Toxicity of Binary Chemical Munition Destruction Products: Methylphosphonic Acid, Methylphosphinic Acid, 2-Diisopropylaminoethanol, DF Neutralent, and QL Neutralent

2007 ◽  
Vol 26 (6) ◽  
pp. 503-512 ◽  
Author(s):  
Rebecca E. Watson ◽  
Ahmed M. Hafez ◽  
Jonathan N. Kremsky ◽  
George O. Bizzigotti
Keyword(s):  
Ames Test ◽  
Lethal Dose ◽  
Methylphosphonic Acid ◽  
Major Constituent ◽  
Toxicity Tests ◽  
Chemical Agent ◽  
Sprague Dawley ◽  
Ecotoxicity Tests ◽  
Good Laboratory ◽  
Hydrolysis Of

This paper reports the toxicity and environmental impact of neutralents produced from the hydrolysis of binary chemical agent precursor chemicals DF (methylphosphonic difluoride) and QL (2-[bis(1-methylethyl)amino]ethyl ethyl methylphosphonite). Following a literature review of the neutralent mixtures and constituents, basic toxicity tests were conducted to fill data gaps, including acute oral and dermal median lethal dose assays, the Ames mutagenicity test, and ecotoxicity tests. For methylphosphonic acid (MPA), a major constituent of DF neutralent, the acute oral LD50 in the Sprague-Dawley rat was measured at 1888 mg/kg, and the Ames test using typical tester strains of Salmonella typhimurium and Escherichia coli was negative. The 48-h LC50 values for pH-adjusted DF neutralent with Daphnia magna and Cyprinodon variegatus were >2500 mg/L and 1593 mg/L, respectively. The acute oral LD50 values in the rat for QL neutralent constituents methylphosphinic acid (MP) and 2-diisopropylaminoethanol (KB) were both determined to be 940 mg/kg, and the Ames test was negative for both. Good Laboratory Practice (GLP)-compliant ecotoxicity tests for MP and KB gave 48-h D. magna EC50 values of 6.8 mg/L and 83 mg/L, respectively. GLP-compliant 96-h C. variegatus assays on MP and KB gave LC50 values of 73 and 252 mg/L, respectively, and NOEC values of 22 and 108 mg/L. QL neutralent LD50 values for acute oral and dermal toxicity tests were both > 5000 mg/kg, and the 48-h LD50 values for D. magna and C. variegatus were 249 and 2500 mg/L, respectively. Using these data, the overall toxicity of the neutralents was assessed.

Acute and Genetic Toxicity of Essential Oil Extracted from Litsea cubeba (Lour.) Pers.

2005 ◽  
Vol 68 (3) ◽  
pp. 581-588 ◽  
Author(s):  
MAN LUO ◽  
LI-KE JIANG ◽  
GUO-LIN ZOU
Keyword(s):  
Cancer Research ◽  
Essential Oil ◽  
Bone Marrow Cells ◽  
Lethal Dose ◽  
Raw Material ◽  
Toxicity Tests ◽  
Sprague Dawley ◽  
Genetic Toxicity ◽  
Litsea Cubeba

Litsea cubeba oil is an aromatic essential oil extracted from the fresh fruits of Litsea cubeba (Lour.) Pers. It is used as a flavor enhancer in foods, cosmetics, and cigarettes; as a raw material in the manufacture of citral, vitamins A, E, and K, ionone, methyl ionone, and perfumes; and as an antimicrobial and insecticide. Based on the widespread use of L. cubeba oil, its insolubility in water, resulting in its partition in soil sediment, and its volatility when exposed to the atmosphere, risk of injury due to consumption and occupational exposure may be significant. In the present study, we studied the toxicity of L. cubeba oil with a battery of acute and genetic toxicity tests in Institute of Cancer Research mice and Sprague-Dawley rats. The oral, dermal, and inhalation 50% lethal dose and concentration (LD50 and LC50) of L. cubeba oil were determined. Results indicated that the oral LD50, the dermal LD50, and the inhalation LC50 are approximately 4,000 mg/kg of body weight, in excess of 5,000 mg/kg, and approximatively 12,500 ppm, respectively. We therefore conclude that L. cubeba oil is slightly toxic. In addition, the genetic toxicity of L. cubeba oil was assessed with Salmonella Typhimurium, by determination of the induction of micronuclei in bone marrow cells, and also by testing for chromosome aberration in spermatocyte cells of Institute of Cancer Research mice. The results of genetic toxicity testing of L. cubeba oil in vitro and in vivo were negative.

scholarly journals Multi-omics phenotyping of the gut-liver axis reveals metabolic perturbations from a low-dose pesticide mixture in rats

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Robin Mesnage ◽  
Maxime Teixeira ◽  
Daniele Mandrioli ◽  
Laura Falcioni ◽  
Mariam Ibragim ◽  
...  
Keyword(s):  
Stress Response ◽  
Microbial Community Composition ◽  
Serum Biochemistry ◽  
Feed Consumption ◽  
Laboratory Animals ◽  
Toxicity Tests ◽  
Sprague Dawley ◽  
Shotgun Metagenomics ◽  
Low Concentrations ◽  
Sprague Dawley Rats

AbstractHealth effects of pesticides are not always accurately detected using the current battery of regulatory toxicity tests. We compared standard histopathology and serum biochemistry measures and multi-omics analyses in a subchronic toxicity test of a mixture of six pesticides frequently detected in foodstuffs (azoxystrobin, boscalid, chlorpyrifos, glyphosate, imidacloprid and thiabendazole) in Sprague-Dawley rats. Analysis of water and feed consumption, body weight, histopathology and serum biochemistry showed little effect. Contrastingly, serum and caecum metabolomics revealed that nicotinamide and tryptophan metabolism were affected, which suggested activation of an oxidative stress response. This was not reflected by gut microbial community composition changes evaluated by shotgun metagenomics. Transcriptomics of the liver showed that 257 genes had their expression changed. Gene functions affected included the regulation of response to steroid hormones and the activation of stress response pathways. Genome-wide DNA methylation analysis of the same liver samples showed that 4,255 CpG sites were differentially methylated. Overall, we demonstrated that in-depth molecular profiling in laboratory animals exposed to low concentrations of pesticides allows the detection of metabolic perturbations that would remain undetected by standard regulatory biochemical measures and which could thus improve the predictability of health risks from exposure to chemical pollutants.

THE WATER-SOLUBLE POLYSACCHARIDES OF DERMATOPHYTES: IV. GALACTOMANNANS I FROM TRICHOPHYTON GRANULOSUM, TRICHOPHYTON INTERDIGITALE, MICROSPORUM QUINCKEANUM, TRICHOPHYTON RUBRUM, AND TRICHOPHYTON SCHÖNLEINII

1965 ◽  
Vol 43 (1) ◽  
pp. 30-39 ◽  
Author(s):  
C. T. Bishop ◽  
M. B. Perry ◽  
F. Blank ◽  
F. P. Cooper
Keyword(s):  
Aqueous Solutions ◽  
Copper Complexes ◽  
Trichophyton Rubrum ◽  
Periodate Oxidation ◽  
Structural Features ◽  
Water Soluble ◽  
Major Constituent ◽  
Branch Points ◽  
Terminal Units ◽  
Hydrolysis Of

A group of polysaccharides, called galactomannans I, were precipitated as their insoluble copper complexes from aqueous solutions of the crude polysaccharides obtained from each of the organisms designated in the title. The five galactomannans I were homogeneous under conditions of electrophoresis and ultracentrifugation and had high positive specific rotations. The major constituent monosaccharide was D-mannose; amounts of D-galactose ranged from nil for the polysaccharide from T. rubrum to 13% for that from T. schönleinii. Methylation and hydrolysis of the five galactomannans I yielded varying amounts of the following: 2,3,5,6-tetra-O-methyl-D-galactose (not present in the products from T. rubrum), 2,3,4,6-tetra-O-methyl-D-mannose, 2,3,4-tri-O-methyl-D-mannose, 2,4,6-tri-O-methyl-D-mannose, 3,4-di-O-methyl-D-mannose, and 3,5-di-O-methyl-D-mannose. Periodate oxidation results agreed with the methylation studies. The gross structural features of each galactomannan I appear to be the same, namely, a basic chain of 1 → 6 linked α-D-mannopyranose units for approximately every 22 of which there is a 1 → 3 linked α-D-mannopyranose residue. Branch points occur along the 1 → 6 linked chain at the C2 positions of the D-mannopyranose units and once in every 45 units at the C2 position of a 1 → 6 linked D-mannofuranose residue. The D-galactose in the polysaccharides is present exclusively as non-reducing terminal furanose units; non-reducing terminal units of D-mannopyranose are also present. The variations in the identities and relative amounts of the non-reducing terminal units were the only apparent differences in the gross structural features within this group of polysaccharides.

Treatment of VX Hydrolysate with Ultraviolet Light and Hydrogen Peroxide

1997 ◽  
Vol 2 (3) ◽  
Author(s):  
Michael G. MacNaughton ◽  
James R. Scott
Keyword(s):  
Hydrogen Peroxide ◽  
Ultraviolet Light ◽  
Pilot Scale ◽  
Methylphosphonic Acid ◽  
Chemical Agent ◽  
Organosulfur Compounds ◽  
Two Phase ◽  
First Order ◽  
Engineering Study ◽  
Inorganic Sulfate

AbstractAn engineering study was performed to evaluate the use of ultraviolet light and hydrogen peroxide to destroy caustic-neutralized VX nerve agent in the U.S. chemical agent stockpile as an alternative to incineration. Whereas caustic neutralization completely destroys VX, (3-ethyl-S-2-(diisopropylamino)ethyl methylphosphonothiolate, the reaction leaves a complex two-phase mixture containing organic phosphates and organosulfur compounds which require treatment prior to ultimate disposal. Studies performed in laboratory-scale (320-mL), bench-scale (10-L) and pilot-scale (20-L) reactors demonstrated that the principal products of the caustic neutralization-ethyl methylphosphonic acid (EMPA), methylphosphonic acid (MPA), 2-(diisopropylamino)ethyl sulfide (RSR), disulfide (RSSR) and the other mixed sulfides-could be oxidized to inorganic sulfate, phosphate, ammonia and carbon dioxide. The reaction was zero order above 1000 mg/L and pseudo first order below. To mineralize 10,000 lb of VX per day to less than 10 mg/L organic carbon would require more than 1100 lamps of 30 kW each.

scholarly journals 707. QPX9003: Pharmacology of a Novel Polymyxin in Mice and Rats

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S319-S319
Author(s):  
Mojgan Sabet ◽  
Ziad Tarazi ◽  
Jonathan Parkinson ◽  
Kade Roberts ◽  
Philip Thompson ◽  
...  
Keyword(s):  
Post Infection ◽  
Lethal Dose ◽  
Lung Infection ◽  
Infection Model ◽  
Rat Lung ◽  
Sprague Dawley ◽  
Bacterial Killing ◽  
Swiss Mice ◽  
Infection Models

Abstract Background Currently available polymyxins are limited by toxicity and poor efficacy at tolerated doses. We have developed a new series of polymyxin derivatives with improved safety profiles and in vitro potency against major MDR bacteria. The following describes studies on the in vivo antimicrobial activity and toxicity of QPX9003 in mice and rats. Methods Mouse studies. The minimum lethal dose (MLD by IV bolus) and nephrotoxicity (6 IP doses administered 2 hours apart) of QPX9003 and polymyxin B (PMB) were determined in Swiss mice. For the neutropenic mouse thigh infection using A. baumannii, Swiss mice were infected with ~106 CFU/thigh. Doses were administered IP at various intervals starting 2-hour post-infection and continued over 24 hours. Rat studies. For the rat lung infection model, Sprague-Dawley rats were infected with ~107 CFU/lung. QPX9003 and PMB were administered IV every 4 hours starting 2 hours post-infection and continued over 24 hours. Bacteria. For both infection models, animals were infected with A. baumannii AB1016 (QPX9003 MIC of 0.5 mg/L and PMB MIC of 1.0 mg/L). Untreated control groups were sacrificed at the start of treatment and both untreated and treated groups were sacrificed 24 hours after the start of treatment, infected tissues harvested, homogenized, and plated to determine colony counts. Results QPX9003 had reduced acute toxicity and nephrotoxicity compared with PMB in mice. QPX9003 showed better bacterial killing of A. baumannii than PMB at similar plasma exposures in both the mouse thigh model (−0.41 vs. +0.83 log CFU/thigh) and rat lung infection model (−1.10 vs. +1.44 log CFU/lung). Conclusion QPX9003 was less acutely toxic, less nephrotoxic, and was more efficacious in mouse and rat infection models compared with PMB. QPX9003 is a promising new polymyxin. (This work was supported in part by federal funds from the National Institutes of Allergy and Infectious Diseases [R01AI098771], and the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under OTA number HHSO100201600026C). Disclosures All authors: No reported disclosures.

Dexmedetomidine elevates the lethal dose threshold of bupivacaine in rats: A dosing study

2019 ◽  
Vol 39 (3) ◽  
pp. 365-373
Author(s):  
L Pan ◽  
Y Zhang ◽  
Y He ◽  
Z Chen ◽  
S Wang ◽  
...  
Keyword(s):  
Femoral Vein ◽  
Lethal Dose ◽  
Control Group ◽  
Sprague Dawley ◽  
Dose Threshold ◽  
Sd Rats ◽  
Group 12 ◽  
Group 3 ◽  
The Right ◽  
Group 1

Dexmedetomidine (DMED), an alpha-2 adrenoreceptor agonist, has been widely used in regional anesthesia procedures. However, the effect of DMED on local anesthetic cardiotoxicity has not been well delineated. This study consisted of two experiments. In experiment A, 42 Sprague–Dawley (SD) rats were randomly divided into 6 groups ( n = 7), each group was pretreated with DMED 0 μg kg−1 (D0 group), 1 μg kg−1 (D1 group), 3 μg kg−1 (D3 group), 6 μg kg−1 (D6 group), 12 μg kg−1 (D12 group), and 24 μg kg−1 (D24 group), administered through the right femoral vein. In experiment B, 20 SD rats were randomly divided into 4 groups ( n = 5), such as control group, DMED group, yohimbine (YOH) group, and DMED + YOH group. Each subgroup in experiment B was also pretreated similarly as in experiment A. After pretreatment of rats as described above (in experiments A and B), bupivacaine 2.5 mg kg−1 min−1 was infused to induce cardiac arrest. In experiment A, the lethal dose threshold of bupivacaine and plasma bupivacaine concentration in D3 and D6 group were higher than the other groups. In experiment B, there was no interaction between DMED and YOH in lethal dose threshold, arrhythmia time, plasma concentration of bupivacaine, and myocardial content of bupivacaine. DMED doses of 3–6 μg kg−1 elevated the lethal dose threshold of bupivacaine without involvement of the alpha-2 adrenoceptors.

Evaluation of the Toxicity of Intravenous Delivery of Auroshell Particles (Gold–Silica Nanoshells)

2012 ◽  
Vol 31 (6) ◽  
pp. 584-594 ◽  
Author(s):  
Shayne C. Gad ◽  
Kelly L. Sharp ◽  
Charles Montgomery ◽  
J. Donald Payne ◽  
Glenn P. Goodrich
Keyword(s):  
Water Solution ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Gold Nanoshells ◽  
Sprague Dawley ◽  
Ovary Cells ◽  
Good Laboratory ◽  
Chromosomal Aberration Assay

Gold nanoshells (155 nm in diameter with a coating of polyethylene glycol 5000) were evaluated for preclinical biocompatibility, toxicity, and biodistribution as part of a program to develop an injectable device for use in the photothermal ablation of tumors. The evaluation started with a complete good laboratory practice (GLP) compliant International Organization for Standardization (ISO)-10993 biocompatibility program, including cytotoxicity, pyrogenicity (US Pharmacopeia [USP] method in the rabbit), genotoxicity (bacterial mutagenicity, chromosomal aberration assay in Chinese hamster ovary cells, and in vivo mouse micronucleus), in vitro hemolysis, intracutaneous reactivity in the rabbit, sensitization (in the guinea pig maximization assay), and USP/ISO acute systemic toxicity in the mouse. There was no indication of toxicity in any of the studies. Subsequently, nanoshells were evaluated in vivo by intravenous (iv) infusion using a trehalose/water solution in a series of studies in mice, Sprague-Dawley rats, and Beagle dogs to assess toxicity for time durations of up to 404 days. Over the course of 14 GLP studies, the gold nanoshells were well tolerated and, when injected iv, no toxicities or bioincompatibilities were identified.

CHEMICAL WEED KILLERS: I. RELATIVE TOXICITY OF VARIOUS CHEMICALS TO FOUR ANNUAL WEEDS

1937 ◽  
Vol 15c (7) ◽  
pp. 299-323 ◽  
Author(s):  
W. H. Cook
Keyword(s):  
Chenopodium Album ◽  
Lethal Dose ◽  
Ammonium Thiocyanate ◽  
Copper Nitrate ◽  
Toxicity Tests ◽  
Appreciable Effect ◽  
Thlaspi Arvense ◽  
Sodium Bichromate ◽  
Other Substances ◽  
Annual Weeds

Toxicity tests on four annual weeds, Thlaspi arvense L.; Brassica arvensis L. Ktze.; Chenopodium album L.; and Avena fatua L.; showed no definite evidence of a specific susceptibility of a given species to a given substance. The relative resistance of these four weeds to most substances, judging from the certainly lethal dose, was in the order 1:1:2:7. Of the 76 chemicals tested, the following most toxic compounds killed all four species at the dosages employed; selenic and chloric acids, sodium hydroxide, arsenic pentoxide, sodium arsenite, sodium and ammonium chlorate, ammonium thiocyanate, sodium cyanide, zinc chloride, sodium bichromate, sodium selenite, copper nitrate, sodium sulphide, formic acid, gasoline, phenol, creosote, tetralin, sodium benzoate, aniline, benzene and furfural. The residual toxic effect on the soil, three to four weeks after treatment, showed that of the 35 more toxic chemicals tested, only selenic acid and the five chlorates used had any appreciable effect at low and intermediate dosages, while eleven other substances depressed growth following the application of high dosages.

Detection of heavy metal toxicity and genotoxicity in wastewaters by microbial assay

1994 ◽  
Vol 30 (10) ◽  
pp. 145-151 ◽  
Author(s):  
J. C. Codina ◽  
A. Pérez-García ◽  
A. de Vicente
Keyword(s):  
Escherichia Coli ◽  
Heavy Metals ◽  
Heavy Metal ◽  
Metal Toxicity ◽  
Ames Test ◽  
Deionized Water ◽  
Toxicity Tests ◽  
Water Solutions ◽  
Microbial Assay ◽  
Higher Sensitivity

The effect of wastewater on the sensitivity of toxicity and genotoxicity assays for the detection of heavy metals was evaluated. Five microbiological toxicity tests were used to compare the toxicity of cadmium, copper, chromium, mercury, nickel, and zinc, both in deionized water solutions and in wastewater. The toxicity assays employed were: Microtox®, two tests of growth inhibition using Pseudomonas fluorescens, and two spectrophotometric assays of the inhibition of respiration test using baker's yeast and P. fluorescens. Also, the genotoxic effect of the assayed metals was evaluated by using the Ames test, the Escherichia coli WP2 test, and the SOS test. The sensitivity to metals decreases in most of the toxicity and genotoxicity assays; in general, higher sensitivity thresholds (EC20) in wastewater than in water solutions were determined. Each test shows different sensitivities to each metal, which is related to different sensitivities of the organisms used in the assays, as well as to other factors.

scholarly journals RECOVERY OF PECTIC OLIGOSACCHARIDE (POS) FROM PECTIN HYDOLYSATE FOR FUNTIONAL FOODS

2018 ◽  
Vol 54 (4A) ◽  
pp. 81
Author(s):  
Nguyen Thi Kim Dung
Keyword(s):  
Food Safety ◽  
Air Temperature ◽  
Liquid Flow Rate ◽  
Lethal Dose ◽  
Total Yield ◽  
Pathogenic Microorganisms ◽  
New Class ◽  
Recovery Processes ◽  
Plastic Bags ◽  
Hydrolysis Of

Pectic oligosaccharide (POS) obtained bypartial hydrolysis of pectin is proposed as a new class of prebioticwhich has many beneficial propertiesfor the health of humans and animals. Currently only a small number of researcheshave explored the production process of POS products in laboratory-scale and pilot, however the manufacturing process, as well as the product, has not yet been offered for sale on the market. In this study, several parameters of arecovery processofPOS powder from the pectin hydrolysatehave been established: condense(5 times, by tangential filtration with nanofiltration column 0.3 kDa), precipitate (ratio of ethanol / concentrates: 3/1), spray drying (5 % maltodextrin, inlet air temperature 170 oC, liquid flow rate 2.5 L/h). The total yield of the recovery processes is 67.7 %. The POS product is still stable after 12 months of storage in plastic bags and in bags of tin. Food safety analysis indicate that POS products do not contain mycotoxins, heavymetals, pathogenic microorganisms and the lethal dose LD 50 can not be detected.

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