitant with maternal to...

Assessing acute toxicity of effluent from a textile industry and nearby river waters using sulfur-oxidizing bacteria in continuous mode.

PubMed

Gurung, Anup; Hassan, Sedky H A; Oh, Sang-Eun

2011-10-01

Bioassays are becoming an important tool for assessing the toxicity of complex mixtures of substances in aquatic environments in which Daphnia magna is routinely used as a test organism. Bioassays outweigh physicochemical analyses and are valuable in the decision-making process pertaining to the final discharge of effluents from wastewater treatment plants as they measure the total effect of the discharge which is ecologically relevant. In this study, the aquatic toxicity of a textile plant effluent and river water downstream from the plant were evaluated with sulfur-oxidizing bacterial biosensors in continuous mode. Collected samples were analysed for different physicochemical parameters and 1,4-dioxane was detected in the effluent. The effluent contained a relatively high chemical oxygen demand of 60 mg L(-1), which exceeded the limit set by the Korean government for industrial effluent discharges. Results showed that both the effluent and river waters were toxic to sulfur-oxidizing bacteria. These results show the importance of incorporating bioassays to detect toxicity in wastewater effluents for the sustainable management of water resources.

Pb Neurotoxicity: Neuropsychological Effects of Lead Toxicity

PubMed Central

Mason, Lisa H.; Harp, Jordan P.; Han, Dong Y.

2014-01-01

Neurotoxicity is a term used to describe neurophysiological changes caused by exposure to toxic agents. Such exposure can result in neurocognitive symptoms and/or psychiatric disturbances. Common toxic agents include heavy metals, drugs, organophosphates, bacterial, and animal neurotoxins. Among heavy metal exposures, lead exposure is one of the most common exposures that can lead to significant neuropsychological and functional decline in humans. In this review, neurotoxic lead exposure's pathophysiology, etiology, and epidemiology are explored. In addition, commonly associated neuropsychological difficulties in intelligence, memory, executive functioning, attention, processing speed, language, visuospatial skills, motor skills, and affect/mood are explored. PMID:24516855

Sensitivity or artifact? -- IQ Toxicity Test -- effluent values

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hayes, K.R.; Novotny, A.N.; Batista, N.

1995-12-31

Several complex effluents were DAPHNIA MAGNA IQ TOXICITY TESTED -- (1.25 hours) and conventionally tested with Daphnia magna (48 hours). In many samples the IQ Technology yielded low EC50 values while the 48 hour exposures yielded no acute toxicity. Possible explanations have been suggested for this occurrence such as: genotoxicity, mutagenicity, substrate interference, and enzyme satiation. To identify the causative agent(s) of this response a Toxicity Identification Evaluation was performed on one of the samples. To define the nature of the response, THE SOS-CHROMOTEST KIT and THE MUTA-CHROMOPLATE KIT were utilized to characterize genotoxicity and mutagenicity respectively. The sample didmore » not test positive for genotoxicity but tested positive for mutagenicity only after activation with S9 enzymes, suggesting the presence of promutagens. Additional work needs to be performed to correlate IQ TOXICITY TEST sensitivity with positive MUTA-CHROMOPLATE response.« less

Towards new methods for the determination of dose limiting toxicities and the assessment of the recommended dose for further studies of molecularly targeted agents--dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies, an European Organisation for Research and Treatment of Cancer-led study.

PubMed

Postel-Vinay, Sophie; Collette, Laurence; Paoletti, Xavier; Rizzo, Elisa; Massard, Christophe; Olmos, David; Fowst, Camilla; Levy, Bernard; Mancini, Pierre; Lacombe, Denis; Ivy, Percy; Seymour, Lesley; Le Tourneau, Christophe; Siu, Lillian L; Kaye, Stan B; Verweij, Jaap; Soria, Jean-Charles

2014-08-01

Traditional dose-limiting toxicity (DLT) definition, which uses grade (G) 3-4 toxicity data from cycle 1 (C1) only, may not be appropriate for molecularly targeted agents (MTAs) of prolonged administration, for which late or lower grade toxicities also deserve attention. In collaboration with pharmaceutical companies and academia, an European Organisation for Research and Treatment of Cancer (EORTC)-led initiative, Dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies (DLT-TARGETT), collected data from completed phase 1 trials evaluating MTAs as monotherapy. All toxicities at least possibly related to the study drugs that occurred during C1-6, their type, grade (CTCAEv3.0), and duration as well as patients' relative dose-intensity (RDI), were recorded. The 54 eligible trials enrolled 2084 evaluable adult patients with solid tumours between 1999 and 2013, and evaluated small molecules (40), antibodies (seven), recombinant peptides (five) and antisense oligodeoxynucleotides (two). A maximum tolerated dose was set in 43 trials. Fifteen percent of the patients received <75% of the intended RDI in C1, but only 9.1% of them presented protocol-defined DLTs. After C1, 16-19% of patients received <75% of the intended RDI. A similar proportion of G ⩾ 3 toxicities was recorded in C1 and after C1 (936 and 1087 toxicities, respectively), with the first G⩾3 toxicity occurring after C1 in 18.6% of patients. Although protocol-defined DLT period is traditionally limited to C1, almost 20% of patients present significant reductions in RDI at any time in phase 1 trials of MTAs. Recommended phase 2 dose assessment should incorporate all available information from any cycle (notably lower grade toxicities leading to such RDI decrease), and be based on achieving >75% RDI. Copyright © 2014 Elsevier Ltd. All rights reserved.

Emergency management of chemical weapons injuries.

PubMed

Anderson, Peter D

2012-02-01

The potential for chemical weapons to be used in terrorism is a real possibility. Classes of chemical weapons include nerve agents, vesicants (blister agents), choking agents, incapacitating agents, riot control agents, blood agents, and toxic industrial chemicals. The nerve agents work by blocking the actions of acetylcholinesterase leading to a cholinergic syndrome. Nerve agents include sarin, tabun, VX, cyclosarin, and soman. The vesicants include sulfur mustard and lewisite. The vesicants produce blisters and also damage the upper airways. Choking agents include phosgene and chlorine gas. Choking agents cause pulmonary edema. Incapacitating agents include fentanyl and its derivatives and adamsite. Riot control agents include Mace and pepper spray. Blood agents include cyanide. The mechanism of toxicity for cyanide is blocking oxidative phosphorylation. Toxic industrial chemicals include agents such as formaldehyde, hydrofluoric acid, and ammonia.

AGENT-BASED MODELING OF INDUSTRIAL ECOSYSTEMS

EPA Science Inventory

The objectives of this research are to investigate behavioral and organizational questions associated with environmental regulation of firms, and to test specifically whether a bottom-up approach that highlights principal-agent problems offers new insights and empirical validi...

Contamination levels, toxicity profiles, and emission sources of polycyclic aromatic hydrocarbons (PAHs) in the soils of an emerging industrial town and its environs in the Southeastern Nigeria.

PubMed

Ofomatah, Anthony C; Okoye, Chukwuma O B

2017-11-09

Polycyclic aromatic hydrocarbon (PAH) concentrations in Nnewi and its environs were determined. Soil samples were extracted by sonication using hexane:dichloromethane (3:1) mixture and determined by gas chromatography-flame ionization detection. The total PAHs concentrations (μg/kg) were 16.681 to 46.815, being three orders of magnitude lower than the maximum permissible level recommended by the Agency for Toxic Substances and Disease Registry (ATSDR). These concentrations followed this order: industrial ˃ farmlands ˃ commercial ˃ residential. Industrialized areas showed higher concentrations (p ˂ 0.05) than the other areas. Diagnostic ratios show that the major source of PAHs was the open burning of industrial and agricultural wastes, as shown by the occurrence of highest concentrations in the industrial areas, followed by agricultural areas. Benzo[a]pyrene equivalent values showed non-pollution and very low toxicity. Nevertheless, it was clear that industrialization has had some impact on the PAHs levels in soils and the total environment in this area and could be problematic with time, except with proper environmental management.

Chemical technology for the toxic gas flow control through process water system.

PubMed

Broussard, G; Bramanti, O; Salvatore, A; Marchese, F M

2001-01-01

The aim of this work is focused on the safety and toxicological aspects due to under-pressure industrial plant management, above all in the case which the gas is very dangerous for human health and environment. Here is illustrated the safe method of control of risks through specific choices of engineering devices and chemical process: in this way we have shown the mathematical calculation regarding the case of ammonia flow gas running in the piping and plant under-pressure. In this paper the Authors show the assessment of the technological solution for falling down of a toxic gas as NH3, which lets off from safety values facilities. The under pressure industrial plants with ammonia are protected through the safety valves, settled at 20 bar pressure. The out-let gas flow is capted by a tank of a water bulk of five time theoretical water amount necessary to the complete absorption of gas. In order to prevent any health risk and carry out a safety management, it needs to verify two basic aspects, with connected specific techniques: 1. The safety valves technology through the mathematical calculation of operating device; 2. The absorption process of the toxic agent for controlling of dangerous runaway of gas.

Portable Sensor for Chemical Nerve Agents and Organophosphorus Compounds

DTIC Science & Technology

2015-08-18

as pesticides in crop, livestock, and poultry products and as chemical and biological warfare agents. As a result of the high toxicity and the...agents have been exploited for use as pesticides in crop, livestock, and poultry products and as chemical and biological warfare agents. As a result of

Comparison of the clinical efficacy between single-agent and dual-agent concurrent chemoradiotherapy in the treatment of unresectable esophageal squamous cell carcinoma: a multicenter retrospective analysis.

PubMed

Li, Jie; Gong, Youling; Diao, Peng; Huang, Qingmei; Wen, Yixue; Lin, Binwei; Cai, Hongwei; Tian, Honggang; He, Bing; Ji, Lanlan; Guo, Ping; Miao, Jidong; Du, Xiaobo

2018-01-22

Some Chinese patients with esophageal squamous cell carcinomaare often treated with single-agent concurrent chemoradiotherapy. However, no results have been reported from randomized controlled clinical trials comparing single-agent with double-agent concurrent chemoradiotherapy. It therefore remains unclear whether these regimens are equally clinically effective. In this study, we retrospectively analyzed and compared the therapeutic effects of single-agent and double-agent concurrent chemoradiotherapy in patients with unresectable esophageal squamous cell carcinoma. This study enrolled 168 patients who received definitive concurrent chemoradiotherapy for locally advanced unresectable esophageal squamous carcinoma at 10 hospitals between 2010 and 2015. We evaluated survival time and toxicity. The Kaplan-Meier method was used to estimate survival data. The log-rank test was used in univariate analysis A Cox proportional hazards regression model was used to conduct a multivariate analysis of the effects of prognostic factors on survival. In this study, 100 (59.5%) and 68 patients (40.5%) received single-agent and dual-agent combination chemoradiotherapy, respectively. The estimate 5-year progression-free survival (PFS) rate and overall survival (OS) rate of dual-agent therapy was higher than that of single-agent therapy (52.5% and 40.9%, 78.2% and 60.7%, respectively), but there were no significant differences (P = 0.367 and 0.161, respectively). Multivariate analysis showed that sex, age,and radiotherapy dose had no significant effects on OS or PFS. Only disease stage was associated with OS and PFS in the multivariable analysis (P = 0.006 and 0.003, respectively). In dual-agent group, the incidence of acute toxicity and the incidence of 3 and4 grade toxicity were higher than single-agent group. The 5-year PFS and OS rates of dual-agent therapy were higher than those of single-agent concurrent chemoradiotherapy for patients with unresectable esophageal

Synthesis, molecular properties, toxicity and biological evaluation of some new substituted imidazolidine derivatives in search of potent anti-inflammatory agents

PubMed Central

Husain, Asif; Ahmad, Aftab; Khan, Shah Alam; Asif, Mohd; Bhutani, Rubina; Al-Abbasi, Fahad A.

2015-01-01

The aim of this study was to design and synthesize pharmaceutical agents containing imidazolidine heterocyclic ring in the hope of developing potent, safe and orally active anti-inflammatory agents. A number of substituted-imidazolidine derivatives (3a–k) were synthesized starting from ethylene diamine and aromatic aldehydes. The imidazolidine derivatives (3a–k) were investigated for their anticipated anti-inflammatory, and analgesic activity in Wistar albino rats and Swiss albino mice, respectively. Bioactivity score, molecular and pharmacokinetic properties of the imidazolidine derivatives were calculated by online computer software programs viz. Molinspiration and Osiris property explorer. The results of biological testing indicated that among the synthesized compounds only three imidazolidine derivatives namely 4-[1,3-Bis(2,6-dichlorobenzyl)-2-imidazolidinyl]phenyl-diethylamine (3g), 4-[1,3-Bis(3-hydroxy-4-methoxybenzyl)-2-imidazolidinyl]phenyl-diethylamine (3i) and 4-(1,3-Bis(4-methoxybenzyl)-4-methylimidazolidin-2-yl)-phenyl-diethylamine (3j) possess promising anti-inflammatory and analgesic actions. Additionally these derivatives displayed superior GI safety profile (low severity index) with respect to the positive control, Indomethacin. All synthesized compounds showed promising bioactivity score for drug targets by Molinspiration software. Almost all the compounds were predicted to have very low toxicity risk by Osiris online software. Compound number (3i) emerged as a potential candidate for further research as it obeyed Lipinski’s rule of five for drug likeness, exhibited promising biological activity in-vivo and showed no risk of toxicity in computer aided screening. PMID:26903774

Effect of poly-α, γ, L-glutamic acid as a capping agent on morphology and oxidative stress-dependent toxicity of silver nanoparticles

PubMed Central

Stevanović, Magdalena; Kovačević, Branimir; Petković, Jana; Filipič, Metka; Uskoković, Dragan

2011-01-01

Highly stable dispersions of nanosized silver particles were synthesized using a straightforward, cost-effective, and ecofriendly method. Nontoxic glucose was utilized as a reducing agent and poly-α, γ, L-glutamic acid (PGA), a naturally occurring anionic polymer, was used as a capping agent to protect the silver nanoparticles from agglomeration and render them biocompatible. Use of ammonia during synthesis was avoided. Our study clearly demonstrates how the concentration of the capping agent plays a major role in determining the dimensions, morphology, and stability, as well as toxicity of a silver colloidal solution. Hence, proper optimization is necessary to develop silver colloids of narrow size distribution. The samples were characterized by Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, and zeta potential measurement. MTT assay results indicated good biocompatibility of the PGA-capped silver nanoparticles. Formation of intracellular reactive oxygen species was measured spectrophotometrically using 2,7-dichlorofluorescein diacetate as a fluorescent probe, and it was shown that the PGA-capped silver nanoparticles did not induce intracellular formation of reactive oxygen species. PMID:22131829

Interaction, transformation and toxicity assessment of particles and additives used in the semiconducting industry.

PubMed

Dumitrescu, Eduard; Karunaratne, Dinusha P; Babu, S V; Wallace, Kenneth N; Andreescu, Silvana

2018-02-01

Chemical mechanical planarization (CMP) is a widely used technique for the manufacturing of integrated circuit chips in the semiconductor industry. The process generates large amounts of waste containing engineered particles, chemical additives, and chemo-mechanically removed compounds. The environmental and health effects associated with the release of CMP materials are largely unknown and have recently become of significant concern. Using a zebrafish embryo assay, we established toxicity profiles of individual CMP particle abrasives (SiO 2 and CeO 2 ), chemical additives (hydrogen peroxide, proline, glycine, nicotinic acid, and benzotriazole), as well as three model representative slurries and their resulting waste. These materials were characterized before and after use in a typical CMP process in order to assess changes that may affect their toxicological profile and alter their surface chemistry due to polishing. Toxicity outcome in zebrafish is discussed in relation with the physicochemical characteristics of the abrasive particles and with the type and concentration profile of the slurry components pre and post-polishing, as well as the interactions between particle abrasives and additives. This work provides toxicological information of realistic CMP slurries and their polishing waste, and can be used as a guideline to predict the impact of these materials in the environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ocular toxicity of fludarabine

PubMed Central

Ding, Xiaoyan; Herzlich, Alexandra A; Bishop, Rachel; Tuo, Jingsheng; Chan, Chi-Chao

2008-01-01

The purine analogs, fludarabine and cladribine represent an important class of chemotherapy agents used to treat a broad spectrum of lymphoid malignancies. Their toxicity profiles include dose-limiting myelosuppression, immunosuppression, opportunistic infection and severe neurotoxicity. This review summarizes the neurotoxicity of high- and standard-dose fludarabine, focusing on the clinical and pathological manifestations in the eye. The mechanisms of ocular toxicity are probably multifactorial. With increasing clinical use, an awareness of the neurological and ocular vulnerability, particularly to fludarabine, is important owing to the potential for life- and sight-threatening consequences. PMID:18461151

Gadolinium based contrast agents in current practice: Risks of accumulation and toxicity in patients with normal renal function

PubMed Central

Ranga, Anju; Agarwal, Yatish; Garg, Kanika J

2017-01-01

Despite being decked as the most prized compounds in the nugget box of contrast agents for clinical radiologists, and carrying an indisputable tag of safety of the US Food and Drug Administration for close to three decades, all may not be seemingly well with the family of gadolinium compounds. If the first signs of violations of primum non nocere in relation to gadolinium-based contrast agents (GBCAs) appeared in the millennium year with the first published report of skin fibrosis in patients with compromised renal function, the causal relationship between the development of nephrogenic systemic fibrosis (NSF) and GBCAs, first proposed by two European groups in 2006, further precluded their use in renocompromised patients. The toxicity, pharmacokinetics, and pharmacodynamics of GBCAs, however, has come under hawk-eyed scrutiny with recent reports that gadolinium tends to deposit cumulatively in the brain of patients with normal hepatobiliary function and intact blood–brain barrier. While the jury on the long-term hazard significance of this critical scientific finding is still out, the use of GBCAs must be guided by due clinical diligence, avoidance of repeated doses, and preferring GBCAs with the best safety profiles. PMID:28744073

Human Carboxylesterase 1 Stereoselectively Binds the Nerve Agent Cyclosarin and Spontaneously Hydrolyzes the Nerve Agent Sarin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hemmert, Andrew C.; Otto, Tamara C.; Wierdl, Monika

Organophosphorus (OP) nerve agents are potent toxins that inhibit cholinesterases and produce a rapid and lethal cholinergic crisis. Development of protein-based therapeutics is being pursued with the goal of preventing nerve agent toxicity and protecting against the long-term side effects of these agents. The drug-metabolizing enzyme human carboxylesterase 1 (hCE1) is a candidate protein-based therapeutic because of its similarity in structure and function to the cholinesterase targets of nerve agent poisoning. However, the ability of wild-type hCE1 to process the G-type nerve agents sarin and cyclosarin has not been determined. We report the crystal structure of hCE1 in complex withmore » the nerve agent cyclosarin. We further use stereoselective nerve agent analogs to establish that hCE1 exhibits a 1700- and 2900-fold preference for the P{sub R} enantiomers of analogs of soman and cyclosarin, respectively, and a 5-fold preference for the P{sub S} isomer of a sarin analog. Finally, we show that for enzyme inhibited by racemic mixtures of bona fide nerve agents, hCE1 spontaneously reactivates in the presence of sarin but not soman or cyclosarin. The addition of the neutral oxime 2,3-butanedione monoxime increases the rate of reactivation of hCE1 from sarin inhibition by more than 60-fold but has no effect on reactivation with the other agents examined. Taken together, these data demonstrate that hCE1 is only reactivated after inhibition with the more toxic P{sub S} isomer of sarin. These results provide important insights toward the long-term goal of designing novel forms of hCE1 to act as protein-based therapeutics for nerve agent detoxification.« less

Research on environmental impact of water-based fire extinguishing agents

NASA Astrophysics Data System (ADS)

Wang, Shuai

2018-02-01

This paper offers current status of application of water-based fire extinguishing agents, the environmental and research considerations of the need for the study of toxicity research. This paper also offers systematic review of test methods of toxicity and environmental impact of water-based fire extinguishing agents currently available, illustrate the main requirements and relevant test methods, and offer some research findings for future research considerations. The paper also offers limitations of current study.

Sampling the stratum corneum for toxic chemicals.

PubMed

Coman, Garrett; Blickenstaff, Nicholas R; Blattner, Collin M; Andersen, Rosa; Maibach, Howard I

2014-01-01

Dermal exposure is an important pathway in environmental health. Exposure comes from contaminated water, soil, treated surfaces, textiles, aerosolized chemicals, and agricultural products. It can occur in homes, schools, play areas, and work settings in the form of industrial sources, consumer products, or hazardous wastes. Dermal exposure is most likely to occur through contact with liquids, water, soil, sediment, and contaminated surfaces. The ability to detect and measure exposure to toxic materials on the skin is an important environmental health issue. The stratum corneum is the skin's first and principal barrier layer of protection from the outside world. It has a complex structure that can effectively protect against a wide variety of physical, chemical, and biological contaminants. However, there are a variety of chemical agents that can damage the stratum corneum and the underlying epidermis, dermis and subcutis, and/or enter systemic circulation through the skin. There are numerous ways of sampling the stratum corneum for these toxic materials like abrasion techniques, biopsy, suction blistering, imaging, washing, wipe sampling, tape stripping, and spot testing. Selecting a method likely depends on the particular needs of the situation. Hence, there is a need to review practical considerations for their use in sampling the stratum corneum for toxins.

Complex mixture-associated hormesis and toxicity: the case of leather tanning industry.

PubMed

Pagano, Giovanni; Castello, Giuseppe; Gallo, Marialuisa; Borriello, Ilaria; Guida, Marco

2008-01-01

A series of studies investigated the toxicities of tannery-derived complex mixtures, i.e. vegetable tannin (VT) from Acacia sp. or phenol-based synthetic tannin (ST), and waste-water from tannin-based vs. chromium-based tanneries. Toxicity was evaluated by multiple bioassays including developmental defects and loss of fertilization rate in sea urchin embryos and sperm (Paracentrotus lividus and Sphaerechinus granularis), and algal growth inhibition (Dunaliella tertiolecta and Selenastrum capricornutum). Both VT and ST water extracts resulted in hormetic effects at concentrations ranging 0.1 to 0.3%, and toxicity at levels > or =1%, both in sea urchin embryo and sperm, and in algal growth bioassays. When comparing tannin-based tannery wastewater (TTW) vs. chromium-based tannery effluent (CTE), a hormesis to toxicity trend was observed for TTW both in terms of developmental and fertilization toxicity in sea urchins, and in algal growth inhibition, with hormetic effects at 0.1 to 0.2% TTW, and toxicity at TTW levels > or =1%. Unlike TTW, CTE showed a monotonic toxicity increase from the lowest tested level (0.1%) and CTE toxicity at higher levels was significantly more severe than TTW-induced toxicity. The results support the view that leather production utilizing tannins might be regarded as a more environmentally friendly procedure than chromium-based tanning process.

Aloe-induced Toxic Hepatitis

PubMed Central

Yang, Ha Na; Kim, Young Mook; Kim, Byoung Ho; Sohn, Kyoung Min; Choi, Myung Jin; Choi, Young Hee

2010-01-01

Aloe has been widely used in phytomedicine. Phytomedicine describes aloe as a herb which has anti-inflammatory, anti-proliferative, anti-aging effects. In recent years several cases of aloe-induced hepatotoxicity were reported. But its pharmacokinetics and toxicity are poorly described in the literature. Here we report three cases with aloe-induced toxic hepatitis. A 57-yr-old woman, a 62-yr-old woman and a 55-yr-old woman were admitted to the hospital for acute hepatitis. They had taken aloe preparation for months. Their clinical manifestation, laboratory findings and histologic findings met diagnostic criteria (RUCAM scale) of toxic hepatitis. Upon discontinuation of the oral aloe preparations, liver enzymes returned to normal level. Aloe should be considered as a causative agent in hepatotoxicity. PMID:20191055

Biochemical basis of 4-hydroxyanisole induced cell toxicity towards B16-F0 melanoma cells.

PubMed

Moridani, Majid Y

2006-11-18

In the current work we investigated for the first time the biochemical basis of 4-hydroxyanisole (4-HA) induced toxicity in B16-F0 melanoma cells. It was found that dicoumarol, a diaphorase inhibitor, and 1-bromoheptane, a GSH depleting agent, increased 4-HA induced toxicity towards B16-F0 cells whereas dithiothreitol, a thiol containing agent, and ascorbic acid (AA), a reducing agent, largely prevented 4-HA toxicity. TEMPOL and pyrogallol, free radical scavengers, did not significantly prevent 4-HA toxicity towards B16-F0 cells. GSH>AA>NADH prevented the o-quinone formation when 4-HA was metabolized by tyrosinase/O(2). 4-HA metabolism by horseradish peroxidase/H(2)O(2) was prevented more effectively by AA than NADH>GSH. We therefore concluded that quinone formation was the major pathway for 4-HA induced toxicity in B16-F0 melanoma cells whereas free radical formation played a negligible role in the 4-HA induced toxicity.

Complex Mixture-Associated Hormesis and Toxicity: The Case of Leather Tanning Industry

PubMed Central

Pagano, Giovanni; Castello, Giuseppe; Gallo, Marialuisa; Borriello, Ilaria; Guida, Marco

2008-01-01

A series of studies investigated the toxicities of tannery-derived complex mixtures, i.e. vegetable tannin (VT) from Acacia sp. or phenol-based synthetic tannin (ST), and waste-water from tannin-based vs. chromium-based tanneries. Toxicity was evaluated by multiple bioassays including developmental defects and loss of fertilization rate in sea urchin embryos and sperm (Paracentrotus lividus and Sphaerechinus granularis), and algal growth inhibition (Dunaliella tertiolecta and Selenastrum capricornutum). Both VT and ST water extracts resulted in hormetic effects at concentrations ranging 0.1 to 0.3%, and toxicity at levels ≥1%, both in sea urchin embryo and sperm, and in algal growth bioassays. When comparing tannin-based tannery wastewater (TTW) vs. chromium-based tannery effluent (CTE), a hormesis to toxicity trend was observed for TTW both in terms of developmental and fertilization toxicity in sea urchins, and in algal growth inhibition, with hormetic effects at 0.1 to 0.2% TTW, and toxicity at TTW levels ≥1%. Unlike TTW, CTE showed a monotonic toxicity increase from the lowest tested level (0.1%) and CTE toxicity at higher levels was significantly more severe than TTW-induced toxicity. The results support the view that leather production utilizing tannins might be regarded as a more environmentally friendly procedure than chromium-based tanning process. PMID:19088903

Save the Bay's "Toxic Diet" Project.

ERIC Educational Resources Information Center

Wilder, Diana

1994-01-01

Although progress has been made in curbing industrial pollutants in larger communities, small, nonindustrial communities lack strategies for reducing unregulated toxic sources to the influent stream. This article outlines one environmental organization's model for reducing these toxic sources that can be used to help small communities nationwide.…

Method and apparatus for enhanced detection of toxic agents

DOEpatents

Greenbaum, Elias [Knoxville, TN; Rodriguez, Jr., Miguel; Wu, Jie Jayne [Knoxville, TN; Qi, Hairong [Knoxville, TN

2012-06-12

A water quality analyzer for real-time detection according to the invention comprises a biased AC electro-osmosis (ACEO) cell for receiving a fluid to be analyzed having a plurality photosynthetic organisms therein, and concentrating the plurality photosynthetic organisms into at least one concentrated region. A photodetector is provided for obtaining a measured photosynthetic activity of the plurality of photosynthetic organisms in the concentrated region, wherein chemical, biological or radiological agents reduce a nominal photosynthetic activity of the photosynthetic organisms. An electronics package analyzes the measured photosynthetic activity to indicate a presence of the chemical, biological or radiological agents in the fluid.

The Problem with Toxic Wastes.

ERIC Educational Resources Information Center

Beecher, John L.; Fossa, Arthur J.

1980-01-01

Traced is the historical development of toxic waste problems in western New York State from 1825 to the present. Three major data sources are described: Industrial Chemical Survey, Inventory of Industrial Waste Generation Study, and the Interagency Task Force Study, developed by the Department of Environmental Conservation to prevent future…

Toxicity reduction of photo processing wastewaters

USGS Publications Warehouse

Wang, W.

1992-01-01

The photo processing industry can be characterized by treatment processes and subsequent silver recovery. The effluents generated all contain various amounts of silver. The objectives of this study were to determine toxicity of photo processing effluents and to explore their toxicity mitigation. Six samples, from small shops to a major photo processing center, were studied. Two samples (I and VI) were found to be extremely toxic, causing 100 and 99% inhibition of duckweed frond reproduction, respectively, and were used for subsequent toxicity reduction experiments. Lime and sodium sulfide were effective for the toxicity reduction of Sample VI; both reduced its toxicity to negligible. Sample I was far more toxic and was first diluted to 2.2% and then treated with 0.5 g lime/100 mL, reducing toxicity from 100% to 12% inhibition.

Cosmetic Preservatives as Therapeutic Corneal and Scleral Tissue Cross-Linking Agents

PubMed Central

Babar, Natasha; Kim, MiJung; Cao, Kerry; Shimizu, Yukari; Kim, Su-Young; Takaoka, Anna; Trokel, Stephen L.; Paik, David C.

2015-01-01

Purpose. Previously, aliphatic β-nitroalcohols (BNAs) have been studied as a means to chemically induce tissue cross-linking (TXL) of cornea and sclera. There are a number of related and possibly more potent agents, known as formaldehyde releasers (FARs), that are in commercial use as preservatives in cosmetics and other personal care products. The present study was undertaken in order to screen such compounds for potential clinical utility as therapeutic TXL agents. Methods. A chemical registry of 62 FARs was created from a literature review and included characteristics relevant to TXL such as molecular weight, carcinogenicity/mutagenicity, toxicity, hydrophobicity, and commercial availability. From this registry, five compounds [diazolidinyl urea (DAU), imidazolidinyl urea (IMU), sodium hydroxymethylglycinate (SMG), DMDM hydantoin (DMDM), 5-Ethyl-3,7-dioxa-1-azabicyclo [3.3.0] octane (OCT)] were selected for efficacy screening using two independent systems, an ex vivo rabbit corneal cross-linking simulation setup and incubation of cut scleral tissue pieces. Treatments were conducted at pH 7.4 or 8.5 for 30 minutes. Efficacy was evaluated using thermal denaturation temperature (Tm), and cell toxicity was studied using the trypan blue exclusion method. Results. Cross-linking effects in the five selected FARs were pH and concentration dependent. Overall, the Tm shifts were in agreement with both cornea and sclera. By comparison with BNAs previously reported upon, the FARs identified in this study were significantly more potent but with similar or better cytotoxicity. Conclusions. The FARs, a class of compounds well known to the cosmetic industry, may have utility as therapeutic TXL agents. The compounds studied thus far show promise and will be further tested. PMID:25634979

Oxaliplatin-Related Ocular Toxicity

PubMed Central

Mesquida, Marina; Sanchez-Dalmau, Bernardo; Ortiz-Perez, Santiago; Pelegrín, Laura; Molina-Fernandez, Juan José; Figueras-Roca, Marc; Casaroli-Marano, Ricardo; Adán, Alfredo

2010-01-01

We report the case of a 52-year-old woman with advanced colorectal cancer who was treated with oxaliplatin on a FOLFOX schedule. After 3 cycles of chemotherapy, she started to complain of visual loss, altered color vision and neurological symptoms. Due to the suspicion of ocular and neurological toxicity, antineoplastic treatment was stopped. Her visual field showed a concentric bilateral scotoma and the electrooculogram test revealed severe impairment of the retinal pigment epithelium. Visual acuity, color vision and visual field recovered completely 8 months later, although electrooculogram remained abnormal. Ocular toxicity has been reported as an infrequent adverse event of oxaliplatin. Findings in this case indicate toxicity of this chemotherapeutic agent on the retinal pigment epithelium, which has not been reported before. This damage could be permanent, and it thus differs from previously described oxaliplatin-induced ocular toxicities, which are usually transient and reversible. With increasing use of oxaliplatin as first-line treatment in advanced colorectal cancer, we have to be aware of this possible toxicity. PMID:21151636

Strain improvement of industrially important microorganisms based on resistance to toxic metabolites and abiotic stress.

PubMed

Fiedurek, Jan; Trytek, Mariusz; Szczodrak, Janusz

2017-06-01

Improvement of the biosynthetic capabilities of industrially relevant microbes to produce desired metabolites in higher quantities is one of the important topics of modern biotechnology. In this article, different strategies of improvement of mutated microbial strains are briefly described. This is followed by the first comprehensive review of the literature on obtaining high yielding microorganisms, that is, mutants exhibiting resistance to antimetabolites, nutritional repression, and abiotic stresses as well as tolerance to solvents and toxic substrates or products. Furthermore, the efficiency of the microbial metabolites produced by improved microbial strains, advantages, and limitations, as well as future prospects for strategies of strain development are discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fibrous Filter to Protect Building Environments from Polluting Agents: A Review

NASA Astrophysics Data System (ADS)

Chavhan, Md. Vaseem; Mukhopadhyay, Arunangshu

2016-04-01

This paper discusses the use of fibrous filter to protect the building environments from air born polluting agents and especially of concern chemical, biological and radiological agents. Air-filtration includes removal of particulate from air and toxic gases from air. In air filtration, particulate which are mostly biological and radioactive types of agents can be removed by using mechanical and electrostatic filters. Some biological agents, which cannot be removed by air filtration alone, special techniques like antimicrobial finish, UV germicides, coated filters etc. are required. Biocide agent can be added into the fibre itself by grafting reaction to impart antimicrobial activity. Chemical agents like toxic gases can be removed by integrating adsorbents and sorbents in filters or by fibre modifications. It is also possible to impart catalytic conversion properties into the fibre to remove volatile gasous. Radioactive agents can be removed by particulate filter if present in the form of aerosol or by gas cleaning by the use of specific fibre impregnate.

Using S and Pb isotope ratios to trace leaching of toxic substances from an acid-impacted industrial-waste landfill (Pozdatky, Czech Republic).

PubMed

Novak, Martin; Pacherova, Petra; Erbanova, Lucie; Veron, Alain J; Buzek, Frantisek; Jackova, Ivana; Paces, Tomas; Rukavickova, Lenka; Blaha, Vladimir; Holecek, Jan

2012-10-15

Slightly elevated concentrations of toxic species in waters sampled in the surroundings of a leaky landfill may be both a sign of an approaching contaminant plume, or a result of water-rock interaction. Isotopes can be instrumental in distinguishing between anthropogenic and geogenic species in groundwater. We studied sulfur and lead isotope ratios at an abandoned industrial-waste landfill, located in a densely populated part of Central Europe. Stable isotope variability in space and time was used to follow the movement of a groundwater plume, contaminated with toxic metals (Cd, Cr, Be), in fractured granitoids. Toxic metals had been mobilized from industrial waste by a strong pulse of sulfuric acid, also deposited in the landfill. Both tracers exhibited a wide range of values (δ(34)S between +2.6 and +18.9‰; (206)Pb/(207)Pb between 1.16 and 1.39), which facilitated identification of mixing end-members, and made it possible to assess the sources of the studied species. In situ fractionations did not hinder source apportionment. Influx of contaminated groundwater was observed neither in irrigation wells in a nearby village, nor at distances greater than 300 m from the landfill. Combination of stable isotope tracers can be used as part of an early-warning system in landscapes affected by landfills. Copyright © 2012 Elsevier B.V. All rights reserved.

Corneal toxicity induced by vesicating agents and effective treatment options

PubMed Central

Goswami, Dinesh G.; Tewari-Singh, Neera; Agarwal, Rajesh

2016-01-01

The vesicating agents sulfur mustard (SM) and lewisite (LEW) are potent chemical warfare agents that primarily cause damage to the ocular, skin, and respiratory systems. However, ocular tissue is the most sensitive organ, and vesicant exposure results in a biphasic injury response, including photophobia, corneal lesions, corneal edema, ulceration, and neovascularization, and may cause loss of vision. There are several reports on ocular injury from exposure to SM, which has been frequently used in warfare. However, there are very few reports on ocular injury by LEW, which indicate that injury symptoms appear instantly after exposure and faster than SM. In spite of extensive research efforts, effective therapies for vesicant-induced ocular injuries, mainly to the most affected corneal tissue, are not available. Hence, we have established primary human corneal epithelial (HCE) cells and rabbit corneal organ culture models with the SM analog nitrogen mustard (NM), which have helped to test the efficacy of potential therapeutic agents. These agents will then be further evaluated against in vivo SM- and LEW-induced corneal injury models, which will assist in the development of potential broad-spectrum therapies against vesicant-induced ocular injuries. PMID:27327041

Subchronic oral toxicity and metabolite profiling of the p53 stabilizing agent, CP-31398, in rats and dogs.

PubMed

Johnson, William D; Muzzio, Miguel; Detrisac, Carol J; Kapetanovic, Izet M; Kopelovich, Levy; McCormick, David L

2011-11-18

maximum tolerated dose (MTD) for subchronic oral administration of CP-31398 is 80mg/kg/day (480mg/m(2)/day) in rats and 20mg/kg/day (400mg/m(2)/day) in dogs. Although only modest and apparently reversible toxicities (microscopic changes in rats; reductions in body weight gain and alterations in red cell parameters in dogs) were seen in the low dose groups, no observed adverse effect levels (NOAELs) for CP-31398 could not be established for either species. The toxicity of CP-31398 suggests that this agent may not be suitable for use in cancer prevention. However, should in vivo antitumor efficacy be achievable at doses that do not induce limiting toxicity, CP-31398 may have utility as a cancer therapeutic. Modification of the primary sites of CP-31398 metabolism (N-demethylation of the alkyl side chain; hydroxylation and O-demethylation of the styryl benzene group) may result in the development of CP-31398 analogs with comparable pharmacologic activity and reduced toxicity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Subchronic oral toxicity and metabolite profiling of the p53 stabilizing agent, CP-31398, in rats and dogs

PubMed Central

Johnson, William D.; Muzzio, Miguel; Detrisac, Carol J.; Kapetanovic, Izet M.; Kopelovich, Levy; McCormick, David L.

2011-01-01

Maximum Tolerated Dose (MTD) for subchronic oral administration of CP-31398 is 80 mg/kg/day (480 mg/m2/day) in rats and 20 mg/kg/day (400 mg/m2/day) in dogs. Although only modest and apparently reversible toxicities (microscopic changes in rats; reductions in body weight gain and alterations in red cell parameters in dogs) were seen in the low dose groups, No Observed Adverse Effect Levels (NOAELs) for CP-31398 could not be established for either species. The toxicity of CP-31398 suggests that this agent may not be suitable for use in cancer prevention. However, should in vivo antitumor efficacy be achievable at doses that do not induce limiting toxicity, CP-31398 may have utility as a cancer therapeutic. Modification of the primary sites of CP-31398 metabolism (N-demethylation of the alkyl side chain; hydroxylation and O-demethylation of the styryl benzene group) may result in the development of CP-31398 analogs with comparable pharmacologic activity and reduced toxicity. PMID:21864638

An automated microphysiological assay for toxicity evaluation.

PubMed

Eggert, S; Alexander, F A; Wiest, J

2015-08-01

Screening a newly developed drug, food additive or cosmetic ingredient for toxicity is a critical preliminary step before it can move forward in the development pipeline. Due to the sometimes dire consequences when a harmful agent is overlooked, toxicologists work under strict guidelines to effectively catalogue and classify new chemical agents. Conventional assays involve long experimental hours and many manual steps that increase the probability of user error; errors that can potentially manifest as inaccurate toxicology results. Automated assays can overcome many potential mistakes that arise due to human error. In the presented work, we created and validated a novel, automated platform for a microphysiological assay that can examine cellular attributes with sensors measuring changes in cellular metabolic rate, oxygen consumption, and vitality mediated by exposure to a potentially toxic agent. The system was validated with low buffer culture medium with varied conductivities that caused changes in the measured impedance on integrated impedance electrodes.

Toxicity of a polymer-graphene oxide composite against bacterial planktonic cells, biofilms, and mammalian cells

NASA Astrophysics Data System (ADS)

Mejías Carpio, Isis E.; Santos, Catherine M.; Wei, Xin; Rodrigues, Debora F.

2012-07-01

It is critical to develop highly effective antimicrobial agents that are not harmful to humans and do not present adverse effects on the environment. Although antimicrobial studies of graphene-based nanomaterials are still quite limited, some researchers have paid particular attention to such nanocomposites as promising candidates for the next generation of antimicrobial agents. The polyvinyl-N-carbazole (PVK)-graphene oxide (GO) nanocomposite (PVK-GO), which contains only 3 wt% of GO well-dispersed in a 97 wt% PVK matrix, presents excellent antibacterial properties without significant cytotoxicity to mammalian cells. The high polymer content in this nanocomposite makes future large-scale material manufacturing possible in a high-yield process of adiabatic bulk polymerization. In this study, the toxicity of PVK-GO was assessed with planktonic microbial cells, biofilms, and NIH 3T3 fibroblast cells. The antibacterial effects were evaluated against two Gram-negative bacteria: Escherichia coli and Cupriavidus metallidurans; and two Gram-positive bacteria: Bacillus subtilis and Rhodococcus opacus. The results show that the PVK-GO nanocomposite presents higher antimicrobial effects than the pristine GO. The effectiveness of the PVK-GO in solution was demonstrated as the nanocomposite ``encapsulated'' the bacterial cells, which led to reduced microbial metabolic activity and cell death. The fact that the PVK-GO did not present significant cytotoxicity to fibroblast cells offers a great opportunity for potential applications in important biomedical and industrial fields.It is critical to develop highly effective antimicrobial agents that are not harmful to humans and do not present adverse effects on the environment. Although antimicrobial studies of graphene-based nanomaterials are still quite limited, some researchers have paid particular attention to such nanocomposites as promising candidates for the next generation of antimicrobial agents. The polyvinyl

Production of Lipopeptide Biosurfactant by a Marine Nesterenkonia sp. and Its Application in Food Industry

PubMed Central

Kiran, George S.; Priyadharsini, Sethu; Sajayan, Arya; Priyadharsini, Gopal B.; Poulose, Navya; Selvin, Joseph

2017-01-01

Biosurfactants are smart biomolecules which have wide spread application in medicines, processed foods, cosmetics as well as in bioremediation. In food industry, biosurfactants are used as emulsion stabilizing agents, antiadhesives, and antimicrobial/antibiofilm agents. Nowadays biosurfactant demands in industries has increased tremendously and therefore new bacterial strains are being explored for large scale production of biosurfactants. In this study, an actinobacterial strain MSA31 was isolated from a marine sponge Fasciospongia cavernosa which showed high activity in biosurfactant screening assays such as drop collapsing, oil displacement, lipase and emulsification. Lipopeptide produced by MSA31 was found to be thermostable which was evident in differential scanning calorimetry analysis. The spectral data obtained in the Fourier transform infrared spectroscopy showed the presence of aliphatic groups combined with peptide moiety which is a characteristic feature of lipopeptides. The stability index of lipopeptide MSA31 revealed “halo-alkali and thermal tolerant biosurfactant” which can be used in the food industry. Microtiter plate assay showed 125 μg/ml of lipopeptide was effective in reducing the biofilm formation activity of pathogenic multidrug resistant Staphylococcus aureus. The confocal laser scanning microscopic images provided further evidences that lipopeptide MSA31 was an effective antibiofilm agent. The antioxidant activity of lipopeptide MSA31 may be due to the presence of unsaturated fatty acid present in the molecule. The brine shrimp cytotoxicity assay showed lipopeptide MSA31 was non-toxic and can be used as food additives. Incorporation of lipopeptide MSA31 in muffin showed improved organoleptic qualities compared to positive and negative control. This study provides a valuable input for this lipopeptide to be used in food industry as an effective emulsifier, with good antioxidant activity and as a protective agent against S. aureus. PMID

Calcium dependence of eugenol tolerance and toxicity in Saccharomyces cerevisiae.

PubMed

Roberts, Stephen K; McAinsh, Martin; Cantopher, Hanna; Sandison, Sean

2014-01-01

Eugenol is a plant-derived phenolic compound which has recognised therapeutical potential as an antifungal agent. However little is known of either its fungicidal activity or the mechanisms employed by fungi to tolerate eugenol toxicity. A better exploitation of eugenol as a therapeutic agent will therefore depend on addressing this knowledge gap. Eugenol initiates increases in cytosolic Ca2+ in Saccharomyces cerevisiae which is partly dependent on the plasma membrane calcium channel, Cch1p. However, it is unclear whether a toxic cytosolic Ca2+elevation mediates the fungicidal activity of eugenol. In the present study, no significant difference in yeast survival was observed following transient eugenol treatment in the presence or absence of extracellular Ca2+. Furthermore, using yeast expressing apoaequorin to report cytosolic Ca2+ and a range of eugenol derivatives, antifungal activity did not appear to be coupled to Ca2+ influx or cytosolic Ca2+ elevation. Taken together, these results suggest that eugenol toxicity is not dependent on a toxic influx of Ca2+. In contrast, careful control of extracellular Ca2+ (using EGTA or BAPTA) revealed that tolerance of yeast to eugenol depended on Ca2+ influx via Cch1p. These findings expose significant differences between the antifungal activity of eugenol and that of azoles, amiodarone and carvacrol. This study highlights the potential to use eugenol in combination with other antifungal agents that exhibit differing modes of action as antifungal agents to combat drug resistant infections.

Toxicity assessment of individual ingredients of synthetic-based drilling muds (SBMs).

PubMed

Bakhtyar, Sajida; Gagnon, Marthe Monique

2012-09-01

Synthetic-based drilling muds (SBMs) offer excellent technical characteristics while providing improved environmental performance over other drilling muds. The low acute toxicity and high biodegradability of SBMs suggest their discharge at sea would cause minimal impacts on marine ecosystems, however, chronic toxicity testing has demonstrated adverse effects of SBMs on fish health. Sparse environmental monitoring data indicate effects of SBMs on bottom invertebrates. However, no environmental toxicity assessment has been performed on fish attracted to the cutting piles. SBM formulations are mostly composed of synthetic base oils, weighting agents, and drilling additives such as emulsifiers, fluid loss agents, wetting agents, and brine. The present study aimed to evaluate the impact of exposure to individual ingredients of SBMs on fish health. To do so, a suite of biomarkers [ethoxyresorufin-O-deethylase (EROD) activity, biliary metabolites, sorbitol dehydrogenase (SDH) activity, DNA damage, and heat shock protein] have been measured in pink snapper (Pagrus auratus) exposed for 21 days to individual ingredients of SBMs. The primary emulsifier (Emul S50) followed by the fluid loss agent (LSL 50) caused the strongest biochemical responses in fish. The synthetic base oil (Rheosyn) caused the least response in juvenile fish. The results suggest that the impact of Syndrill 80:20 on fish health might be reduced by replacement of the primary emulsifier Emul S50 with an alternative ingredient of less toxicity to aquatic biota. The research provides a basis for improving the environmental performance of SBMs by reducing the environmental risk of their discharge and providing environmental managers with information regarding the potential toxicity of individual ingredients.

A combined approach to investigate the toxicity of an industrial landfill's leachate: Chemical analyses, risk assessment and in vitro assays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baderna, D., E-mail: diego.baderna@marionegri.it; Maggioni, S.; Boriani, E.

2011-05-15

Solid wastes constitute an important and emerging problem. Landfills are still one of the most common ways to manage waste disposal. The risk assessment of pollutants from landfills is becoming a major environmental issue in Europe, due to the large number of sites and to the importance of groundwater protection. Furthermore, there is lack of knowledge for the environmental, ecotoxicological and toxicological characteristics of most contaminants contained into landfill leacheates. Understanding leachate composition and creating an integrated strategy for risk assessment are currently needed to correctly face the landfill issues and to make projections on the long-term impacts of amore » landfill, with particular attention to the estimation of possible adverse effects on human health and ecosystem. In the present study, we propose an integrated strategy to evaluate the toxicity of the leachate using chemical analyses, risk assessment guidelines and in vitro assays using the hepatoma HepG2 cells as a model. The approach was applied on a real case study: an industrial waste landfill in northern Italy for which data on the presence of leachate contaminants are available from the last 11 years. Results from our ecological risk models suggest important toxic effects on freshwater fish and small rodents, mainly due to ammonia and inorganic constituents. Our results from in vitro data show an inhibition of cell proliferation by leachate at low doses and cytotoxic effect at high doses after 48 h of exposure. - Research highlights: {yields} We study the toxicity of leachate from a non-hazardous industrial waste landfill. {yields} We perform chemical analyses, risk assessments and in vitro assays on HepG2 cells. {yields} Risk models suggest toxic effects due to ammonia and inorganic constituents. {yields} In vitro assays show that leachate inhibits cell proliferation at low doses. {yields} Leachate can induce cytotoxic effects on HepG2 cells at high doses.« less

Regulatory Forum Opinion Piece: Review of FDA Draft Guidance Testicular Toxicity-Evaluation during Drug Development Guidance for Industry.

PubMed

Hukkanen, Renee R; Halpern, Wendy G; Vidal, Justin D

2016-10-01

In July 2015, the U.S. Food and Drug Administration (FDA) posted a new draft guidance entitled "Testicular Toxicity: Evaluation during Drug Development Guidance for Industry," with a 90-day public comment period. As the nonclinical assessment of testicular toxicity often relies on the expert interpretation of pathology affecting the male reproductive tract, this draft guidance is considered directly relevant to the toxicologic pathology community. Therefore, a working group was formed through the Scientific and Regulatory Policy Committee of the Society of Toxicologic Pathologists (STPs) to provide a detailed review of the draft guidance. Specific comments on the guidance were submitted to the FDA by the STP. The draft guidance and all comments received are currently under review with the FDA. This commentary provides a summary of the components of the draft guidance and the comments submitted by the STP with acknowledgment of different perspectives reflected in comments from other respondents. © The Author(s) 2016.

Identification of water soluble and particle bound compounds causing sublethal toxic effects. A field study on sediments affected by a chlor-alkali industry.

PubMed

Bosch, Carme; Olivares, Alba; Faria, Melissa; Navas, Jose M; del Olmo, Iván; Grimalt, Joan O; Piña, Benjamín; Barata, Carlos

2009-08-13

A combination of cost effective sublethal Daphnia magna feeding tests, yeast- and cell culture-based bioassays and Toxicity Identification Evaluation (TIE) procedures was used to characterize toxic compounds within sediments collected in a river area under the influence of the effluents from a chlor-alkali industry (Ebro River, NE Spain). Tests were designed to measure and identify toxic compounds in the particulate and filtered water fractions of sediment elutriates. The combined use of bioassays responding to elutriates and dioxin-like compounds evidenced the existence of three major groups of hazardous contaminants in the most contaminated site: (A) metals such as cadmium and mercury bound to sediment fine particles that could be easily resuspended and moved downstream, (B) soluble compounds (presumably, lye) able to alkalinize water to toxic levels, and (C) organochlorine compounds with high dioxin-like activity. These results provided evidence that elutriate D. magna feeding responses can be used as surrogate assays for more tedious chronic whole sediment tests, and that the incorporation of such tests in sediment TIE procedures may improve the ability to identify the toxicity of particle-bound and water-soluble contaminants in sediments.

Human health risk assessment database, "the NHSRC toxicity value database": supporting the risk assessment process at US EPA's National Homeland Security Research Center.

PubMed

Moudgal, Chandrika J; Garrahan, Kevin; Brady-Roberts, Eletha; Gavrelis, Naida; Arbogast, Michelle; Dun, Sarah

2008-11-15

The toxicity value database of the United States Environmental Protection Agency's (EPA) National Homeland Security Research Center has been in development since 2004. The toxicity value database includes a compilation of agent property, toxicity, dose-response, and health effects data for 96 agents: 84 chemical and radiological agents and 12 biotoxins. The database is populated with multiple toxicity benchmark values and agent property information from secondary sources, with web links to the secondary sources, where available. A selected set of primary literature citations and associated dose-response data are also included. The toxicity value database offers a powerful means to quickly and efficiently gather pertinent toxicity and dose-response data for a number of agents that are of concern to the nation's security. This database, in conjunction with other tools, will play an important role in understanding human health risks, and will provide a means for risk assessors and managers to make quick and informed decisions on the potential health risks and determine appropriate responses (e.g., cleanup) to agent release. A final, stand alone MS ACESSS working version of the toxicity value database was completed in November, 2007.

Atmospheric PCDD/F concentration and source apportionment in typical rural, Agent Orange hotspots, and industrial areas in Vietnam.

PubMed

Ngo, Tuan Hung; Hien, To Thi; Thuan, Ngo Thi; Minh, Nguyen Hung; Chi, Kai Hsien

2017-09-01

Vietnam has a double burden of dioxin from both industrial sources and historical sources. To evaluate the concentration of PCDD/Fs in ambient air in different areas of Vietnam and their possible sources, atmospheric samples were collected from three areas namely Son La (rural area) and Da Nang (harbor - Agent Orange hotspot area), and Ho Chi Minh City (metropolitan - industrial city). Vapor and solid phases of PCDD/Fs were collected and analyzed following the TO-9A sampling method. Principal Component Analysis and Positive Matrix Factorization model were applied to characterize the possible source. The average concentrations of PCDD/Fs were found to be 21.3 ± 13 fg I-TEQ/m 3 in Son La (n = 32), 65.2 ± 34 fg I-TEQ/m 3 in Da Nang (n = 16) and 139 ± 84 fg I-TEQ/m 3 in Ho Chi Minh City (n = 8). The findings of this study targeted open burning (42%) and biomass burning (51%) as the major emission sources of PCDD/Fs in ambient air of Son La, Vietnam. Major possible sources of PCDD/Fs in Da Nang could be transportation activities (64%), however, the other factor (36%) was suspected to be contaminated with 2,3,7,8-TeCDD from Agent Orange. Most of PCDD/Fs emitted in Ho Chi Minh City related to industrial activities (93%). Copyright © 2017 Elsevier Ltd. All rights reserved.

Toxic emissions during co-combustion of biomass-waste wood-lignite blends in an industrial boiler.

PubMed

Samaras, P; Skodras, G; Sakellaropoulos, G P; Blumenstock, M; Schramm, K W; Kettrup, A

2001-01-01

The objectives of this work were to study the PCDD/F emissions during the co-combustion of waste wood/coal co-combustion in an industrial boiler and to determine the relation of the toxic emissions to the fuel properties. Co-combustion experiments were performed in a 13.8 MWthermal industrial moving grate combustor. The fuels which were examined in this study included Greek lignite, natural uncontaminated wood, power poles and medium density fibers (MDFs) which were by-products of the plant production process. Fuel blends were prepared by mixing single components in various concentrations. PCDD/F emissions were collected during experimental runs and were analyzed according to standard methods. Low PCDD/F emissions were obtained during the co-combustion tests, lower than the limit value of 0.1 ng TEQ/Nm3. The lowest values were observed during the combustion of fuel blends containing MDF, possibly due to the inhibitory action of some of the N-containing MDF ingredients, such as urea. No direct correlation was found between the PCDD/F and the copper emissions, while examination of the PCDD/F homologue patterns revealed the predominance of the lower chlorinated isomers over the higher ones.

Industrial pollution load assessment in Phnom Penh, Cambodia using an industrial pollution projection system.

PubMed

San, Vibol; Spoann, Vin; Schmidt, Johannes

2018-02-15

Approximately 56% out of the total 1302 Cambodian firms are operated in the Capital city of Cambodia. The necessary information on industrial pollution to set strategies, priorities and action plans on environmental protection issues is absent in Cambodia. In the absence of this data, effective environmental protection cannot be implemented. The objective of this study is to estimate industrial pollution load by employing the Industrial Pollution Projection System, a rapid environmental management tool for assessment of pollution load, to produce a scientific rational basis for preparing future policy direction to reduce industrial pollution in Phnom Penh city. Factory data between 1994 and 2014 obtained from the Ministry of Industry and Handicraft of Cambodia were used in our study. Due to the high number of employees, the total environmental load generated in Phnom Penh city was estimated to be 476,981Mg in 2014. Phnom Penh city generated 189,109Mg of VOC, 165,411Mg of toxic chemicals to air, 38,523Mg of toxic chemicals to land, and 28,968Mg of SO 2 in 2014. The results of the estimation show that the Textiles and Apparel sector was the highest generators of toxic chemicals into land and air, and toxic metals into land, air and water, while the Basic Metal sector was the greatest contributor of toxic chemicals to water. The Textiles and Apparel sector alone emitted 436,016Mg of total pollution load. The results indicate that the Dangkao and Meanchey districts were the greatest emitters of all pollutants in Phnom Penh. The results suggest that reduction in industrial pollution could be achieved by focusing on the most polluting sectors and areas. Adopting waste minimization strategies, which include cleaner production processes, will not only reduce the cost of controlling pollution, it will also make manufacturing more efficient thereby increasing profits while reducing pollution load in the long run. Copyright © 2017 Elsevier B.V. All rights reserved.

[Streptococcal toxic shock syndrome].

PubMed

Gvozdenović, Ljiljana; Pasternak, Janko; Milovanović, Stanislav; Ivanov, Dejan; Milić, Sasa

2010-01-01

Streptococcal toxic shock syndrome is now recognized as a toxin-mediated, multisystem illness. It is characterized by an early onset of shock with multiorgan failure and continues to be associated with high morbidity and mortality, caused by group A Streptococcus pyogenes. The symptoms for staphylococcal and streptococcal toxic shock syndrome are similar. Streptococcal toxic shock syndrome was not well described until 1993, when children who had suffered from varicella presented roughly 2-4 weeks later with a clinical syndrome highly suggestive of toxic shock syndrome. It is characterized by a sudden onset of fever, chills, vomiting, diarrhea, muscle aches and rash. It can rapidly progress to severe and intractable hypotension and multisystem dysfunction. Almost every organ system can he involved. Complications of streptococcal toxic shock syndrome may include kidney failure, liver failure (and even death. Crystalloids and inotropic agents are used to treat the hypovolemic shock aggressively, with close monitoring of the patient's mean arterial pressure and central venous pressure. An immediate and aggressive management of hypovolemic shock is essential in streptococcal toxic shock syndrome. Targeted antibiotics are indicated: penicillin or a beta-lactam antibiotic is used for treating group A streptococci, and clindamycin has emerged as a key portion of the standard treatment.

Gadolinium toxicity and treatment.

PubMed

Ramalho, Joana; Ramalho, Miguel; Jay, Michael; Burke, Lauren M; Semelka, Richard C

2016-12-01

Gadolinium based contrast agents (GBCAs) play an important role in the diagnostic evaluation of many patients. The safety of these agents has been once again questioned after gadolinium deposits were observed and measured in brain and bone of patients with normal renal function. This retention of gadolinium in the human body has been termed "gadolinium storage condition". The long-term and cumulative effects of retained gadolinium in the brain and elsewhere are not as yet understood. Recently, patients who report that they suffer from chronic symptoms secondary to gadolinium exposure and retention created gadolinium-toxicity on-line support groups. Their self-reported symptoms have recently been published. Bone and joint complaints, and skin changes were two of the most common complaints. This condition has been termed "gadolinium deposition disease". In this review we will address gadolinium toxicity disorders, from acute adverse reactions to GBCAs to gadolinium deposition disease, with special emphasis on the latter, as it is the most recently described and least known. Copyright © 2016 Elsevier Inc. All rights reserved.

The risk of recrystallization: changes to the toxicity and morphology of pyrimethamine.

PubMed

Perold, Zak; Caira, Mino R; Brits, Marius

2014-01-01

Pyrimethamine, an anti-malarial agent known to exhibit solid state polymorphism, may be purified by means of recrystallization. Recrystallization may alter the solid state chemistry of pharmaceuticals, which may impact the toxicity and/or manufacturability thereof. We evaluated the risks associated with the recrystallization of pyrimethamine. Pyrimethamine was recrystallized using several organic solvents. X-ray diffraction, thermal analysis, infra-red spectroscopy, microscopy, flowability -, solubility and dissolution testing as well as computational work were employed to evaluate the recrystallized products. A toxic solvatomorph of pyrimethamine (Pyr-MeOH) was found to be the product from methanol recrystallization. The elucidation of - and the elaboration on the unique characteristics of Pyr-MeOH provides the pharmaceutical industry with several means to identify Pyr-MeOH and to distinguish it from the pharmaceutically preferred anhydrous form (Pyr). Thermal methods of analysis found that the toxicity of Pyr-MeOH may be reversed by overcoming a desolvation activation energy of 148 kJ/mol. In addition it was found that recrystallization altered the morphology of Pyr. Angle of repose and tapped density determinations identified that the different morphologies of Pyr displayed differences in powder flow and compressibility behaviour and In Silico calculations were successful in rendering morphologies resembling that found experimentally. We present a solvatomorph of pyrimethamine and provide several characteristic means to identify this unwanted toxic form and quantified the energy required to overcome its toxicity. In addition we describe that Pyr may present in different morphologies and show how it may impact the manufacturability thereof.

Acute toxic nephropathies: clinical pathologic correlations.

PubMed

Muehrcke, R C; Volini, F I; Morris, A M; Moles, J B; Lawrence, A G

1976-01-01

Man's ever increasing exposure to numerous drugs and chemicals, which are the results of medical and industrial progress, produces a by-product of acute toxic nephropathies. These include acute toxic renal failure, drug-induced acute oliguric renal failure, acute hemorrhagic glomerulonephritis, nephrotic syndrome, tubular disturbances and potassium deficiency. In depth information is provided for the previously mentioned disorders.

Nasal manifestations in chromium industry workers.

PubMed

Aiyer, R G; Kumar, Gaurav

2003-04-01

People working in mines, plating factories, cement industries are mainly exposed to chrome substances, IIexavalent chromium has been implicated for its toxic effect on the nasal mucosa. Hereby we present a rare study of 28 patients who attended out patient department of Otorhinolaryngology at SSG Hospital, Baroda from a nearby chromium industry. This study aims to present various nasal manifestations of toxic effects of prolonged chromium exposure.

Toxicity of the pyrolysis products of spacecraft materials

NASA Technical Reports Server (NTRS)

Lawrence, W. H.

1974-01-01

A number of spacecraft construction materials are evaluated for the toxic effects of their thermodegradation products on rats. Pyrolysis toxicity testing of pyrolysate fumes establish carbon monoxide, carbon dioxide and hydrogen cyanide as the most common intoxicating agents. Generally, COHb levels of animals expiring in the test chamber suggest higher concentrations of CO are produced with larger samples of most materials.

Migration of nonylphenol from food-grade plastic is toxic to the coral reef fish species Pseudochromis fridmani.

PubMed

Hamlin, Heather J; Marciano, Kathleen; Downs, Craig A

2015-11-01

Nonylphenol (NP) is a non-ionic surfactant used extensively in industrial applications, personal care products, and many plastics. We exposed marine orchid dottybacks (Pseudochromis fridmani) for 48h to either glass, Teflon, or two bags labeled as FDA food-grade polyethylene (PE1 and PE2) from different manufacturers. The PE2 bags leached high levels of NP into the contact water, which were taken up by the fish, and decreased short and long-term survival. Concentrations of NP that leached from the bags were consistent with 96h LC50 values determined in this study, indicating NP is the likely toxic agent. Despite being similarly labeled, the NP concentrations that leached from the bags and the resultant toxicity to the fish varied dramatically between manufacturers. This study highlights that some plastics, labeled as food-safe, can be highly toxic to aquatic animals, and could pose a greater threat to humans than previously realized. This study also highlights risks for aquatic animals exposed to increasing quantities of plastic waste. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sequential application of chelating agents and innovative surfactants for the enhanced electroremediation of real sediments from toxic metals and PAHs.

PubMed

Hahladakis, John N; Lekkas, Nikolaos; Smponias, Andreas; Gidarakos, Evangelos

2014-06-01

This study focused on the sequential application of a chelating agent (citric acid) followed by a surfactant in the simultaneous electroremediation of real contaminated sediments from toxic metals and Polycyclic Aromatic Hydrocarbons (PAHs). Furthermore, the efficiency evaluation of two innovative non-ionic surfactants, commercially known as Poloxamer 407 and Nonidet P40, was investigated. The results indicated a removal efficacy of approximately 43% and 48% for the summation of PAHs (SUM PAHs), respectively for the aforementioned surfactants, much better than the one obtained by the use of Tween 80 (nearly 21%). Individual PAHs (e.g. fluorene) were removed in percentages that reached almost 84% and 92% in the respective electrokinetic experiments when these new surfactants were introduced. In addition, the combined-enhanced sequential electrokinetic treatment with citric acid improved dramatically the removal of Zn and As, compared to the unenhanced run, but did not favor the other toxic metals examined. Since no improvement in metal removal percentages occurred when Tween 80 was used, significant contribution to this matter should also be attributed to the solubilization capacity of these innovative, in electrokinetic remediation, non-ionic surfactants. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reliable Prescreening of Candidate NerveAgent Prophylaxes via 3D QSAR

DTIC Science & Technology

2005-12-31

recognize and predict prospective toxicity among covalent -binding AChE inhibitors of potential application to nerve agent prophylaxis and...is below since many authors do not follow the 200 word limit 14. SUBJECT TERMS nerve agents , acetylcholinesterase, prophylaxis, QSAR, virtual...Report: Reliable Prescreening of Candidate NerveAgent Prophylaxes via 3D QSAR Report Title ABSTRACT Organophosphorus (OP) nerve agents are among the

Virtual Embryo: Cell-Agent Based Modeling of Developmental Processes and Toxicities (CSS BOSC)

EPA Science Inventory

Spatial regulation of cellular dynamics is fundamental to morphological development. As such, chemical disruption of spatial dynamics is a determinant of developmental toxicity. Incorporating spatial dynamics into AOPs for developmental toxicity is desired but constrained by the ...

MONITORING THE AIR FOR TOXIC AND GENOTOXIC COMPOUNDS

EPA Science Inventory

A time-integrated sampling system interfaced with a toxicity-based assay is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethyl sulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor p...

Antibiotic prophylaxis for skin toxicity induced by antiepidermal growth factor receptor agents: a systematic review and meta-analysis.

PubMed

Petrelli, F; Borgonovo, K; Cabiddu, M; Coinu, A; Ghilardi, M; Lonati, V; Barni, S

2016-12-01

Topical and systemic prophylactic measures, which are administered before the development of epidermal growth factor receptor (EGFR)-related acneiform rash, are appropriate interventions to mitigate the intensity of skin toxicity. We have performed a systematic review and meta-analysis to evaluate whether prophylactic antibiotics may reduce the occurrence and severity of anti-EGFR drug-related skin rashes. A systematic review was performed by searching Medline, Scopus, Embase, CINAHL, LILACS, Web of Science and the Cochrane Library from inception until March 2016 for publications regarding the pre-emptive role of antibiotics for EGFR-induced skin rashes. Fixed- or random-effects meta-analyses, according to heterogeneity, were used to summarize odds ratios of skin toxicity with antibiotic use. Of the 827 citations found in the search, 13 studies comprising 1073 patients were included in the analysis. In 12 studies, patients in the prophylactic antibiotic arms had a lower risk of developing a skin rash (odds ratio 0·53, 95% confidence interval 0·39-0·72, P < 0·01) than patients without antibiotic prophylaxis. In particular, moderate-to-severe toxicities (grades 2-4) were reduced by nearly two-thirds (odds ratio 0·36, 95% confidence interval 0·22-0·60, P < 0·01) in 13 studies. This translated to a 26% absolute difference of high-grade skin rash compared with the control arms (from 50% to 24%). The results of this meta-analysis show that the risk of skin rash after treatment with anti-EGFR agents for solid tumours was significantly lower in patients taking prophylaxis with antibiotics than in those who were not. Therefore, taking pre-emptive tetracyclines for several weeks at the start of anti-EGFR treatment can significantly reduce the incidence and severity of cutaneous acneiform rash. © 2016 British Association of Dermatologists.

Miniaturized low-cost ion mobility spectrometer for fast detection of chemical warfare agents.

PubMed

Zimmermann, Stefan; Barth, Sebastian; Baether, Wolfgang K M; Ringer, Joachim

2008-09-01

Ion mobility spectrometry (IMS) is a well-known method for detecting hazardous compounds in air. Typical applications are the detection of chemical warfare agents, highly toxic industrial compounds, explosives, and drugs of abuse. Detection limits in the low part per billion range, fast response times, and simple instrumentation make this technique more and more popular. In particular, there is an increasing demand for miniaturized low-cost IMS for hand-held devices and air monitoring of public areas by sensor networks. In this paper, we present a miniaturized aspiration condenser type ion mobility spectrometer for fast detection of chemical warfare agents. The device is easy to manufacture and allows single substance identification down to low part per billion-level concentrations within seconds. The improved separation power results from ion focusing by means of geometric constraints and fluid dynamics. A simple pattern recognition algorithm is used for the identification of trained substances in air. The device was tested at the German Armed Forces Scientific Institute for Protection Technologies-NBC-Protection. Different chemical warfare agents, such as sarin, tabun, soman, US-VX, sulfur mustard, nitrogen mustard, and lewisite were tested. The results are presented here.

DISTRIBUTED STRUCTURE-SEARCHABLE TOXICITY ...

EPA Pesticide Factsheets

The ability to assess the potential genotoxicity, carcinogenicity, or other toxicity of pharmaceutical or industrial chemicals based on chemical structure information is a highly coveted and shared goal of varied academic, commercial, and government regulatory groups. These diverse interests often employ different approaches and have different criteria and use for toxicity assessments, but they share a need for unrestricted access to existing public toxicity data linked with chemical structure information. Currently, there exists no central repository of toxicity information, commercial or public, that adequately meets the data requirements for flexible analogue searching, SAR model development, or building of chemical relational databases (CRD). The Distributed Structure-Searchable Toxicity (DSSTox) Public Database Network is being proposed as a community-supported, web-based effort to address these shared needs of the SAR and toxicology communities. The DSSTox project has the following major elements: 1) to adopt and encourage the use of a common standard file format (SDF) for public toxicity databases that includes chemical structure, text and property information, and that can easily be imported into available CRD applications; 2) to implement a distributed source approach, managed by a DSSTox Central Website, that will enable decentralized, free public access to structure-toxicity data files, and that will effectively link knowledgeable toxicity data s

Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents.

PubMed

Albuquerque, Edson X; Pereira, Edna F R; Aracava, Yasco; Fawcett, William P; Oliveira, Maristela; Randall, William R; Hamilton, Tracey A; Kan, Robert K; Romano, James A; Adler, Michael

2006-08-29

The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer's disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning.

Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents

PubMed Central

Albuquerque, Edson X.; Pereira, Edna F. R.; Aracava, Yasco; Fawcett, William P.; Oliveira, Maristela; Randall, William R.; Hamilton, Tracey A.; Kan, Robert K.; Romano, James A.; Adler, Michael

2006-01-01

The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer’s disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning. PMID:16914529

Toxic gases used in the microelectronics industry.

PubMed

Wald, P H; Becker, C E

1986-01-01

Toxic gases are among the most dangerous materials used in manufacturing semiconductors and related devices. The storage, handling, and disposal of these gases pose a major hazard to workers and to communities located near high-technology companies. It must be anticipated that accidents, acts of terrorism, and natural calamities will result in exposure. Flammability, corrosiveness, and concentration must be considered, as well as the immediate danger to life and known human health effects of the gases used.

Toxicity evaluation and prediction of toxic chemicals on activated sludge system.

PubMed

Cai, Bijing; Xie, Li; Yang, Dianhai; Arcangeli, Jean-Pierre

2010-05-15

The gaps of data for evaluating toxicity of new or overloaded organic chemicals on activated sludge system resulted in the requirements for methodology of toxicity estimation. In this study, 24 aromatic chemicals typically existed in the industrial wastewater were selected and classified into three groups of benzenes, phenols and anilines. Their toxicity on activated sludge was then investigated. Two indexes of IC(50-M) and IC(50-S) were determined respectively from the respiration rates of activated sludge with different toxicant concentration at mid-term (24h) and short-term (30min) time intervals. Experimental results showed that the group of benzenes was the most toxic, followed by the groups of phenols and anilines. The values of IC(50-M) of the tested chemicals were higher than those of IC(50-S). In addition, quantitative structure-activity relationships (QSARs) models developed from IC(50-M) were more stable and accurate than those of IC(50-S). The multiple linear models based on molecular descriptors and K(ow) presented better reliability than single linear models based on K(ow). Among these molecular descriptors, E(lumo) was the most important impact factor for evaluation of mid-term toxicity. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Exposure to Crystal Violet, Its Toxic, Genotoxic and Carcinogenic Effects on Environment and Its Degradation and Detoxification for Environmental Safety.

PubMed

Mani, Sujata; Bharagava, Ram Naresh

2016-01-01

Crystal Violet (CV), a triphenylmethane dye, has been extensively used in human and veterinary medicine as a biological stain, as a textile dye in textile processing industries and also used to provide a deep violet color to paints and printing ink. CV is also used as a mutagenic and bacteriostatic agent in medical solutions and antimicrobial agent to prevent the fungal growth in poultry feed. Inspite of its many uses, CV has been reported as a recalcitrant dye molecule that persists in environment for a long period and pose toxic effects in environment. It acts as a mitotic poison, potent carcinogen and a potent clastogene promoting tumor growth in some species of fish. Thus, CV is regarded as a biohazard substance. Although, there are several physico-chemical methods such as adsorption, coagulation and ion-pair extraction reported for the removal of CV, but these methods are insufficient for the complete removal of CV from industrial wastewaters and also produce large quantity of sludge containing secondary pollutants. However, biological methods are regarded as cost-effective and eco-friendly for the treatment of industrial wastewaters, but these methods also have certain limitations. Therefore, there is an urgent need to develop such eco-friendly and cost-effective biological treatment methods, which can effectively remove the dye from industrial wastewaters for the safety of environment, as well as human and animal health.

Impact of toxic chemicals on local wastewater treatment plant and the environment

NASA Astrophysics Data System (ADS)

Bennett, Gary F.

1989-05-01

Because toxic chemicals being discharged to sewers were simultaneously interfering with wastewater treatment processes of municipal, biological treatment plants and were passing through these plants to negatively impact the bodies of water to which these plants were discharging, the U.S. Environmental Protection Agency issued regulations governing industrial discharges to municipal sewers. These “Pretreatment Regulations” limit industrial discharges to municipal sewers of heavy metals, oil and grease, acids and bases, and toxic organic chemicals. This paper discusses the evolution of these regulations, the basis for them, the types of regulations (categorical and local), and the rationale for their promulgation based on the impacts of toxics chemicals on the treatment plant and receiving system. Finally, the expected results of these regulations in reducing industrial discharges of toxic chemicals is discussed.

Anaerobic Toxicity of Cationic Silver Nanoparticles

EPA Science Inventory

The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag⁺ under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged p...

In Vitro Methods To Measure Toxicity Of Chemicals

DTIC Science & Technology

2004-12-01

industrial compounds for toxicity will require high-throughput in vitro assays with which to select candidate compounds for more intensive animal...for estimating the starting dose for the rat oral acute toxicity test, thus reducing and refining the use of animals in the toxicological

Toxicity evaluations of various carbon nanomaterials.

PubMed

Uo, Motohiro; Akasaka, Tsukasa; Watari, Fumio; Sato, Yoshinori; Tohji, Kazuyuki

2011-01-01

After the discovery of fullerene and carbon nanotubes, various carbon nanomaterials were discovered or synthesized. The carbon nanomaterials have remarkable properties, different from bulk materials with the same chemical composition, and are therefore useful for industrial applications. However, the toxicity of nanomaterials may also differ from that of the bulk materials; this difference poses a concern. The physical similarity of nanomaterials to asbestos has led to evaluations for toxicity by many researchers using various methods. In this review, we compile and compare the toxicity evaluations of each carbon nanomaterial.

Gancidin W, a potential low-toxicity antimalarial agent isolated from an endophytic Streptomyces SUK10

PubMed Central

Zin, Noraziah Mohamad; Baba, Mohd Shukri; Zainal-Abidin, Abu Hassan; Latip, Jalifah; Mazlan, Noor Wini; Edrada-Ebel, RuAngelie

2017-01-01

Endophytic Streptomyces strains are potential sources for novel bioactive molecules. In this study, the diketopiperazine gancidin W (GW) was isolated from the endophytic actinobacterial genus Streptomyces, SUK10, obtained from the bark of Shorea ovalis tree, and it was tested in vivo against Plasmodium berghei PZZ1/100. GW exhibited an inhibition rate of nearly 80% at 6.25 and 3.125 μg kg−1 body weight on day four using the 4-day suppression test method on male ICR strain mice. Comparing GW at both concentrations with quinine hydrochloride and normal saline as positive and negative controls, respectively, 50% of the mice treated with 3.125 μg kg−1 body weight managed to survive for more than 11 months after infection, which almost reached the life span of normal mice. Biochemical tests of selected enzymes and proteins in blood samples of mice treated with GW were also within normal levels; in addition, no abnormalities or injuries were found on internal vital organs. These findings indicated that this isolated bioactive compound from Streptomyces SUK10 exhibits very low toxicity and is a good candidate for potential use as an antimalarial agent in an animal model. PMID:28223778

Clinical aspects of percutaneous poisoning by the chemical warfare agent VX: effects of application site and decontamination.

PubMed

Hamilton, Murray G; Hill, Ira; Conley, John; Sawyer, Thomas W; Caneva, Duane C; Lundy, Paul M

2004-11-01

O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) is an extremely toxic organophosphate nerve agent that has been weaponized and stockpiled in a number of different countries, and it has been used in recent terrorist events. It differs from other well-known organophosphate nerve agents in that its primary use is as a contact poison rather than as an inhalation hazard. For this reason, we examined the effects of application site and skin decontamination on VX toxicity in anesthetized domestic swine after topical application. VX applied to the surface of the ear rapidly resulted in signs of toxicity consistent with the development of cholinergic crisis, including apnea and death. VX on the epigastrium resulted in a marked delayed development of toxic signs, reduced toxicity, and reduction in the rate of cholinesterase depression compared with animals exposed on the ear. Skin decontamination (15 minutes post-VX on the ear) arrested the development of clinical signs and prevented further cholinesterase inhibition and death. These results confirm earlier work that demonstrates the importance of exposure site on the resultant toxicity of this agent and they also show that decontamination postexposure has the potential to be an integral and extremely important component of medical countermeasures against this agent.

Agent-based services for B2B electronic commerce

NASA Astrophysics Data System (ADS)

Fong, Elizabeth; Ivezic, Nenad; Rhodes, Tom; Peng, Yun

2000-12-01

The potential of agent-based systems has not been realized yet, in part, because of the lack of understanding of how the agent technology supports industrial needs and emerging standards. The area of business-to-business electronic commerce (b2b e-commerce) is one of the most rapidly developing sectors of industry with huge impact on manufacturing practices. In this paper, we investigate the current state of agent technology and the feasibility of applying agent-based computing to b2b e-commerce in the circuit board manufacturing sector. We identify critical tasks and opportunities in the b2b e-commerce area where agent-based services can best be deployed. We describe an implemented agent-based prototype system to facilitate the bidding process for printed circuit board manufacturing and assembly. These activities are taking place within the Internet Commerce for Manufacturing (ICM) project, the NIST- sponsored project working with industry to create an environment where small manufacturers of mechanical and electronic components may participate competitively in virtual enterprises that manufacture printed circuit assemblies.

Prospects and challenges of developing new agents for tough Gram-negatives.

PubMed

Meyer, Annette L

2005-10-01

Historically, the medical profession has been successful in treating most bacterial infections in humans with synthetic second- and third-generation antibiotics. Recently, the prospects for continued success have dimmed with the increase in multidrug-resistant stains of bacteria. Infections caused by the Gram-negative bacteria Pseudomonas aeruginosa and Acinetobacter spp. in particular have increased in frequency and severity, and become progressively more difficult to treat. Contributors to disease severity include chronic infections due to mutator strains, persister cells and biofilms. The worst-case scenario of infections susceptible only to toxic polymixins is now a reality. The need to address the treatment of multidrug-resistant pathogens with innovative combination approaches and/or novel antibacterial agents is occurring in the context of reduced investment in antimicrobial drug discovery by the pharmaceutical industry.

[Exposure to biological agents used in Polish enterprises: analysis of data derived from the National Register of Biological Agent].

PubMed

Kozajda, Anna; Szadkowska-Stańczyk, Irena

2011-01-01

The National Register of Biological Agents at Work and the National Information Centre for Biological Agents Present at Workplaces were established in the Nofer Institute of Occupational Medicine in 2005. The National Information Centre carries out consultation and education activities concerning occupational exposure and risk assessment, development and implementation of preventive programs and accurate registration of reliable information about the use of biological agents. Educational materials on biological exposure are published on the website. The National Register of Biological Agents (database) collects and periodically analyzes the information obtained from employers about the use of biological agents for research, diagnostic or industrial purposes. As of 10 December 2010 there were 240 notifications from companies, which use biological agents for the following purposes: research--69, industrial--30 and diagnostic--321. Near 75% of all notifications were obtained from different diagnostic laboratories (public and private). In total, 3226 workers, including 2967 (92%) women and 256 (8%) men were exposed to biological agents. In general, occupational exposure to 209 biological agents (186 of risk group 2 and 23 of risk group 3, of which 16 are additionally marked by 3**) were registered in the data base.

Acute Toxicity and Environmental Risks of Five Veterinary Pharmaceuticals for Aquatic Macroinvertebrates.

PubMed

Bundschuh, Mirco; Hahn, Torsten; Ehrlich, Bert; Höltge, Sibylla; Kreuzig, Robert; Schulz, Ralf

2016-02-01

Due to the high use of antibiotics and antiparasitics for the treatment of livestock, there is concern about the potential impacts of the release of these compounds into freshwater ecosystems. In this context, the present study quantified the acute toxicity of two antibiotics (sulfadiazine and sulfadimidine), and three antiparasitic agents (flubendazole, fenbendazole, ivermectin) for nine freshwater invertebrate species. These experiments revealed a low degree of toxicity for the sulfonamide antibiotics, with limited implications in the survival of all test species at the highest test concentrations (50 and 100 mg/L). In contrast, all three antiparasitic agents indicated on the basis of their acute toxicity risks for the aquatic environment. Moreover, chronic toxicity data from the literature for antiparasitics, including effects on reproduction in daphnids, support the concern about the integrity of aquatic ecosystems posed by releases of these compounds. Thus, these pharmaceuticals warrant further careful consideration by environmental risk managers.

Chemotherapy induced toxicity is highly heritable in Drosophila melanogaster

PubMed Central

Kislukhin, Galina; Murphy, Maura L.; Jafari, Mahtab; Long, Anthony D.

2012-01-01

Objectives Identifying the genes responsible for chemotherapy toxicity in Drosophila melanogaster may allow for the identification of human orthologs that similarly mediate toxicity in humans. In order to develop Drosophila melanogaster as a model of dissecting chemotoxicity, we first need to develop standardized high throughput toxicity assays and prove that inter-individual variation in toxicity as measured by such assays is highly heritable. Methods We developed a method for the oral delivery of commonly used chemotherapy drugs to Drosophila. Post-treatment female fecundity displayed a dose dependent response to varying levels of the chemotherapy drug delivered. We fixed the dose for each drug at a level that resulted in a 50% reduction in fecundity and used a paternal half-sibling heritability design to calculate the heritability attributable to chemotherapy toxicity assayed via a decrease in female fecundity. Chemotherapy agents tested were carboplatin, floxuridine, gemcitabine hydrochloride, methotrexate, mitomycin C, and topotecan hydrochloride. Results We found that six currently widely prescribed chemotherapeutic agents lowered fecundity in D. melanogaster in both a dose dependent and highly heritable manner. The following heritability estimates were found: carboplatin – 0.72, floxuridine – 0.52, gemcitabine hydrochloride – 0.72, methotrexate – 0.99, mitomycin C – 0.64, and topotecan hydrochloride – 0.63. Conclusions The high heritability estimates observed in this study, irrespective of the particular class of drug examined, suggest that human toxicity may also have a sizable genetic component. PMID:22336958

Radioprotective agents in medicine.

PubMed

Duraković, A

1993-12-01

The diminished probability of strategic nuclear confrontation alleviates some of the global concerns about large numbers of radiation casualties in the event of a nuclear war. As a result of the protection of the environment, the management of smaller numbers of radiation casualties assumes a more predictable and more specific role confined to accidents in nuclear energy projects, industry, technology and science. Recent experience of the consequences of accidents in nuclear power plants, in the field of radiotherapy and in the disposal of radioactive waste and spent fuel, present the medical and scientific communities with formidable problems if such events are to lead to minimal adverse effects on the biosphere. Whereas it is not possible to predict a nuclear or radiation accident, radioprotection is hardly an issue of health science alone, but rather an issue of the strictest quality assurance in all aspects of the utilization of nuclear energy and ionizing radiation. Thus, the medical community concerned with radioprotection will have to confine its emphasis on the management of radiation-induced alterations of the human organism from acute radiation syndromes to the stochastic concepts of chronic alterations of radiosensitive organic systems. Current multidisciplinary research in the field of radioprotection involves all aspects of basic and clinical research ranging from the subatomic mechanisms of free radical formation, macromolecular and intracellular radiation-induced alterations, biochemical and physiological homeostatic mechanisms and organ level manifestations to the clinical management of radiation casualties in a controlled hospital environment. Radioprotective agents, although widely studied in the past four decades and including several thousand agents, have not reached the level of providing the field of medicine with an agent that conforms to all criteria of an optimal radioprotectant, including effectiveness, toxicity, availability, specificity

Effects of the calcium channel blocker verapamil and sulphydryl reducing agent dithiothreitol on atractyloside toxicity in precision-cut rat renal cortical and liver slices.

PubMed

Obatomi, D K; Blackburn, R O; Bach, P H

2001-10-01

The effects of dithiothreitol (DTT), a sulfhydryl-containing agent and verapamil (VRP), a calcium channel blocker as possible cytoprotectants against the atractyloside-induced toxicity were characterized in rat kidney and liver slices in vitro using multiple markers of toxicity. Precision-cut slices (200 microM thick) were either incubated with atractyloside (2 mM) or initially preincubated with either DTT (5 mM) or VRP (100 microM) for 30 min followed by exposure to atractyloside (2 mM) for 3 h at 37 degrees C on a rocker platform rotated at approximately 3 rpm. All of the toxicity parameters were sensitive to exposure to atractyloside, but treatment with DTT or VRP alone did not provide any indication of damage to the tissues. Preincubation of slices containing either DTT or VRP for 30 min provided total protection against atractyloside-induced increase in LDH leakage in both kidney and liver slices. Increased induction of lipid peroxidation by atractyloside in liver slices was completely abolished by DTT and VRP. Both DTT and VRP provided partial protection against atractyloside-induced inhibition of gluconeogenesis in both kidney and liver slices. Atractyloside-induced ATP depletion in both kidney and liver slices was partially abolished by VRP but not DTT. The significant depletion of GSH in the kidney slices by atractyloside was completely reversed by DTT only, while VRP alone reversed the same process in liver slices. Decreased MTT reductive capacity and significant increase in ALT leakage caused by atractyloside in liver slices was partially reversed. Complete protection was achieved with both DTT and VRP against atractyloside-induced inhibition of PAH uptake in kidney slices. These findings suggest that both DTT and VRP exert cytoprotective effects in atractyloside-induced biochemical perturbation, effects that differ in liver and kidney. The effect of these agents on atractyloside has provided us with a further understanding of the molecular mechanism of

Toxicity of vesicant agents scheduled for destruction by the Chemical Stockpile Disposal Program.

PubMed Central

Watson, A P; Griffin, G D

1992-01-01

The vesicant agents of the unitary chemical munitions stockpile include various formulations of sulfur mustard [bis-(2-chloroethyl) sulfide; agents H, HD, and HT] and small quantities of the organic arsenical Lewisite [dichloro(2-chlorovinyl) arsine; agent L]. These agents can be dispersed in liquid, aerosol, or vapor form and are capable of producing severe chemical burns upon direct contact with tissue. Moist tissues such as the eyes, respiratory tract, and axillary areas are particularly affected. Available data summarizing acute dose response in humans and laboratory animals are summarized. Vesicant agents are also capable of generating delayed effects such as chronic bronchitis, carcinogenesis, or keratitis/keratopathy of the eye under appropriate conditions of exposure and dose. These effects may not become manifest until years following exposure. Risk analysis derived from carcinogenesis data indicates that sulfur mustard possesses a carcinogenic potency similar to that of benzo[a]pyrene. Because mustard agents are alkylating compounds, they destroy individual cells by reaction with cellular proteins, enzymes, RNA, and DNA. Once begun, tissue reaction is irreversible. Mustard agents are mutagenic; data for cellular and laboratory animal assays are presented. Reproductive effects have not been demonstrated in the offspring of laboratory rats. Acute Lewisite exposure has been implicated in cases of Bowen's disease, an intraepidermal squamous cell carcinoma. Lewisite is not known to generate reproductive or teratogenic effects. PMID:1486858

VX toxicity in the Göttingen minipig.

PubMed

Langston, Jeffrey L; Myers, Todd M

2016-12-15

The present experiments determined the intramuscular LD 50 of VX in male Göttingen minipigs at two stages of development. In pubertal animals (115 days old), the LD 50 of VX was indeterminate, but approximated 33.3μg/kg. However, in sexually mature animals (152 days old), the LD 50 was estimated to be only 17.4μg/kg. Signs of nerve agent toxicity in the Göttingen minipig were similar to those described for other species, with some notable exceptions (such as urticaria and ejaculation). Latencies to the onset of sustained convulsions were inversely related to the administered dose of VX in both ages of minipigs. Additionally, actigraphy was used to quantify the presence of tremor and convulsions and, in some cases, was useful for precisely estimating time of death. The main finding indicates that in minipigs, as in other species, even relatively small differences in age can substantially alter the toxicity of nerve agents. Additionally, actigraphy can serve as a non-invasive method of characterizing the tremors and convulsions that often accompany nerve agent intoxication. Published by Elsevier Ireland Ltd.

Source identification, environmental risk assessment and human health risks associated with toxic elements present in a coastal industrial environment, India.

PubMed

Satapathy, Shreemayee; Panda, C R

2018-03-26

This study investigated the source and contamination levels of toxic elements (Cd, Cr, As, Pb, Ni and Hg) present in a coastal environment, Paradip-an industrial hub of the east coast of India. The ecological risk assessment indices and human exposure models were used to evaluate the pollution status. Enrichment factor indicated that all the metal(loid)s found in the sediment are mostly derived from the anthropogenic source. According to the sediment quality quotient, 8.33% of sediments have crossed the ERM limit for Ni that can be fatal to biota. Meanwhile, 66.66, 41.66 and 8.33% of sediments have exceeded PEL range for Cr, Ni and As, respectively, that can register frequent lethal toxicity to benthic biota. As had the highest potential ecological harm coefficient (Er f  > 80), and Hg had moderate ecological harm coefficient (40 < Er f  < 80). Summarily, the sediment quality of this site is moderate to heavily toxic to benthic organisms. The concentration of toxic metals in seawater was below the permissible limit (CCC and CMC) set by USEPA indicating that water is relatively safer for free floating aquatic biota. The health risk index of toxic metal (loid)s present in soils of the residential sites has confirmed that there is a severe non-carcinogenic threat for children (HI child > 1) and a borderline carcinogenic risk for both adult and children. THQ Cr possesses highest non-carcinogenic threat, which contributed approximately 50% to HI followed by THQ As . The contribution of carcinogenic risk of chromium (CR Cr ) to TCR is approximately 60%. Cr is the significant contaminant of this site that has highest health effects. Highest exposure risks were associated with ingestion pathway accounting for about 85% of the total for most of the elements.

Warfarin Toxicity and Individual Variability—Clinical Case

PubMed Central

Piatkov, Irina; Rochester, Colin; Jones, Trudi; Boyages, Steven

2010-01-01

Warfarin is a widely used anticoagulant in the treatment and prevention of thrombosis, in the treatment for chronic atrial fibrillation, mechanical valves, pulmonary embolism, and dilated cardiomyopathy. It is tasteless and colorless, was used as a poison, and is still marketed as a pesticide against rats and mice. Several long-acting warfarin derivatives—superwarfarin anticoagulants—such as brodifacoum, diphenadione, chlorophacinone, bromadiolone, are used as pesticides and can produce profound and prolonged anticoagulation. Several factors increase the risk of warfarin toxicity. However, polymorphisms in cytochrome P450 genes and drug interactions account for most of the risk for toxicity complications. Each person is unique in their degree of susceptibility to toxic agents. The toxicity interpretation and the health risk of most toxic substances are a subject of uncertainty. Genetically determined low metabolic capacity in an individual can dramatically alter the toxin and metabolite levels from those normally expected, which is crucial for drugs with a narrow therapeutic index, like warfarin. Personalized approaches in interpretation have the potential to remove some of the scientific uncertainties in toxicity cases. PMID:22069565

The acute toxicity of local anesthetics.

PubMed

Mather, Laurence E

2010-11-01

Systemic toxicity, usually from overdose or intravascular dose, is feared because it mainly affects the heart and brain, and may be acutely life-threatening. Pharmacological studies of local anesthetic toxicity have largely been reviewed primarily relating to the evaluation of ropivacaine and levobupivacaine during the past decade. This review/opinion focuses more on the principles and concepts underlying the main models used, from chemical pharmacological and pharmacokinetic perspectives. Research models required to produce pivotal toxicity data are discussed. The potencies for neural blockade and systemic toxicity are associated across virtually all models, with some deviations through molecular stereochemistry. These models show that all local anesthetics can produce direct cardiovascular system toxicity and CNS excitotoxicity that may further affect the cardiovascular system response. Whereas the longer-acting local anesthetics are more likely to cause cardiac death by malignant arrhythmias, the shorter-acting agents are more likely to cause cardiac contraction failure. In most models, equi-anesthetic doses of ropivacaine and levobupivacaine are less likely to produce serious toxicity than bupivacaine. Of the various models, this reviewer favors a whole-body large animal preparation because of the comprehensive data collection possible. The conscious sheep preparation has contributed more than any other, and may be regarded as the de facto 'standard' experimental model for concurrent study of local anesthetic toxicity ± pharmacokinetics, using experimental designs that can reproduce the toxicity seen in clinical accidents.

77 FR 69548 - Proposed Information Collection (Agent Orange Registry Code Sheet); Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-19

... of any increased health risks resulting from exposure to dioxin or other toxic agents. VA may also... 1968 or 1969, and/or any U.S. veteran who may have been exposed to dioxin, or other toxic substance in...

78 FR 77471 - Prospective Grant of Exclusive License for: Convection Enhanced Delivery of a Therapeutic Agent...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-23

...-toxic macromolecular MRI contrast agents such as chelated Gd(III). These macromolecular imaging agents... Exclusive License for: Convection Enhanced Delivery of a Therapeutic Agent With a Surrogate Tracer for... Enhanced Delivery of Therapeutic Agents'', U.S. Provisional Patent Application 60/413,673 (filed September...

Genotoxicity and toxicity assay of water sampled from a radium production industry storage cell territory by means of Allium-test.

PubMed

Evseeva, Tatiana I; Geras'kin, Stanislav A; Shuktomova, Ida I

2003-01-01

Water from natural reservoirs located near the radium production industry storage cell were analyzed using the anaphase-telophase chromosome aberration assay that was carried out on Allium schoenoprasum L. meristematic root tip cells. (262)Ra, (228)U, (232)Th, (210)Pb and (210)Po concentrations in all samples were found not to exceed the radioactivity concentration guides. The concentrations of 10 heavy metal ions were measured in water samples, but only Zn and Mn levels exceeded the maximum permissible concentration for the natural reservoirs. All water samples caused a significant increase of the chromosome aberration frequency as compared to control. The chromosome aberration spectrum analysis shows that the genotoxic effect was a result of chemical toxicity mainly. Two samples from the brook springhead were found to be toxic. The regression analysis results show that the mitotic index increased in parallel to Zn ion levels, and decreased with higher (238)U concentrations. The water samples genotoxicity positively correlated with the Zn concentration. The present work demonstrates that in order to achieve pollutant screening, it is not sufficient to determine the pollutants concentration only. Adequate conclusions on the risk due to environment contamination need to be based on the additional simultaneous use of toxicity and genotoxicity tests. When bioassays indicate some genotoxic and toxic effects, the determination of the chemical composition of the samples is then required. A combination of these two methods allows the identification of the elements that require constant biological monitoring. In the study reported here, those elements are Zn and (238)U.

[The development of neurotoxic agents as chemical weapons during the National Socialist period in Germany].

PubMed

López-Muñoz, F; Alamo, C; Guerra, J A; García-García, P

The discovery and development of the so-called 'nerve agents' (neurotoxic substances to be used as weapons) took place in the Third Reich, largely thanks to the vast amount of progress being made in pharmacology in Germany at that time, both in academic and industrial terms. Furthermore, successive National Socialist governments set up a collaborative network made up of the academia, the chemical industry and military chiefs that also favoured this line of research. The first neurotoxic substance to be incorporated into the category of 'chemical warfare agent' did so almost wholly by chance. As part of the work being carried out on organophosphate-type pesticides and insecticides, Gerald Schrader, a chemist at the I.G. Farben company, synthesised tabun (ethyl N,N-dimethylphosphoramidocyanidate) and an incident involving accidental contamination of laboratory staff with this substance highlighted its potential toxicity. The same group of researchers later synthesised another substance with the same properties, sarin (isopropyl methylphosphonofluoridate). Both agents were studied for use as chemical weapons by Wolfgang Wirth. At the same time, a group led by Richard Kuhn, who won the Nobel Prize in Chemistry in 1938, synthesised pinacolyl methylphosphonofluoridate, otherwise known as soman. Pharmacological studies confirmed that the neurotoxic mechanism of action of these substances was the irreversible inhibition of the enzyme acetylcholinesterase, which is responsible for metabolising acetylcholine. Results also showed that an excess of this neurotransmitter led to a continuous over-stimulation of the cholinergic (nicotinic and muscarinic) receptors, which is what triggers the appearance of the wide range of symptoms of poisoning and their swift fatal effect.

Lethal and sublethal toxicity of the industrial chemical epichlorohydrin on Rhinella arenarum (Anura, Bufonidae) embryos and larvae.

PubMed

Hutler Wolkowicz, Ianina R; Aronzon, Carolina M; Pérez Coll, Cristina S

2013-12-15

Lethal and sublethal toxicity of the major chemical used in epoxide compounds, epichlorohydrin (ECH) was evaluated on the early life cycle of the common South American toad, Rhinella arenarum (Anura, Bufonidae). The stages evaluated were (according to Del Conte and Sirlin): early blastula (S.3-S.4), gastrula (S.10-S.12), rotation (S.15), tail bud (S.17), muscular response (S.18), gill circulation (S.20), open mouth (S.21), opercular folds (S.23) and complete operculum (S.25). The LC50 and EC50 values for lethal and sublethal effects were calculated. The early blastula was the most sensitive stage to ECH both for continuously and pulse-exposures (LC50-24h=50.9 mg L(-1)), while S.20 was the most resistant (LC50-24h=104.9 mg L(-1)). Among sublethal effects, early blastula was also the most sensitive stage (LOEC-48 h=20 mg L(-1)) and it has a Teratogenic Index of 2.5, which indicates the teratogenic potential of the substance. The main abnormalities were persistent yolk plugs, cell dissociation, tumors, hydropsy, oral malformations, axial/tail flexures, delayed development and reduced body size. ECH also caused neurotoxicity including scarce response to stimuli, reduction in the food intake, general weakness, spasms and shortening, erratic or circular swimming. Industrial contamination is considered an important factor on the decline of amphibian populations. Considering the available information about ECH's toxicity and its potential hazard to the environment, this work shows the first results of its developmental toxicity on a native amphibian species, Rhinella arenarum. Copyright © 2013 Elsevier B.V. All rights reserved.

Screening of Compounds Toxicity against Human Monocytic cell line-THP-1 by Flow Cytometry

PubMed Central

Pick, Neora; Cameron, Scott; Arad, Dorit

2004-01-01

The worldwide rapid increase in bacterial resistance to numerous antibiotics requires on-going development of new drugs to enter the market. As the development of new antibiotics is lengthy and costly, early monitoring of compound's toxicity is essential in the development of novel agents. Our interest is in a rapid, simple, high throughput screening method to assess cytotoxicity induced by potential agents. Some intracellular pathogens, such as Mycobacterium tuberculosis primary site of infection is human alveolar macrophages. Thus, evaluation of candidate drugs for macrophage toxicity is crucial. Protocols for high throughput drug toxicity screening of macrophages using flow cytometry are lacking in the literature. For this application we modified a preexisting technique, propidium iodide (PI) exclusion staining and utilized it for rapid toxicity tests. Samples were prepared in 96 well plates and analyzed by flow cytometry, which allowed for rapid, inexpensive and precise assessment of compound's toxicity associated with cell death. PMID:15472722

Nonrenal toxicities of acetaminophen, aspirin, and nonsteroidal anti-inflammatory agents.

PubMed

Matzke, G R

1996-07-01

Approximately 2% of the United States population consumes an analgesic, antipyretic, or nonsteroidal antiinflammatory drug (NSAID) each day. Aspirin and acetaminophen have been available to the public without a prescription (over-the-counter) for decades, while most NSAIDs are still only available with a prescription from a physician. The recent trend of switching NSAIDs from prescription to over-the-counter status may be perceived by some as an indication of their inherent safety. However, all these agents have been associated with a unique but overlapping safety profile. In fact, significant adverse events (AEs) on multiple organ systems, including the kidney and gastrointestinal tract, have been reported with most of these agents. In this review, the incidence of the nonrenal AEs of aspirin, acetaminophen, and selected NSAIDs are tabulated. The strengths of the causative associations are highlighted, the relative risks for the gastrointestinal and cardiovascular AEs are discussed, and the relationship to patient risk factors and drug characteristics, such as dose and half-life, are reviewed. The selection of the optimal agent for an individual patient depends on the balance between the desired pharmacodynamic response, the patient's pharmacotherapy history, and the degree of AE risk one is willing to accept. Therapy should be initiated in all settings with the lowest possible dosage since the incidence of the major AEs is dose related.

Sediment toxicity in Savannah Harbor

USGS Publications Warehouse

Winger, P.V.; Lasier, P.J.

1995-01-01

Savannah Harbor, located near the mouth of the Savannah River, Georgia and South Carolina, is impacted by industrial and municipal effluents. Potential release of contaminants stored in harbor sediments through dredging and shipping operations requires that contaminated areas be identified for proper management of the system and protection of wildlife resources. During 1991, Hyalella azteca were exposed in 10-d static-renewal toxicity tests to pore-water and solid-phase sediment samples collected from 26 sites within Savannah Harbor. Pore-water toxicity was more pronounced than that for solidphase sediment. Toxicity and reduced leaf consumption demonstrated impaired sediment quality at specific sites within Savannah Harbor and Back River. Factors responsible for the decreased sediment quality were ammonia, alkalinity, and metal concentrations (cadmium, chromium, lead, molybdenum, and nickel). Elevated concentrations of metals and toxicities in Back River sediments indicated impacts from adjacent dredge-spoil areas.

Sulfur mustard toxicity: history, chemistry, pharmacokinetics, and pharmacodynamics.

PubMed

Ghabili, Kamyar; Agutter, Paul S; Ghanei, Mostafa; Ansarin, Khalil; Panahi, Yunes; Shoja, Mohammadali M

2011-05-01

Sulfur mustard (SM) and similar bifunctional agents have been used as chemical weapons for almost 100 years. Victims of high-dose exposure, both combatants and civilians, may die within hours or weeks, but low-dose exposure causes both acute injury to the eyes, skin, respiratory tract and other parts of the body, and chronic sequelae in these organs are often debilitating and have a serious impact on quality of life. Ever since they were first used in warfare in 1917, SM and other mustard agents have been the subjects of intensive research, and their chemistry, pharmacokinetics and mechanisms of toxic action are now fairly well understood. In the present article we review this knowledge and relate the molecular-biological basis of SM toxicity, as far as it has been elucidated, to the pathological effects on exposure victims.

[Developmental neurotoxicity of industrial chemicals].

PubMed

Labie, Dominique

2007-10-01

"A Silent Pandemic : Industrial Chemicals Are Impairing the Brain Development of Children Worldwide" Fetal and early childhood exposures to industrial chemicals in the environment can damage the developing brain and can lead to neurodevelopmental disorders (NDDs)--autism, attention deficit disorder (ADHD), and mental retardation. In a new review study, published in The Lancet, Philip Grandjean and Philip Landrigan from the Harvard School of Public Health systematically examined publicly available data on chemical toxicity in order to identify the industrial chemicals that are the most likely to damage the developing brain. The researchers found that 202 industrial chemicals have the capacity to damage the human brain, and they conclude that chemical pollution may have harmed the brains of millions of children worldwide. The authors conclude further that the toxic effects of industrial chemicals on children have generally been overlooked. In North Amercia, the commission for environmental cooperation, and in European Union the DEVNERTOX projects had reached to the same conclusions. We analyse this review and discuss these rather pessimistic conclusions.

Development of an Integrated Toxicity Assessment System for use in Operational Deployment and Materials Development

DTIC Science & Technology

2006-05-01

In addition to NBC concerns, there are issues in many current military settings for exposures to toxic industrial chemicals or materials (TICs or TIMs...Significant health issues caused by use of legacy chemicals have emphasized the need for more effective predication of chemical toxicity . This paper...current military settings for exposures to toxic industrial chemicals or materials (TICs or TIMs). Significant health issues caused by use of legacy

Enzyme-Based Ultrasensitive Electrochemical Biosensors for Rapid Assessment of Nitrite Toxicity: Recent Advances and Perspectives.

PubMed

Gahlaut, Anjum; Hooda, Vinita; Gothwal, Ashish; Hooda, Vikas

2018-05-14

In the present era of rapid international globalization and industrialization, intensive use of nitrite as a fertilizing agent in agriculture, preservative, dyeing agent, food additive and as corrosion inhibitor in industrial sectors is adversely effecting environment, natural habitats and human health. The issue of toxicity and carcinogenicity due to excessive ingestion of nitrites via the dietary intake has led to an imminent need for its efficient real-time monitoring in situ. Nitrite detection employing electrochemical biosensors has been gaining high credibility in the field of clinical research. Nitrite biosensors have emerged as an outstanding choice for portable point of care testing of nitrite quantification owing to the excellent properties, such as rapidity, miniaturization, ultra-low limits of detection, multiplexing and enhanced detection sensitivity. The article is enclosed with an interesting outlook on latest emerging trends in the development of nitrite biosensors utilizing nanomaterials, such as metal nanoparticles, carbon nanotubes, metal oxide nanoparticles, nanocomposites, polymers and biomaterials. The present review embarks on the highlights relevant to the nitrite quantification in real samples, then proceeds with a meticulous description of the most pertinent electrochemical nitrite biosensors, which have been proposed by adopting diverse materials and strategies of fabrication and finally end with the achievements and future outlook signifying the application of these nanoengineered biosensors for environmental surveillance and human safety.

Reversed enantioselectivity of diisopropyl fluorophosphatase against organophosphorus nerve agents by rational design.

PubMed

Melzer, Marco; Chen, Julian C-H; Heidenreich, Anne; Gäb, Jürgen; Koller, Marianne; Kehe, Kai; Blum, Marc-Michael

2009-12-02

Diisopropyl fluorophosphatase (DFPase) from Loligo vulgaris is an efficient and robust biocatalyst for the hydrolysis of a range of highly toxic organophosphorus compounds including the nerve agents sarin, soman, and cyclosarin. In contrast to the substrate diisopropyl fluorophosphate (DFP) the nerve agents possess an asymmetric phosphorus atom, which leads to pairs of enantiomers that display markedly different toxicities. Wild-type DFPase prefers the less toxic stereoisomers of the substrates which leads to slower detoxification despite rapid hydrolysis. Enzyme engineering efforts based on rational design yielded two quadruple enzyme mutants with reversed enantioselectivity and overall enhanced activity against tested nerve agents. The reversed stereochemical preference is explained through modeling studies and the crystal structures of the two mutants. Using the engineered mutants in combination with wild-type DFPase leads to significantly enhanced activity and detoxification, which is especially important for personal decontamination. Our findings may also be of relevance for the structurally related enzyme human paraoxonase (PON), which is of considerable interest as a potential catalytic in vivo scavenger in case of organophosphorus poisoning.

[Decontamination of chemical and biological warfare agents].

PubMed

Seto, Yasuo

2009-01-01

Chemical and biological warfare agents (CBWA's) are diverse in nature; volatile acute low-molecular-weight toxic compounds, chemical warfare agents (CWA's, gaseous choking and blood agents, volatile nerve gases and blister agents, nonvolatile vomit agents and lacrymators), biological toxins (nonvolatile low-molecular-weight toxins, proteinous toxins) and microbes (bacteria, viruses, rickettsiae). In the consequence management against chemical and biological terrorism, speedy decontamination of victims, facilities and equipment is required for the minimization of the damage. In the present situation, washing victims and contaminated materials with large volumes of water is the basic way, and additionally hypochlorite salt solution is used for decomposition of CWA's. However, it still remains unsolved how to dispose large volumes of waste water, and the decontamination reagents have serious limitation of high toxicity, despoiling nature against the environments, long finishing time and non-durability in effective decontamination. Namely, the existing decontamination system is not effective, nonspecifically affecting the surrounding non-target materials. Therefore, it is the urgent matter to build up the usable decontamination system surpassing the present technologies. The symposiast presents the on-going joint project of research and development of the novel decontamination system against CBWA's, in the purpose of realizing nontoxic, fast, specific, effective and economical terrorism on-site decontamination. The projects consists of (1) establishment of the decontamination evaluation methods and verification of the existing technologies and adaptation of bacterial organophosphorus hydrolase, (2) development of adsorptive elimination technologies using molecular recognition tools, and (4) development of deactivation technologies using photocatalysis.

The role of genetic background in susceptibility to chemical warfare nerve agents across rodent and non-human primate models.

PubMed

Matson, Liana M; McCarren, Hilary S; Cadieux, C Linn; Cerasoli, Douglas M; McDonough, John H

2018-01-15

Genetics likely play a role in various responses to nerve agent exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses to environmental stimuli. Mouse strains or selected lines can be used to identify susceptibility based on background genetic features to nerve agent exposure. Additional genetic techniques can then be used to identify mechanisms underlying resistance and sensitivity, with the ultimate goal of developing more effective and targeted therapies. Here, we discuss the available literature on strain and selected line differences in cholinesterase activity levels and response to nerve agent-induced toxicity and seizures. We also discuss the available cholinesterase and toxicity literature across different non-human primate species. The available data suggest that robust genetic differences exist in cholinesterase activity, nerve agent-induced toxicity, and chemical-induced seizures. Available cholinesterase data suggest that acetylcholinesterase activity differs across strains, but are limited by the paucity of carboxylesterase data in strains and selected lines. Toxicity and seizures, two outcomes of nerve agent exposure, have not been fully evaluated for genetic differences, and thus further studies are required to understand baseline strain and selected line differences. Published by Elsevier B.V.

Toxicity of nano- and micro-sized silver particles in human hepatocyte cell line L02

NASA Astrophysics Data System (ADS)

Liu, Pengpeng; Guan, Rongfa; Ye, Xingqian; Jiang, Jiaxin; Liu, Mingqi; Huang, Guangrong; Chen, Xiaoting

2011-07-01

Silver nanoparticles (Ag NPs) previously classified as antimicrobial agents have been widely used in consumers and industrial products, especially food storage material. Ag NPs used as antimicrobial agents may be found in liver. Thus, examination of the ability of Ag NPs to penetrate the liver is warranted. The aim of the study was to determine the optimal viability assay for using with Ag NPs in order to assess their toxicity to liver cells. For toxicity evaluations, cellular morphology, mitochondrial function (3-(4, 5-dimethylazol-2-yl)-2, 5-diphenyl-tetrazolium bromide, MTT assay), membrane leakage of lactate dehydrogenase (lactate dehydrogenase, LDH release assay), Oxidative stress markers (malonaldehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD)), DNA damage (single cell gel eletrophoresis, SCGE assay), and protein damage were assessed under control and exposed conditions (24 h of exposure). The results showed that mitochondrial function decreased significantly in cells exposed to Ag NPs at 25 μg·mL-1. LDH leakage significantly increased in cells exposed to Ag NPs (>= 25 μg mL-1) while micro-sized silver particles tested displayed LDH leakage only at higher doses (100 μg·mL-1). The microscopic studies demonstrated that nanoparticle-exposed cells at higher doses became abnormal in size, displaying cellular shrinkage, and an acquisition of an irregular shape. Due to toxicity of silver, further study conducted with reference to its oxidative stress. The results exhibited significant depletion of GSH level, increase in SOD levels and lead to lipid peroxidation, which suggested that cytotoxicity of Ag NPs in liver cells might be mediated through oxidative stress. The results demonstrates that Ag NPs lead to cellular morphological modifications, LDH leakage, mitochondrial dysfunction, and cause increased generation of ROS, depletion of GSH, lipid peroxidation, oxidative DNA damage and protein damage. Though the exact mechanism behind Ag NPs

Gut microbiota modulation of chemotherapy efficacy and toxicity.

PubMed

Alexander, James L; Wilson, Ian D; Teare, Julian; Marchesi, Julian R; Nicholson, Jeremy K; Kinross, James M

2017-06-01

Evidence is growing that the gut microbiota modulates the host response to chemotherapeutic drugs, with three main clinical outcomes: facilitation of drug efficacy; abrogation and compromise of anticancer effects; and mediation of toxicity. The implication is that gut microbiota are critical to the development of personalized cancer treatment strategies and, therefore, a greater insight into prokaryotic co-metabolism of chemotherapeutic drugs is now required. This thinking is based on evidence from human, animal and in vitro studies that gut bacteria are intimately linked to the pharmacological effects of chemotherapies (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and novel targeted immunotherapies such as anti-PD-L1 and anti-CLTA-4 therapies. The gut microbiota modulate these agents through key mechanisms, structured as the 'TIMER' mechanistic framework: Translocation, Immunomodulation, Metabolism, Enzymatic degradation, and Reduced diversity and ecological variation. The gut microbiota can now, therefore, be targeted to improve efficacy and reduce the toxicity of current chemotherapy agents. In this Review, we outline the implications of pharmacomicrobiomics in cancer therapeutics and define how the microbiota might be modified in clinical practice to improve efficacy and reduce the toxic burden of these compounds.

Effect of biochar activation by different methods on toxicity of soil contaminated by industrial activity.

PubMed

Kołtowski, Michał; Charmas, Barbara; Skubiszewska-Zięba, Jadwiga; Oleszczuk, Patryk

2017-02-01

The objective of the study was to determine the effect of various methods of biochar activation on the ecotoxicity of soils with various properties and with various content and origin of contaminants. The biochar produced from willow (at 700°C) was activated by 1) microwaves (in a microwave reactor under an atmosphere of water vapour), 2) carbon dioxide (in the quartz fluidized bed reactor) and 3) superheated steam (in the quartz fluidized bed reactor). Three different soils were collected from industrial areas. The soils were mixed with biochar and activated biochars at the dose of 5% and ecotoxicological parameters of mixture was evaluated using two solid phase test - Phytotoxkit F (Lepidium sativum) and Collembolan test (Folsomia candida) and one liquid phase test - Microtox® (Vibrio fischeri). Biochar activation had both positive and negative impacts, depending on the activation method, kind of bioassay and kind of soil. Generally, biochar activated by microwaves increased the effectiveness of ecotoxicity reduction relative to non-activated biochars. Whereas, biochar activated with CO 2 most often cause a negative effect manifested by deterioration or as a lack of improvement in relation to non-activated biochar or to non-amended soil. It was also demonstrated that the increase of biochar specific surface area caused a significant reduction of toxicity of water leachates from the studied soils. Effectiveness of the reduction of leachate toxicity was weakened in the presence of dissolved organic carbon in the soil. Copyright © 2016 Elsevier Inc. All rights reserved.

Vaginal microbicides: detecting toxicities in vivo that paradoxically increase pathogen transmission

PubMed Central

Cone, Richard A; Hoen, Timothy; Wong, XiXi; Abusuwwa, Raed; Anderson, Deborah J; Moench, Thomas R

2006-01-01

Background Microbicides must protect against STD pathogens without causing unacceptable toxic effects. Microbicides based on nonoxynol-9 (N9) and other detergents disrupt sperm, HSV and HIV membranes, and these agents are effective contraceptives. But paradoxically N9 fails to protect women against HIV and other STD pathogens, most likely because it causes toxic effects that increase susceptibility. The mouse HSV-2 vaginal transmission model reported here: (a) Directly tests for toxic effects that increase susceptibility to HSV-2, (b) Determines in vivo whether a microbicide can protect against HSV-2 transmission without causing toxicities that increase susceptibility, and (c) Identifies those toxic effects that best correlate with the increased HSV susceptibility. Methods Susceptibility was evaluated in progestin-treated mice by delivering a low-dose viral inoculum (0.1 ID50) at various times after delivering the candidate microbicide to detect whether the candidate increased the fraction of mice infected. Ten agents were tested – five detergents: nonionic (N9), cationic (benzalkonium chloride, BZK), anionic (sodium dodecylsulfate, SDS), the pair of detergents in C31G (C14AO and C16B); one surface active agent (chlorhexidine); two non-detergents (BufferGel®, and sulfonated polystyrene, SPS); and HEC placebo gel (hydroxyethylcellulose). Toxic effects were evaluated by histology, uptake of a 'dead cell' dye, colposcopy, enumeration of vaginal macrophages, and measurement of inflammatory cytokines. Results A single dose of N9 protected against HSV-2 for a few minutes but then rapidly increased susceptibility, which reached maximum at 12 hours. When applied at the minimal concentration needed for brief partial protection, all five detergents caused a subsequent increase in susceptibility at 12 hours of ~20–30-fold. Surprisingly, colposcopy failed to detect visible signs of the N9 toxic effect that increased susceptibility at 12 hours. Toxic effects that occurred

Toxicity of carbon nanotubes: A review.

PubMed

Francis, Arul Prakash; Devasena, Thiyagarajan

2018-03-01

Carbon nanotubes (CNTs) are widely used in the aerospace, automotive, and electronics industries because of their stability, enhanced metallic, and electrical properties. CNTs are also being investigated for biomedical applications such as drug delivery systems and biosensors. However, the toxic potential of CNTs was reported in various cell lines and animal models. The toxicity depends on diverse properties of the CNTs, such as length, aspect ratio, surface area, degree of aggregation, purity, concentration, and dose. In addition, CNTs and/or associated contaminants were well known for oxidative stress, inflammation, apoptosis, pulmonary inflammation, fibrosis, and granuloma in lungs. The increased production of CNTs likely enhanced the possibility of its exposure in people. Studies on the toxicity of CNTs are mainly focused on the pulmonary effects after intratracheal administration, and only a few studies are reported about the toxicity of CNTs via other routes of exposure. So, it is essential to consider the chronic toxicity of CNTs before using them for various biomedical applications. This review focuses on the potential toxicities of CNTs.

Allergy-related disorders in the construction industry.

PubMed

Carino, Mauro; Romita, Paolo; Foti, Caterina

2013-01-01

Working conditions in the construction industry have improved in many industrialized countries, but heavy physical work with recurrent exposure to chemical agents, dust, and climatic influences still represents considerable risk for construction workers and may affect their health. The aim of this review is to analyze available data of the literature on allergy-related respiratory and skin disorders with emphasis on a preventive appraisal in order to produce statements and recommendations based on research evidence. The most common agents involved in the construction industry as a cause of occupational asthma (OA) in industrialized countries are isocyanates, wood dust, resins, glues, cobalt, and chromium. Allergic contact dermatitis (ACD) is an immunologic cell-mediated response to a sensitizing agent and the most common sensitizing agents associated with construction workers are epoxy resins, thiurams and thiazoles, and chromates. Medical surveillance must consider individual risk factors such as differences in individual susceptibility and sensitization to agents at workplace. Once work-related disorder is confirmed, adequate fitness for work should be assessed for the worker impaired by health condition. A reliable diagnosis of an index case is a sentinel event that may reveal risks for workers with similar exposure, leading to a revised risk assessment at the workplace that should reduce the risk and prevent further cases.

Influence of cultivation procedure for Saccharomyces cerevisiae used as pitching agent in industrial spent sulphite liquor fermentations.

PubMed

Johansson, Emma; Brandberg, Tomas; Larsson, Christer

2011-11-01

The cell viability and fermentation performance often deteriorate in fermentations of spent sulphite liquor (SSL). This investigation therefore addresses the question of how different cultivation conditions for yeast cells influence their ability to survive and boost the ethanol production capacity in an SSL-based fermentation process. The strains used as pitching agents were an industrially harvested Saccharomyces cerevisiae and commercial dry baker's yeast. This study therefore suggests that exposure to SSL in combination with nutrients, prior to the fermentation step, is crucial for the performance of the yeast. Supplying 0.5 g/l fresh yeast cultivated under appropriate cultivation conditions may increase ethanol concentration more than 200%.

RRx-001: a systemically non-toxic M2-to-M1 macrophage stimulating and prosensitizing agent in Phase II clinical trials.

PubMed

Oronsky, Bryan; Paulmurugan, Ramasamy; Foygel, Kira; Scicinski, Jan; Knox, Susan J; Peehl, Donna; Zhao, Hongjuan; Ning, Shoucheng; Cabrales, Pedro; Summers, Thomas A; Reid, Tony R; Fitch, William L; Kim, Michelle M; Trepel, Jane B; Lee, Min-Jung; Kesari, Santosh; Abrouk, Nacer D; Day, Regina M; Oronsky, Arnold; Ray, Carolyn M; Carter, Corey A

2017-01-01

According to Hanahan and Weinberg, cancer manifests as six essential physiologic hallmarks: (1) self-sufficiency in growth signals, (2) insensitivity to growth-inhibitory signals, (3) evasion of programmed cell death, (4) limitless replicative potential, (5) sustained angiogenesis, and (6) invasion and metastasis. As a facilitator of these traits as well as immunosuppression and chemoresistance, the presence of tumor-associated macrophages (TAMs) may serve as the seventh hallmark of cancer. Anticancer agents that successfully reprogram TAMs to target rather than support tumor cells may hold the key to better therapeutic outcomes. Areas covered: This article summarizes the characteristics of the macrophage-stimulating agent RRx-001, a molecular iconoclast, sourced from the aerospace industry, with a particular emphasis on the cell-to-cell transfer mechanism of action (RBCs to TAMs) underlying its antitumor activity as well as its chemo and radioprotective properties, consolidated from various preclinical and clinical studies. Expert opinion: RRx-001 is macrophage-stimulating agent with the potential to synergize with chemotherapy, radiotherapy and immunotherapy while simultaneously protecting normal tissues from their cytotoxic effects. Given the promising indications of activity in multiple tumor types and these normal tissue protective properties, RRx-001 may be used to treat a broad spectrum of malignancies, if it is approved in the future.

Animal Models of Peripheral Neuropathy Due to Environmental Toxicants

PubMed Central

Rao, Deepa B.; Jortner, Bernard S.; Sills, Robert C.

2014-01-01

Despite the progress in our understanding of pathogeneses and the identification of etiologies of peripheral neuropathy, idiopathic neuropathy remains common. Typically, attention to peripheral neuropathies resulting from exposure to environmental agents is limited relative to more commonly diagnosed causes of peripheral neuropathy (diabetes and chemotherapeutic agents). Given that there are more than 80,000 chemicals in commerce registered with the Environmental Protection Agency and that at least 1000 chemicals are known to have neurotoxic potential, very few chemicals have been established to affect the peripheral nervous system (mainly after occupational exposures). A wide spectrum of exposures, including pesticides, metals, solvents, nutritional sources, and pharmaceutical agents, has been related, both historically and recently, to environmental toxicant-induced peripheral neuropathy. A review of the literature shows that the toxicity and pathogeneses of chemicals adversely affecting the peripheral nervous system have been studied using animal models. This article includes an overview of five prototypical environmental agents known to cause peripheral neuropathy—namely, organophosphates, carbon disulfide, pyridoxine (Vitamin B6), acrylamide, and hexacarbons (mainly n-hexane, 2,5-hexanedione, methyl n-butyl ketone). Also included is a brief introduction to the structural components of the peripheral nervous system and pointers on common methodologies for histopathologic evaluation of the peripheral nerves. PMID:24615445

78 FR 6853 - Agency Information Collection (Agent Orange Registry Code Sheet) Activities Under OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-31

... resulting from exposure to dioxin or other toxic agents. VA may also provide, upon request, a health... who may have been exposed to dioxin, or other toxic substance in a herbicide or defoliant, during the...

Where the chips fall: environmental health in the semiconductor industry.

PubMed

Chepesiuk, R

1999-09-01

Three recent lawsuits are focusing public attention on the environmental and occupational health effects of the world's largest and fastest growing manufacturing sector-the $150 billion semiconductor industry. The suits allege that exposure to toxic chemicals in semiconductor manufacturing plants led to adverse health effects such as miscarriage and cancer among workers. To manufacture computer components, the semiconductor industry uses large amounts of hazardous chemicals including hydrochloric acid, toxic metals and gases, and volatile solvents. Little is known about the long-term health consequences of exposure to chemicals by semiconductor workers. According to industry critics, the semiconductor industry also adversely impacts the environment, causing groundwater and air pollution and generating toxic waste as a by-product of the semiconductor manufacturing process. In contrast, the U.S. Bureau of Statistics shows the semiconductor industry as having a worker illness rate of about one-third of the average of all manufacturers, and advocates defend the industry, pointing to recent research collaborations and product replacement as proof that semiconductor manufacturers adequately protect both their employees and the environment.

Where the chips fall: environmental health in the semiconductor industry.

PubMed Central

Chepesiuk, R

1999-01-01

Three recent lawsuits are focusing public attention on the environmental and occupational health effects of the world's largest and fastest growing manufacturing sector-the $150 billion semiconductor industry. The suits allege that exposure to toxic chemicals in semiconductor manufacturing plants led to adverse health effects such as miscarriage and cancer among workers. To manufacture computer components, the semiconductor industry uses large amounts of hazardous chemicals including hydrochloric acid, toxic metals and gases, and volatile solvents. Little is known about the long-term health consequences of exposure to chemicals by semiconductor workers. According to industry critics, the semiconductor industry also adversely impacts the environment, causing groundwater and air pollution and generating toxic waste as a by-product of the semiconductor manufacturing process. In contrast, the U.S. Bureau of Statistics shows the semiconductor industry as having a worker illness rate of about one-third of the average of all manufacturers, and advocates defend the industry, pointing to recent research collaborations and product replacement as proof that semiconductor manufacturers adequately protect both their employees and the environment. PMID:10464084

77 FR 13061 - Electronic Reporting of Toxics Release Inventory Data

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-05

...--Reporting Year SIC--Standard Industrial Code TRI--Toxics Release Inventory TRI-ME--TRI-Made Easy Desktop... EPA to ``publish a uniform toxic chemical release form for facilities covered'' by the TRI Program. 42... practicable. Similarly, EPA's Cross-Media Electronic Reporting Regulation (CROMERR) (40 CFR Part 3), published...

The international electronics industry.

PubMed

LaDou, J; Rohm, T

1998-01-01

High-technology microelectronics has a major presence in countries such as China, India, Indonesia, and Malaysia, now the third-largest manufacturer of semiconductor chips. The migration of European, Japanese, and American companies accommodates regional markets. Low wage rates and limited enforcement of environmental regulations in developing countries also serve as incentives for the dramatic global migration of this industry. The manufacture of microelectonics products is accompanied by a high incidence of occupational illnesses, which may reflect the widespread use of toxic materials. Metals, photoactive chemicals, solvents, acids, and toxic gases are used in a wide variety of combinations and workplace settings. The industry also presents problems of radiation exposure and various occupational stressors, including some unresolved ergonomic issues. The fast-paced changes of the technology underlying this industry, as well as the stringent security precautions, have added to the difficulty of instituting proper health and safety measures. Epidemiologic studies reveal an alarming increase in spontaneous abortions among cleanroom manufacturing workers; no definitive study has yet identified its cause. Other health issues, including occupational cancer, are yet to be studied. The microelectronics industry is a good example of an industry that is exported to many areas of the world before health and safety problems are properly addressed and resolved.

The role of natural indigo dye in alleviation of genotoxicity of sodium dithionite as a reducing agent.

PubMed

Bektaş, İdris; Karaman, Şengül; Dıraz, Emel; Çelik, Mustafa

2016-12-01

Indigo blue is a natural dye used for thousands of years by civilizations to dye fabric blue and it is naturally obtained from Isatis tinctoria. I. tinctoria is not only used for extraction of indigo blue color but also used medicinally in Traditional Chinese Medicine because of its active compounds. Sodium dithionite (Na 2 S 2 O 4 ) is used in dye bath for indigo blue extraction, but this reducing agent and its derivatives are major pollutants of textile industry and subsequently have hazardous influences on public health. Herein, the present study was designed to obtain the high yield of natural indigo dye but with low possible toxic effect. In this context, genotoxic effects of particular combinations of natural dye solutions obtained from Isatis tinctoria subsp. tomentolla with Na 2 S 2 O 4 as reducing agent were investigated. Dye solutions were obtained using two different pH levels (pH 9 and 11) and three different concentrations of Na 2 S 2 O 4 (2.5, 5 and 10 mg/ml). In addition to the dye solutions and reducing agent, aqueous extracts of I. tinctoria were assessed for their genotoxicity on human lymphocytes. For in vitro testing of genotoxicity, chromosomal aberrations (CAs), sister chromatid exchanges (SCEs) and mitotic indexes (MI) assays were used. Accordingly, Na 2 S 2 O 4 caused significant increases in CA and SCE as well decrease in MI but the genotoxic effects of sodium dithionite were reduced with natural indigo dye. As a result, aqueous extracts of Isatis leaves removed the toxic effects of sodium dithionite and showed anti-genotoxic effect. For the optimal and desired quality but with less toxic effects of natural dye, 2.5 mg/ml (for wool yarn) and 5 mg/ml (for cotton yarn) of Na 2 S 2 O 4 doses were found to be the best doses for reduction in the dye bath at Ph 9.

Dermal Toxicity Evaluation of Neutralized Chemical Agent Identification Sets (CAIS) with an Overview of the Dermal Toxicity of Vesicant Agents and their Degradation Products.

DTIC Science & Technology

1996-10-01

Food and Water Consumption and Locomotor Movement in Rats, Lab Animals, 26:180-189 (1992). Mann, F.G. and Pope, W.J., "Production and Reactions of ý...and Use: t-butyl alcohol is used in the manufacture of flotation agents, flavors, perfumes, used extensively as a solvent, as a gasoline additive

Inhibition of Sulfide Mineral Oxidation by Surface Coating Agents: Batch

NASA Astrophysics Data System (ADS)

Choi, J.; Ji, M. K.; Yun, H. S.; Park, Y. T.; Gee, E. D.; Lee, W. R.; Jeon, B.-H.

2012-04-01

Mining activities and mineral industries have impacted on rapid oxidation of sulfide minerals such as pyrite (FeS2) which leads to Acid Mine Drainage (AMD) formation. Some of the abandoned mines discharge polluted water without proper environmental remediation treatments, largely because of financial constraints in treating AMD. Magnitude of the problem is considerable, especially in countries with a long history of mining. As metal sulfides become oxidized during mining activities, the aqueous environment becomes acid and rich in many metals, including iron, lead, mercury, arsenic and many others. The toxic heavy metals are responsible for the environmental deterioration of stream, groundwater and soils. Several strategies to remediate AMD contaminated sites have been proposed. Among the source inhibition and prevention technologies, microencapsulation (coating) has been considered as a promising technology. The encapsulation is based on inhibition of O2 diffusion by surface coating agent and is expected to control the oxidation of pyrite for a long time. Potential of several surface coating agents for preventing oxidation of metal sulfide minerals from both Young-Dong coal mine and Il-Gwang gold mine were examined by conducting batch experiments and field tests. Powdered pyrite as a standard sulfide mineral and rock samples from two mine outcrops were mixed with six coating agents (KH2PO4, MgO and KMnO4 as chemical agents, and apatite, cement and manganite as mineral agents) and incubated with oxidizing agents (H2O2 or NaClO). Batch experiments with Young-Dong coal mine samples showed least SO42- production in presence of KMnO4 (16% sulfate production compared to no surface coating agents) or cement (4%) within 8 days. In the case of Il-Gwang mine samples, least SO42- production was observed in presence of KH2PO4 (8%) or cement (2%) within 8 days. Field-scale pilot tests at Il-Gwang site also showed that addition of KH2PO4 decreased sulfate production from 200 to

[Toxic ulcerative contact dermatitis due to prefabricated concrete (cement burns)].

PubMed

Bandmann, H J; Agathos, M

1977-01-01

In the present report the case of a toxic ulcerous contact dermatitis (cement burns) by pre-fabricated concrete is described. This can be clearly distinguished by anamnesis, findings and development from the allergic and cumulative-toxic contact dermatitis caused by cement and related substances. It is pointed out, that in the few cases of "cement burns" made known up to now, pre-fabricated concrete was always the triggering agent.

Replacement of hazardous chromium impregnating agent from silver/copper/chromium-impregnated active carbon using triethylenediamine to remove hydrogen sulfide, trichloromethane, ammonia, and sulfur dioxide.

PubMed

Wu, Li-Chun; Chung, Ying-Chien

2009-03-01

Activated carbon (AC) is widely used as an effective adsorbent in many applications, including industrial-scale air purification systems and air filter systems in gas masks. In general, ACs without chemical impregnation are good adsorbents of organic vapors but poor adsorbents of low-molecular-weight or polar gases such as chlorine, sulfur dioxide (SO2), formaldehyde, and ammonia (NH3). Impregnated ACs modified with metallic impregnating agents (ASC-carbons; e.g., copper, chromium, and silver) enhance the adsorbing properties of the ACs for simultaneously removing specific poisonous gases, but disposal of the chromium metal salt used to impregnate the ACs has the potential to result in situations that are toxic to both humans and the environment, thereby necessitating the search for replaceable organic impregnating agents that represent a much lower risk. The aim of this study was to assess the gas removal efficiency of an AC in which the organic impregnating agent triethylenediamine (TEDA) largely replaced the metallic impregnating agent chromium. We assessed batch and continuous adsorption capacities in situ for removing simulated hydrogen sulfide (H2S), trichloromethane (CHCl3), NH3, and SO2 gases. Brunauer-Emmet-Teller measurements and scanning electron microscopy analyses identified the removal mechanism by which TEDA-impregnated AS-carbon (dechromium ASC-carbon) adsorbs gases and determined the removal capacity for H2S, CHCl3, NH3, and SO2 to be 311, 258, 272, and 223 mg/g-C, respectively. These results demonstrate that TEDA-impregnated AS-carbon is significantly more efficient than ASC-carbon in adsorbing these four gases. Organic TEDA-impregnating agents have also been proven to be a reliable and environmental friendly agent and therefore a safe replacement of the hazardous chromium found in conventional ASC-carbon used in removing toxic gases from the airstream.

Prevalence of Rhabdomyolysis in Sympathomimetic Toxicity: a Comparison of Stimulants.

PubMed

O'Connor, Ayrn D; Padilla-Jones, Angie; Gerkin, Richard D; Levine, Michael

2015-06-01

Synthetic cathinones have emerged as popular drugs of abuse and produce sympathomimetic toxicity. It is unknown if rhabdomyolysis occurs more frequently following the use of synthetic cathinones compared to other stimulants. This retrospective study sought to determine the prevalence of rhabdomyolysis in patients with sympathomimetic toxicity and compare rates among patients using specific agents. Patients greater than 14 years of age with sympathomimetic toxicity and detection of a stimulant agent in urine via gas chromatography-mass spectroscopy (GC-MS) were included. Patients were excluded if clinical sympathomimetic toxicity was not present, a serum creatine kinase (CK) was not measured, or urine GC-MS was not performed. Rhabdomyolysis and severe rhabdomyolysis were defined as CK > 1000 and 10,000 IU/L, respectively. Prevalence of rhabdomyolysis and severe rhabdomyolysis were reported. Logistic regression was performed to determine the relative effect in single-agent exposures of a synthetic cathinone compared to other sympathomimetics on rhabdomyolysis. A secondary outcome, a composite endpoint defined as need for mechanical ventilation, renal replacement therapy, development of compartment syndrome, or death, was also analyzed. One hundred two subjects met inclusion criteria; median age (IQR) was 32 (25-42) years with a range of 14-65 years; 74 % were male. Rhabdomyolysis occurred in 42 % (43/102) of subjects. Patients whose sympathomimetic toxicity could be ascribed to a single agent were considered for further statistical analysis and placed into four groups: methamphetamine (n = 55), synthetic cathinone (n = 19), cocaine (n = 9), and other sympathomimetic (n = 6). In 89 subjects with single stimulant exposure, the prevalence of rhabdomyolysis was as follows: synthetic cathinone, 12/19 (63 %); methamphetamine, 22/55 (40 %); cocaine, 3/9 (33 %); and other single agent, 0/6 (0 %). The occurrence of severe rhabdomyolysis (CK > 10

Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity

PubMed Central

Isbister, Geoffrey K; Hackett, L P; Dawson, Andrew H; Whyte, Ian M; Smith, Anthony J

2003-01-01

Aims To investigate the spectrum of toxicity of moclobemide overdose, the occurrence of serotonin toxicity, and to estimate toxicokinetic parameters. Methods All moclobemide overdoses presenting over a 10-year period to the Hunter Area Toxicology Service were reviewed. Clinical features, complications, length of stay (LOS) and intensive care (ICU) admission rate were extracted from a standardized, prospectively collected database. Comparisons were made between moclobemide alone and moclobemide with a serotonergic coingestant poisoning. Serotonin toxicity was defined by a combination of Sternbach's criteria and a clinical toxicologist's diagnosis. In five patients serial moclobemide concentrations were measured. Time to maximal plasma concentration (Tmax), peak plasma concentration (Cmax) and terminal elimination half-lives were estimated. Results Of 106 included patients, 33 ingested moclobemide alone, 21 ingested moclobemide with another serotonergic agent (in some cases in therapeutic doses) and 52 ingested moclobemide with a nonserotonergic agent. Eleven (55%) of 21 patients coingesting a serotonergic drug developed serotonin toxicity, which was significantly more than one (3%) of 33 moclobemide-alone overdoses (odds ratio 35, 95% confidence inteval 4, 307; P < 0.0001). In six of these 21 cases severe serotonin toxicity developed with temperature> 38.5 °C and muscle rigidity requiring intubation and paralysis. The 21 patients had a significantly increased LOS (34 h) compared with moclobemide alone overdoses (12 h) (P < 0.0001) and a significantly increased ICU admission rate of 57% vs. 3% (P < 0.0001). Time to peak plasma concentration was delayed in two patients where prepeak samples were obtained. Cmax increased slightly with dose, but all three patients ingesting ≥ 6 g vomited or had charcoal. The mean elimination half-life of moclobemide in the five patients in whom serial moclobemide concentrations were measured was 6.3 h and elimination was first order

Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity.

PubMed

Isbister, Geoffrey K; Hackett, L P; Dawson, Andrew H; Whyte, Ian M; Smith, Anthony J

2003-10-01

To investigate the spectrum of toxicity of moclobemide overdose, the occurrence of serotonin toxicity, and to estimate toxicokinetic parameters. All moclobemide overdoses presenting over a 10-year period to the Hunter Area Toxicology Service were reviewed. Clinical features, complications, length of stay (LOS) and intensive care (ICU) admission rate were extracted from a standardized, prospectively collected database. Comparisons were made between moclobemide alone and moclobemide with a serotonergic coingestant poisoning. Serotonin toxicity was defined by a combination of Sternbach's criteria and a clinical toxicologist's diagnosis. In five patients serial moclobemide concentrations were measured. Time to maximal plasma concentration (Tmax), peak plasma concentration (Cmax) and terminal elimination half-lives were estimated. Of 106 included patients, 33 ingested moclobemide alone, 21 ingested moclobemide with another serotonergic agent (in some cases in therapeutic doses) and 52 ingested moclobemide with a nonserotonergic agent. Eleven (55%) of 21 patients coingesting a serotonergic drug developed serotonin toxicity, which was significantly more than one (3%) of 33 moclobemide-alone overdoses (odds ratio 35, 95% confidence interval 4, 307; P < 0.0001). In six of these 21 cases severe serotonin toxicity developed with temperature >38.5 degrees C and muscle rigidity requiring intubation and paralysis. The 21 patients had a significantly increased LOS (34 h) compared with moclobemide alone overdoses (12 h) (P < 0.0001) and a significantly increased ICU admission rate of 57% vs. 3% (P < 0.0001). Time to peak plasma concentration was delayed in two patients where prepeak samples were obtained. Cmax increased slightly with dose, but all three patients ingesting > or = 6 g vomited or had charcoal. The mean elimination half-life of moclobemide in the five patients in whom serial moclobemide concentrations were measured was 6.3 h and elimination was first order in all

INCREASE IN THE CHEMOTHERAPEUTIC COEFFICIENT OF MECHLORETHAMINE BY THE ACTION OF THE RADIOPROTECTIVE AGENT SODIUM DIETHYLDITHIOCARBAMATE (in Italian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cima, L; Pozza, F

1963-01-01

In mice of the SMZ strain the protective effect of various kinds of radioprotectant agents against the toxicity of the alkylating agent mechiorethamine (HN2) was investigated. HN2 was injected subcutaneously in doses of 6 mg/kg, corresponding to the LD/sub 99/6/. The most effective protective agent tested was the chelating agent Na diethyldithiocarbamate (DEDTC), which when injected intraperitoneally in doses of 335 mg/kg raised the 4-day survival rate to 90% from a control value of 20%. Other chelating agents were less effective, showing the specific action of the dithiocarbamate anion: tetraethylthiuram disulfide (disulfiram), 2-guanidinothiazolidone, and diethylamine. Moderately effective against the toxicitymore » of HN2 were (in decreasing order): reserpine, chlorpromazine, propylene glycol, malononitrile, glutathione, cysteamine, oxytocin, and Na ethylenediaminetatraacetate. Tryptamine was ineffective and cysteine augmented the toxicity of HN2. DEDTC did not modify the carcinostatic effect of HN2 against Ehrlich ascites tumor and thus, by markedly reducing the toxicity of HN2, enhances the therapeutic index of HN2 3 fold. The protective effect of DEDTC and the other radioprotectant agents against HN2 suggest that alkylating agents and ionizing radiation have analogous effects on tissue constituents. (H.H.D.)« less

Challenges of Toxicity Management in Immuno-Oncology.

PubMed

Andrews, Stephanie

2017-05-01

Immunotherapies are conveying unprecedented efficacy in some tumor types, but with this success comes challenges in managing toxicities that are distinct from those of cytotoxic agents. Although most immune-related adverse events can be ameliorated by temporarily withholding the drug and administering steroids, grade 3 to 4 toxicities can be challenging and some adverse effects can be long-lasting. NCCN has developed an immunotherapy teaching and monitoring tool that can help in evaluating and managing these autoimmune-mediated inflammatory conditions, which can affect virtually all organ systems. Copyright © 2017 by the National Comprehensive Cancer Network.

Prioritization of reproductive toxicants in unconventional oil and gas operations using a multi-country regulatory data-driven hazard assessment.

PubMed

Inayat-Hussain, Salmaan H; Fukumura, Masao; Muiz Aziz, A; Jin, Chai Meng; Jin, Low Wei; Garcia-Milian, Rolando; Vasiliou, Vasilis; Deziel, Nicole C

2018-08-01

Recent trends have witnessed the global growth of unconventional oil and gas (UOG) production. Epidemiologic studies have suggested associations between proximity to UOG operations with increased adverse birth outcomes and cancer, though specific potential etiologic agents have not yet been identified. To perform effective risk assessment of chemicals used in UOG production, the first step of hazard identification followed by prioritization specifically for reproductive toxicity, carcinogenicity and mutagenicity is crucial in an evidence-based risk assessment approach. To date, there is no single hazard classification list based on the United Nations Globally Harmonized System (GHS), with countries applying the GHS standards to generate their own chemical hazard classification lists. A current challenge for chemical prioritization, particularly for a multi-national industry, is inconsistent hazard classification which may result in misjudgment of the potential public health risks. We present a novel approach for hazard identification followed by prioritization of reproductive toxicants found in UOG operations using publicly available regulatory databases. GHS classification for reproductive toxicity of 157 UOG-related chemicals identified as potential reproductive or developmental toxicants in a previous publication was assessed using eleven governmental regulatory agency databases. If there was discordance in classifications across agencies, the most stringent classification was assigned. Chemicals in the category of known or presumed human reproductive toxicants were further evaluated for carcinogenicity and germ cell mutagenicity based on government classifications. A scoring system was utilized to assign numerical values for reproductive health, cancer and germ cell mutation hazard endpoints. Using a Cytoscape analysis, both qualitative and quantitative results were presented visually to readily identify high priority UOG chemicals with evidence of multiple

ZnO and TiO2 nanoparticles as novel antimicrobial agents for oral hygiene: a review

NASA Astrophysics Data System (ADS)

Khan, Shams Tabrez; Al-Khedhairy, Abdulaziz A.; Musarrat, Javed

2015-06-01

Oral cavity is inhabited by more than 25,000 different bacterial phylotypes; some of them cause systemic infections in addition to dental and periodontal diseases. Emergence of multiple antibiotic resistance among these bacteria necessitates the development of alternative antimicrobial agents that are safe, stable, and relatively economic. This review focuses on the significance of metal oxide nanoparticles, especially zinc oxide and titanium dioxide nanoparticles as supplementary antimicrobials for controlling oral infections and biofilm formation. Indeed, the ZnO NPs and TiO2 NPs have exhibited significant antimicrobial activity against oral bacteria at concentrations which is not toxic in in vivo toxicity assays. These nanoparticles are being produced at an industrial scale for use in a variety of commercial products including food products. Thus, the application of ZnO and TiO2 NPs as nanoantibiotics for the development of mouthwashes, dental pastes, and other oral hygiene materials is envisaged. It is also suggested that these NPs could serve as healthier, innocuous, and effective alternative for controlling both the dental biofilms and oral planktonic bacteria with lesser side effects and antibiotic resistance.

Speciation in Metal Toxicity and Metal-Based Therapeutics

PubMed Central

Templeton, Douglas M.

2015-01-01

Metallic elements, ions and compounds produce varying degrees of toxicity in organisms with which they come into contact. Metal speciation is critical to understanding these adverse effects; the adjectives “heavy” and “toxic” are not helpful in describing the biological properties of individual elements, but detailed chemical structures are. As a broad generalization, the metallic form of an element is inert, and the ionic salts are the species that show more significant bioavailability. Yet the salts and other chelates of a metal ion can give rise to quite different toxicities, as exemplified by a range of carcinogenic potential for various nickel species. Another important distinction comes when a metallic element is organified, increasing its lipophilicity and hence its ability to penetrate the blood brain barrier, as is seen, for example, with organic mercury and tin species. Some metallic elements, such as gold and platinum, are themselves useful therapeutic agents in some forms, while other species of the same element can be toxic, thus focusing attention on species interconversions in evaluating metal-based drugs. The therapeutic use of metal-chelating agents introduces new species of the target metal in vivo, and this can affect not only its desired detoxification, but also introduce a potential for further mechanisms of toxicity. Examples of therapeutic iron chelator species are discussed in this context, as well as the more recent aspects of development of chelation therapy for uranium exposure. PMID:29056656

Toxic effects of antiparasitic pesticides used by the salmon industry in the marine amphipod Monocorophium insidiosum.

PubMed

Tucca, Felipe; Díaz-Jaramillo, Mauricio; Cruz, Gabriel; Silva, Jeannette; Bay-Schmith, Enrique; Chiang, Gustavo; Barra, Ricardo

2014-08-01

The use of antiparasitic pesticides (APs) has been widely required by the salmon industry to treat diseases. The direct emission of chemicals in the seawater has produced uncertainty about the potential effects on nontarget organisms, such as crustaceans. The aim of this study was to assess the toxicity of three APs used by the salmon farm industry, such as emamectin benzoate (EB), cypermethrin (CP), and deltamethrin (DE), in the amphipod Monocorophium insidiosum during 10 days through whole-sediment bioassay tests. Lethal concentration by 50 % (LC50-10d) and biochemical responses, such as glutathione S-transferase (GST) and thiobarbituric acid reactive substances (TBARS), were measured as exposure and effects end points, respectively. Acute assays for DE (7.8 μg kg(-1), confidence interval, CI95% 5-11) and CP (57 μg kg(-1), CI95% 41-77) showed more mortality than EB (890 μg kg(-1), CI95% 672-1,171). In this study, it was possible to observe sublethal responses in amphipods after 2 days of exposure to APs. Significant induction in GST and TBARS (p < 0.05) were measured for CP and EB. Lower DE concentrations showed no significant biochemical responses. M. insidiosum was sensitive to AP concentrations at μg kg(-1) in sediments. This information would allow considering the possible consequences of detected concentrations for APs in areas with intensive salmon farming activity.

Modern toxic antipersonnel projectiles.

PubMed

Gaillard, Yvan; Regenstreif, Philippe; Fanton, Laurent

2014-12-01

In the spring of 1944, Kurt von Gottberg, the SS police chief in Minsk, was shot and injured by 2 Soviet agents. Although he was only slightly injured, he died 6 hours later. The bullets were hollow and contained a crystalline white powder. They were 4-g bullets, semi-jacketed in cupronickel, containing 28 mg of aconitine. They were later known as akonitinnitratgeschosse. The Sipo (the Nazi security police) then ordered a trial with a 9-mm Parabellum cartridge containing Ditran, an anticholinergic drug with hallucinogenic properties causing intense mental confusion. In later years, QNB was used and given the NATO code BZ (3-quinuclidinyl-benzylate). It was proven that Saddam Hussein had this weapon (agent 15) manufactured and used it against the Kurds. Serbian forces used the same type of weapon in the Bosnian conflict, particularly in Srebrenica.The authors go on to list the Cold War toxic weapons developed by the KGB and the Warsaw pact countries for the discreet elimination of dissidents and proindependence leaders who had taken refuge in the West. These weapons include PSZh-13 launchers, the Troika electronic sequential pistol, and the ingenious 4-S110T captive piston system designed by the engineer Stechkin. Disguised as a cigarette case, it could fire a silent charge of potassium cyanide. This rogues gallery also includes the umbrella rigged to inject a pellet of ricin (or another phytalbumin of similar toxicity, such as abrin or crotin) that was used to assassinate the Bulgarian writer and journalist Georgi Markov on September 7, 1978, in London.During the autopsy, the discovery of a bullet burst into 4 or 5 parts has to make at once suspecting the use of a toxic substance. Toxicological analysis has to look for first and foremost aconitine, cyanide, suxamethonium, Ditran, BZ, or one of the toxic phytalbumins. The use of such complex weapons has to make suspect a powerful organization: army, secret service, terrorism. The existence of the Russian UDAR spray

Dielectrophoretic Field-Flow Fractionation System for Detection of Aquatic Toxicants

PubMed Central

Pui-ock, Sittisak; Ruchirawat, Mathuros; Gascoyne, Peter

2009-01-01

Dielectrophoretic field-flow fractionation (dFFF) was applied as a contact-free way to sense changes in the plasma membrane capacitances and conductivities of cultured human HL-60 cells in response to toxicant exposure. A micropatterned electrode imposed electric forces on cells in suspension in a parabolic flow profile as they moved through a thin chamber. Relative changes in the dFFF peak elution time, reflecting changes in cell membrane area and ion permeability, were measured as indices of response during the first 150 min of exposure to eight toxicants having different single or mixed modes of action (acrylonitrile, actinomycin D, carbon tetrachloride, endosulfan, N-nitroso-N-methylurea (NMU), paraquat dichloride, puromycin, and styrene oxide). The dFFF method was compared with the cell viability assay for all toxicants and with the mitochondrial potentiometric dye assay or DNA alkaline comet assay according to the mode of action of the specific agents. Except for low doses of nucleic acid-targeting agents (actinomycin D and NMU), the dFFF method detected all toxicants more sensitively than other assays, in some cases up to 105 times more sensitively than the viability approach. The results suggest the dFFF method merits additional study for possible applicability in toxicology. PMID:18788754

Treosulfan induces distinctive gonadal toxicity compared with busulfan

PubMed Central

Levi, Mattan; Stemmer, Salomon M.; Stein, Jerry; Shalgi, Ruth; Ben-Aharon, Irit

2018-01-01

Treosulfan (L-treitol-1,4-bis-methanesulfonate) has been increasingly incorporated as a main conditioning protocol for hematopoietic stem cell transplantation in pediatric malignant and non-malignant diseases. Treosulfan presents lower toxicity profile than other conventional alkylating agents containing myeloablative and immunosuppressive traits such as busulfan. Yet, whereas busulfan is considered highly gonadotoxic, the gonadal toxicity profile of treosulfan remains to be elucidated. To study the gonadotoxicity of treosulfan, pubertal and prepubertal male and female mice were injected with treosulfan or busulfan and sacrificed one week, one month or six months later. Testicular function was assessed by measurements of sperm properties, testes and epididymides weights as well as markers for testicular reserve, proliferation and apoptosis. Ovarian function was assessed by measurements of ovary weight and markers for ovarian reserve, proliferation and apoptosis. Treosulfan testicular toxicity was milder than that of busulfan toxicity; possibly by sparing the stem spermatogonia in the testicular sanctuary. By contrast, ovarian toxicity of both treosulfan and busulfan was severe and permanent and displayed irreversible reduction of reserve primordial follicles in the ovaries. Our data indicate that treosulfan exerts a different gonadal toxicity profile from busulfan, manifested by mild testicular toxicity and severe ovarian toxicity. PMID:29721205

Toxic hepatitis in occupational exposure to solvents

PubMed Central

Malaguarnera, Giulia; Cataudella, Emanuela; Giordano, Maria; Nunnari, Giuseppe; Chisari, Giuseppe; Malaguarnera, Mariano

2012-01-01

The liver is the main organ responsible for the metabolism of drugs and toxic chemicals, and so is the primary target organ for many organic solvents. Work activities with hepatotoxins exposures are numerous and, moreover, organic solvents are used in various industrial processes. Organic solvents used in different industrial processes may be associated with hepatotoxicity. Several factors contribute to liver toxicity; among these are: species differences, nutritional condition, genetic factors, interaction with medications in use, alcohol abuse and interaction, and age. This review addresses the mechanisms of hepatotoxicity. The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress. The health impact of exposure to solvents in the workplace remains an interesting and worrying question for professional health work. PMID:22719183

A FLUORESCENCE-BASED SCREENING ASSAY FOR DNA DAMAGE INDUCED BY GENOTOXIC INDUSTRIAL CHEMICALS

EPA Science Inventory

The possibility of deliberate or accidental release of toxic chemicals in industrial, commercial or residential settings has indicated a need for rapid, cost-effective and versatile monitoring methods to prevent exposures to humans and ecosystems. Because many toxic industrial c...

[Comparative evaluation of health hazards associated with industrial chemicals and their derivates forming during water chlorination].

PubMed

Zholdakova, Z I; Poliakova, E E; Lebedev, A T

2006-01-01

Many industrial chemicals found in waste waters are able to form organochlorine by-products during water disinfection. The transformation of seven model compounds, cyclohexene, n-butanol, diphenylmethane, acetophenone, aniline, 1-methylnaphthalene, and phenylxylylethane during a reaction with active chlorine was studied. Aqueous chlorine and sodium hypochlorite were used as chlorinating agents. The products of the reaction were analyzed by means of chromatomass-spectrometry. A schematic model of diphenylmethane transformation was proposed. Comparative evaluation of hazards associated with the model chemicals and their derivates confirmed that chlorination products can be more toxic and dangerous than the initial compounds, and may possess mutagenic and cancerigenic properties.

Final Rule for Industrial Process Cooling Towers: Fact Sheet

EPA Pesticide Factsheets

Fact sheet concerning a final rule to reduce air toxics emissions from industrial process cooling towers. Air toxics are those pollutants known or suspected of causing cancer or other serious health effects.

Toxic industrial chemical (TIC) source emissions modeling for pressurized liquefied gases

NASA Astrophysics Data System (ADS)

Britter, Rex; Weil, Jeffrey; Leung, Joseph; Hanna, Steven

2011-01-01

The objective of this article is to report current toxic industrial chemical (TIC) source emissions formulas appropriate for use in atmospheric comprehensive risk assessment models so as to represent state-of-the-art knowledge. The focus is on high-priority scenarios, including two-phase releases of pressurized liquefied gases such as chlorine from rail cars. The total mass released and the release duration are major parameters, as well as the velocity, thermodynamic state, and amount and droplet sizes of imbedded aerosols of the material at the exit of the rupture, which are required as inputs to the subsequent jet and dispersion modeling. Because of the many possible release scenarios that could develop, a suite of model equations has been described. These allow for gas, two-phase or liquid storage and release through ruptures of various types including sharp-edged and "pipe-like" ruptures. Model equations for jet depressurization and phase change due to flashing are available. Consideration of the importance of vessel response to a rupture is introduced. The breakup of the jet into fine droplets and their subsequent suspension and evaporation, or rainout is still a significant uncertainty in the overall modeling process. The recommended models are evaluated with data from various TIC field experiments, in particular recent experiments with pressurized liquefied gases. It is found that there is typically a factor of two error in models compared with research-grade observations of mass flow rates. However, biases are present in models' estimates of the droplet size distributions resulting from flashing releases.

THERMOREGULATION AND ITS INFLUENCE ON TOXICITY ASSESSMENT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gordon, Christopher J.; Spencer, Pamela J.; Hotchkiss, Jon

2008-02-28

The thermoregulatory system of laboratory rodents is susceptible to a variety of chemical toxicants. Because temperature directly affects the reaction of virtually all biological processes, it is critical to consider how changes in the thermoregulatory response to a toxicant may affect physiological, behavioral, and pathological endpoints. Researchers in industry and government laboratories are often faced with addressing how changes in body temperature of their experimental subjects may affect the outcome of a particular toxicity test and/or screening panel. However, many toxicologists are either unaware of the importance or ignore the potential impact of a toxic-induced change in body temperature. Thismore » paper endeavors to summarize the importance of thermoregulation in the study of toxicology and propose recommendations for thermometry that researchers may utilize in their toxicological studies.« less

Evolution of camel CYP2E1 and its associated power of binding toxic industrial chemicals and drugs.

PubMed

Kandeel, Mahmoud; Altaher, Abdullah; Kitade, Yukio; Abdelaziz, Magdi; Alnazawi, Mohamed; Elshazli, Kamal

2016-10-01

Camels are raised in harsh desert environment for hundreds of years ago. By modernization of live and the growing industrial revolution in camels rearing areas, camels are exposed to considerable amount of chemicals, industrial waste, environmental pollutions and drugs. Furthermore, camels have unique gene evolution of some genes to withstand living in harsh environments. In this work, the camel cytochrome P450 2E1 (CYP2E1) is compromised to detect its evolution rate and its power to bind with various chemicals, protoxins, procarcinogens, industrial toxins and drugs. In comparison with human CYP2E1, camel CYP2E1 more efficiently binds to small toxins as aniline, benzene, catechol, amides, butadiene, toluene and acrylamide. Larger compounds were more preferentially bound to the human CYP2E1 in comparison with camel CYP2E1. The binding of inhalant anesthetics was almost similar in both camel and human CYP2E1 coinciding with similar anesthetic effect as well as toxicity profiles. Furthermore, evolutionary analysis indicated the high evolution rate of camel CYP2E1 in comparison with human, farm and companion animals. The evolution rate of camel CYP2E1 was among the highest evolution rate in a subset of 57 different organisms. These results indicate rapid evolution and potent toxin binding power of camel CYP2E1. Copyright © 2016. Published by Elsevier Ltd.

Role of Glutamate Release and Metabotropic Autoreceptors in Seizureogenic Actions of Cholinomimetic Agents

DTIC Science & Technology

2001-10-01

produced by centrally-active cholinomimetic agents and to evaluate possible palliative treatments for central cholinomimetic toxicity. The scope of...REPORT: 10/01/00-09/30/01 AWARD NUMBER: DAMD17-98-1-8617 evaluation of the effects by intracerebral infusion of the organophosphate agent paraoxon on EEG...agents. Previously, we had reported successful induction of seizure-like changes in EEG activity of anesthetized rats following intracerebral infusion

Systemic use of tumor necrosis factor alpha as an anticancer agent

PubMed Central

Roberts, Nicholas J.; Zhou, Shibin; Diaz, Luis A.; Holdhoff, Matthias

2011-01-01

Tumor necrosis factor-α (TNF-α) has been discussed as a potential anticancer agent for many years, however initial enthusiasm about its clinical use as a systemic agent was curbed due to significant toxicities and lack of efficacy. Combination of TNF-α with chemotherapy in the setting of hyperthermic isolated limb perfusion (ILP), has provided new insights into a potential therapeutic role of this agent. The therapeutic benefit from TNF-α in ILP is thought to be not only due to its direct anti-proliferative effect, but also due to its ability to increase penetration of the chemotherapeutic agents into the tumor tissue. New concepts for the use of TNF-α as a facilitator rather than as a direct actor are currently being explored with the goal to exploit the ability of this agent to increase drug delivery and to simultaneously reduce systemic toxicity. This review article provides a comprehensive overview on the published previous experience with systemic TNF-α. Data from 18 phase I and 10 phase II single agent as well as 18 combination therapy studies illustrate previously used treatment and dose schedules, response data as well as the most prominently observed adverse effects. Also discussed, based on recent preclinical data, is a potential future role of systemic TNF-α in combination with liposomal chemotherapy to facilitate increased drug uptake into tumors. PMID:22036896

POTENTIAL DEVELOPMENTAL TOXICITY OF ANATOXIN-A, A CYANOBACTERIAL TOXIN

EPA Science Inventory

Anatoxin-a acts as a neuro-muscular blocking agent. Acute toxicity is characterized by rapid onset of paralysis, tremors, convulsions, and death. Human exposures may occur from recreational water activities and dietary supplements, but are primarily through drinking water. The...

Fluorescent Chemosensors for Toxic Organophosphorus Pesticides: A Review

PubMed Central

Obare, Sherine O.; De, Chandrima; Guo, Wen; Haywood, Tajay L.; Samuels, Tova A.; Adams, Clara P.; Masika, Noah O.; Murray, Desmond H.; Anderson, Ginger A.; Campbell, Keith; Fletcher, Kenneth

2010-01-01

Many organophosphorus (OP) based compounds are highly toxic and powerful inhibitors of cholinesterases that generate serious environmental and human health concerns. Organothiophosphates with a thiophosphoryl (P=S) functional group constitute a broad class of these widely used pesticides. They are related to the more reactive phosphoryl (P=O) organophosphates, which include very lethal nerve agents and chemical warfare agents, such as, VX, Soman and Sarin. Unfortunately, widespread and frequent commercial use of OP-based compounds in agricultural lands has resulted in their presence as residues in crops, livestock, and poultry products and also led to their migration into aquifers. Thus, the design of new sensors with improved analyte selectivity and sensitivity is of paramount importance in this area. Herein, we review recent advances in the development of fluorescent chemosensors for toxic OP pesticides and related compounds. We also discuss challenges and progress towards the design of future chemosensors with dual modes for signal transduction. PMID:22163587

Fluorescent chemosensors for toxic organophosphorus pesticides: a review.

PubMed

Obare, Sherine O; De, Chandrima; Guo, Wen; Haywood, Tajay L; Samuels, Tova A; Adams, Clara P; Masika, Noah O; Murray, Desmond H; Anderson, Ginger A; Campbell, Keith; Fletcher, Kenneth

2010-01-01

Many organophosphorus (OP) based compounds are highly toxic and powerful inhibitors of cholinesterases that generate serious environmental and human health concerns. Organothiophosphates with a thiophosphoryl (P=S) functional group constitute a broad class of these widely used pesticides. They are related to the more reactive phosphoryl (P=O) organophosphates, which include very lethal nerve agents and chemical warfare agents, such as, VX, Soman and Sarin. Unfortunately, widespread and frequent commercial use of OP-based compounds in agricultural lands has resulted in their presence as residues in crops, livestock, and poultry products and also led to their migration into aquifers. Thus, the design of new sensors with improved analyte selectivity and sensitivity is of paramount importance in this area. Herein, we review recent advances in the development of fluorescent chemosensors for toxic OP pesticides and related compounds. We also discuss challenges and progress towards the design of future chemosensors with dual modes for signal transduction.

APPLICATION OF BENCHMARK DOSE METHODOLOGY TO DATA FROM PRENATAL DEVELOPMENTAL TOXICITY STUDIES

EPA Science Inventory

The benchmark dose (BMD) concept was applied to 246 conventional developmental toxicity datasets from government, industry and commercial laboratories. Five modeling approaches were used, two generic and three specific to developmental toxicity (DT models). BMDs for both quantal ...

Effects-Directed Analysis (EDA) and Toxicity Identification Evaluation (TIE): Complementary but Different Approaches for Diagnosing Causes of Environmental Toxicity

EPA Science Inventory

Currently, two approaches are available for performing environmental diagnostics on samples like municipal and industrial effluents, interstitial waters and whole sediments in order to identify anthropogenic contaminants causing toxicological effects. One approach is Toxicity Id...

Manganese toxicity upon overexposure

PubMed Central

Crossgrove, Janelle; Zheng, Wei

2014-01-01

Manganese (Mn) is a required element and a metabolic byproduct of the contrast agent mangafodipir trisodium (MnDPDP). The Mn released from MnDPDP is initially sequestered by the liver for first-pass elimination, which allows an enhanced contrast for diagnostic imaging. The administration of intravenous Mn impacts its homeostatic balance in the human body and can lead to toxicity. Human Mn deficiency has been reported in patients on parenteral nutrition and in micronutrient studies. Mn toxicity has been reported through occupational (e.g. welder) and dietary overexposure and is evidenced primarily in the central nervous system, although lung, cardiac, liver, reproductive and fetal toxicity have been noted. Mn neurotoxicity results from an accumulation of the metal in brain tissue and results in a progressive disorder of the extrapyramidal system which is similar to Parkinson's disease. In order for Mn to distribute from blood into brain tissue, it must cross either the blood–brain barrier (BBB) or the blood–cerebrospinal fluid barrier (BCB). Brain import, with no evidence of export, would lead to brain Mn accumulation and neurotoxicity. The mechanism for the neurodegenerative damage specific to select brain regions is not clearly understood. Disturbances in iron homeostasis and the valence state of Mn have been implicated as key factors in contributing to Mn toxicity. Chelation therapy with EDTA and supplementation with levodopa are the current treatment options, which are mildly and transiently efficacious. In conclusion, repeated administration of Mn, or compounds that readily release Mn, may increase the risk of Mn-induced toxicity. PMID:15617053

Atmospheric toxic metals emission inventory and spatial characteristics from anthropogenic sources of Guangdong province, China

NASA Astrophysics Data System (ADS)

Cher, S.; Menghua, L.; Xiao, X.; Yuqi, W.; Zhuangmin, Z.; Zhijiong, H.; Cheng, L.; Guanglin, J.; Zibing, Y.; Junyu, Z.

2017-12-01

Atmospheric toxic metals (TMs) are part of particulate matters, and may create adverse effects on the environment and human health depending upon their bioavailability and toxicity. Localized emission inventory is fundamental for parsing of toxic metals to identify key sources in order to formulate efficient toxic metals control strategies. With the use of the latest municipal level environment statistical data, this study developed a bottom-up emission inventory of five toxic metals (Hg, As, Pb, Cd, Cr) from anthropogenic activities in Guangdong province for the year of 2014. Major atmospheric toxic metals sources including combustion sources (coal, oil, biomass, municipal solid waste) and industrial process sources (cement production, nonferrous metal smelting, iron and steel industry, battery and fluorescent lamp production) were investigated. Results showed that: (1) The total emissions of Hg, As, Pb, Cd, Cr in Guangdong province were 18.14, 32.59, 411.34, 13.13, 84.16 t, respectively. (2) Different pollutants have obvious characteristics of emission sources. For total Hg emission, 46% comes from combustion sources, of which 32% from coal combustion and 8% from MSW combustion. Other 54% comes from industrial processes, which dominated by the cement (19%), fluorescent lamp (18%) and battery production (13%). Of the total Hg emission, 69% is released as Hg0 , 29% as Hg2+ , and only 2% as Hgp due to strict particulate matters controls policies. For As emissions, coal combustion, nonferrous metal smelting and iron and steel industry contributed approximate 48%, 25% and 24%, respectively. Pb emissions primarily come from battery production (42%), iron and steel industry (21%) and on-road mobile gasoline combustion (17%). Cd and Cr emissions were dominated by nonferrous metal smelting (71%) and iron and steel industry (82%), respectively. (3) In term of the spatial distribution, emissions of atmospheric toxic metals are mainly concentrated in the central region of

OVERVIEW OF HAZARDOUS/TOXIC WASTE INCINERATION

EPA Science Inventory

Effective hazardous/toxic waste disposal and safe dumpsite cleanup are two of EPA's major missions in the 1980s. Incineration has been recognized as a very efficient process to destroy the hazardous wastes generated by industry or by the dumpsite remediations. The paper provides ...

Repeated dose 28-day oral toxicity study of DEAE-Dextran in mice: An advancement in safety chemotherapeutics.

PubMed

Bakrania, Anita K; Variya, Bhavesh C; Madan, Prem; Patel, Snehal S

2017-08-01

Cancer has emerged as a global threat with challenges for safe chemotherapeutics. Most of the currently available anti-cancer drugs exhibit significant toxicity. Amongst novel agents, interferons have exhibited anti-proliferative and cytoprotective roles. However, due to stability drawbacks of interferons, we have identified an interferon inducer DEAE-Dextran, which resolves the stability issues. Based on the previous history of toxicity pertaining to the current chemotherapeutic agents, it is equally essential to determine the safety of DEAE-Dextran. In the present study, repeated dose 28 day oral toxicity of DEAE-Dextran has been evaluated in accordance to OECD-407. We found absence of any CNS behavioral changes related to self-mutilation, walking backwards, aggressiveness on handling or tonic-clonic seizures during the 28 day study. Neither the motor activity nor grip strength was altered during the treatment duration with DEAE-Dextran implying absence of any effect on the skeletal muscles. Interestingly, we also found that treatment with DEAE-Dextran did not present any significant cardiac, hepatic, renal, gastrointestinal, lymphatic or reproductive system toxicity or alteration in the body's normal physiology based upon the various organ function tests. Henceforth, it may be concluded that DEAE-Dextran is a safe anti-cancer agent devoid of any sub-acute toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Toxicity of silver nanoparticles in zebrafish models

NASA Astrophysics Data System (ADS)

Asharani, P. V.; Lian Wu, Yi; Gong, Zhiyuan; Valiyaveettil, Suresh

2008-06-01

This study was initiated to enhance our insight on the health and environmental impact of silver nanoparticles (Ag-np). Using starch and bovine serum albumin (BSA) as capping agents, silver nanoparticles were synthesized to study their deleterious effects and distribution pattern in zebrafish embryos (Danio rerio). Toxicological endpoints like mortality, hatching, pericardial edema and heart rate were recorded. A concentration-dependent increase in mortality and hatching delay was observed in Ag-np treated embryos. Additionally, nanoparticle treatments resulted in concentration-dependent toxicity, typified by phenotypes that had abnormal body axes, twisted notochord, slow blood flow, pericardial edema and cardiac arrhythmia. Ag+ ions and stabilizing agents showed no significant defects in developing embryos. Transmission electron microscopy (TEM) of the embryos demonstrated that nanoparticles were distributed in the brain, heart, yolk and blood of embryos as evident from the electron-dispersive x-ray analysis (EDS). Furthermore, the acridine orange staining showed an increased apoptosis in Ag-np treated embryos. These results suggest that silver nanoparticles induce a dose-dependent toxicity in embryos, which hinders normal development.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, K.; Xu, J.

1999-04-06

Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. 2 figs.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, Kenneth; Xu, Jide

1999-01-01

Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity.

Wildlife toxicity testing

USGS Publications Warehouse

Hoffman, David J.; Hoffman, David J.; Rattner, Barnett A.; Burton, G. Allen; Cairns, John

1995-01-01

Reports of anthropogenic environmental contaminants affecting free-ranging wildlife first began to accumulate during the Industrial Revolution of the 1850s. early reports included cases of arsenic and lead shot ingestion, and industrial smokestack emission toxicity. One early report described the death of fallow deer (Dama dama) due to arsenic emissions from a silver foundry in Germany in 1887, whereas another report described hydrogen sulfide fumes in the vicinity of a Texas oil field that resulted in a large die-off of both wild birds and mammals.1 Mortality in waterfowl and ring-necked pheasants (Phaisanus colchicus) due to the ingestion of spent lead shot was recognized at least as early as 1874 when lead-poisoned birds were reported in Texas and North Carolina.

Preclinical evaluation of biodegradable macromolecular contrast agents for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Feng, Yi

Macromolecular contrast agents have been shown to be superior to small molecular weight contrast agents for MRI in blood pool imaging, tumor diagnosis and grading. However, none has been approved by the FDA because they circulate in the bloodstream much longer than small molecular weight contrast agents and result in high tissue accumulation of toxic Gd(III) ions. Biodegradable macromolecular contrast agents (BMCA) were invented to alleviate the toxic accumulation. They have a cleavable disulfide bond based backbone that can be degraded in vivo and excreted out of the body via renal filtration. Furthermore, the side chain of the backbone can be modified to achieve various degradation rates. Three BMCA, (Gd-DTPA)-cystamine copolymers (GDCC), Gd-DTPA cystine copolymers (GDCP), and Gd-DTPA cystine diethyl ester copolymers (GDCEP), were evaluated as blood pool contrast agents in a rat model. They have excellent blood pool enhancement, preferred pharmacokinetics, and only minimal long-term tissue retention of toxic Gd(III) ions. GDCC and GDCP, the lead agents with desired degradation rates, with molecular weights of 20 KDa and 70 KDa, were chosen for dynamic contrast enhanced MRI (DCE-MRI) to differentiate human prostate tumor models of different malignancy and growth rates. GDCC and GDCP could differentiate these tumor models, providing more accurate estimations of plasma volume, flow leakage rate, and permeability surface area product than a small molecular weight contrast agent Gd-DTPA-BMA when compared to the prototype macromolecular contrast agent albumin-Gd-DTPA. GDCC was favored for its neutral charge side chain and reasonable uptake rate by the tumors. GDCC with a molecular weight of 40 KDa (GDCC-40, above the renal filtration cutoff size) was used to assess the efficacy of two photothermal therapies (interstitial and indocyanine green enhanced). GDCC-40 provided excellent tumor enhancement shortly after its injection. Acute tumor response (4 hr) after therapies

Contrast agent choice for intravenous coronary angiography

NASA Astrophysics Data System (ADS)

Zeman, H. D.; Siddons, D. P.

1990-05-01

magnetic resonance imaging. Experiments have already been performed with Yb-DTPA in animals, and it appears to have a lower toxicity than that of Gd-DTPA. Reported animal experiments with Gd-DOTA contrast agent show no toxicity at all.

Prediction of the effect of formulation on the toxicity of chemicals.

PubMed

Mistry, Pritesh; Neagu, Daniel; Sanchez-Ruiz, Antonio; Trundle, Paul R; Vessey, Jonathan D; Gosling, John Paul

2017-01-01

Two approaches for the prediction of which of two vehicles will result in lower toxicity for anticancer agents are presented. Machine-learning models are developed using decision tree, random forest and partial least squares methodologies and statistical evidence is presented to demonstrate that they represent valid models. Separately, a clustering method is presented that allows the ordering of vehicles by the toxicity they show for chemically-related compounds.

Black and white teas as potential agents to combine with amphotericin B and protect red blood cells from amphotericin B-mediated toxicity.

PubMed

Oliveira, V M; Khalil, N M; Carraro, E

2018-02-01

Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with black tea or white tea and protective of citotoxic effect. The present study shows that white and black teas have additive effects with amphotericin B against some species Candida. In addition, the combination of white and black tea with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that white and black tea is a potential agent to combine with amphotericin for antifungal efficacy and to reduce the amphotericin dose to lessen side effects.

Foliar nitrogen, phosphorus and potassium content in trees in environmentally toxic plastic industry area.

PubMed

Sett, Rupnarayan; Soni, Bhawna

2013-04-01

In plants, nitrogen deficiency causes stunted growth and chlorosis or yellowing of the leaves due to decreased levels of chlorophyll, while excess nitrogen uptake may cause dark green overly vigorous foliage which may have increased susceptibility to disease and insect attacks. Phosphorus is an important nutrient in crop production, since many soils in their native state do not have sufficient available phosphorus to maximize crop yield. Potassium deficiency may cause necrosis or interveinal chlorosis. Plastics are synthetic or semi-synthetic moldable organic solids that are organic polymers of high molecular mass, most commonly derived from petrochemicals; these polymers are based on chains of carbon atoms alone or with oxygen, sulfur, or nitrogen. Plastic is a non- biodegradable major toxic pollutant. It pollutes earth and leads to air pollution and water pollution. Merely there is any safe way to dispose the hazardous plastic wastes. The study was targeted to estimate foliar level of NPK content of three plant species, viz. Cassia tora (Herb), Ailanthus excelsa (Tree) and Dalbergia sissoo (Tree) from polluted areas associated to polythene-industries as well as control areas having least pollution, where all the parameters were found to be higher than the control experiments.

Blaptica dubia as sentinels for exposure to chemical warfare agents - a pilot study.

PubMed

Worek, Franz; Seeger, Thomas; Neumaier, Katharina; Wille, Timo; Thiermann, Horst

2016-11-16

The increased interest of terrorist groups in toxic chemicals and chemical warfare agents presents a continuing threat to our societies. Early warning and detection is a key component for effective countermeasures against such deadly agents. Presently available and near term solutions have a number of major drawbacks, e.g. lack of automated, remote warning and detection of primarily low volatile chemical warfare agents. An alternative approach is the use of animals as sentinels for exposure to toxic chemicals. To overcome disadvantages of vertebrates the present pilot study was initiated to investigate the suitability of South American cockroaches (Blaptica dubia) as warning system for exposure to chemical warfare nerve and blister agents. Initial in vitro experiments with nerve agents showed an increasing inhibitory potency in the order tabun - cyclosarin - sarin - soman - VX of cockroach cholinesterase. Exposure of cockroaches to chemical warfare agents resulted in clearly visible and reproducible reactions, the onset being dependent on the agent and dose. With nerve agents the onset was related to the volatility of the agents. The blister agent lewisite induced signs largely comparable to those of nerve agents while sulfur mustard exposed animals exhibited a different sequence of events. In conclusion, this first pilot study indicates that Blaptica dubia could serve as a warning system to exposure of chemical warfare agents. A cockroach-based system will not detect or identify a particular chemical warfare agent but could trigger further actions, e.g. specific detection and increased protective status. By designing appropriate boxes with (IR) motion sensors and remote control (IR) camera automated off-site warning systems could be realized. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Behavioral toxicity of selected radioprotectors

NASA Astrophysics Data System (ADS)

Landauer, M. R.; Davis, H. D.; Kumar, K. S.; Weiss, J. F.

1992-10-01

Effective radioprotection with minimal behavioral disruption is essential for the selection of protective agents to be used in manned spaceflight. This overview summarizes the studies on the behavioral toxicity of selected radioprotectors classified as phosphorothioates (WR-2721, WR-3689), bioactive lipids (16, 16 dimethylprostaglandin E2(DiPGE2), platelet activating factor (PAF), leukotriene C4), and immunomodulators (glucan, synthetic trehalose dicorynomycolate, and interleukin-1). Behavioral toxicity was examined in laboratory mice using a locomotor activity test. For all compounds tested, there was a dose-dependent decrease in locomotor behavior that paralleled the dose-dependent increase in radioprotection. While combinations of radioprotective compounds (DiPGE2 plus WR-2721) increased radioprotection, they also decreased locomotor activity. The central nervous system stimulant, caffeine, was able to mitigate the locomotor decrement produced by WR-3689 or PAF.

Small molecule fluoride toxicity agonists.

PubMed

Nelson, James W; Plummer, Mark S; Blount, Kenneth F; Ames, Tyler D; Breaker, Ronald R

2015-04-23

Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here, we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride. Copyright © 2015 Elsevier Ltd. All rights reserved.

Small Molecule Fluoride Toxicity Agonists

PubMed Central

Nelson1, James W.; Plummer, Mark S.; Blount, Kenneth F.; Ames, Tyler D.; Breaker, Ronald R.

2015-01-01

SUMMARY Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch-reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride. PMID:25910244

L-β-N-methylamino-l-alanine (BMAA) nitrosation generates a cytotoxic DNA damaging alkylating agent: An unexplored mechanism for neurodegenerative disease.

PubMed

Potjewyd, G; Day, P J; Shangula, S; Margison, G P; Povey, A C

2017-03-01

L-β-N-methylamino-l-alanine (BMAA) is a non-proteinic amino acid, that is neurotoxic in vitro and in animals, and is implicated in the causation of amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS-PDC) on Guam. Given that natural amino acids can be N-nitrosated to form toxic alkylating agents and the structural similarity of BMAA to other amino acids, our hypothesis was that N-nitrosation of BMAA might result in a toxic alkylating agent, providing a novel mechanistic hypothesis for BMAA action. We have chemically nitrosated BMAA with sodium nitrite to produce nitrosated BMAA (N-BMAA) which was shown to react with the alkyl-trapping agent, 4-(p-nitrobenzyl)pyridine, cause DNA strand breaks in vitro and was toxic to the human neuroblastoma cell line SH-SY5Y under conditions in which BMAA itself was minimally toxic. Our results indicate that N-BMAA is an alkylating agent and toxin suggesting a plausible and previously unrecognised mechanism for the neurotoxic effects of BMAA. Copyright © 2017 Elsevier B.V. All rights reserved.

Intercellular communications-redox interactions in radiation toxicity; potential targets for radiation mitigation.

PubMed

Farhood, Bagher; Goradel, Nasser Hashemi; Mortezaee, Keywan; Khanlarkhani, Neda; Salehi, Ensieh; Nashtaei, Maryam Shabani; Shabeeb, Dheyauldeen; Musa, Ahmed Eleojo; Fallah, Hengameh; Najafi, Masoud

2018-06-17

Nowadays, using ionizing radiation (IR) is necessary for clinical, agricultural, nuclear energy or industrial applications. Accidental exposure to IR after a radiation terror or disaster poses a threat to human. In contrast to the old dogma of radiation toxicity, several experiments during the last two recent decades have revealed that intercellular signaling and communications play a key role in this procedure. Elevated level of cytokines and other intercellular signals increase oxidative damage and inflammatory responses via reduction/oxidation interactions (redox system). Intercellular signals induce production of free radicals and inflammatory mediators by some intermediate enzymes such as cyclooxygenase-2 (COX-2), nitric oxide synthase (NOS), NADPH oxidase, and also via triggering mitochondrial ROS. Furthermore, these signals facilitate cell to cell contact and increasing cell toxicity via cohort effect. Nitric oxide is a free radical with ability to act as an intercellular signal that induce DNA damage and changes in some signaling pathways in irradiated as well as non-irradiated adjacent cells. Targeting of these mediators by some anti-inflammatory agents or via antioxidants such as mitochondrial ROS scavengers opens a window to mitigate radiation toxicity after an accidental exposure. Experiments which have been done so far suggests that some cytokines such as IL-1β, TNF-α, TGF-β, IL-4 and IL-13 are some interesting targets that depend on irradiated organs and may help mitigate radiation toxicity. Moreover, animal experiments in recent years indicated that targeting of toll like receptors (TLRs) may be more useful for radioprotection and mitigation. In this review, we aimed to describe the role of intercellular interactions in oxidative injury, inflammation, cell death and killing effects of IR. Moreover, we described evidence on potential mitigation of radiation injury via targeting of these mediators.

A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY TOXIC INDUSTRIAL CHEMICALS

EPA Science Inventory

Numerous natural and man-made agents are continuously released into the environment due to human activity. Many of these agents cause irreversible damage to the normal biological functions leading to morbidity and mortality in the exposed organisms. The possibility of deliberat...

[Influence of smoking and industrial air pollutants on respiratory health of nickel industry workers].

PubMed

Shilov, V V; Siurin, S A

2015-01-01

Studies covered respiratory health of 1530 workers of nickel industry, among which were 796 (52.0%) smokers. Findings are that tobacco smoke combined with nickel industry hazards cause potentized negative effects in respiratory organs, with earlier and more frequent chronic bronchitis. For isolated influence of these factors, chronic bronchitis risk is higher from exposure to tobacco smoke vs. occupational hazards (OR = 2.48; DI 1.49-4.13). Chronic obstructive lung disease development in nickel industry workers is caused by smoking. Industrial air pollutants appeared to have no potentizing effect on COLD formation, as well as on toxic pneumosclerosis formation.

Evaluating porewater polycyclic aromatic hydrocarbon-related toxicity at a contaminated sediment site using a spiked field-sediment approach.

PubMed

Hartzell, Sharon E; Unger, Michael A; Vadas, George G; Yonkos, Lance T

2018-03-01

Although the complexity of contaminant mixtures in sediments can confound the identification of causative agents of adverse biological response, understanding the contaminant(s) of primary concern at impacted sites is critical to sound environmental management and remediation. In the present study, a stock mixture of 18 polycyclic aromatic hydrocarbon (PAH) compounds was prepared to reflect the variety and relative proportions of PAHs measured in surface sediment samples collected from discrete areas of a historically contaminated industrial estuary. This site-specific PAH stock mixture was spiked into nontoxic in-system and out-of-system field-collected reference sediments in dilution series spanning the range of previously measured total PAH concentrations from the region. Spiked sediments were evaluated in 10-d Leptocheirus plumulosus tests to determine whether toxicity in laboratory-created PAH concentrations was similar to the toxicity found in field-collected samples with equivalent PAH concentrations. The results show that toxicity of contaminated sediments was not explained by PAH exposure, while indicating that toxicity in spiked in-system (fine grain, high total organic carbon [TOC]) and out-of-system (course grain, low TOC) sediments was better explained by porewater PAH concentrations, measured using an antibody-based biosensor that quantified 3- to 5-ring PAHs, than total sediment PAH concentrations. The study demonstrates the application of site-specific spiking experiments to evaluate sediment toxicity at sites with complex mixtures of multiple contaminant classes and the utility of the PAH biosensor for rapid sediment-independent porewater PAH analysis. Environ Toxicol Chem 2018;37:893-902. © 2017 SETAC. © 2017 SETAC.

Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors

PubMed Central

2017-01-01

Metal-free magnetic resonance imaging (MRI) agents could overcome the established toxicity associated with metal-based agents in some patient populations and enable new modes of functional MRI in vivo. Herein, we report nitroxide-functionalized brush-arm star polymer organic radical contrast agents (BASP-ORCAs) that overcome the low contrast and poor in vivo stability associated with nitroxide-based MRI contrast agents. As a consequence of their unique nanoarchitectures, BASP-ORCAs possess per-nitroxide transverse relaxivities up to ∼44-fold greater than common nitroxides, exceptional stability in highly reducing environments, and low toxicity. These features combine to provide for accumulation of a sufficient concentration of BASP-ORCA in murine subcutaneous tumors up to 20 h following systemic administration such that MRI contrast on par with metal-based agents is observed. BASP-ORCAs are, to our knowledge, the first nitroxide MRI contrast agents capable of tumor imaging over long time periods using clinical high-field 1H MRI techniques. PMID:28776023

Noncardiac Vascular Toxicities of Vascular Endothelial Growth Factor Inhibitors in Advanced Cancer: A Review

PubMed Central

Bowen, Joanne; Gibson, Rachel; Tan, Thean; Okera, Meena; Stringer, Andrea

2011-01-01

Summary. The introduction of molecularly targeted anticancer therapies has brought the promise of longer survival times for select patients with cancers previously considered untreatable. However, it has also brought new toxicities that require understanding and management, sometimes for long periods of time. Vascular endothelial growth factor inhibitors are associated with a broad range of adverse effects, with vascular toxicity being particularly serious. This review focuses on the current understanding of the pathophysiology and mechanisms of macrovascular toxicities (hypertension, hemorrhage, and thromboembolism), their incidence and severity, the current clinical management, and implications in the advanced cancer setting. Movement of these agents into the early disease setting will alter the impact of these toxicities. Search Strategy and Selection Criteria. Information for this review was collected by searching PubMed/Medline and American Society of Clinical Oncology abstract databases. The medical subject heading terms used included toxicity, hypertension, thromboembolism, hemorrhage, intestinal perforation, risk factors, pharmacokinetics, and metabolism, combined with free text search terms including, but not limited to, VEGF inhibitor*, bevacizumab, sunitinib, and sorafenib. Articles published in English before March 2010 were included, in addition to information from case reports and pharmaceutical agent package inserts. PMID:21441297

Joint chemical agent detector (JCAD): the future of chemical agent detection

NASA Astrophysics Data System (ADS)

Laljer, Charles E.

2003-08-01

The Joint Chemical Agent Detector (JCAD) has continued development through 2002. The JCAD has completed Contractor Validation Testing (CVT) that included chemical warfare agent testing, environmental testing, electromagnetic interferent testing, and platform integration validation. The JCAD provides state of the art chemical warfare agent detection capability to military and homeland security operators. Intelligence sources estimate that over twenty countries have active chemical weapons programs. The spread of weapons of mass destruction (and the industrial capability for manufacture of these weapons) to third world nations and terrorist organizations has greatly increased the chemical agent threat to U.S. interests. Coupled with the potential for U.S. involvement in localized conflicts in an operational or support capacity, increases the probability that the military Joint Services may encounter chemical agents anywhere in the world. The JCAD is a small (45 in3), lightweight (2 lb.) chemical agent detector for vehicle interiors, aircraft, individual personnel, shipboard, and fixed site locations. The system provides a common detection component across multi-service platforms. This common detector system will allow the Joint Services to use the same operational and support concept for more efficient utilization of resources. The JCAD detects, identifies, quantifies, and warns of the presence of chemical agents prior to onset of miosis. Upon detection of chemical agents, the detector provides local and remote audible and visual alarms to the operators. Advance warning will provide the vehicle crew and other personnel in the local area with the time necessary to protect themselves from the lethal effects of chemical agents. The JCAD is capable of being upgraded to protect against future chemical agent threats. The JCAD provides the operator with the warning necessary to survive and fight in a chemical warfare agent threat environment.

Reconsidering betaine as a natural anti-heat stress agent in poultry industry: a review.

PubMed

Saeed, Muhammad; Babazadeh, Daryoush; Naveed, Muhammad; Arain, Muhammad Asif; Hassan, Faiz Ul; Chao, Sun

2017-10-01

Betaine is found ubiquitously in plants, animals, microorganisms, and rich dietary sources including seafood, spinach, and wheat bran. The chief physiological role of betaine is to function as a methyl donor and an osmolyte. Betaine also acts as an osmolyte, to maintain the avian's cellular water and ion balance to improve the avian's capacity against heat stress via preventing dehydration and osmotic inactivation. It helps in maintaining the protective osmolytic activity, especially in heat-stressed birds. Betaine may promote various intestinal microbes against osmotic variations and thus improve microbial fermentation activity. Previous studies showed that dietary supplementation of betaine in poultry diets could positively affect nutrients' digestibility, reduce abdominal fat weight, and increase breast meat yield. In addition, betaine has been reported to protect internal organs and boost their performance. Its inclusion in poultry diet is sparing essential amino acids like choline and methionine. In addition, it may play an important role in lean meat production by positively affecting the lipid metabolism with increased fatty acids catabolism and thus reducing carcass fat deposition. The aim of this review article was to broaden the knowledge regarding betaine and its importance in the poultry industry to cope with the heat stress problem. Moreover, it should be added to the diet as a natural anti-stressor through different routes (water/feed) to overcome the heat stress problem. However, further studies need to be conducted at the genetic and molecular basis to elucidate the mechanism behind the betaine as a natural anti-heat agent to decrease the heat stress problem in the poultry industry.

Optimization of electrocoagulation (EC) process for the purification of a real industrial wastewater from toxic metals.

PubMed

Gatsios, Evangelos; Hahladakis, John N; Gidarakos, Evangelos

2015-05-01

In the present work, the efficiency evaluation of electrocoagulation (EC) in removing toxic metals from a real industrial wastewater, collected from Aspropyrgos, Athens, Greece was investigated. Manganese (Mn), copper (Cu) and zinc (Zn) at respective concentrations of 5 mg/L, 5 mg/L and 10 mg/L were present in the wastewater (pH=6), originated from the wastes produced by EBO-PYRKAL munitions industry and Hellenic Petroleum Elefsis Refineries. The effect of operational parameters such as electrode combination and distance, applied current, initial pH and initial metal concentration, was studied. The results indicated that Cu and Zn were totally removed in all experiments, while Mn exhibited equally high removal percentages (approximately 90%). Decreasing the initial pH and increasing the distance between electrodes, resulted in a negative effect on the efficiency and energy consumption of the process. On the other hand, increasing the applied current, favored metal removal but resulted in a power consumption increase. Different initial concentrations did not affect metal removal efficiency. The optimal results, regarding both cost and EC efficiency, were obtained with a combination of iron electrodes, at 2 cm distance, at initial current of 0.1 A and pH=6. After 90 min of treatment, maximum removal percentages obtained were 89% for Mn, 100% for Cu and 100% for Zn, at an energy consumption of 2.55 kWh/m(3). Copyright © 2015 Elsevier Ltd. All rights reserved.

DOSE-DEPENDENT TRANSITIONS IN MECHANISMS OF TOXICITY: CASE STUDIES

EPA Science Inventory

Experience with dose response and mechanisms of toxicity has shown that multiple mechanisms may exist for a single agent along the continuum of the full dose-response curve. It is highly likely that critical, limiting steps in any given mechanistic pathway may become overwhelmed ...

Clearance Properties of Nano-sized Particles and Molecules as Imaging Agents: Considerations and Caveats

PubMed Central

Longmire, Michelle; Choyke, Peter L.; Kobayashi, Hisataka

2009-01-01

Summary Nanoparticles possess enormous potential as diagnostic imaging agents and hold promise for the development of multimodality agents with both imaging and therapeutic capabilities. Yet, some of the most promising nanoparticles demonstrate prolonged tissue retention and contain heavy metals. This presents serious concerns for toxicity. The creation of nanoparticles with optimal clearance characteristics will minimize toxicity risks by reducing the duration of exposure to these agents. Given that many nanoparticles possess easily modifiable surface and interior chemistry, if nanoparticle characteristics associated with optimal clearance from the body were well established, it would be feasible to design and create agents with more favorable clearance properties. This paper presents a thorough discussion of the physiologic aspects of nanoparticle clearance, focusing on renal mechanisms, as well as provides an overview of current research investigating clearance of specific types of nanoparticles and nano-sized macromolecules, including dendrimers, quantum dots, liposomes and carbon, gold, and silica-based nanoparticles. PMID:18817471

Real-world efficacy, toxicity and clinical management of ipilimumab treatment in metastatic melanoma.

PubMed

Khoja, Leila; Atenafu, Eshetu G; Ye, Qian; Gedye, Craig; Chappell, Maryanne; Hogg, David; Butler, Marcus O; Joshua, Anthony M

2016-02-01

Approved by the Food and Drug Administration in 2011, the anti-cytotoxic T-lymphocyte-associated protein 4 checkpoint inhibitor ipilimumab has delivered a survival benefit of ≥3 years in a subset of metastatic melanoma patients. After participating in the registration trial, patients were treated with this agent in routine practice. Toxicity and efficacy of agents in "real world" settings may differ from trials. The present study aimed to evaluate, with respect to toxicity and outcome, all patients treated with ipilimumab to date at the Princess Margaret Hospital (Toronto, Canada). Patients treated with ipilimumab between 2008 and 2013 were identified, and patient characteristics (age, gender, tumour burden, oncogenic mutation status, number of treatments received and toxicities from treatment) were collected. Progression-free survival (PFS) and overall survival (OS) were calculated from the commencement of ipilimumab treatment. Associations between clinical characteristics and outcome or toxicity were assessed. Between 2008 and 2013, 129 patients with metastatic cutaneous melanoma were treated. Since, during this period, ipilimumab was approved in the second line setting, ipilimumab was delivered in the second or subsequent line in all patients, and 70% did not receive any further anticancer therapy. Immune-related toxicities were observed, the onset of which varied from 1 to 162 days. The majority resolved within 6 weeks of the final treatment, with the exception of endocrinopathies and bowel related toxicity. The median PFS and OS were 2.83 and 8.44 months, respectively. No pre-treatment factor independently predicted toxicity. The number of infusions (4 vs. ≤3) and presence of toxicity were significantly associated with superior survival. The onset of toxicity secondary to ipilimumab could occur later than previously reported. Toxicities were manageable, but required long-term vigilance.

ATM regulates 3-methylpurine-DNA glycosylase and promotes therapeutic resistance to alkylating agents.

PubMed

Agnihotri, Sameer; Burrell, Kelly; Buczkowicz, Pawel; Remke, Marc; Golbourn, Brian; Chornenkyy, Yevgen; Gajadhar, Aaron; Fernandez, Nestor A; Clarke, Ian D; Barszczyk, Mark S; Pajovic, Sanja; Ternamian, Christian; Head, Renee; Sabha, Nesrin; Sobol, Robert W; Taylor, Michael D; Rutka, James T; Jones, Chris; Dirks, Peter B; Zadeh, Gelareh; Hawkins, Cynthia

2014-10-01

Alkylating agents are a first-line therapy for the treatment of several aggressive cancers, including pediatric glioblastoma, a lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed, increasing therapeutic response while minimizing toxicity. Using an siRNA screen targeting over 240 DNA damage response genes, we identified novel sensitizers to alkylating agents. In particular, the base excision repair (BER) pathway, including 3-methylpurine-DNA glycosylase (MPG), as well as ataxia telangiectasia mutated (ATM), were identified in our screen. Interestingly, we identified MPG as a direct novel substrate of ATM. ATM-mediated phosphorylation of MPG was required for enhanced MPG function. Importantly, combined inhibition or loss of MPG and ATM resulted in increased alkylating agent-induced cytotoxicity in vitro and prolonged survival in vivo. The discovery of the ATM-MPG axis will lead to improved treatment of alkylating agent-resistant tumors. Inhibition of ATM and MPG-mediated BER cooperate to sensitize tumor cells to alkylating agents, impairing tumor growth in vitro and in vivo with no toxicity to normal cells, providing an ideal therapeutic window. ©2014 American Association for Cancer Research.

Valorization of titanium metal wastes as tanning agent used in leather industry.

PubMed

Crudu, Marian; Deselnicu, Viorica; Deselnicu, Dana Corina; Albu, Luminita

2014-10-01

The development of new tanning agents and new technologies in the leather sector is required to cope with the increasingly higher environmental pressure on the current tanning materials and processes such as tanning with chromium salts. In this paper, the use of titanium wastes (cuttings) resulting from the process of obtaining highly pure titanium (ingots), for the synthesis of new tanning agent and tanning bovine hides with new tanning agent, as alternative to tanning with chromium salts are investigated. For this purpose, Ti waste and Ti-based tanning agent were characterized for metal content by inductively coupled plasma mass spectrometry (ICP-MS) and chemical analysis; the tanned leather (wet white leather) was characterized by Scanning Electron Microscope/Energy Dispersive Using X-ray (Analysis). SEM/EDX analysis for metal content; Differential scanning calorimetric (DSC), Micro-Hot-Table and standard shrinkage temperature showing a hydrothermal stability (ranged from 75.3 to 77°C) and chemical analysis showing the leather is tanned and can be processed through the subsequent mechanical operations (splitting, shaving). On the other hand, an analysis of major minor trace substances from Ti-end waste (especially vanadium content) in new tanning agent and wet white leather (not detected) and residue stream was performed and showed that leachability of vanadium is acceptable. The results obtained show that new tanning agent obtained from Ti end waste can be used for tanning bovine hides, as eco-friendly alternative for chrome tanning. Copyright © 2014 Elsevier Ltd. All rights reserved.

Internet-enabled collaborative agent-based supply chains

NASA Astrophysics Data System (ADS)

Shen, Weiming; Kremer, Rob; Norrie, Douglas H.

2000-12-01

This paper presents some results of our recent research work related to the development of a new Collaborative Agent System Architecture (CASA) and an Infrastructure for Collaborative Agent Systems (ICAS). Initially being proposed as a general architecture for Internet based collaborative agent systems (particularly complex industrial collaborative agent systems), the proposed architecture is very suitable for managing the Internet enabled complex supply chain for a large manufacturing enterprise. The general collaborative agent system architecture with the basic communication and cooperation services, domain independent components, prototypes and mechanisms are described. Benefits of implementing Internet enabled supply chains with the proposed infrastructure are discussed. A case study on Internet enabled supply chain management is presented.

Effectiveness and reaction networks of H2O2 vapor with NH3 gas for decontamination of the toxic warfare nerve agent, VX on a solid surface.

PubMed

Gon Ryu, Sam; Wan Lee, Hae

2015-01-01

The nerve agent, O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) must be promptly eliminated following its release into the environment because it is extremely toxic, can cause death within a few minutes after exposure, acts through direct skin contact as well as inhalation, and persists in the environment for several weeks after release. A mixture of hydrogen peroxide vapor and ammonia gas was examined as a decontaminant for the removal of VX on solid surfaces at ambient temperature, and the reaction products were analyzed by gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectrometry (NMR). All the VX on glass wool filter disks was found to be eliminated after 2 h of exposure to the decontaminant mixtures, and the primary decomposition product was determined to be non-toxic ethyl methylphosphonic acid (EMPA); no toxic S-[2-(diisopropylamino)ethyl] methylphosphonothioic acid (EA-2192), which is usually produced in traditional basic hydrolysis systems, was found to be formed. However, other by-products, such as toxic O-ethyl S-vinyl methylphosphonothioate and (2-diisopropylaminoethyl) vinyl disulfide, were detected up to 150 min of exposure to the decontaminant mixture; these by-products disappeared after 3 h. The two detected vinyl byproducts were identified first in this study with the decontamination system of liquid VX on solid surfaces using a mixture of hydrogen peroxide vapor and ammonia gas. The detailed decontamination reaction networks of VX on solid surfaces produced by the mixture of hydrogen peroxide vapor and ammonia gas were suggested based on the reaction products. These findings suggest that the mixture of hydrogen peroxide vapor and ammonia gas investigated in this study is an efficient decontaminant mixture for the removal of VX on solid surfaces at ambient temperature despite the formation of a toxic by-product in the reaction process.

TOXICITY-BASED CHEMICAL AGENT DETECTION SYSTEMS: CONTINUOUS MONITOR AND EXPOSURE HISTORY

EPA Science Inventory

This project will develop and characterize chemical agent detection systems that will provide broad toxicological screening information to first responders and building decontamination personnel. The primary goal for this technology is to detect the presence of airborne chemic...

Chemical structure and pharmacokinetics of novel quinolone agents represented by avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and nemonoxacin.

PubMed

Kocsis, Bela; Domokos, J; Szabo, D

2016-05-23

Quinolones are potent antimicrobial agents with a basic chemical structure of bicyclic ring. Fluorine atom at position C-6 and various substitutions on the basic quinolone structure yielded fluoroquinolones, namely norfloxacin, ciprofloxacin, levofloxacin, moxifloxacin and numerous other agents. The target molecules of quinolones and fluoroquinolones are bacterial gyrase and topoisomerase IV enzymes. Broad-spectrum and excellent tissue penetration make fluoroquinolones potent agents but their toxic side effects and increasing number of resistant pathogens set limits on their use. This review focuses on recent advances concerning quinolones and fluoroquinolones, we will be summarising chemical structure, mode of action, pharmacokinetic properties and toxicity. We will be describing fluoroquinolones introduced in clinical trials, namely avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and non-fluorinated nemonoxacin. These agents have been proved to have enhanced antibacterial effect even against ciprofloxacin resistant pathogens, and found to be well tolerated in both oral and parenteral administrations. These features are going to make them potential antimicrobial agents in the future.

Toxicity of N-substituted aromatics to acetoclastic methanogenic activity in granular sludge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donlon, B.A.; Razo-Flores, E.; Field, J.A.

1995-11-01

N-substituted aromatics are important priority pollutants entering the environment primarily through anthropogenic activities associated associated with the industrial production of dyes, explosives, pestides, and pharmaceuticals. Anaerobic treatment of wastewaters discharged by these industries could potentially be problematical as a result of the high toxicity of N-substituted aromatics. The objective of this study was to examine the structure-toxicity relationship of N-substituted aromatic compounds to acetoclastic methanogenic bacteria. The toxicity was assayed to serum flasks by measuring methane production in granular sludge. Unacclimated cultures were used to minimize the biotransformation of the toxic organic chemicals during the test. The nature and themore » degree of the aromatic substitution were observed to have a profound effect on the toxicity of the test compound. Nitroaromatic compounds were, on the average, over 500-fold more toxic than their corresponding aromatic amines. Considering the facile reduction of nitro groups by anerobic microorganisms, a dramatic detoxification of nitroaromatics towards methanogens can be expected to occur during anaerobic wastewater treatment. While the toxicity exerted by the N-substituted aromatic compounds was closely correlated with compound apolarity (log P), it was observed that at any given log P, N-substituted phenols had a toxicity that was 2 orders of magnitude higher than that of chlorophenols and alkylphenols. This indicates that toxicity due to the chemical reactivity of nitroaromatics is much more important than partitioning effects in bacterial membranes. 41 refs., 3 figs., 1 tab.« less

Natural remedies for non-steroidal anti-inflammatory drug-induced toxicity.

PubMed

Simon, Jerine Peter; Evan Prince, Sabina

2017-01-01

The liver is an important organ of the body, which has a vital role in metabolic functions. The non-steroidal anti-inflammatory drug (NSAID), diclofenac causes hepato-renal toxicity and gastric ulcers. NSAIDs are noted to be an agent for the toxicity of body organs. This review has elaborated various scientific perspectives of the toxicity caused by diclofenac and its mechanistic action in affecting the vital organ. This review suggests natural products are better remedies than current clinical drugs against the toxicity caused by NSAIDs. Natural products are known for their minimal side effects, low cost and availability. On the other hand, synthetic drugs pose the danger of adverse effects if used frequently or over a long period. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, K.N.; Xu, J.

1997-04-29

Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities. 2 figs.

3-hydroxy-2(1H)-pyridinone chelating agents

DOEpatents

Raymond, Kenneth N.; Xu, Jide

1997-01-01

Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of said chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to said 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities.

An Embedded Multi-Agent Systems Based Industrial Wireless Sensor Network.

PubMed

Taboun, Mohammed S; Brennan, Robert W

2017-09-14

With the emergence of cyber-physical systems, there has been a growing interest in network-connected devices. One of the key requirements of a cyber-physical device is the ability to sense its environment. Wireless sensor networks are a widely-accepted solution for this requirement. In this study, an embedded multi-agent systems-managed wireless sensor network is presented. A novel architecture is proposed, along with a novel wireless sensor network architecture. Active and passive wireless sensor node types are defined, along with their communication protocols, and two application-specific examples are presented. A series of three experiments is conducted to evaluate the performance of the agent-embedded wireless sensor network.

Combined treatment of toxic cyanobacteria Microcystis aeruginosa with hydrogen peroxide and microcystin biodegradation agents results in quick toxin elimination.

PubMed

Dziga, Dariusz; Maksylewicz, Anna; Maroszek, Magdalena; Marek, Sylwia

2018-01-01

Under some conditions the growth of toxic cyanobacteria must be controlled by treatment with algicidal compounds. Hydrogen peroxide has been proposed as an efficient and relatively safe chemical which can remove cyanobacteria from the environment selectively, without affecting other microorganisms. However, the uncontrolled release of secondary metabolites, including toxins may occur after such a treatment. Our proposal presented in this paper concerns fast biodegradation of microcystin released after cell lysis induced by hydrogen peroxide. The effectiveness of both, Sphingomonas sp. and heterologously expressed MlrA enzyme, in the removal of the toxin from Microcystis aeruginosa culture was investigated. The results indicate that neither Sphingomonas cells nor MlrA are affected by hydrogen peroxide at the concentrations which stop the growth of cyanobacteria. A several-fold reduction in microcystin levels was documented in the presence of these agents with biodegradation ability. Our results provide evidence that such a combined treatment of water reservoirs dominated by microcystin-producing cyanobacteria may be a promising alternative which allows fast elimination of both, the bloom forming species and toxins, from the environment.

EPA’s ToxCast Program for Predicting Toxicity and Prioritizing Chemicals for Further Screening and Testing