Hasil untuk "Toxicology. Poisons"

S. Safe

The American Academy of Clinical Toxicology Ad Hoc, D. Barceloux, G. Randall Bond et al.

D. Gummin, J. Mowry, Michael C Beuhler et al.

Abstract Introduction This is the 41st Annual Report of America’s Poison Centers® National Poison Data System®. As of 1 January, 2023, all 55 of the nation’s poison centers uploaded case data automatically to NPDS. Methods We analyzed the case data, tabulating specific indices from the NPDS®. The methodology was as in previous years. Where changes were introduced, the differences are identified. Cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologists using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality of the exposure. Results In 2023, 2,421,251 closed encounters were logged by the National Poison Data System®: 2,080,659 human exposures, 41,857 animal exposures, 293,663 information requests, 5,046 human confirmed nonexposures, and 26 animal confirmed nonexposures. The upload interval was 4.88 [4.43, 9.33] (median [25%, 75%]) minutes, creating a near real-time national exposure and information database and surveillance system. Total encounters showed a 2.49% decrease from 2022 while human exposure cases increased by 0.764% and health care facility human exposure cases increased by 2.38%. All information requests decreased by 19.1%, medication identification (Drug ID) requests decreased by 14.0%, and medical information requests showed a 61.3% decrease, returning to pre-COVID-19 pandemic numbers. Drug Information requests showed a 17.6% decrease, due to continued declining COVID-19 vaccine calls to poison centers, but these still comprised 21.7% of all information contacts. Human exposures with less serious outcomes have decreased by 1.58% per year since 2008, while those with more serious outcomes (moderate, major or death) have increased by 4.25% per year since 2000. Consistent with the previous year, the top 4 substance classes most frequently involved in all human exposures were analgesics (11.00%), household cleaning substances (7.12%), antidepressants (5.58%), and cosmetics/personal care products (5.01%). Cardiovascular drugs (4.97%) replaced antihistamines as the 5th most common substance class. As a class, analgesic exposures increased most rapidly, by 1,260 cases/year (2.72%/year) over the past 10 years for cases with more serious outcomes. The top 5 most common exposures in children aged 5 years or less were household cleaning substances (10.1%), analgesics (9.13%), cosmetics/personal care products (9.10%), foreign bodies/toys/miscellaneous (8.03%), and dietary supplements/herbals/homeopathic (6.88%). The National Poison Data System® documented 3,272 human exposures resulting in death; 2,700 (82.5%) of these were judged as related (Relative Contribution to Fatality of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory). Conclusions These data support the continued value of poison center expertise and the need for specialized medical toxicology information to manage the increasing number of more serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time nature of the National Poison Data System® represents a national public health resource for collecting and monitoring US exposure cases and information requests. The continuing mission of the National Poison Data System® is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, infectious, venomous, chemical agent, or commercial product), and the identification and tracking of significant public health events. The National Poison Data System® is a model system for the near real-time surveillance of national and global public health.

Laura Escorihuela, Rajesh Kumar Pathak, Rajesh Kumar Pathak et al.

Understanding the toxicological mechanisms of food contaminants is critical for assessing risks to human health. This review comprehensively examines their adverse effects, tracing the pathway from molecular initiation to systemic organ-level damage. A central focus is placed on the growing trust on computational methods as ethical and practical alternatives to traditional animal testing. The discussion encompasses a multi-scale assessment, detailing atomic-level interactions through Density Functional Tight Binding Molecular docking and Molecular Dynamics (MD) simulations, analyses of toxicity pathway, and prediction of systemic fate using Physiologically Based Pharmacokinetic (PBPK) modeling. We further explore how these in silico insights are integrated with experimental data to build predictive models, including Quantitative Structure-Activity Relationship and machine learning frameworks. Ultimately, this review aims to inform the development of effective strategies for mitigating contaminant risks, thereby advancing public health objectives and supporting the 3Rs principles (Replacement, Reduction, and Refinement) in toxicological science.

Marcus Stangeland, Ola Dale, Arnre Kristian Skulberg

Abstract Introduction Nitazenes are a class of potent synthetic opioids that have emerged in illicit drug markets and have been identified in combination with other opioids in cases of poisoning and fatalities. Originally developed in the 1950s, these compounds were abandoned due to their high toxicity and unfavourable therapeutic index. Recent reports indicate that nitazenes exhibit a wide range of potencies, with some exceeding that of fentanyl. Understanding the pharmacological and toxicological profiles of nitazenes is critical for public health and clinical management. This review synthesizes literature on the pharmacology, toxicity, and antagonist action of nitazenes, particularly their response to naloxone. Methods A comprehensive literature review was conducted using EMBASE, Ovid MEDLINE(R), APA PsycInfo, Scopus, and Web of Science up to 26 July 2024. The main search terms used were: “nitazen*”, “2-benzylbenzimidazole”, “aminoisotonitazene” OR “butonitazeneor clonitazene” OR “desnitazene” OR “etodesnitazene” OR “etonitazene” OR “flunitazene” OR “isotonitazene” OR “metodesnitazene” OR “metonitazene” OR “protonitazene”. Inclusion criteria encompassed in vitro and animal studies, post-mortem toxicology, clinical trials, and case reports on nitazene poisoning. Data regarding naloxone dosing in confirmed cases of nitazene poisoning were also analyzed. Results We identified 1,383 studies, and after removing duplicates, 557 abstracts were screened. Based on the eligibility criteria, 78 articles underwent full-text screening, and 35 were included in the final review. Nitazenes exhibit variability in potency and toxicity. In vitro studies suggest that their receptor affinity and potency often surpass those of both morphine and fentanyl. Real-world data indicate that in vivo potency is often lower than experimental findings. Case reports and clinical series indicate that naloxone remains an effective antidote for nitazene poisoning. A median dose of parenteral naloxone 1.20 mg effectively reversed poisoning, with a median dose of 0.8 mg in the pre-hospital setting. However, a subset of patients received prolonged naloxone infusions due to the persistence of opioid effects. Six out of 30 patients were treated with naloxone infusions. This ratio is higher than that reflected in current clinical guidelines, in which shorter observation time is deemed sufficient. Post-mortem toxicological analyses reveal highly variable nitazene concentrations, with overlap with those concentrations found in patients. This complicates the establishment of lethal thresholds. In several cases, nitazene metabolites were detected in isolation, suggesting independent pharmacological activity or alternative routes of administration. Additionally, nitazene poisoning often involves polysubstance use, further complicating diagnosis and management. Discussion Data on nitazene potency in humans are scarce. Nitazenes are a heterogeneous group with very high experimental potency compared to morphine. The potency in in vivo outcome studies in humans is far lower than that in in vitro studies. Post-mortem concentrations of many nitazenes are similar to the post-mortem concentrations of fentanyl and indicate a similar potency. Treatment of nitazene poisoning should follow the guidelines for opioid poisoning, that is, instituting airway management and administering naloxone. All cases reviewed had several opioids and other sedating drugs in addition to nitazenes in their analytical workup. The median parenteral dose for successful reversal of features was 1.20 mg. This finding provides reassurance that naloxone is effective for the treatment of poisoning due to nitazene as well as other potent opioids. Conclusions Nitazenes represent an emerging public health challenge due to their high potency, unknown pharmacokinetics, and increasing presence in illicit drug supplies. While naloxone is effective in reversing nitazene poisoning, cases of prolonged toxicity suggest the need for extended monitoring and repeated naloxone dosing. The findings of this review highlight the importance of enhanced drug surveillance, improved clinical awareness, and the development of targeted harm reduction strategies, including the potential for novel opioid antagonists with prolonged efficacy. Future research should focus on defining nitazene receptor kinetics, post-mortem redistribution effects, and optimizing naloxone administration protocols for these emerging synthetic opioids.

Deepika Deepika, Deepika Deepika, Kanchan Bharti et al.

New Approach Methodologies (NAMs) hold great potential to fill data gaps for chemicals and modernisation of chemical risk assessment practices. Current toxicity testing is based on conventional approaches with high reliability on in-vivo studies, but with time, regulators are trying to move towards in-vitro and in silico tools enabling efficient risk assessment strategies. Herein, we discuss about different emerging techniques which are or can become a NAM including both in-vitro and in silico models with particular focus on reducing animal studies and improving decision-making for hazard and exposure assessment. We also discussed about the way to strengthen the regulatory and public confidence in different NAMs and automation of these approaches. Some of these NAMs can help in identifying biochemical mechanisms for toxicity, calculate the point of departure (PoD), develop adverse outcome pathways (AOP), translate risk to multiple species and quantify uncertainty from predictions for multiple chemicals. Scientists and regulators can work together to frame robust guidelines for the practical application of these tools and ensure reproducible results.

Fern Findlay-Greene, Samantha Donnellan, Sharron Vass

The use of alternative tobacco products such as vaping devices has significantly increased over the last 5-years, with the largest increase being amongst 18–25-year-olds. While the quantity of nicotine is tightly regulated, the composition of e-liquid flavourings is largely unregulated, and often absent from product labels. Herein, we compare the toxicity of carrier liquids propylene glycol (PG) &amp; vegetable glycerine (VG) with five popular flavour concentrates: menthol, cherry, butterscotch, vanilla bourbon and tobacco on human alveolar type II cell-like A549 cells. The flavourings were tested in both liquid and vapour form and a vapour assay was developed to assess cytotoxicity of the flavourings. Our results conclude that menthol liquid was the most cytotoxic (LD50 = <0.5 % over a <4 h exposure). Followed by cherry and vanilla bourbon which elicited a similar response at 4 % over 8 h exposure. Tobacco only reached 50 % toxicity at a concentration > 4 % over 24 h exposure. Butterscotch displayed similar toxicity profiles to PG and VG where cytotoxicity exceeded 20 % at 8 % concentration at all time points. The cytotoxicity of menthol was further evaluated as a vapour, with a significant reduction in viable cells and a 5-fold increase in the number of necrotic cells with only 11 % of cells remaining viable after 5 vaping episodes. Analysis revealed the presence of toxic chemicals and heavy metals in the fluids therefore further research is required to fully elucidate the long-term usage of flavourings with vaping devices and the impact this may have on human lung health.

David Lozano-Paniagua

Somnath Basak, Rekha S. Singhal

Abstract The search for new functional ingredients that meet the nutritional and technological requirements from the available resources cost‐effectively has been an ongoing activity by both academia and industry. In this respect, coextraction of the ingredients is a promising approach for valorization of food wastes as can be seen from reports that have been emerging since the last decade. The process can be used for the coextraction of all major food ingredients, namely, lipids, proteins, and polysaccharides. The approach being presented in this review is based on using two or more resources to obtain ingredients through a single process. This review looks into some of these possibilities, presents future perspectives, and calls for attention from the scientific community to explore this area of research with high translational capabilities. Coextraction offers an opportunity for valorization of wastes with energy conservation and minimizing solvent usage, wherein the bioactives present therein can be coextracted with a major food ingredient and used in the formulations, while using the principles of circular economy. Apart from the processing advantage it provides, coextraction from different sources has been reported to positively influence the structural, nutritional, and functional properties of food ingredients.

Choo Hock Tan, Aymeric Bourges, Kae Yi Tan

Abstract King Cobra (Ophiophagus hannah) has a significant place in many cultures, and is a medically important venomous snake in the world. Envenomation by this snake is highly lethal, manifested mainly by neurotoxicity and local tissue damage. King Cobra may be part of a larger species complex, and is widely distributed across Southeast Asia, southern China, northern and eastern regions as well as the Western Ghats of India, indicating potential geographical variation in venom composition. There is, however, only one species-specific King Cobra antivenom available worldwide that is produced in Thailand, using venom from the snake of Thai origin. Issues relating to the management of King Cobra envenomation (e.g., variation in the composition and toxicity of the venom, limited availability and efficacy of antivenom), and challenges faced in the research of venom (in particular proteomics), are rarely addressed. This article reviews the natural history and sociocultural importance of King Cobra, cases of snakebite envenomation caused by this species, current practice of management (preclinical and clinical), and major toxinological studies of the venom with a focus on venom proteomics, toxicity and neutralization. Unfortunately, epidemiological data of King Cobra bite is scarce, and venom proteomes reported in various studies revealed marked discrepancies in details. Challenges, such as inconsistency in snake venom sampling, varying methodology of proteomic analysis, lack of mechanistic and antivenomic studies, and controversy surrounding antivenom use in treating King Cobra envenomation are herein discussed. Future directions are proposed, including the effort to establish a standard, comprehensive Pan-Asian proteomic database of King Cobra venom, from which the venom variation can be determined. Research should be undertaken to characterize the toxin antigenicity, and to develop an antivenom with improved efficacy and wider geographical utility. The endeavors are aligned with the WHO´s roadmap that aims to reduce the disease burden of snakebite by 50% before 2030.

Mi Jin Lee, Jae Wan Cho, Haewon Jung et al.

AbstractAcute poisoning may necessitate identification of the toxic agent; however, several acutely poisoned patients are treated with minimal laboratory assistance. We investigated whether focused reference to laboratory toxicology tests conducted during a pilot project for a subregional analytical toxicology service influences treatment decisions. Patients with acute poisoning presented to the level 1 regional emergency medical center from May 2018 to April 2019 were initially reviewed. Poison samples were referred to the subregional toxicological analytical service. In total, 253 substance samples were tested among 111 patients during the study. According to the reported drug levels, 3 (1.2%) samples contained lethal doses, 49 (19%) had toxic levels, and 28 (11%) contained detectable levels of a lethal toxin or pesticide. Disagreement between the clinical assessment and laboratory analyses was found for 62 patients (fair kappa = 0.24, 56%), and they often had lower Glasgow Coma Scale, higher severity scores, older age, and less likelihood of receiving gastrointestinal decontamination. The regional analytical toxicology services were helpful for diagnostic planning and therapeutic management of acute poisoning. For seriously poisoned patients with inconsistent histories, it is necessary to reevaluate the classic therapeutic process based on the medical history.

Kimberly P. Keil Stietz, Conner L. Kennedy, Sunjay Sethi et al.

Bladder dysfunction, including incontinence, difficulty emptying the bladder, or urgency to urinate is a pervasive health and quality of life concern. However, risk factors for developing these symptoms are not completely understood, and the influence of exposure to environmental chemicals, especially during development, on the formation and function of the bladder is understudied. Environmental contaminants such as polychlorinated biphenyls (PCBs) are known to pose a risk to the developing brain; however, their influence on the development of peripheral target organs, such as bladder, are unknown. To address this data gap, C57Bl/6J mouse dams were exposed to an environmentally-relevant PCB mixture at 0, 0.1, 1 or 6 mg/kg daily beginning two weeks prior to mating and continuing through gestation and lactation. Bladders were collected from offspring at postnatal days (P) 28–31. PCB concentrations were detected in bladders in a dose-dependent manner. PCB effects on the bladder were sex- and dose-dependent. Overall, PCB effects were observed in male, but not female, bladders. PCBs increased bladder volume and suburothelial βIII-tubulin-positive nerve density compared to vehicle control. A subset of these nerves were sensory peptidergic axons indicated by increased calcitonin gene-related protein (CGRP) positive nerve fibers in mice exposed to the highest PCB dose compared to the lowest PCB dose. PCB-induced increased nerve density was also positively correlated with the number of mast cells in the bladder, suggesting inflammation may be involved. There were no detectable changes in epithelial composition or apoptosis as indicated by expression of cleaved caspase 3, suggesting PCBs do not cause overt toxicity. Bladder volume changes were not accompanied by changes in bladder mass or epithelial thickness, indicating that obstruction was not likely involved. Together, these results are the first to suggest that following developmental exposure, PCBs can distribute to the bladder and alter neuroanatomic development and bladder volume in male mice.

Piyali Sarkar, Parimal Kanti Sen, Shashwat Bhattacharyya et al.

Background: Diabetes Mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycemia. It becomes a global epidemic and day by day it is increasing, expecting more than 200 million type 2 DM cases will be seen in next decade predicted by World Health Organization (WHO). India has 31.7 million diabetic patients and the number is expected to increase upto 79.4 million by 2030. Diabetic retinopathy (DR) remains a leading cause of visual disability and blindness. It is a major microvascular complication of diabetes and is frequently accompanied by lipid exudation. The elevated level of blood glucose and HbA1c is highly associated with changes in central corneal thickness. Objective: To estimate the changes of central corneal thickness (CCT) and optic disc in type-2 diabetes mellitus patients with or without retinopathy. Materials and Methods: It was a hospital base cross sectional study. The study population were selected according to inclusion and exclusion criteria after proper evaluation. The study population was divided into two groups. Group A (control) and group B (study) were considered as patients who had type 2 DM without DR and with DR respectively. The data were collected and tabulated in excel sheet. The statistical analysis was done as percentage, proportion Pearson’s chi square test/ Mann-Whitney U test. The statistical significant was considered if p value < 0.05. Results: The mean CCT of control and study groups were 549.60±4.56µm and 555.45 ± 5.71µm respectively. (p ≤ 0.001). The mean IOP of control and study groups were 19.88±1.82 mm Hg and 23.55 ± 1.77 mm Hg respectively. (p ≤ 0.001). Among study groups, optic atrophy, disc hemorrhage, disc neovascularization (NVD) and nerve fiber damage were 4%, 2%, 4% and 4% respectively. Conclusion: The Type2 diabetes with retinopathy patients had higher CCT, increase risk of optic atrophy, NVD and nerve fiber damage.

Rosso Ana María

The decadent Lagids’dynasty was especially interested in drugs and poisons meanwhile Alexandria became a prestigious center of learning and the first medical center of the ancient world. Scholars dedicated to toxicology would research in the famous Museion and the Hellenistic rulers of Alexandria and other kingdoms had court physicians specialized in pharmacology and venoms. As the last member of Ptolemaic Dynasty, Cleopatra VII inherited the throne and also the great inclination of Ptolemies towards medicine and science. In this city toxicological education seems to have had its most systematic development, and for Galen [1] “human and prompt executions’ were made in Alexandria with the intervention of cobras”.Attracted by the knowledge of venoms and poison, Cleopatra began to test them on condemned prisoners to see the different reactions produced in the body and found toxic limits. When she decided to commit suicide, the use of poison would make sense given the possibility to choose the best one to get a quick and relatively pain free death. Knowing that oral poisons would cause disturbances as painful spasms, nauseas, abdominal cramps and slow end, she presumably compared the major effects of venemous snakebites caused by the various species living in Egypt, specially three families: vipers, hydrophids and elapids.Cleopatra probably realized that viper bites generally produce violent local pain with inflammation, oedema, skin discoloration, pustules, vomiting and blood loss. With the cobra venom, hemotoxic or neurotoxic, instead, death could happen within half an hour, by respiratory failure and general paralysis without leaving any trace on the flesh, though. It has been said that Cleopatra used the cobra to kill herself because it would also make sense in terms of Egyptian mythology, being associated with the sacred uraeus worn by the pharaohs. However, there are several problems with this theory and some scholars recently argue it’s more likely she would drank a cocktail of drugs or applied a toxic ointment, as Strabo suggested.Studying the different poisons and the snakes that she could have selected and the symptoms and consequences that they could produce in her body, we’ll try to delve into her possible lucubrations and reflexions, weighing the difficulties in each case. Undoubtedly, the mysterious end of Cleopatra remains unsolved, offering a constant source of legends and theories. Keeping this in mind we will try to present the pros and cons of each of her possible decisions.

Tilahun Alelign, Dinkenesh Chalchisa, Netsanet Fekadu et al.

Introduction: Achyranthes aspera, Chenopodium murale, Satureja punctata, Rumex abyssinicus and Aloe pulcherrima are traditionally used to treat urolithiasis in Ethiopia. However, there are limited reports on toxicity studies. Objective: This study was intended to evaluate the acute and sub-acute toxicity effects of plants. Materials and Methods: The crude extracts of A. aspera and C. murale leaves, S. punctata aerial parts, R. abyssinicus rhizomes, and A. Pulcherrima gel were prepared using 70 % ethanol. In acute toxicity, 125, 500 and 2000 mg/kg were tested in a stepwise manner; whereas 2000 mg/kg administrated to female rats using gavage during sub-acute toxicity. On day 14 and 28, blood samples were collected from retro-orbital sinus; liver and kidneys of each animal were collected under anaesthesia. Data were analyzed using one-way ANOVA, Dunnett's comparison test of the Graph Pad Prism. Results: No mortality and significant weight loss for all extracts in both toxicity tests. In acute toxicity, C. murale extract significantly reduced hemoglobin and platelets (P < 0.01) compared with the control. Likewise, S. punctata (P < 0.05) and R. abyssinicus (P < 0.01) extracts revealed significant reduction in platelet count. An exposure to C. murale and R. abyssinicus extracts reduced the concentrations of platelet distribution width and platelet larger cell ratio (p < 0.05) during sub-acute toxicity test. The level of creatinine reduced due to A. aspera extract administrations(P < 0.05). Liver histopathological examinations revealed focal periportal hepatitis following sub-acute toxicity test of C. murale. Histopathological studies of liver demonstrated that R. abyssinicus, A. aspera and S. punctata extracts showed mild acute liver injury. A. pulcherrima was not associated with any toxicity. Conclusion: C. murale extract showed hematological, and histopathological toxicity profiles in rats. Furthermore, chronic toxicity studies of A. aspera, S. punctata and R. abyssinicus extracts would be beneficial to ensure safety.

M. Parsons, K. Aligizaki, M. Bottein et al.

FS Abtahi

Background: Ethnobotany is the study of a regionchr('39')s plants and their practical uses through the traditional knowledge of a local culture and people. Traditional plant usage for medicinal purposes is a main part of indigenous people culture which has been formed during centuries in rural area. This knowledge has played important role in the development of new drugs on the modern medicine. Objective: The present study was conducted with the purpose of introducing the traditional usage of medicinal plants of Shazand city for medicinal purposes. Methods: The data were collected through field surveys, face-to face interviews with local botanist and documentary studies. After samples collection, plant species were identified and local name, life form, therapeutic characteristics, used plant organs, routes of administration were gathered. Results: In this study, 56 plant species belong to 23 families were identified. The most frequently used plant was as comforting, healing wounds, stomach tonic, painkiller and anti-inflammation and other use in traditional medicine that they can be exploited with careful planning and management. Conclusion: Shazand with 56 medicinal plant species is considered a rich source of these valuable plant; and this provide suitable field to increase the area under cultivation of medicinal and aromatic plants, afterwards to reduce wild-harvesting medicinal plants from natural areas.

Mohammad Hosseinpour, Jamil Zargan, Hossein Honari et al.

Background: The production and secretion of defense proteins are one of the protective mechanisms exploited by plants against pathogens. The production and secretion of defense proteins are one of the protective mechanisms exploited by plants against pathogens. Ribosome-Inactivating Proteins (RIPs), as the main class of these proteins, are considered to facilitate cancer therapy worldwide, because of the potential anticancer activity. Indeed, some of these proteins have cytotoxic and anticancer properties. Extracted from the carnation (Dianthus caryophyllus), Dianthin inhibits protein synthesis in many different cells. Methods: In this research, the Dianthins was isolated and purified from the leaves of D. caryophyllus, using ion-exchange chromatography column (CM-Sephadex G-50). Subsequently, its cytotoxicity effect on MCF-7 cell line was investigated. The cell cytotoxicity assessment was performed, using 3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT), neutral red uptake, and alkaline comet assays at the concentrations of 1.25μg/ mL to 10μg/mL of the protein applying the MCF-7 cell line. Results: the toxin induces cell death, mostly via necrosis rather than apoptosis, but in the special range of concentrations. Conclusion: because of the severe side effects of chemotherapy drugs, this toxin can undergo more research as a new drug candidate against breast cancer

N. Gunja

F. Thévenod, Wing-Kee Lee