Toxicity Assessment

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Machine learning algorithms for mode-of-action classification in toxicity assessment

Machine learning algorithms for mode-of-action classification in toxicity assessment

In this paper, we present an innovative approach using machine learning for toxicity assessment. The computational tools are developed based on ANN and SVM, which are capable of learning data from given TCRCs with known MOA clustering information and then making MOA classification for untested chemical compounds. There are two chal- lenges and difficulties of this work. First the input data arising from the time-series TCRC data contains more than 850 data, and secondly, only limited data set are available for some clusters. A novel data processing technique using wavelet transform is introduced, so that not only a great reduction in input data is achieved but the MOA classification is more accurate due to wavelet coefficients have the ability to extract important fea- tures from the original TCRC data. Instead of using more than 850 data from the TCRCs with 11 concentrations, we only require 229 and 157 wavelet coefficients as input data to the developed data mining tools. In this study, it is also revealed that taking account the information from the negative control curve enhances the performance of the MOA clas- sification. It has been illustrated that the machine learning algorithm can be improved by utilizing information from DRC, so that a time interval leading to higher classifica- tion success rate can be selected as input. From the computational simulations, SVM is more effective compared to ANN for MOA classification. The developed SVM classi- fier has been tested for multi-cluster MOA classification, and impressive SR in the range

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Bioengineered human kidney for toxicity assessment

Bioengineered human kidney for toxicity assessment

vitro human kidney model. Tissues given to 100 uM of cisplatin shows greater cytotoxicity with similarities of 10 uM of cisplatin possessing almost a same curve with less percentage. The current data might show higher vulnerability of the NRK 52E and 49F cells to cisplatin- related cytotoxic after effects and here immortalized cells were utilized. The experiments show us that the greater level of cytotoxicity in case of kidney tissues but as lower concentration levels did not justify the earlier studies, by using tissue distillation or concentration equipment or parameters for example seeding density of cells and ECM materials might had an impact for making a viable design which illustrates the reduction of cell feasibility at high levels concentrations of cisplatin (>10 uM) in case 2D analysis, as the counter opposite of high amounts of cytotoxicity in all 3D LDH tests or analysis. Distinctions are also possible because the 3D and 2D was in cisplatin regulated media for 7 days (336 hours) and 48 hours respectively before the absorbance was calculated and so the extra time length of 288 had greater effects and tissue media in the trans-well plates was replaced every 3-4 day which could have promoted immature death of cell if and if it is not replaced then concentration level might enhance and cause toxicity to those cells, thus it might be understandable about the death capacity of H and E even though they were thought to be in good health. For better results the tissue culture media has to replaced often that is every 2 days and if is introduced to a bioreactor structure it might be in touch with fresh and healthy media and ensure better quality of the final product.

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TOXICITY ASSESSMENT OF CLARITHROMYCIN IN DIABETIC WISTAR RATS TREATED WITH ROSIGLITAZONE

TOXICITY ASSESSMENT OF CLARITHROMYCIN IN DIABETIC WISTAR RATS TREATED WITH ROSIGLITAZONE

Objectives: In clinical situations, diabetic patients already on prescription of Rosiglitazone are prone to bacterial infection. To cure such infection Clarithromycin is prescribed particularly in Respiratory Tract Infections. Materials and Methods: Diabetes was induced experimentally in overnight fasted Rats by intraperitoneal injection of Nicotinamide, 15 min prior to intraperitoneal injection of Streptozotocin (60 mg/kg). Nicotinamide (160 mg/kg) was freshly prepared by dissolving in distilled water and Streptozotocin was dissolved in freshly prepared 0.1M Citrate buffer. Since Rosiglitazone and Clarithromycin have found to exert minimal to mild toxicity in animals on these doses, i.e. 80 mg/kg and 400 mg/kg respectively, both these drugs were administered for 14 days to the animals to study the toxicity in diabetic condition. Parameters included for the study includes body weight changes, oral glucose tolerance test, biochemistry, hematology, urine analysis and histopathology.

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MEDICINAL PLANTS – FROM TRADITIONAL USE TO TOXICITY ASSESSMENT: A REVIEW

MEDICINAL PLANTS – FROM TRADITIONAL USE TO TOXICITY ASSESSMENT: A REVIEW

Toxicology is the fundamental science of poisons. A poison is generally considered to be any substance that can cause severe injury or death as a result of a physicochemical interaction with living tissue. However, all substances are potential poisons since all of them can cause injury or death following excessive exposure. On the other hand, all chemicals can be used safely if exposure of people or susceptible organisms to chemicals is kept below defined tolerable limits 10 . Appropriate dose of a drug should be determined by preliminary studies of acute toxicity. Such studies are essential to prevent any overdose of drug which may interfere with results of experiment.

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Toxicity Assessment of Municipal Solid Waste: A Case Study

Toxicity Assessment of Municipal Solid Waste: A Case Study

municipal solid waste management system (MSWMS) for compost processing unit at Mysuru city on the environment. Attempt has been made to identify the major toxic pollutant emission from the compost unit by GaBi software. Environmental impacts from the composting unit and the scenario with respect to other major cities has been evaluated. Finally the fate of the composting unit has been studied by integrating the inventories for GaBi software. This work is formulated as per principles, framework of Life Cycle Assessment (LCA) and work carried according to the phases and applications of an LCA (IS/ISO 14040, 2006). The first mandatory element is the selection of a manageable number of impact categories of resource use and second is environmental impact indicators. The selected impact categories are evaluated considering the indicators such as Human toxicity potential (HTP), Fresh water aquatic eco- toxicity potential (FWAETP) and Terrestrial eco-toxicity potential (TETP) other categories as per necessities. The selected categories are quantified for their impact contribution with different inputs and emissions obtained or analyzed from the study area.

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Toxicity Assessment of SiO2 Nanoparticles to Pear Seedlings

Toxicity Assessment of SiO2 Nanoparticles to Pear Seedlings

[7] with few studies on woody plants [8, 9]. On a global scale, trees account for the majority of biomass [10, 11] and are dominant constituents of terrestrial ecosystems [7]. Trees are characterized by a large woody component, the secondary xylem. The xylem is made up of a continuous porous structure of tracheides or tracheae and xylem elements that are responsible for nutrient and water transport from roots to leaves [10]. The size of these pores in these structures is in the micrometer range. Nanoparticles have a diameter in the range as the name indicates of nanometers and would thus be of a size that may allow xylem transport and accumulation in the xylem structures, eventually blocking the continuity and disturbing or destroying xylem function. This might give woody plants a special vulnerability towards nanomaterials. On the other hand, woody plants have a protective endodermis and the differentially permeable Casparian strip [12], reducing the potential for NP uptake. Currently, many metal oxide nanoparticles and carbon- based materials have phytotoxicity and environmental toxicity [13, 14, 15]. However, the investigations on behavior of nanometal oxides such as nano silica in plants and the mechanism of interaction, its influence, and agricultural application are still in the rudimentary stage [16, 17], and visible Si deficiency or toxicity symptoms are not documented. Thus, plant physiologists have largely ignored it [18]. After oxygen, silicon (Si) is the most abundant element in the earth's crust and using Si instead of herbicides and pesticides could reduce harmful environment effects [19]. In recent years, effects of silicon in nanoscale on herbal plants have received increased attention, but researches on woody plant are still limited.

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Photodegradation of Atrazine on TiO2―Products Toxicity Assessment

Photodegradation of Atrazine on TiO2―Products Toxicity Assessment

Ralston-Hooper et al. [11] evaluted the acute and chronic toxicity in the amphipods Hyalella azteca and Di- poreia spp., and in the unicellular algae Pseudokirchneriella subcapitata. They found that acute and chronic toxicities were ranked ATRAZINE > DEA > DIPA. All 96-h median inhibition concentrations, IC(50), were above concentrations found in the environment (>1.500 mg/l), with the highest sensitivity seen in the algae. An atrazine toxicity reduction to the yeast cells due to its photocatalytic decomposition on TiO 2 has previously been reported

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Computational toxicology using the OpenTox application programming interface and Bioclipse

Computational toxicology using the OpenTox application programming interface and Bioclipse

Conclusions: A novel computational toxicity assessment platform was generated from integration of two open science platforms related to toxicology: Bioclipse, that combines a rich scriptable and graphical workbench environment for integration of diverse sets of information sources, and OpenTox, a platform for interoperable toxicology data and computational services. The combination provides improved reliability and operability for handling large data sets by the use of the Open Standards from the OpenTox Application Programming Interface. This enables simultaneous access to a variety of distributed predictive toxicology databases, and algorithm and model resources, taking advantage of the Bioclipse workbench handling the technical layers.

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Features In Creating Polymer Forms Of Drugs

Features In Creating Polymer Forms Of Drugs

Thus, it is preferable to use polymers as carriers that are metabolized with cleavage of the main chain that avoids their accumulation in the organs and tissues. 4. In the case of undesirable consequences, such as overdose, allergy, etc. the rapid release of LPs from the body is difficult. In this view, a check of the MP tolerability and a precise determination of the drug doses is necessary after re-application. The drug polymers molecular design includes the following steps: selection of a carrier polymer and assessment of its biological inertness, acute chronic toxicity, bio-solubility and biodegradability, and, if necessary, its functionalization; the type of bond between the carrier polymer and low molecular weight DS; choice of the type of low-molecular DS, and the need for prolongation of its action; possible ways of DS joining to carrier polymers; choice of type and the chemical bonds between polymer and MP; MP specific transport and selectivity. In MP molecular designing, not all DS are included in the polymer structure. Creation of a polymeric form of MP is relevant and important:

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Evaluation of Acute Dermal Irritation and Wound Contraction by Gymnema Sylvestre and Datura Metel Extracts in Rats

Evaluation of Acute Dermal Irritation and Wound Contraction by Gymnema Sylvestre and Datura Metel Extracts in Rats

Currently, there are numerous plants used for industrial applications due to their beneficial properties. These plants (G. sylvestre and D. metel) also have significant potential for other purposes, including utilization as cosmetic ingredient. To ensure the safe use of these and other ingredients, only animal data should be submitted, such as results from Draize eye mucosal irritancy, skin irritancy and phototoxicity tests. These tests involve applying reagents/substances to rabbit/guinea pig eyes or skin. When assessing the safety of the ingredients, guidelines for use of a test material should be based on data from several skin toxicity tests. Major factors correlated with toxicity are associated with amines, nitrous compounds or detrimental substances which may be produced during plant growth, storage, preservation, processing or cooking. However, there are studies describing the antidiabetic and other biologic effects of G. sylvestre (Sugihara et al., 2000; Shanmugasundaram et al., 1981).

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Assessment of Musculoskeletal Toxicity 5 Years After Therapy With Levofloxacin

Assessment of Musculoskeletal Toxicity 5 Years After Therapy With Levofloxacin

physical examinations, laboratory fi nd- ings, or imaging and determined the re- lationship to study drug: not related, doubtfully related, possibly related, or likely related. PDMSDs were categorized as tendinopathy, arthritis, arthralgia, or gait abnormality. A single subject may have had . 1 PDMSD over the 5-year follow-up period. The DSMC was not blinded to drug assignment at the 12- month assessment. The committee also assessed the need for 5-year long-term follow-up based on PDMSD, MSAEs, growth abnormalities, or other con- cerns and reviewed subjects with emergent musculoskeletal events dur- ing years 1 through 5 of the LTFU study by the same criteria as those used for the 12-month SPFU evaluation except they were blinded to study drug as- signment at the year 5 evaluation. The DSMC assessments were used for this data analysis.

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Assessment of Aquatic Toxicity of River Keya Using Daphnia magna

Assessment of Aquatic Toxicity of River Keya Using Daphnia magna

taken at the discharge point (D01) of the Hsin Chu Science-based Park Sewage Treatment Plant and the downstream of the convergence, the former is two times higher than the latter. This indicates that an integral investigation be conducted downstream after the convergence of UWTP-HCSIP effluent. The aquatic toxicity monitoring and toxicity measurement on the effluents should be programmed. In addition, this study suggests that a carry capacity of River Keya, especially for aquatic toxicity should be established to well conserve the ecology and environment.

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An evaluation of the fixed concentration procedure for assessment of acute inhalation toxicity

An evaluation of the fixed concentration procedure for assessment of acute inhalation toxicity

vary from 2 to 10. For example, for dusts and mists the concentrations tested are 0.05, 0.5, 1.0 and 5.0 mg/L (Table 2). Sewell et al. (2015) considered how this would affect classifications by the FCP method. It seemed possible that lethality at the higher concentration would be more likely if the concentration ratio was larger and that conversely, a smaller change in concentration might lead to a greater number of false positives i.e. lethality not seen at the higher concentration despite evident toxicity at the lower. This has now been looked at in two ways. Sewell et al. (2015) found that, for a small number of signs, the average concentration ratio for false positives was smaller than for true posi- tives, in agreement with this idea. However, of the four signs selected as markers of evident toxicity, two were never associated with false po- sitives (PPVs of 100%) and in the other two cases, the e ff ect of con- centration ratio did not reach statistical signi fi cance.

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Investigation of tutin, a naturally-occurring plant toxin, as a novel, culturally acceptable rodenticide in New Zealand

Investigation of tutin, a naturally-occurring plant toxin, as a novel, culturally acceptable rodenticide in New Zealand

For acute-acting toxins, such as tutin, a bait is only likely to be effective if a lethal amount of toxin is ingested during an individual’s first consumption of the bait (Buckle & Eason, 2015). There is a large amount of variation in the amount of bait that a rat will consume in one meal, but Le Magnen and Tallon (1967) in their study with 1500 observations of R. norvegicus, showed that 2.5 g was an average meal size. Clearly, it would not be possible to incorporate 4.45 g of tutu plant material into 2.5 g baits. On the assumption that tutin is the only toxic component in the naturally occurring plant material, naturally-sourced tutu plant material is of inadequate potency to be considered the toxic ingredient for a new rat bait. However, further investigation is warranted because tutin may be more potent if the animal consumes the tutin in its natural form. A pharmacokinetic study of tutin in honey revealed that other toxic compounds, such as hyenanchin, may also be naturally present (Fields et al. 2014). However, it is important to note that to be present in honey, the toxins have been through the gut of plant hoppers and then honeybees, so there is uncertainty over whether they were originally present in the plant, or are metabolic products of plant hopper and honeybee digestion. Multiple toxic compounds can have a synergistic effect, resulting in higher toxicity (Hayes & Kruger

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Assessment of the In Vivo Toxicity of Gold Nanoparticles

Assessment of the In Vivo Toxicity of Gold Nanoparticles

Study of GNP transport using Hela cells indicated that the maximal endocytosis of GNPs occurs when the particles have a diameter of 50 nm [11]. In the current study, injection of 50 nm or larger GNPs, however, did not lead to the death of mice, consistent with the observation that the cell membrane prevents the passage of particles larger than 200 nm. In vivo aggregation of GNPs may have occurred to increase the apparent particle size and lead to the retardation of cellular uptake [24]. We observed that GNPs smaller than 37 nm were lethal to mice, while a further reduction to 5 nm was nontoxic. The alleviation of the lethal effect for 3 and 5 nm GNPs remains to be explored. It is possible that the difference in lethality may reflect a difference in cellular toxicity. A colorimetric methyl-thia- zol-tetrazolium (MTT) assay was performed to measure the cytotoxicity of GNPs in cultured Hela cells. The viability of cells exceeded 80% at the highest concentration of GNP (0.4 mM), indicating that regardless of their size, all GNPs were essentially non-toxic to Hela cells (Fig. 6). The inconsistency of cytotoxicity and lethality indicated that factors other than cytotoxicity may be involved in the amelioration of the lethal effect for 3 and 5 nm GNPs.

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Comprehensive Safety Evaluation of the Chemicals with Human and Environmental Relevance

Comprehensive Safety Evaluation of the Chemicals with Human and Environmental Relevance

i. Fish Acute Toxicity Read-Across version 1.0.0 performs a read-across on a dataset of 972 chemicals and provides a quantitative prediction of acute toxicity in fish, given in -log(mg/L). This dataset has been made by Istituto di Ricerche Farmacologiche Mario Negri, merging experimental data from several reliable sources: the database compiled by the MED-Duluth group, the OECD Toolbox, the DEMETRA Project (Rainbow Trout toxicity model) and the work of Su et al. (SuLMLiuX2014 ). The read-across model has been built with the istKNN application (developed by Kode srl, http://chm.kode-solutions.net) and it is based on the similarity index developed inside the VEGA platform.

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Health Risk Assessment of Volatile Organic Compounds Emitted from Wastewater Treatment Plants in Tapioca Industry

Health Risk Assessment of Volatile Organic Compounds Emitted from Wastewater Treatment Plants in Tapioca Industry

as input data for air dispersion model. The predicted ambient concentrations were estimated. According to the analysis results and combined with the exposure and toxicity of their parameters, the health risk assessment of compounds through the inhalation route was applied to evaluate the potential health effect of odor on the people from tapioca wastewater treatment plant.

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Toxicological and analytical assessment of e cigarette refill components on airway epithelia

Toxicological and analytical assessment of e cigarette refill components on airway epithelia

of exposure (IC 50 =70%), but became more toxic the longer the cells were exposed (IC 50 in the range of 30–20%). Furthermore, the cells also looked very unhealthy after the initial times of exposure, but showed remarkable recovery towards the 72 h period of incubation. Possibilities could include the cells managed to metabolise the toxic contents to less damaging agents. The menthol samples were in general very toxic with IC 50 values for all incubation times lower than 20%. The cells looked to be elongated and in the majority of cases quite isolated. It is interesting to notice that samples from different suppliers have different toxicity, giving rise to the question what the ingredients are or at least the percentages in these refills.

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Acute toxicity and risk to lizards of rodenticides and herbicides commonly used in New Zealand

Acute toxicity and risk to lizards of rodenticides and herbicides commonly used in New Zealand

Many herbicides have plant-specific modes of action that do not affect animal physiologic processes. An example is glyphosate, the active ingredient in Roundup brand herbicides. The mode of action for glyphosate is inhibition of essential amino acid synthesis. The biochemical pathway appears to be unique to plants and some microorganisms, and is generally of low toxicity to animals (Giesy et al. 2000). However, preliminary research on glyphosates and their adjuvants suggests herbicides used in New Zealand can have measurable physiological effects on native lizards (Carpenter et al. 2016). As such, research into potential sub-lethal effects of rodenticides and herbicides on reptiles is warranted. As an example, an important sub-lethal effect of rodenticides could be coagulopathy (a condition in which the blood’s ability to clot is impaired) which may not directly result in mortality, but when combined with another stressor (e.g. being attacked by a predator) may combine to result in lethal excess bleeding or hemorrhaging (Rattner et al. 2011). The toxicity of triclopyr to lizards was somewhat surprising. Triclopyr is a carboxylic acid herbicide (also known as pyridinoxy and picolinic acid herbicides), which generally has a hormone mimic mode of action (Ware & Whitacre 2004). Because the hormones are not found in animal cells, these herbicides generally do not have high toxicity to animals. It is important to note that while we recorded lizard toxicity from triclopyr, the toxicity values were still quite high (LD50 = 550 µg g –1 )

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Development and preliminary testing of a brief clinical tool to enable daily monitoring of chemotherapy toxicity : The Daily Chemotherapy Toxicity self-Assessment Questionnaire (DCTAQ)

Development and preliminary testing of a brief clinical tool to enable daily monitoring of chemotherapy toxicity : The Daily Chemotherapy Toxicity self-Assessment Questionnaire (DCTAQ)

In recent years, the use of patient-reported outcome (PRO) measures in routine cancer care practice has been advocated as a means to overcome the aforementioned limitations by facilitating a systematic approach that is based on the perspective of the patient (Flores et al., 2012; Gilbert, Sebag-Montefiore, Davidson, & Velikova, 2015; Howell et al., 2015). The use of PRO measures may result in the quicker reporting of symptoms through more frequent discussions with health professionals, improvement in the identification of bio-psychosocial problems that are often overlooked within routine practice, enhanced management of treatment toxicity, reduced hospitalisations, better adherence to chemotherapy, increased quality of life, and increased satisfaction with care (Basch et al., 2016; Donaldson, 2008; Kotronoulas et al., 2014; Snyder et al., 2012; Wu & Snyder, 2011). Several PRO measures and systems, including the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system (Basch et al., 2014) and patient-reported adverse events (PRAE) system (Holch et al., 2016), have thus far been developed specifically to facilitate detection of chemotherapy toxicity (Armes et al., 2014; Brown et al., 2001; Kushner et al., 2008; Leonard et al., 2005; Postma et 2

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