Comparison Of Acute Toxicity Research Articles

Three-Dimensional Conformal External Beam Radiotherapy versus the Combination of External Radiotherapy with High-Dose Rate Brachytherapy in Localized Carcinoma of the Prostate: Comparison of Acute Toxicity

Radiotherapy represents one of the basic therapeutic methods in treatment of localized carcinoma of the prostate. Optimal irradiation dose is the cornerstone of a successful treatment. Along with local control of the disease and overall survival of the patient, possible acute and long-term side effects need to be monitored very closely. A non-randomized prospective study comparing the acute genitourinary and gastrointestinal toxicity in patients irradiated for localized carcinoma of the prostate. Fifty-seven patients were treated with three-dimensional conformal external beam radiotherapy alone, and in the second treatment arm a combination of external beam radiotherapy and high-dose rate brachytherapy was employed in 40 patients. Three-dimensional conformal external beam radiotherapy. Acute G1 genitourinary toxicity was recorded in 35.1% of patients, G2 in 22.8%, and G2-3 in one patient (1.7%). Acute gastrointestinal toxicity was experienced by 54.4% of patients, G1 in 28.1%, G2 in 17.5%, and G3 in 8.8%. Three-dimensional conformal external beam radiotherapy + brachytherapy. Acute G1 genitourinary toxicity was recorded in 37.5% and grade 2 in 15% of the patients. Only G1 acute gastrointestinal toxicity was recorded in 40% of the patients. Acute G1 genitourinary toxicity was experienced by a similar percentage of patients in both treatment arms. Acute G2 genitourinary toxicity was more frequent in the three-dimensional conformal radiotherapy arm. Higher acute genitourinary toxicity, G3 or G4, was recorded only in one patient per treatment arm. Acute gastrointestinal toxicity was more frequent in the three-dimensional conformal radiotherapy arm. Higher acute gastrointestinal toxicity, G2 and G3, was only observed in the three-dimensional conformal radiotherapy arm. The acute toxicity observed was of a low grade. The combination of external beam radiotherapy with brachytherapy resulted in a lower incidence of gastrointestinal toxicity than external beam radiotherapy alone.

Comparative acute toxicity of potassium permanganate to nontarget aquatic organisms

Potassium permanganate (KMnO4) is used worldwide in freshwater pond aquaculture for treatment and prevention of waterborne external parasitic, bacterial, and fungal diseases. Nevertheless, KMnO4 has not been approved by the U.S. Food and Drug Administration, and insufficient information exists to allow evaluation of the environmental risk of KMnO4 exposures. Limited data exist concerning KMnO4 toxicity to nontarget species in systems receiving aquaculture effluent from treated ponds. The goal of this research is to generate effects data for use in developing an ecological risk assessment of KMnO4. Toxicity tests were used to compare the relative sensitivities of five standard aquatic test species to KMnO4. Acute toxicity test results using synthetic moderately hard water show static 96-h mean median lethal concentration (LC50) values +/- standard deviation (SD) of 0.058 +/- 0.006 mg/L for Ceriodaphnia dubia, 0.053 +/- 0.009 mg/L for Daphnia magna, 2.13 +/- 0.07 mg/L for Pimephales promelas, 4.74 +/- 1.05 mg/L for Hyalella azteca, and 4.43 +/- 0.79 mg/L for Chironomus tentans. Most of these values are below the recommended KMnO4 treatment rate of at least 2.0 mg/L or 2.5 times the water's potassium permanganate demand (PPD; an estimation of the available reducing agents in the exposure water), suggesting significant environmental risk. However, repeating these laboratory tests using pond water resulted in significantly reduced toxicity, with static 96-h mean LC50 values (+/-SD) of 2.39 +/- 0.36 mg/L for C. dubia, 1.98 +/- 0.12 mg/L for D. magna, 11.22 +/- 1.07 mg/L for P. promelas, 13.55 +/- 2.24 mg/L for H. azteca, and 12.30 +/- 2.83 mg/L for C. tentans. The PPD of synthetic moderately hard water was 0.329 +/- 0.114 mg/L; however, pond water PPD was 5.357 +/- 0.967 mg/L. The effective disease-treating dose based on 2.5 times the PPD would thus be 0.823 and 13.392 mg KMnO4/L, respectively, exceeding the LC50 for most of these nontarget organisms, even in pond water, immediately after treatment.

2591: Comparison of Acute Toxicities When Utilizing Image Guidance for Prostate Cancer External Beam Radiation - Ultrasound vs. Fiducial Markers

2591: Comparison of Acute Toxicities When Utilizing Image Guidance for Prostate Cancer External Beam Radiation - Ultrasound vs. Fiducial Markers

Comparative acute and combinative toxicity of aflatoxin B 1 and fumonisin B 1 in animals and human cells

Aflatoxin B 1 (AFB 1) and fumonisin B 1 (FB 1) are important food-borne mycotoxins. The co-contamination of food stuffs with these two mycotoxins is well known and has been possibly implicated in the development of human hepatocellular carcinoma in high risk regions around the world. In this study the acute and combinative toxicity of AFB 1 and FB 1 were tested in F-344 rats, mosquitofish ( Gambusia affinis), immortalized human hepatoma cells (HepG2) and human bronchial epithelial cells (BEAS-2B). Preliminary experiments were conducted in order to assess the acute toxicity and obtain LD 50, LC 50 and IC 50 values for individual toxins in each model, respectively. This was followed by testing combinations of AFB 1 and FB 1 to obtain LD 50, LC 50 and IC 50 values for the combination in each model. All models demonstrated a significant dose response in relation to toxin treatment. The potency of the mixture was gauged through the determination of the interaction index metric. Results of this study demonstrate that these two toxins interacted to produce alterations in the toxic responses with a strong additive interaction noted in the cases of F344 rats and mosquitofish. It can be gathered that this combination may pose a significant threat to public health and further research needs to be completed addressing alterations in metabolism and detoxification that may influence the toxic manifestations in combination. These results will provide foundational knowledge for future studies on long-term combinative toxic and health effects of these mycotoxins.

Comparative acute and combinative toxicity of aflatoxin B1 and T-2 toxin in animals and immortalized human cell lines

Aflatoxin B1 (AFB1) and T-2 toxin (T-2) are important food-borne mycotoxins that have been implicated in human health and as potential biochemical weapons threats. In this study the acute and combinative toxicity of AFB1 and T-2 were tested in F-344 rats, mosquitofish (Gambusia affinis), immortalized human hepatoma cells (HepG2) and human bronchial epithelial cells (BEAS-2B). Preliminary experiments were conducted in order to assess the acute toxicity and to obtain LD50, LC50 and IC50 values for individual toxins in each model, respectively. This was followed by testing combinations of AFB1 and T-2 to obtain LD50, LC50 and IC50 values for the combination in each model. All models demonstrated a significant dose response in the observed parameters to treatment. The potency of the mixture was gauged through the determination of the interaction index metric. The results of this study demonstrate that these two toxins interacted to produce alterations in the toxic responses generally classifiable as additive; however, a synergistic interaction was noted in the case of BEAS-2B. It can be gathered that this combination may pose a significant threat to public health and further research needs to be completed addressing alterations in metabolism and detoxification that may influence the toxic manifestations in combination.

Up-and-down procedure (UDP) determinations of acute oral toxicity of nitroso degradation products of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)

Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), a widely used military explosive and soil and ground water contaminant of munitions manufacturing and artillery training sites, undergoes microbial nitroreductase metabolism to hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX), hexahydro-1,3-dinitroso-5-nitro-1,3,5-triazine (DNX), and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX). Human occupational and accidental exposures to RDX, as well as acute oral exposures in rats, result in seizures, but little is known about the toxicity of the RDX degradation products. The main objective of the present study was to determine the oral LD50 of the most potent RDX N-nitroso product in female Sprague-Dawley rats using the recently validated up-and-down procedure (UDP). With only 26 rats, MNX was identified as the most potent metabolite and a maximum likelihood estimate of 187 mg kg(-1) (95% confidence interval 118-491 mg kg(-1)) for its LD50 was established and found equivalent to that of RDX determined with the same protocol. CNS toxicity, manifested as forelimb clonic seizures progressing to generalized clonic-tonic seizures, was the critical adverse effect. Further, confirmation of the UDP LD50 for MNX with a fixed-dose design enabled identification of 94 mg kg(-1) as the highest nonlethal dose. An ED50 of 57 mg kg(-1) was determined for neurotoxicity, while splenic hemosiderosis and decreased blood hematocrit and hemoglobin concentration occurred with a threshold at 94 mg kg(-1) in 14-day survivors. These studies, while providing new toxicity data necessary for the management of RDX-contaminated sites, illustrate the efficiency of the UDP for comparative acute toxicity determinations and its value in guiding further characterization of dose dependency of identified adverse effects.

950 poster A comparison of acute toxicity of the prostate cancer patients treated with high dose rate and low dose rate interstitial brachytherapy

950 poster A comparison of acute toxicity of the prostate cancer patients treated with high dose rate and low dose rate interstitial brachytherapy

Comparative acute toxicity of herbicides to photosynthesis of coral zooxanthellae.

Comparative acute toxicity of herbicides to photosynthesis of coral zooxanthellae.

Cytotoxic effects and induction of cytochromes P450 1A1/2 by insecticides, in hepatic or epidermal cells: binding capability to the Ah receptor

Insecticides deserve particular attention since the general population is potentially exposed to such chemicals through many routes. We therefore tested the comparative acute and chronic toxicity of chemicals belonging to the major insecticides families (DDT, malathion and tetrachlorvinphos, carbaryl, cypermethrin, diflubenzuron), in hepatocytes, HepG2 and HaCaT cell lines. Two kinds of end-points were used: cytotoxicity parameters and CYP1A1 induction. Except for cypermethrin and diflubenzuron, all these chemicals exerted a cytotoxic effect in hepatocytes and HaCaT, but not in HepG2 cells. However, the induction of the EROD activity appeared more sensitive since a response was detected at lower concentrations. Significant differences were observed between the cell types and the insecticides. Furthermore, these chemicals were unable to displace [ 3H]TCDD from its binding sites, suggesting that they would not be a ligand of the Ah receptor. The experimental approach used herein may be a good means for predicting the acute and chronic toxicity of pesticides.

Comparison of Acute Toxicity and Genotoxic Concentrations of Single Compounds and Waste Elutriates Using the Microtox/Mutatox Test System

The Mutatox test has been developed by Microbics Corp., U.S.A., in addition to the widely used acute toxicity test Microtox. The Mutatox test indicates the presence of any material in a test sample that causes genetic damage to dark variants of the luminescent bacteriaVibrio fischeri.As the Microtox test is less time-consuming and more cost-effective than the Mutatox test, the possibility of using the EC50measured by Microtox for range-finding of genotoxic concentrations for the Mutatox test was examined. Both tests were applied on single compounds and several waste elutriates. The genotoxic potential of two PAH metabolites—1-hydroxypyrene and 9-fluorenone-1-carboxylic acid—was detected. According to the present results the highest concentration of a sample in the Mutatox test should in general exceed the EC50by about 5–10 times. Elutriates were submitted to analyses of TOC, heavy metals, phenols, and PAH; additionally GC/MS screening analyses were carried out. In most cases correlations of ecotoxicological effects with single contaminants were not possible, but it can be assumed that these effects were produced by the interaction of inorganic and organic compounds present in the elutriates.

Comparative Acute and Chronic Toxicity of Diethylenetriamine Pentaacetic Acid (DTPA) and Ferric-Complexed DTPA to Daphnia carinata

Comparative Acute and Chronic Toxicity of Diethylenetriamine Pentaacetic Acid (DTPA) and Ferric-Complexed DTPA to Daphnia carinata

Comparative Acute Toxicity of Two Herbicides, Paraquat and Glyphosate, to Daphnia magna and D. spinulata

Comparative Acute Toxicity of Two Herbicides, Paraquat and Glyphosate, to Daphnia magna and D. spinulata

Comparative acute ammonia toxicity in marine fish and plasma ammonia response

Using a continuous-flow method a total of 14 acute toxicity bioassays were conducted using seabass ( Dicentrarchus labrax), seabream ( Spams aurata) and turbot ( Scophthalmus maximus) juveniles weighing from 6 to 163 g (wet weight). Median LC50s of un-ionized ammonia-nitrogen (UIA-N) and median LT50s (plus their confidence intervals) were calculated for 6, 12, 24, 48 and 96-h exposures for each trial. Under optimal environmental conditions (17–18 °C, 34%. S, 8.15 pH and oxygen over 75% saturation), median 96-h LC50s averaged 1.7 mg 1 −1 UIA-N (40 mg 1 −1 TAN, total ammonia nitrogen) in seabass compared with 2.5–2.6 mg 1 −1 UIA-N (57–59 mg 1 −1 TAN) in seabream and turbot. Median LC50s did not change significantly from 24 to 96-h exposure and were not related to fish size. Significant variations in fish sensitivity were observed from one group to another and seabass juveniles appeared to be more susceptible to ammonia than seabream and turbot. In all species, mortality occurred over a relatively narrow range of ammonia concentrations. Lethal threshold concentrations (LTC) were estimated to be over 90% of 96-h LC50s. In starved fish, blood plasma levels of ammonia, which were positively correlated with ambient ammonia, can be used to estimate the extent of ammonia toxicity. The same increase in plasma TAN vs. ambient ammonia level was observed in seabass, seabream and turbot. A mortality of 50% was observed after a 4-day exposure when the increase in TAN was 4 times the initial level in seabass and more than 10 times the normal level in seabream and turbot. These results show, for the first time, that seabass unlike seabream and turbot have lower thresholds of physiological disturbances, which explains why they are more sensitive to ammonia.

Comparative acute toxicity of the first 50 Multicentre Evaluation of In Vitro Cytotoxicity chemicals to aquatic non-vertebrates

The acute toxicity data of the first 50 chemicals of the Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) programme is compared for three “cyst-based toxicity tests” (Artoxkit M with Artemia salina, Streptoxkit F with Streptocephalus proboscideus, and Rotoxkit F with Brachionus calyciflorus), and two other tests (the Daphnia magna and the Photobacterium phosphoreum Microtox™ tests) commonly used in ecotoxicology. The difference in sensitivity for the 50 chemicals was as high as 19 orders of magnitude (on a molecular weight basis) between the most and least sensitive species. Generally, a similar toxicity ranking of the 5 test species was found for most of the chemicals and the interspecies correlations were high. Results from Principal Component Analysis (PCA) and cluster analysis indicated that the groupings are not related to a clear and defined chemical structure. However, the loading plot of the first two principal components may aid in selecting the minimum number and type of tests that have to be included in a battery which encompasses a broad spectrum of toxicity levels. Consequently, this study supports the use of a selected battery of tests to evaluate ecotoxicity and suggests its possible importance for screening of biologically-active compounds from natural sources.

Comparative acute toxicity and bioconcentration of selenium by the midge Chironomus decorus exposed to selenate, selenite, and seleno-DL-methionine

The increased flux of selenium into aquatic ecosystems due to anthropogenic activities has resulted in the degradation of several systems. Initial experiments examined the comparative acute toxicity of waterborne selenate, selenite, and seleno-DL-methionine to fourth instar Chironomus decorus larvae resulting in 48-h LC50 concentrations of 23.7, 48.2, and 194 mg Se/L, respectively. The relative toxicities of the selenium forms are reversed compared to previous studies on other species and demonstrate that relative waterborne selenium toxicity is species specific. Studies examining the kinetics of selenate and selenite (the dominant waterborne forms) accumulation by C. decorus larvae exposed to the 48-h LC50 selenium concentrations showed initial rapid uptake and subsequent plateauing with maximum concentrations attained by 16 h. The final whole body selenium levels were approximately 63 mg Se/kg for selenate and 85 mg Se/kg for selenite. Comparative bioconcentration experiments demonstrated that after 48 h selenium accumulation was greater in larval C. decorus exposed to 25 mg Se/L as seleno-DL-methionine than in those exposed to 25 mg Se/L as selenate and selenite.

Comparative Acute Inhalation Toxicity of a Saline Suspension and an Ethanol Solution of T-2 Mycotoxin in Mice

AbstractWe compared retention, distribution, toxicity, and histopathological change in mice after exposure to aerosols of T-2 suspended in saline or dissolved in ethanol. We found that the LC50 for mice exposed for 10 min to an aerosol of a saline suspension of T-2 was 0.035 ± 0.02 mg T-2 per liter air, which was lower than the LC50 (0.380 ± 0.08 mg T-2 per liter air) for an aerosol of T-2 dissolved in ethanol. However, within about 15 min postexposure, most of the T-2 deposited in the respiratory tract was translocated from the respiratory tract regardless of whether the T-2 aerosol was from a saline suspension or ethanol solution. Also, although T-2 is an inflammatory agent to dermis and gastrointestinal epithelium, T-2 from either aerosol did not produce any histological evidence of inflammation in the respiratory tract.

Comparative acute toxicity of diethyleneglycol dinitrate to freshwater aquatic organisms

AbstractThe acute toxicity of diethyleneglycol dinitrate (DEGDN) to nine freshwater aquatic organisms was determined. Juvenile fathead minnow, bluegill, channel catfish and rainbow trout were exposed to the compound for 96 h. The invertebrates tested for 48 h included the neonate water flea, early‐young amphipod, midge larva and the mayfly larva. The effect of DEGDN on the growth of the green alga Selenastrum capricornutum was also studied.The toxicity of DEGDN was relatively low to the nine freshwater species tested. Toxicity values ranged from a 5‐d EC50 (standing crop) of less than 58.4 mg/L for the alga to a 96‐h LC50 of 491.4 mg/L for the fathead minnow. The most sensitive invertebrate, the daphnid, was more sensitive than the most sensitive fish, the bluegill.

Comparative acute toxicity of thermal degradation aerosols generated by a chlorinated aromatic substitute to PCBs and by a PCB based fluid

The acute toxicity of thermal degradation aerosols produced by heating dielectric fluids has been studied in rats, using the experimental protocol recommended by the 6th Report of the Commission of the European Communities Safety and Health Commission for the Mining and Extractive Industry. A PCB-based fluid was compared to a fluid called UGILEC T, a new nonflammable aromatic chlorinated substitute. Results show that UGILEC T as well as the PCB-based fluid gave aerosols that induced no serious toxic effects when the oven is heated to 500°C and 700°C. By contrast, other non-chlorinated fluids such as a mineral oil, because they are less resistant to heating, were much more decomposed and gave aerosols that produced severe lung lesions and death.

Comparative toxicity and speciation of two hexavalent chromium salts in acute toxicity tests

AbstractThe comparative acute toxicity of potassium chromate and dichromate salts to six aquatic species including both freshwater and marine forms was investigated. A thermodynamic equilibrium model was developed to aid in interpreting toxicity data with respect to hexavalent chromium speciation. Although parallel acute toxicity tests conducted with both salts yielded similar LC50 values, toxicity differences tended to become more pronounced as the sensitivity of the test species to the chemical decreased. Observed changes in pH and predicted changes in chromium speciation that occurred between the two salts in tests with less sensitive species were postulated to explain these findings. The implication of the aqueous chromium species to the relative toxicity of the hexavalent chromium are discussed. If hexavalent chromium is widely adopted as a standard reference toxicant for aquatic toxicity testing then the chromate salt should be used since it does not appreciably alter the initial pH of the dilution water and subsequent speciation to the extent that would be expected if the dichromate salt was employed. Standardization of the source of hexavalent chromium used in reference tests will facilitate intralaboratory comparison of toxicity data.

Comparative acute toxicity of chlorocitrate and fluorocitrate in dogs

The high-dose effects of chlorocitrate [(−)- threo-chlorocitric acid] were compared in vivo to another halogenated citrate analog, and a well-known inhibitor of the tricarboxylic acid (TCA) cycle, fluorocitrate. The compounds were given iv to two dogs per sex per group, and a control group received an equimolar amount of citric acid. Chlorocitrate (100 mg/kg) showed TCA cycle inhibition as did fluorocitrate (8 mg/kg) in that both caused depletion of ATP and accumulation of citrate in the liver. Chlorocitrate was a significantly weaker inhibitor of citrate metabolism than fluorocitrate as evidenced by a substantially lower accumulation of serum citrate despite a much higher dose. Both halocitrates produced a similar diabetes-like syndrome (hyperglycemia, glycosuria) mediated by a significant hyperglucagonemia and slight hypoinsulinemia. Chlorocitrate was more potent in this effect and a much greater buildup of plasma lactate ensued (18- versus 3.7-fold increase), enough to explain lethality observed in earlier studies. In contrast, fluorocitrate produced a severe life-threatening hypocalcemia (−30%), and hypercalcuria was observed. This effect on calcium distribution was only minimal with chlorocitrate. Both halocitrates had a similar depressive effect on circulation as evidenced by hypothermia, bradycardia, and elongation of the QT-interval. These changes were considered to be the result of lactic acidosis and the ongoing ion imbalance since heart ATP levels were not depleted.