Search results for: fetal toxicity

Authors: Anna Rudzińska, Katarzyna Szklener, Pola Juchaniuk, Anna Rodzajweska, Katarzyna Machulska-Ciuraj, Monika Rychlik- Grabowska, Michał łOziński, Agnieszka Kolak-Bruks, SłAwomir Mańdziuk

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Introduction: Immune checkpoint inhibition (ICI) belongs to the modern forms of anti-cancer treatment. Due to the constant development and continuous research in the field of ICI, many aspects of the treatment are yet to be discovered. One of the less researched aspects of ICI treatment is the influence of the adverse effects on the treatment success rate. It is suspected that adverse events in the course of the ICI treatment indicate a better response rate and correlate with longer progression-free- survival. Methodology: The research was conducted with the usage of the documentation of the Department of Clinical Oncology and Chemotherapy. Data of the patients with a lung cancer diagnosis who were treated between 2019-2022 and received ICI treatment were analyzed. Results: Out of over 133 patients whose data was analyzed, the vast majority were diagnosed with non-small cell lung cancer. The majority of the patients did not experience adverse effects. Most adverse effects reported were classified as grade 1 or grade 2 according to CTCAE classification. Most adverse effects involved skin, thyroid and liver toxicity. Statistical significance was found for the adverse effect incidence and overall survival (OS) and progression-free survival (PFS) (p=0,0263) and for the time of toxicity onset and OS and PFS (p<0,001). The number of toxicity sites was statistically significant for prolonged PFS (p=0.0315). The highest OS was noted in the group presenting grade 1 and grade 2 adverse effects. Conclusions: Obtained results confirm the existence of the prolonged OS and PFS in the adverse-effects-charged patients, mostly in the group presenting mild to intermediate (Grade 1 and Grade 2) adverse effects and late toxicity onset. Simultaneously our results suggest a correlation between treatment response rate and the toxicity grade of the adverse effects and the time of the toxicity onset. Similar results were obtained in several similar research conducted - with the proven tendency of better survival in mild and moderate toxicity; meanwhile, other studies in the area suggested an advantage in patients with any toxicity regardless of the grade. The contradictory results strongly suggest the need for further research on this topic, with a focus on additional factors influencing the course of the treatment.

Keywords: adverse effects, immunotherapy, lung cancer, PD-1/PD-L1 inhibitors

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Authors: Megersa Olumana Dinka, Kassahun Birhanu Tadesse

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Irrigation suitability of shallow groundwater (SGW) was investigated by taking thirty groundwater samples from piezometers and hand-dug wells in Wonji Shoa Sugar Estate (WSSE) (Ethiopia). Many physicochemical parameters (Mg²⁺, Na⁺, Ca²⁺, K⁺, CO₃-, SO4²⁻, HCO₃⁻, Cl⁻, TH, EC, TDS and pH) were analyzed following standard procedures. Different irrigation indices (MAR, SSP, SAR, RSC, KR, and PI) were also used for SGW suitability assessment. If all SGW are blended and used for irrigation, the salinity problem would be slight to moderate, and 100% of potential sugarcane yield could be obtained. The infiltration and sodium ion toxicity problems of the blended water would be none to moderate, and slight to moderate, respectively. As sugarcane is semi-tolerant to sodium toxicity, no significant sodium toxicity problem would be expected from the use of blended water. Blending SGW would also reduce each chloride and boron ion toxicity to none. In general, the rating of SGW was good to excellent for irrigation in terms of average EC (salinity), and excellent in terms of average SAR (infiltration). The SGW of the WSSE was categorized under C3S1 (high salinity and low sodium hazard). In conclusion, the conjunctive use of groundwater for irrigation would help to reduce the potential effect of waterlogging and salinization and their associated problems on soil and sugarcane production and productivity. However, a high value of SSP and RSC indicate a high possibility of infiltration problem. Hence, it is advisable to use the SGW for irrigation after blending with surface water. In this case, the optimum blending ratio of the surface to SGW sources has to be determined for sustainable sugarcane productivity.

Keywords: blending, infiltration, salinity, sodicity, sugarcane, toxicity

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Authors: Tuğba Özdal, Neşe Şahin Yeşilçubuk

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Bisphenol-A (BPA) is one of the highest volume chemicals produced worldwide in the plastic industry. This compound is mostly used in producing polycarbonate plastics that are often used for food and beverage storage, and BPA is also a component of epoxy resins that are used to line food and beverage containers. Studies performed in this area indicated that BPA could be extracted from such products while they are in contact with food. Therefore, BPA exposure is presumed. In this paper, the chemical structure of BPA, factors affecting BPA migration to food and beverages, effects on health, and recent regulations will be reviewed.

Keywords: BPA, health, regulations, toxicity

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Authors: Szilvia Várallyay, Szilvia Veres, Éva Bódi, Farzaneh Garousi, Béla Kovács

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The agricultural environment is contaminated with heavy metals and other toxic elements, which means more and more threats. One of the most important toxic element is the arsenic. Consequences of arsenic toxicity in the plant organism is decreases the weight of the roots, and causes discoloration and necrosis of leaves. The toxicity of arsenic depends on the quality and quantity of the arsenic specialization. The arsenic in the soil and in the plant presents as a most hazardous specialization. A dicotyledon plant were chosen for the experiment, namely sunflower. The sunflower plants were grown in nutrient solution in different As(III) levels. The content of As, P, Fe were measured from experimental plants, using by ICP-MS.Negative correlation was observed between the higher concentration of As(V) and As(III) in the nutrition solution and the content of P in the sunflower tissue. The amount of Fe was decreasing if we used a higher concentration of arsenic (30 mg kg-1). We can tell the conclusion that the arsenic had a negative effect on the sunflower tissue P and Fe content.

Keywords: arsenic, sunflower, ICP-MS, toxicity

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Authors: M. F. El-Barghathi, R. El-Tajouri

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The effect of different concentrations of cadmium sulfate "CdSO4" (0.0, 10, 50, 100, 500 ppm) was tested on seed germination, seedling elongation and growth of Lepidium sativum (garden cress) plants. Results indicated that seed germination and seedling elongation were not inhibited by different concentrations of CdSO4. This could suggest that, Lepidium sativum may be used as a phyto remediation tool of soils contaminated with cadmium.

Keywords: Lepidium sativum, heavy metals, ionic toxicity, phytoremediation

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Authors: Eda Jazexhiu-Postoli, Gladiola Hoxha, Ada Simeoni, Sonila Biba

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Background Neonatal hypotonia represents a commonly encountered issue in the Neonatal Intensive Care Unit and newborn nursery. The differential diagnosis is broad, encompassing chromosome abnormalities, primary muscular dystrophies, neuropathies and inborn errors of metabolism. Aim of study Our study describes some of the main clinical features of hypotonia in newborns and presents clinical cases of neonatal hypotonia we treated in our Neonatal unit in the last 3 years. Case reports Four neonates born in our hospital presented with hypotonia after birth, one preterm newborn 35-36 weeks of gestational age and three other term newborns (38-39 weeks of gestational age). Prenatal data revealed a decrease in fetal movements in both cases. Intrapartum meconium-stained amniotic fluid was found in 75% of our hypotonic newborns. Clinical features included inability to establish effective respiratory movements and need for resuscitation in the delivery room, respiratory distress syndrome, feeding difficulties and need for oro-gastric tube feeding, dysmorphic features, hoarse voice and moderate to severe muscular hypotonia. The genetic workup revealed the diagnosis of Autosomal Recessive Congenital Myasthenic Syndrome 1-B, Sotos Syndrome, Spinal Muscular Atrophy Type 1 and Transient Hypotonia of the Newborn. Two out of four hypotonic neonates were transferred to the Pediatric Intensive Care Unit and died at the age of three to five months old. Conclusion Hypotonia is a concerning finding in neonatal care and it is suggested by decreased intrauterine fetal movements, failure to establish first breaths, respiratory distress and feeding difficulties in the neonate. Prognosis is determined by its etiology and time of diagnosis and intervention.

Keywords: hypotonic neonate, respiratory distress, feeding difficulties, fetal movements

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Authors: Elena G. Salina, Vadim A. Makarov

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With the emergence of primary resistance to the current drugs and wide distribution of latent tuberculosis infection, a need for new compounds with a novel mode of action is growing steadily. Copper-mediated innate immunity and antibacterial toxicity propose novel strategies in TB drug discovery and development. Transcriptome of M. tuberculosis was obtained by RNA-seq, intracellular copper content was measured by ISP MS and complexes of 1-hydroxy-2-thiopyridines with copper were detected by HPLC.1-hydroxy-2-thiopyridine derivatives were found to be highly active in vitro against both actively growing and dormant non-culturable M. tuberculosis. Transcriptome response to 1-hydroxy-2-thiopyridines revealed signs of copper toxicity in M. tuberculosis bacilli. Indeed, Cu was found to accumulate inside cells treated with 1-hydroxy-2-thiopyridines. These compounds were found to form stable charged lipophylic complexes with Cu²⁺ ions which transport into mycobacterial cell. Subsequent metabolic destruction of the complex led to transformation of 1-hydroxy-2-thiopyridines into 2-methylmercapto-2-ethoxycarbonylpyridines, which did not possess antitubercular activity and releasing of free Cu²⁺ in the cytoplasm. 1-hydroxy-2-thiopyridines are a potent class of Cu-dependent inhibitors of M. tuberculosis which may control M. tuberculosis infection by impairment of copper homeostasis. Acknowledgment: This work was financially supported by the Ministry of Education and Science of the RussianFederation (Agreement No 14.616.21.0065; unique identifier RFMEFI61616X0065).

Keywords: copper toxicity, drug discovery, M. tuberculosis inhibitors, 2-thiopyridines

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Authors: T. Pradhan, P. Rijal, M. C. Regmi

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Background: Eclampsia is a multisystem disorder that involves vital organs and failure of these may lead to deterioration of maternal condition and hypoxia and acidosis of fetus resulting in high maternal and perinatal mortality and morbidity. Thus, evaluation of the contributing factors for this condition and its complications leading to maternal deaths should be the priority. Formulating the plan and protocol to decrease these losses should be our goal. Aims and Objectives: To evaluate the risk factors associated with adverse maternal and fetal outcome in patients with eclampsia and to correlate the risk factors associated with maternal and fetal morbidity and mortality. Methods: All patients with eclampsia admitted in Department of Obstetrics and Gynecology, B. P. Koirala Institute of Health Sciences were enrolled after informed consent from February 2013 to February 2014. Questions as per per-forma were asked to patients, and attendants like Antenatal clinic visits, parity, number of episodes of seizures, duration from onset of seizure to magnesium sulfate and the patients were followed as per the hospital protocol, the mode of delivery, outcome of baby, post partum maternal condition like maternal Intensive Care Unit admission, neurological impairment and mortality were noted before discharge. Statistical analysis was done using Statistical Package for the Social Sciences (SPSS 11). Mean and percentage were calculated for demographic variables. Pearson’s correlation test and chi-square test were applied to find the relation between the risk factors and the outcomes. P value less than 0.05 was considered significant. Results: There were 10,000 antenatal deliveries during the study period. Fifty-two patients with eclampsia were admitted. All of the patients were unbooked for our institute. Thirty-nine patients were antepartum eclampsia. Thirty-one patients required mechanical ventilator support. Twenty-four patients were delivered by emergency c-section and 21 babies were Low Birth Weight and there were 9 stillbirths. There was one maternal mortality and 45 patients were discharged with improvement but 3 patients had neurological impairment. Mortality was significantly related with number of seizure episodes and time interval between seizure onset and administration of magnesium sulphate. Conclusion: Early detection and management of hypertensive complicating pregnancy during antenatal clinic check up. Early hospitalization and management with magnesium sulphate for eclampsia can help to minimize the maternal and fetal adverse outcomes.

Keywords: eclampsia, maternal mortality, perinatal mortality, risk factors

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Authors: Julia Ive, Lucia Specia

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Understanding and detecting toxicity is an important problem to support safer human interactions online. Our work focuses on the important problem of contextual toxicity detection, where automated classifiers are tasked with determining whether a short textual segment (usually a sentence) is toxic within its conversational context. We use “toxicity” as an umbrella term to denote a number of variants commonly named in the literature, including hate, abuse, offence, among others. Detecting toxicity in context is a non-trivial problem and has been addressed by very few previous studies. These previous studies have analysed the influence of conversational context in human perception of toxicity in controlled experiments and concluded that humans rarely change their judgements in the presence of context. They have also evaluated contextual detection models based on state-of-the-art Deep Learning and Natural Language Processing (NLP) techniques. Counterintuitively, they reached the general conclusion that computational models tend to suffer performance degradation in the presence of context. We challenge these empirical observations by devising better contextual predictive models that also rely on NLP data augmentation techniques to create larger and better data. In our study, we start by further analysing the human perception of toxicity in conversational data (i.e., tweets), in the absence versus presence of context, in this case, previous tweets in the same conversational thread. We observed that the conclusions of previous work on human perception are mainly due to data issues: The contextual data available does not provide sufficient evidence that context is indeed important (even for humans). The data problem is common in current toxicity datasets: cases labelled as toxic are either obviously toxic (i.e., overt toxicity with swear, racist, etc. words), and thus context does is not needed for a decision, or are ambiguous, vague or unclear even in the presence of context; in addition, the data contains labeling inconsistencies. To address this problem, we propose to automatically generate contextual samples where toxicity is not obvious (i.e., covert cases) without context or where different contexts can lead to different toxicity judgements for the same tweet. We generate toxic and non-toxic utterances conditioned on the context or on target tweets using a range of techniques for controlled text generation(e.g., Generative Adversarial Networks and steering techniques). On the contextual detection models, we posit that their poor performance is due to limitations on both of the data they are trained on (same problems stated above) and the architectures they use, which are not able to leverage context in effective ways. To improve on that, we propose text classification architectures that take the hierarchy of conversational utterances into account. In experiments benchmarking ours against previous models on existing and automatically generated data, we show that both data and architectural choices are very important. Our model achieves substantial performance improvements as compared to the baselines that are non-contextual or contextual but agnostic of the conversation structure.

Keywords: contextual toxicity detection, data augmentation, hierarchical text classification models, natural language processing

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Authors: Rakhyun Kim, Sungho Tae

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Global environmental issues such as abnormal weathers due to global warming, resource depletion, and ecosystem distortions have been escalating due to rapid increase of population growth, and expansion of industrial and economic development. Accordingly, initiatives have been implemented by many countries to protect the environment through indirect regulation methods such as Environmental Product Declaration (EPD), in addition to direct regulations such as various emission standards. Following this trend, life cycle assessment (LCA) techniques that provide quantitative environmental information, such as Human Toxicity Potential (HTP), for buildings are being developed in the construction industry. However, at present, the studies on the environmental database of building materials are not sufficient to provide this support adequately. The purpose of this study is to analysis human toxicity potential of major building material production stage using life cycle assessment. For this purpose, the theoretical consideration of the life cycle assessment and environmental impact category was performed and the direction of the study was set up. That is, the major material in the global warming potential view was drawn against the building and life cycle inventory database was selected. The classification was performed about 17 kinds of substance and impact index, such as human toxicity potential, that it specifies in CML2001. The environmental impact of analysis human toxicity potential for the building material production stage was calculated through the characterization. Meanwhile, the environmental impact of building material in the same category was analyze based on the characterization impact which was calculated in this study. In this study, establishment of environmental impact coefficients of major building material by complying with ISO 14040. Through this, it is believed to effectively support the decisions of stakeholders to improve the environmental performance of buildings and provide a basis for voluntary participation of architects in environment consideration activities.

Keywords: human toxicity potential, major building material, life cycle assessment, production stage

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Authors: Marina Shargorodsky

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Aim: Gestational weight gain (GWG) has been related to altering future weight-gain curves and increased risks of obesity later in life. Obesity may contribute to vascular atherosclerotic changes as well as excess cardiovascular morbidity and mortality observed in these patients. Noninvasive arterial testing, such as ultrasonographic measurement of carotid IMT, is considered a surrogate for systemic atherosclerotic disease burden and is predictive of cardiovascular events in asymptomatic individuals as well as recurrent events in patients with known cardiovascular disease. Currently, there is no consistent evidence regarding the vascular impact of excessive GWG. The present study was designed to investigate the impact of GWG on early atherosclerotic changes during late pregnancy, using intima-media thickness, as well as placental vascular circulation and inflammatory lesions and pregnancy outcomes. Methods: The study group consisted of 59 pregnant women who gave birth and underwent a placental histopathological examination at the Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Israel, in 2019. According to the IOM guidelines the study group has been divided into two groups: Group 1 included 32 women with pregnancy weight gain within recommended range; Group 2 included 27 women with excessive weight gain during pregnancy. The IMT was measured from non-diseased intimal and medial wall layers of the carotid artery on both sides, visualized by high-resolution 7.5 MHz ultrasound (Apogee CX Color, ATL). Placental histology subdivided placental findings to lesions consistent with maternal vascular and fetal vascular malperfusion according to the criteria of the Society for Pediatric Pathology, subdividing placental findings to lesions consistent with maternal vascular and fetal vascular malperfusion, as well as the inflammatory response of maternal and fetal origin. Results: IMT levels differed between groups and were significantly higher in Group 1 compared to Group 2 (0.7+/-0.1 vs 0.6+/-0/1, p=0.028). Multiple linear regression analysis of IMT included variables based on their associations in univariate analyses with a backward approach. Included in the model were pre-gestational BMI, HDL cholesterol and fasting glucose. The model was significant (p=0.001) and correctly classified 64.7% of study patients. In this model, pre-pregnancy BMI remained a significant independent predictor of subclinical atherosclerosis assessed by IMT (OR 4.314, 95% CI 0.0599-0.674, p=0.044). Among placental lesions related to fetal vascular malperfusion, villous changes consistent with fetal thrombo-occlusive disease (FTOD) were significantly higher in Group 1 than in Group 2, p=0.034). In Conclusion, the present study demonstrated that excessive weight gain during pregnancy is associated with an adverse effect on early stages of subclinical atherosclerosis, placental vascular circulation and neonatal complications. The precise mechanism for these vascular changes, as well as the overall clinical impact of weight control during pregnancy on IMT, placental vascular circulation as well as pregnancy outcomes, deserves further investigation.

Keywords: obesity, pregnancy, complications, weight gain

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Authors: Sheraz Gul

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The requirements for progressing a compound to clinical trials is well established and relies on the results from in-vitro and in-vivo animal tests to indicate that it is likely to be safe and efficacious when testing in humans. The typical data package required will include demonstrating compound safety, toxicity, bioavailability, pharmacodynamics (potential effects of the compound on body systems) and pharmacokinetics (how the compound is potentially absorbed, distributed, metabolised and eliminated after dosing in humans). If the desired criteria are met and the compound meets the clinical Candidate criteria and is deemed worthy of further development, a submission to regulatory bodies such as the US Food & Drug Administration for an exploratory Investigational New Drug Study can be made. The purpose of this study is to collect data to establish that the compound will not expose humans to unreasonable risks when used in limited, early-stage clinical studies in patients or normal volunteer subjects (Phase I). These studies are also designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on their effectiveness. In order to reach the above goals, we have developed a pre-clinical high throughput Absorption, Distribution, Metabolism and Excretion–Toxicity (ADME–Toxicity) panel of assays to identify compounds that are likely to meet the Lead and Candidate compound acceptance criteria. This panel includes solubility studies in a range of biological fluids, cell viability studies in cancer and primary cell-lines, mitochondrial toxicity, off-target effects (across the kinase, protease, histone deacetylase, phosphodiesterase and GPCR protein families), CYP450 inhibition (5 different CYP450 enzymes), CYP450 induction, cardio-toxicity (hERG) and gene-toxicity. This panel of assays has been applied to multiple compound series developed in a number of projects delivering Lead and clinical Candidates and examples from these will be presented.

Keywords: absorption, distribution, metabolism and excretion–toxicity , drug discovery, food and drug administration , pharmacodynamics

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Authors: Luísa P. Cruz-Lopes, Artur Figueirinha, Isabel Brás, Bruno Esteves

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Portugal is an important wine and olive oil producer, activities which generate a high quantity of residues commonly called grape stalks and olive cake, respectively. In this work grape stalks and olive cake were used as lignocellulosic adsorbents for wastewater containing lead treatment. To attain a better knowledge of the factors that could influence the quality of the treated wastewater, a chemical characterization of the materials used in the treatment was done. To access the ecotoxicological safety of the treated wastewater, several tests were performed. The results of the toxicity test show that the samples leachate has a mild effect on the living models tested. The tests performed in lemna and bacteria were the most sensible to toxicity effects of the samples. The results obtained in this work evidenced the importance of use of simple and fast toxicity tests to predict impacts in the environment.

Keywords: chemical composition, lignocellulosic residues, ecotoxicological safety, wastewater

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Authors: Awad G. Abdellatif, Huda M. Gargoum, Abdelkader A. Debani, Mudafara Bengleil, Salmin Alshalmani, N. El Zuki, Omran El Fitouri

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In this study, the administration of 660 mg/kg of the ethanolic extract of the Alhgigraecorum (camel thorn) to mice, showed a significant decrease in the level of transaminases in animals treated with a combination of CTE plus carbon tetrachloride (CCl4) or acetaminophen as compared to animals receiving CCl4 or acetaminophen alone. The histopathological investigation also confirmed that camel thorn extract protects the liver against damage-induced either by carbon tetrachloride or acetaminophen. On the other hand, the cardiac toxicity produced by adriamycin was significantly increased in the presence of the ethanolic extract of camel thorn. Our study suggested that camel thorn can protect the liver against the injury produced by carbon tetrachloride or acetaminophen, with an unexpected increase in the cardiac toxicity–induced by adriamycin in rodents.

Keywords: ethanolic, alhgigraecorum, tetrachloride, acetaminophen

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Authors: Gabrielle Peck, Ryan Hayes

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Four façade systems were tested using a reduced height BS 8414-2 (5 m) test rig. An L-shaped masonry test wall was clad with three types of insulation and an aluminum composite panel with a non-combustible filling (meeting Euroclass A2). A large (3 MW) wooden crib was ignited in a recess at the base of the L, and the fire was allowed to burn for 30 minutes. Air velocity measurements and gas samples were taken from the main ventilation duct and also a small additional ventilation duct, like those in an apartment bathroom or kitchen. This provided a direct route of travel for smoke from the building façade to a theoretical room using a similar design to many high-rise buildings where the vent is connected to (approximately) 30 m³ rooms. The times to incapacitation and lethality of the effluent were calculated for both the main exhaust vent and for a vent connected to a theoretical 30 m³ room. The rainscreen façade systems tested were the common combinations seen in many tower blocks across the UK. Three tests using ACM A2 with Stonewool, Phenolic foam, and Polyisocyanurate (PIR) foam. A fourth test was conducted with PIR and ACM-PE (polyethylene core). Measurements in the main exhaust duct were representative of the effluent from the burning wood crib. FEDs showed incapacitation could occur up to 30 times quicker with combustible insulation than non-combustible insulation, with lethal gas concentrations accumulating up to 2.7 times faster than other combinations. The PE-cored ACM/PIR combination produced a ferocious fire, resulting in the termination of the test after 13.5 minutes for safety reasons. Occupants of the theoretical room in the PIR/ACM A2 test reached a FED of 1 after 22 minutes; for PF/ACM A2, this took 25 minutes, and for stone wool, a lethal dose measurement of 0.6 was reached at the end of the 30-minute test. In conclusion, when measuring smoke toxicity in the exhaust duct, there is little difference between smoke toxicity measurements between façade systems. Toxicity measured in the main exhaust is largely a result of the wood crib used to ignite the façade system. The addition of a vent allowed smoke toxicity to be quantified in the cavity of the façade, providing a realistic way of measuring the toxicity of smoke that could enter an apartment from a façade fire.

Keywords: smoke toxicity, large-scale testing, BS8414, FED

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Authors: Elsayed Elmiligy, Dzolkhifili Omar, Norhayu Asib

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Sitophilus oryzae is a primary destructive insect pest. A study on nanoemulsion formulation of C. hystrix peel oil and evaluation of its insecticidal effect on the adults of S. oryzae was held in toxicology laboratory at Faculty of Agriculture, Universiti Putra Malaysia (UPM). Three nanoemulsion formulations (F1, F2, and F3) were prepared using C. hystrix peel oil (a.i), Tween 80 (surfactant), AMD 810 (carrier) and deionized water. The selected formulations have undergone stability tests, surface tension, zeta potential and particle size measurements. The formulations were tested for their contact and fumigant activity against the adults of S. oryzae. LC₅₀ values were obtained from Probit regressions using the Polo-PC program. All the formulations showed stability under storage temperature and centrifugation. They were characterized as nanoemulsions as they remained in the range of nanoscale 200 nm. The formulations revealed lower surface tension in the range of 29.5 to 30.4 mN/m. They showed stable of zeta potential values. The formulations showed the highest toxicity against the adults of S. oryzae. The order of decreasing toxicity was F1 > F2 > F3 with LC₅₀ values of 52.1, 58.5, and 61.7 µl/l for contact toxicity, and 71, 75.5, and 76.7 µl/l air for fumigant bioassay after 72 hours. Formulation of C. hystrix peel oil in a nanoemulsion enhance its effectiveness and reduce the amount of applied essential oil.

Keywords: Citrus hystrix peel oil, Sitophilus oryzae, nanoemulsion, contact toxicity, Fumigant bioassay

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Authors: Abazar Ghorbani, W. M. Wishwajith W. Kandegama, Seyed Mehdi Razavi, Moxian Chen

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The roles of hydrogen sulfide (H₂S) and melatonin (MT) as gasotransmitters in plants are widely recognised. Nevertheless, the precise nature of their involvement in defensive reactions remains uncertain. This study investigates the impact of the ML-H2S interaction on tomato plants exposed to vanadium (V) toxicity, focusing on synthesising secondary metabolites and V metal sequestration. The treatments applied in this study included a control (T1), V stress (T2), MT+V (T3), MT+H2S+V (T4), MT+hypotaurine (HT)+V (T5), and MT+H2S+HT+V (T6). These treatments were administered: MT (150 µM) as a foliar spray pre-treatment (3X), HT treatment (0.1 mM, an H2S scavenger) as root immersion for 12 hours as pre-treatments, and H2S (NaHS, 0.2 mM) and V (40 mg/L) treatments added to the Hoagland solution for 2 weeks. Results demonstrate that ML and H2S+ML treatments alleviate V toxicity by promoting the transcription of key genes (ANS, F3H, CHS, DFR, PAL, and CHI) involved in phenolic and anthocyanin biosynthesis. Moreover, they decreased V uptake and accumulation and enhanced the transcription of genes involved in glutathione and phytochelatin synthesis (GSH1, PCS, and ABC1), leading to V sequestration in roots and protection against V-induced damage. Additionally, ML and H2S+ML treatments optimize chlorophyll metabolism, and increase internal H2S levels, thereby promoting tomato growth under V stress. The combined treatment of ML+H2S shows superior effects compared to ML alone, suggesting synergistic/interactive effects between these two substances. Furthermore, inhibition of the beneficial impact of ML+H2S and ML treatments by HT, an H2S scavenger, underscores the significant involvement of H₂S in the signaling pathway activated by ML during V toxicity. Overall, these findings suggest that ML requires the presence of endogenous H₂S to mitigate V-induced adverse effects on tomato seedlings.

Keywords: vanadium toxicity, secondary metabolites, vanadium sequestration, h2s-melatonin crosstalk

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Authors: G. E. Forcados, M. L. Shu, C. N. Chinyere

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Acalypha wilkesiana is a medicinal plant commonly used in most parts of West Africa as a decoction in treating several human diseases. Existing literature on its toxicity is predominantly on the organic extracts in contrast to the routine use of hot aqueous extracts as decoction. The aim of this study was to examine the phytochemical profile and sub-acute toxicity of A. wilkesiana leaf extracts in albino rats. Three groups of 8 experimental rats each were administered 300 mg/kg, 600 mg/kg and 1200 mg/kg body weight per day for 14 days while a fourth (control) group took tap-water. On day 15, the rats were sacrificed, and blood collected. Biochemical and hematological parameters were analysed and histopathological examination of liver and kidney were performed. There was significant increase (p<0.05) in the levels of some biochemical parameters (AST, ALT, creatinine, urea) in all the test groups compared to control. Histopathological examination of the liver revealed centrilobular degeneration and necrosis with sinusoidal dilatation as well as polymorphonuclear and mononuclear infiltration, likewise severe glomerular and tubular degeneration and necrosis with hemorrhage in the kidney at all dose levels. The results from this study suggest that aqueous leaf extract of A. wilkesiana is hepatotoxic and nephrotoxic at dose levels of 300 mg/kg and above. Therefore, precautionary measures are necessary for home use of the leaf extract of A. wilkesiana.

Keywords: acute toxicity, A. wilkesiana, aqeous extract, albino rats, biochemical and haematological parameters, histopathological examination

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Authors: Moleseng Claude Moshobane

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Alien species cause considerable negative impacts on biodiversity, economy and public health. Impacts of alien species on public health have received a degree of attention worldwide, largely in developed countries, but scarce in developing countries. Here, we provide a review of human exposures and poisonings cases from native and alien plant species reported to poison information centers. A retrospective review of the Tygerberg Poison Information Centre (TPIC) and Poisons Information Centre (PIC) at Red Cross War Memorial Children's Hospital (RCWMCH) was conducted over approximately 2-year period (1 June 2015 through to 06 March 2017). Combined, TPIC and PIC handled 626 cases during the 2-year period. Toxicity cases were more abundant in Gauteng (47.1%), followed by Western Cape (29.4%). The primary mechanism of injury was ingestion (96.7%), and all cases were predominantly accidental. Most reported cases involved infants (20.6%), with few fully-grown adults related cases (5.8%). Adults presented minor to moderate toxicity, while infants none to minor toxicity. We conclude that reported toxicity cases on human health are biased towards few alien species and that several cases relate to unknown species of mushrooms. Public awareness is essential to reducing the poisoning incidences.

Keywords: alien species, poisoning, invasive species, public health

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Authors: Sonia Tamanna, Akramul Hassan, Mohammad Shakil Mahmood, Farzana Ansari, Gowhar Rashid, Mir Fahim Faisal, M. Zakir Hossain Howlader

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Background: Preeclampsia (PE), a pregnancy-specific hypertensive disorder, significantly impacts maternal and fetal health. It is particularly prevalent in underdeveloped countries and is linked to preterm delivery and fetal growth. The renin-angiotensin system (RAS) plays a crucial role in ensuring a successful pregnancy outcome, with Angiotensin-Converting Enzyme 2 (ACE2) being a key component. ACE2 converts ANG II to Ang-(1-7), offering protection against ANG II-induced stress and inflammation while regulating blood pressure and osmotic balance during pregnancy. The reduced maternal plasma angiotensin-converting enzyme 2 (ACE2) seen in preeclampsia might contribute to its pathogenesis. However, there has been a dearth of comprehensive research into the association between ACE2 gene polymorphism and preeclampsia. In the South Asian population, hypertension is strongly linked to two SNPs: rs2285666 and rs879922. This genotype was therefore considered, and the possible association of maternal and fetal ACE2 gene polymorphism with preeclampsia within the Bangladeshi population was evaluated. Method: DNA was extracted from peripheral white blood cells (WBCs) using the organic method, and SNP genotyping was done via PCR-RFLP. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using logistic regression to determine relative risk. Result: A comprehensive case-control study was conducted on 51 PE patients and their infants, along with 56 control subjects and their infants. Maternal single nuvleotide polymorphisms (SNP) (rs2285666) analysis revealed a strong association between the TT genotype and preeclampsia, with a four-fold increased risk in mothers (P=0.024, OR=4.00, 95% CI=1.36-11.37) compared to their ancestral genotype CC. However, the CT genotype (rs2285666) showed no significant difference (P=0.46, OR=1.54, 95% CI=0.57-4.14). Notably, no significant correlation was found in infants, regardless of their gender. For rs879922, no significant association was observed in both mothers and infants. This pioneering study suggests that mothers carrying the ACE2 gene variant rs2285666 (TT allele) may be at higher risk for preeclampsia, potentially influencing hypertension characteristics, whereas rs879922 does not appear to be associated with developing preeclampsia. Conclusion: This study sheds light on the role of ACE2 gene polymorphism, particularly the rs2285666 TT allele, in maternal susceptibility to preeclampsia. However, rs879922 does not appear to be linked to the risk of PE. This research contributes to our understanding of the genetic underpinnings of preeclampsia, offering insights into potential avenues for prevention and management.

Keywords: ACE2, PCR-RFLP, preeclampsia, single nuvleotide polymorphisms (SNPs)

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Authors: Ananya Das, Arun Kumar, Gazala Habib, Vivekanandan Perumal

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Regulatory bodies has proposed limits on Particulate Matter (PM) concentration in air; however, it does not explicitly indicate the incorporation of effects of toxicities of constituents of PM in developing regulatory limits. This study aimed to provide a structured approach to incorporate toxic effects of components in developing regulatory limits on PM. A four-step human health risk assessment framework consists of - (1) hazard identification (parameters: PM and its constituents and their associated toxic effects on health), (2) exposure assessment (parameters: concentrations of PM and constituents, information on size and shape of PM; fate and transport of PM and constituents in respiratory system), (3) dose-response assessment (parameters: reference dose or target toxicity dose of PM and its constituents), and (4) risk estimation (metric: hazard quotient and/or lifetime incremental risk of cancer as applicable). Then parameters required at every step were obtained from literature. Using this information, an attempt has been made to determine limits on PM using component-specific information. An example calculation was conducted for exposures of PM_2.5 and its metal constituents from Indian ambient environment to determine limit on PM values. Identified data gaps were: (1) concentrations of PM and its constituents and their relationship with sampling regions, (2) relationship of toxicity of PM with its components.

Keywords: air, component-specific toxicity, human health risks, particulate matter

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Authors: M. Toygar, I. Aydin, M. Agilli, F. N. Aydin, M. Oztosun, H. Gul, E. Macit, Y. Karslioglu, T. Topal, B. Uysal, M. Honca

Abstract:

Paraquat (PQ) is a well-known quaternary nitrogen herbicide. The major target organ in PQ poisoning is the lung. Reactive oxygen species (ROS) and inflammation play a crucial role in the development of PQ-induced pulmonary injury. Neopterin is synthesized in macrophage by interferon g and other cytokines. We aimed to evaluate the utility of neopterin as a diagnostic marker in PQ-induced lung toxicity. Sprague Dawley rats were randomly divided into two groups (sham and PQ), administered intraperitoneally 1 mL saline and PQ (15 mg/kg/mL) respectively. Blood samples and lungs were collected for analyses. Lung injury and fibrosis were seen in the PQ group. Serum total antioxidant capacity, lactate dehydrogenase (LDH), and lung transforming growth factor-1 (TGF-1) levels were significantly higher than the sham group (in all, p< 0.001). In addition, in the PQ group, serum neopterin and lung malondialdehyde (MDA) levels were also significantly higher than the sham group (in all, p 1/4 0.001). Serum neopterin levels were correlated with LDH activities, lung MDA, lung TGF-1 levels, and the degree of lung injury. These findings demonstrated that oxidative stress, reduction of antioxidant capacity, and inflammation play a crucial role in the PQ-induced lung injury. Elevated serum neopterin levels may be a prognostic parameter to determine extends of PQ-induced lung toxicity. Further studies may be performed to clarify the role of neopterin by different doses of PQ.

Keywords: paraquat, inflammation, oxidative stress, neopterin, lung toxicity

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Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar

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The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.

Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity

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Authors: Kiran Shehzadi, Yasmeen Akhtar, Mujahid Ameen, Tabinda Ijaz, Shoukat Siddique

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Nanoparticles, due to their different sizes and morphologies, are employed in various fields such as the medical field, cosmetics, pharmaceutical, textile industry as well as in paints, adhesives, and electronics. Metal nanoparticles exhibit excellent antimicrobial activity, dye degradation and can be used as anti-cancerous drug loading agents. In this study, sZilver nanoparticles (Ag-NPs) were synthesized employing doxycycline (antibiotic) as a reducing and capping agent (biological/green synthesis). Produced Ag-NPS were characterized using UV/VIS spectrophotometry, XRD, SEM, and FTIR. Surface plasmon resonance (SPR) of silver nanoparticles was observed at 411nm with 90nm size with homogenized spherical shape. These particles revealed good inhibition zones for Fungi such as Candida albicans and Candida tropicalis. In this study, toxic properties of Ag-NPs were monitored by allowing them to penetrate in the cell, causing an abrupt increase in oxidative stress, which resulted ultimately in cell death. Histopathological analysis of mice organs was performed by administering definite concentrations of silver nanoparticles orally to mice for 14 days. Toxic properties were determined, and it was revealed that the toxicity of silver nanoparticles mainly depends on the size. Silver nanoparticles of this work presented mild toxicity for different organs (liver, kidney, spleen, heart, and stomach) of mice.

Keywords: metal nanoparticles, green/biological methods, toxicity, Candida albicans, Candida tropicalis

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Authors: Rini Rahul, Manoj Kumar

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Cadmium (Cd) is a poisonous trace metal, which is responsible for excess reactive oxygen species generation (ROS) in plants, thereby adversely affecting their productivity and commercial potential. Ricinus communis (castor) is an industry-efficient non-edible bioenergy crop used for phytoremediation and re-vegetation. We have determined the total Cd content in castor genotypes and established a relationship between the Cd tolerance mechanism and physiological parameters like chlorophyll fluorescence, the total photosynthetic activity, chlorophyll and carotenoid content as well as ROS generation and malondialdehyde content. This study is an effort to comprehend the interrelation between Cd toxicity (control, 250 µM and 500 µM), proline, various ROS scavenging enzymes (anti-oxidative in nature), nicotianamine synthase (NAS) and Natural resistance-associated macrophage protein (NRAMP) gene. The antioxidant enzyme activity increased for WM hence conferring Cd toxicity in this genotype. RcNRAMP genes showed differential expression in GCH2 and WM genotypes; this can also be one of the reasons for Cd toxicity and sensitivity in WM and GCH2, respectively. The cause of pronounced Cd tolerance in WM leaves can be because of enhanced expression of RcNAS1, RcNAS2 and RcNAS3 genes. Our results demonstrate that there is an interrelation between Cd toxicity (control, 250 µM and 500 µM), proline, various ROS scavenging enzymes (anti-oxidative in nature), NAS and NRAMP gene.

Keywords: ricinus communis, cadmium, reactive oxygen species, nicotianamine synthase, NRAMP, malondialdehyde

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Authors: Yahia Massinissa, Afaf Benhouda, Mouloud Yahia

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Objective: The aim of this study was to investigate the toxicity; analgesic and anti-pyretic properties of standardized HA methanolic extract (HAMeOH) in vivo. Methods: The acute toxicity study was performed on rats while adopting the OECD-420 Guidelines (fixed dose procedure). Assessment of analgesic activity was performed in rats with two analgesic models. One was acetic acid induced writhing response and the other formalin-induced paw licking. The anti-pyretic effect was tested by Brewer’s yeast induced fever in rats. Results: For the acute toxicity test, the higher dose administration of 2000 mg/kg bw. of H.albus did not produce any toxic signs or deaths in rats. There were no significant differences (p>0.05) in the body and organ weights between control and treated groups. The (LD50) of 'H. albus' was higher than 2000 g/kg bw. In subacute toxicity study, no mortality and toxic signs were observed with the doses of 100 and 200 mg/kg bw. of extracts of for 28 consecutive days. These analgesic experimental results indicated that HAMeOH (100 mg/kg and 200 mg/kg) decreased the acetic acid-induced writhing responses and HAMeOH (100 mg/kg and 200 mg/kg) decreased the licking time in the second phase of the formalin test. Moreover, in the model of yeast-induced elevation of the body temperature HAMeOH showed dose-dependent lowering of the body temperature up to 3h at both the doses these results obtained, were comparable to that of paracetamol. Conclusion: The present findings indicate that the leaves of Hyoscyamus albus L. possess potent analgesic and antipyretic activity.

Keywords: Hyoscyamus albus, Umbilicus rupestris, secondary metabolites, NMR with protons, pharmacobiologic activities, methanolic extract

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Authors: Malarvizhi Selvaraj, Paul Fergus, Andy Shaw

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Uterine contractions produced during labour have the potential to damage the foetus by diminishing the maternal blood flow to the placenta. In order to observe this phenomenon labour and delivery are routinely monitored using cardiotocography monitors. An obstetrician usually makes the diagnosis of foetus hypoxia by interpreting cardiotocography recordings. However, cardiotocography capture and interpretation is time-consuming and subjective, often lead to misclassification that causes damage to the foetus and unnecessary caesarean section. Both of these have a high impact on the foetus and the cost to the national healthcare services. Automatic detection of foetal heart rate may be an objective solution to help to reduce unnecessary medical interventions, as reported in several studies. This paper aim is to provide a system for better identification and interpretation of abnormalities of the fetal heart rate using RStudio. An open dataset of 552 Intrapartum recordings has been filtered with 0.034 Hz filters in an attempt to remove noise while keeping as much of the discriminative data as possible. Features were chosen following an extensive literature review, which concluded with FIGO features such as acceleration, deceleration, mean, variance and standard derivation. The five features were extracted from 552 recordings. Using these features, recordings will be classified either normal or abnormal. If the recording is abnormal, it has got more chances of hypoxia.

Keywords: cardiotocography, foetus, intrapartum, hypoxia

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Authors: M. A. Pawar, C. S. Patil

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Investigations were carried out to evaluate the persistent toxicity of imidacloprid, thiamethoxam and dimethoate to Aphis gossypii and Amrasca biguttula biguttula under laboratory condition during 2012. The experiment was conducted in a completely randomized block design with three replications in the glass house of department of Entomology M. P. K. V. Rahuri. Okra plants were raised in glass house following all recommended agronomic practices. The 21 days old plants were used for assessing the effect of insecticides on aphids and jassids. The insecticides were diluted with distilled water to make desired concentrations and used for foliar application. The insecticides included in the study were imidacloprid 17.8 SL, imidacloprid 70 WG, thiamethoxam 25 WG and dimethoate 30 EC. Untreated check was maintained by spraying with distilled water. The mortality of aphids and jassids on treated leaf were recorded at 1, 3, 5, 7, 9, 11, 13, 15, 17, 21, and 25 days after spray till zero per cent mortality observed for each treatment. Treated leaves from the glasshouse were brought to laboratory and were put in tube with moist cotton swab at the bottom of leaf and sucking apparatus was fit to the tube. Ten jassids were sucked in each tube from the plants in the field. Evaluated insecticides differed in their persistence and index of persistence toxicity against both insects of different treatments. Recommended dose of imidacloprid (25 g a.i/ha) persisted for 21 days against both aphids and jassids. However dimethoate, a conventional insecticide persisted for 11 days.

Keywords: Amrasca biguttula biguttula, Aphis gossypii, imidacloprid, persistent toxicity

Procedia PDF Downloads 189

Authors: M. M. Bashandy, A. R. Ahmed, M. El-Gaffary, Sahar S. Abd El-Rahman

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This study evaluated the acute toxicity and tissue distribution of intravenously administered gold nanoparticles (AuNPs) in male rabbits. Rabbits were exposed to single dose of AuNPs (300 µg/ kg). Toxic effects were assessed via general behavior, hematological parameters, serum biochemical parameters and histopathological examination of various rabbits’ organs. Tissue distribution of AuNPs was evaluated at a dose of 300 µg/ kg in male rabbit. Inductively coupled plasma–mass spectrometry (ICP-MS) was used to determine gold concentrations in tissue samples collected at predetermined time intervals. After one week, AuNPs exerted no obvious acute toxicity in rabbits. However, inflammatory reactions in lung and liver cells were induced in rabbits treated at the300 µg/ kg dose level. The highest gold levels were found in the spleen, followed by liver, lungs and kidneys. These results indicated that AuNPs could be distributed extensively to various tissues in the body, but primarily in the spleen and liver.

Keywords: gold nanoparticles, toxicity, pathology, hematology, liver function, kidney function

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Authors: Xiaoquan Huang, Congcong Li, Tingting Wei, Changcun Bai, Na Liu, Meng Tang

Abstract:

Silver is often doped on nano-titanium dioxide photocatalysts (Ag-TiO₂) by photodeposition method to improve their utilization of visible-light while increasing the toxicity of TiO₂。 However, it is not known what factors influence this toxicity and how to reduce toxicity while maintaining the maximum catalytic activity. In this study, Ag-TiO₂ photocatalysts were synthesized by the photodeposition method with different silver content (AgC) and photodeposition time (PDT). Characterization and catalytic experiments demonstrated that silver was well assembled on TiO₂ with excellent visible-light catalytic activity, and the size of silver increased with PDT. In vitro, the cell viability of lung epithelial cells A549 and BEAS-2B showed that the higher content and smaller size of silver doping caused higher toxicity. In vivo, Ag-TiO₂ catalysts with lower AgC or larger silver particle size obviously caused less pulmonary pro-inflammatory and pro-fibrosis responses. However, the visible light catalytic activity decreased with the increase in silver size. Therefore, in order to optimize the Ag-TiO₂ photocatalyst with the lowest pulmonary toxicity and highest catalytic performance, response surface methodology (RSM) was further performed to optimize the two independent variables of AgC and PDT. Visible-light catalytic activity was evaluated by the degradation rate of Rhodamine B, the antibacterial property was evaluated by killing log value for Escherichia coli, and cytotoxicity was evaluated by IC50 to BEAS-2B cells. As a result, the RSM model showed that AgC and PDT exhibited an interaction effect on catalytic activity in the quadratic model. AgC was positively correlated with antibacterial activity. Cytotoxicity was proportional to AgC while inversely proportional to PDT. Finally, the optimization values were AgC 3.08 w/w% and PDT 28 min. Under this optimal condition, the relatively high silver proportion ensured the visible-light catalytic and antibacterial activity, while the longer PDT effectively reduced the cytotoxicity. This study is of significance for the safe and efficient application of silver-doped TiO₂ photocatalysts.

Keywords: Ag-doped TiO₂, cytotoxicity, inflammtion, fibrosis, response surface methodology

Procedia PDF Downloads 67