Toxicology International <div id="i-scholarabout"><img class="media-object" style="width: 222px; float: left; margin: 0px 16px 15px 20px;" src="" /> <p><strong>Editor :</strong> Dr. Milindmitra K Lonare<br /><strong>Online ISSN :</strong> 0976-5131<br /><strong>Print ISSN :</strong> 0971-6580<br /><strong>Frequency :</strong> Quarterly<br /><strong>Publisher/s :</strong> Informatics Publishing Limited and The Society of Toxicology, India</p> <p>Article Processing Charges are to be made only if the manuscript is accepted after Peer Review. If payment is made without acceptance confirmation, then the amount will not be refunded. Toxicology International is a subscription access journal publishing original peer-reviewed research articles. The Journal Publication was Triannual and is now changed to Quarterly. The journal began publishing since 1994.</p> The Journal is Indexed in Scopus, NAAS 5.23, i-Scholar and J-gate, ICI<br /><a href="" target="blank"><img src="" alt="" width="160" height="77" /></a><a href="" target="blank"><img style="font-size: 0.875rem;" src="" alt="" width="160" height="77" /></a></div> Informatics Publishing Limited and The Society of Toxicology, India en-US Toxicology International 0971-6580 Mitigation of Toxic Effects of 2 Naphthalene Sulfonate after its Treatment with Microbial Consortia Present study aimed to treat 2 Napthalene Sulfonate (2NS), a dye intermediate with microbial consortia and assess its potential toxicological impact before and after treatment on the integrity of Deoxyribo-Nucleic Acid (DNA) in blood cells of Channa punctatus. Symbolic elevation in DNA damage with untreated 2NS administered fishes was observed as revealed by comet assay and micronucleus test. However, 2NS after being degraded using mixed bacterial population showed significant reduction in toxicological effects of 2NS. Thus, this study not only illustrated the adverse impact of such toxic contaminant of industrial waste but also suggested a highly efficient and eco-friendly way to remove the harmful xenobiotics from the environment which may help to reduce the exposure of aquatic fauna and flora to such lethal toxicants. Sukanya Mehra Prince Dhammi Pooja Chadha Harvinder Singh Saini Copyright (c) 2022 Toxicology International 2022-07-15 2022-07-15 147 157 10.18311/ti/2022/v29i2/28165 Assessment of the Genotoxic Potential of <i>Rasamanikya</i>, an Ayurvedic Arsenical Formulation in Albino Rats <em>Shodhita Haratala</em> (processed orpiment) is a single ingredient of <em>Rasamanikya</em> (RM). Arsenicals are known for producing toxic effects in humans, if not processed as per classical text therefore, the present study was aim to generate data for the safety of RM in albino rats. In the present study, two samples of RM were prepared by using two different purification media of orpiment, i.e., juice of <em>Benincasa hispida</em> (Thunb.) Cong. and lime water. Extract of <em>Tinospora cordifolia</em> Linn. (GG) was used as an adjuvant. Both the samples of RM along with GG were administered to the albino rats for 60 consecutive days at the therapeutic dose, TED (90 mg/kg) and TED×5 (450 mg/kg) orally in albino rats. Sample of RM along with GG not having the potential to produce any mutagenic or genotoxicity effects in albino rats. Further, there is no significant difference found in the safety of the orpiment on changing of media for purification. Dipali Parekh Om Pandey Mukesh Nariya Swapnil Chudhri B. J. Patgiri Copyright (c) 2022 Toxicology International 2022-07-15 2022-07-15 159 172 10.18311/ti/2022/v29i2/28338 Health Risk Assessment of Paraquat Contaminated in <i>Spirogyra spp.</i> (tao) in Chiang Mai, Thailand <em>Spirogyra</em> spp. (tao) is freshwater green algae which are consumed as an uncooked food especially in the north of Thailand. Aquatic plants especially algae are easily contaminated by pesticide residues from soil and water. Paraquat (1,1β-dimethyl, 4,4β-bipyridinium dichloride; PQ), a widely used herbicide among Thai farmers, is toxic, mutagenic, and carcinogenic to mammals through ingestion, inhalation and skin contact. This study aims to determine the concentrations of paraquat contaminated in <em>Spirogyra</em> spp. (tao) and health risk assessment on the consumption of <em>Spirogyra</em> spp. (tao) in Chiang Mai province, Thailand. The levels of paraquat were analyzed by using a simple, sensitive, and reliable method which was high performance liquid chromatography (HPLC). Seven samples were collected from the different districts. The levels of paraquat contamination were 5.07±0.00 to 12.69±0.10 mg/kg. The results showed that the concentrations of paraquat in all samples were lower than the standard level of the European Commission Regulation. Risk assessment of paraquat found that the hazard quotient was in the range of 0.18-0.46. It indicated that the consumption of <em>Spirogyra</em> spp. (tao) was expected to have no adverse health effects. However, the consumption of <em>Spirogyra</em> spp. (tao) should be a concern in terms of chronic exposure to toxic herbicide contaminated in the environment. Preechaya Tajai Assawin Daducale Sarunya Chuanphongpanich Copyright (c) 2022 Toxicology International 2022-07-15 2022-07-15 173 180 10.18311/ti/2022/v29i2/28851 Prospects of Combinatorial Approach Involving ICD Induction and Adenosine A2A Receptor Pathway Inhibition to Improve Cancer Immunotherapy The purpose of this review is to discuss and summarize the prospects of combinatorial approach involving immunogenic cell death induction and immunosuppressive adenosine A2A receptor pathway inhibition in enhancing anti-tumor immunity. Majority of chemotherapeutic agents can elicit antitumor immunity and modulate the composition, density, function, and distribution of Tumor Infiltrating Lymphocytes (TILs), to influence differential therapeutic responses and prognosis in cancer patients. Accumulating evidence indicates that the clinical success of these agents not only dependents on their cytotoxic activity but also by the enhancement of pre-existing immunity. Over expression of CD39 or CD73 enzymes has been implicated in limiting the ICD caused by chemotherapeutic agents like anthracyclines and oxaliplatin. Conversion of ATP released by chemotherapeutic drugs into adenosine dampens its capacity to attract antigen presenting cells including Dendritic Cells (DC) into the proximity of dying and dead cells. In addition, released adenosine exits potent immunosuppressive activities on different immune cells through A2A receptors in the TME and contributes to the resistance against chemotherapy. Resistance either intrinsic or acquired is the major hurdle for most of the therapeutic interventions. In order to enhance immunogenic cell death by chemotherapeutic agents, it has become clear that blockade of adenosine production or its signaling need to be specifically targeted as they represent highly resistant mechanisms. Given the prominent role of adenosine mediated immune suppression and resistance to ICD induction in TME, combination strategies that involve ICD induction and adenosine signaling blockade are further warranted. Y. Anil Kumar V. Chitra Copyright (c) 2022 Toxicology International 2022-07-15 2022-07-15 181 193 10.18311/ti/2022/v29i2/28974 Effect of Mobile Phone Radiation on Neurobehaviour: Possible Mechanisms from Preclinical Studies Excessive usage of gadgets Emitting Electromagnetic Radiation (EMR), especially smartphones, by people of all age groups, and so forth chronic exposure to the radiation, were indeed sounding the alarm about a multitude of health risks. The nervous system was significantly affected, altering the brain and behavior of people and animals. Many preclinical experimental studies have been performed to uncover the pathways that lead to injury, but the results have been contradictory. A strategic search was conducted to identify studies published between 2011 and 2020, using electronic databases such as PubMed and Science Direct. Based on predefined criteria, studies were identified for study and assessed individually. All of the included studies were assessed for the risk of bias, and no study was found to be free of bias. In preclinical research, heterogenicity was detected in the exposure settings (EMF-RF type, MW, pulsed, SAR value, and length of exposure) after a thorough assessment of the studies included. Exposure to mobile phone radiation can produce oxidative stress, which can lead to the activation of apoptotic and necrotic pathways if not reversed in time. The available scientific literature is insufficient to draw particular conclusions, but the possibility of harmful impacts cannot be ruled out, according to the authors. There is a great need to restrict extensive investigations and instead conduct a systematic and complete blinded study with significant reproducibility and long-term research. This review intended to explain the potential mechanisms and risks associated with mobile phone radiation exposure. Vara Prasad Saka V. Chitra N. D amodharan Copyright (c) 2022 Toxicology International 2022-07-15 2022-07-15 195 213 10.18311/ti/2022/v29i2/29000 Sodium Hypochlorite and its Environmental Impacts; Time to Switch for Herbal Alternatives Sanitizers are anti-microbial products in the form of spray, lotions, and creams. Sodium hypochlorite now plays an essential role in preserving hand cleanliness by denaturing microbial proteins by lysing the cell. These Sanitizers have also been used in medical, dental, and surgical treatments. If consumed, or through cutaneous or ocular exposure, sodium hypochlorite can be hazardous. When combined with acid it forms chlorine gas and when combined with basic solutions, chloramine is formed, both of which contribute to harmful consequences and it is an incredibly powerful oxidant. Furthermore, chlorination of drinking water with sodium hypochlorite oxidase organic pollutants, resulting in trihalomethanes, which are hazardous. It is critical for health care practitioners, particularly physicians, to understand the ways in which NaOCl can cause toxicity. The study of natural cures used to treat human sickness over millennia has laid the foundation for pharmaceutical development. The adaptation of alternative hand sanitizer formulations based on natural and herbal resources is one reasonable solution to address this toxicity problem. More extensive screens of indigenous plants with elevated flavonoids levels for antibacterial activities and the development of ecofriendly and efficient hand sanitizers should be conducted as contrast to artificial formulations. R. Jino Affrald Copyright (c) 2022 Toxicology International 2022-07-15 2022-07-15 215 226 10.18311/ti/2022/v29i2/29010 Effect of Di-(2-Ethylhexyl) Phthalate on Certain Haematological and Histological Parameters of Common Carp (<i>Cyprinus carpio</i>) Di-(2-Ethyl-Hexyl) Phthalate (DEHP) is a plasticizer commonly found in aquatic environment due to wide use of plastics for various purposes. In this study, common carp (<em>Cyprinus carpio</em>) (length 14.2 ± 0.82 cm and weight 32.8 ± 0.66 g) were exposed to DEHP at three different concentration levels i.e., 10, 100 and 1000 ?g l<sup>-1</sup> water for 30 d to find out its effect on certain haematological and histological parameters. Haematological studies revealed significant (p&lt;0.05) decrease in erythrocyte counts, while leukocyte counts were significantly increased in treated group with increasing concentration of DEHP. Further, treatment of DEHP in concentration dependent manner showed deformities in erythrocytes whereas leukocytes were unaffected. The total plasma protein level was significantly (p&lt;0.05) decreased in lower to higher concentration of the exposure. Histological studies showed gill and liver tissues were affected with impaired histoarchitecture in a dose dependent manner. Kampan Bisai Bijay Kumar Behera Sukanta Kumar Nayak Manoj Kumar Pati Copyright (c) 2022 Toxicology International 2022-07-15 2022-07-15 227 237 10.18311/ti/2022/v29i2/29129 Acute Oral Toxicity Studies and Evaluation of Central Analgesic Activity of Various extracts of Leaves of <i>Rhizophora apiculata</i> The present study aimed to determine the acute toxicity and screening of central analgesic activity of various extracts of<em> Rhizophora apiculata</em> leaves. The animals (Mice) were divided into control (no drug) and extract-treated groups (n=5), which were treated with diethyl ether, ethyl alcohol, and aqueous extract of R. apiculata leaves in various doses for specific regulatory needs. The groups which were given the highest safe doses were observed for 14 days. Then, blood samples were collected from high dose treated live mice through the retro-orbital route and were analysed for haematological, biochemical, and histopathological study. Evaluation of central analgesic activity was carried out by using tail immersion and hot plate methods. No considerable alterations were observed in body weight and organ-to-body weight index with the administration of extracts. An increase in albumin, globulin, total protein content and high-density lipoproteins, white blood cells, mean corpuscular volume, and eosinophils were observed. And a decrease in low-density lipoproteins, very low-density lipoproteins, triglycerides, and red blood cells were observed. Lymphocyte and monocyte levels were also reduced. The results also showed that the ethyl alcohol and aqueous extracts have elevated the time taken to flick response in the tail immersion test, and reduced the number of jumps, paw lick responses in the hot plate method. It was concluded that the diethyl ether and ethanolic extracts were found to be safe, which falls under non-toxic chemicals (LD50&gt;2000 smg/kg) whereas the aqueous extract was found safe up to 550 mg/kg beyond which, it was shown mortality. Ethyl alcohol and aqueous extracts were also proved to have analgesic activity. Annie Mande Narender Malothu Nagaraju Banadaru T. E. G. K. Murthy Copyright (c) 2022 Toxicology International 2022-07-15 2022-07-15 239 256 10.18311/ti/2022/v29i2/29161 Melatonin Ameliorates 2,4-Dichlorophenoxyacetic Acid Induced Testicular Steroidogenesis Upset in Mice: An <i>In Vivo</i> and <i>In Silico</i> Study 2,4-Dichlorophenoxyacetic acid (2,4-D) is used as a selective herbicide and associated with a variety of toxicities in mammals. In contrast, melatonin is an antioxidant that promotes the elimination of free radicals. In the present study, the protective effects of melatonin (10 mg/kg body weight) against 2,4- D (low, mid, and high dose-16.5, 33.0, and 66.0 mg/kg body weight) induced testicular steroidogenesis alteration were examined using<em> in vivo</em> and <em>in silico</em> models. Doses of 2,4-D and melatonin were administered orally for 28 days. The evaluated parameters were body weight, total protein, markers for male reproductive function, and steroidogenesis i.e. testis weight, total lipid, cholesterol, testosterone, 3 beta-hydroxysteroid dehydrogenase, 17 betahydroxysteroid dehydrogenase, total sperm count, sperm motility, and sperm viability along with the histopathology of the testis. The statistical significant value was considered at p&lt;0.05. Molecular docking study was performed for interaction of 2,4-D and melatonin with steroid binding proteins. <em>In vivo</em> results revealed that 2,4-D treatment showed a significant dose-dependent alteration in above all studied parameters. No significant auto-recovery was observed in the withdrawal study, on the contrarily, the altered parameters were normalized and comparable to control when melatonin was given alone and in combination with 2,4-D. <em>In silico</em> results also demonstrated that the binding affinity of melatonin with steroid binding proteins is higher than 2,4-D. Collectively, these <em>in vivo</em> and <em>in silico</em> findings indicated that 2,4-D induced testicular toxicity accompanied by steroidogenesis upset and can be reduced by melatonin significantly by interacting directly and strongly with studied molecular markers. Ashlesh M. Upadhyaya Zankruti S. Hathi Sarat K. Dalai Devendrasinh D. Jhala Copyright (c) 2022 Toxicology International 2022-07-15 2022-07-15 257 274 10.18311/ti/2022/v29i2/29271 Protective Effects of Melatonin Against 2,4-Dichlorophenoxyacetic Acid Induced Altered Haematological Variables in Mice: An <i>In Vivo</i> and <i>In Silico</i> Approach 2,4-Dichlorophenoxyacetic acid (2,4-D) is a systemic phenoxy herbicide that induces oxidative stress. In contrast, melatonin is a secretory product of the pineal gland with antioxidant properties. In the present study, the ameliorative potential of melatonin (10 mg/kg body weight) was investigated against 2,4-D (low, mid, and high dose-16.5, 33.0, and 66.0 mg/kg body weight) induced altered haematological variables using in vivo and in silico models. Doses of 2,4-D and melatonin were administered orally for 28 days. The evaluated haematological indices in the present study were Haemoglobin (Hb), Red Blood Corpuscles (RBC), Haematocrit (HCT), Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH), Mean Corpuscular Haemoglobin Concentration (MCHC), White Blood Corpuscles (WBC), Lymphocytes, Monocytes, Granulocytes, Platelet Count (PT), Mean Platelet Volume (MPV), Plateletcrit (PCT), and Erythrocyte Sedimentation Rate (ESR). The statistical significant value was considered at p&lt;0.05. Molecular docking study was performed for interaction of 2,4-D and melatonin with haemoglobin. In vivo results revealed that 2,4-D treatment showed a significant dose-dependent alteration in above all studied haematological indices. No significant auto reversal effects were observed in the withdrawal study, on the contrarily, the altered haematological indices were normalized and comparable to control when melatonin was given alone and in combination with 2,4-D. In silico results also demonstrated that 2,4-D and melatonin showed competitive bindings with haemoglobin. In nutshell, these in vivo and in silico findings depicted those haematological indices were altered by 2,4-D toxicity and can be abridged by melatonin attributed to its ameliorative potential as also evidenced by molecular docking. Ashlesh M. Upadhyaya Zankruti S. Hathi Sarat K. Dalai Devendrasinh D. Jhala Copyright (c) 2022 Toxicology International 2022-07-15 2022-07-15 275 288 10.18311/ti/2022/v29i2/29288 A Review on the Adaptogenic Activity of Potent Rasayana <i>Tinospora cordifolia</i> <em>Tinospora cordifolia</em> is an herbaceous vine that belongs to the Menispermaceae family, a succulent woody shrub genus, native to the tropical Indian sub-continent, and it is known for its common names: “Guduchi”, “giloy”, “amrita”, “gurjo”, and “heart-leaved moonseed”. The recent recognition and biological role of active components in disease management in the plant have contributed to an active interest in the plant worldwide. Extracts of <em>T. cordifolia</em> are widely used as antispasmodic, anti-microbial, antiperiodic, immunomodulatory, anti-inflammatory, anti-arthritic, anti-allergic, endocrine disorders like anti-diabetic, hypolipidaemic, etc. in various herbal formulations to treat different diseases. It helps reduce the resistance to insulin and stress, revitalises all the tissues of the body, and spontaneously promotes metabolism. However, this adaptogenic ability is also under-explored. Stress and ageing disorders need to be treated independently. The current review paper mainly focused on stress, depression, and the anti-stress properties (adaptogen) of <em>T. cordifolia</em>. Depression and stress, along with disrupted metabolic and reproductive properties, are high-risk factors in polycystic ovarian syndrome patients. Further studies are needed to focus on adaptogenic activity to relieve certain endocrine disorders that occur due to stress, often ovarian cysts, female menstrual irregularities, and hormonal imbalance. Murali Krishna Moka M. Sumithra Copyright (c) 2022 Toxicology International 2022-07-15 2022-07-15 289 297 10.18311/ti/2022/v29i2/29358