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ALTEX 2021Handling of chemicals is an often-neglected area of test descriptions. Some important aspects are highlighted here, using methyl-phenyl-tetrahydropyridine (MPTP),...
Handling of chemicals is an often-neglected area of test descriptions. Some important aspects are highlighted here, using methyl-phenyl-tetrahydropyridine (MPTP), ferrous sulfate (FeSO4·xH2O) and ciguatoxin as example compounds. These are used to provide some background on aspects of acid-base equilibria, redox state, crystal water, natural compound mixtures, and chemical naming systems. Also, solvents and impurities are addressed, for instance concerning their often high (millimolar range) concentrations in assay buffers and cell culture media. The discussion of these aspects calls for a more standardized preparation of test solutions and a more extensive disclosure of the procedure in publications; it also suggests more flexibility in data mining, as compounds with clearly different identifiers may have been used to produce highly similar or fully identical test conditions. While this short overview is not intended as definitive guidance, it does demand more active involvement of all test developers and performers with these issues, and it calls for more transparent information disclosure concerning the preparation and use of test and control chemical solutions.
Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Ciguatoxins; Drug Contamination; Ferrous Compounds; Poisons; Quality Control; Reproducibility of Results
PubMed: 33452536
DOI: 10.14573/altex.2012311 -
Bulletin of the World Health... Jul 2023To examine trends in the incidence of carbon monoxide poisoning before and after a ban on domestic use of raw coal in Ulaanbaatar, Mongolia.
OBJECTIVE
To examine trends in the incidence of carbon monoxide poisoning before and after a ban on domestic use of raw coal in Ulaanbaatar, Mongolia.
METHODS
Using injury surveillance data and population estimates, we calculated the incidence per 100 000 person-years of fatal and non-fatal domestic carbon monoxide poisoning before (May 2017 to April 2019) and after (May 2019 to April 2022) the ban in May 2019. We analysed data by age and sex, and compared areas not subjected to the ban with districts where domestic use of raw coal was banned and replaced with refined coal briquettes.
FINDINGS
We obtained complete data on 2247 people with carbon monoxide poisoning during the study period in a population of around 3 million people. In districts with the ban, there were 33 fatal and 151 non-fatal carbon monoxide poisonings before the ban, and 91 fatal and 1633 non-fatal carbon monoxide poisonings after the ban. The annual incidence of poisoning increased in districts with the ban, from 7.2 and 6.4 per 100 000 person-years in the two 12-month periods before the ban to 38.9, 42.0 and 40.1 per 100 000 in the three 12-month periods after the ban. The incidence of poisoning remained high after the ban, despite efforts to educate the public about the correct use of briquettes and the importance of ventilation. The incidence of carbon monoxide poisoning also increased slightly in areas without the ban.
CONCLUSION
Efforts are needed to investigate heating practices among households using briquettes, and to determine factors causing high carbon monoxide concentrations at home.
Topics: Humans; Carbon Monoxide Poisoning; Mongolia; Incidence; Coal
PubMed: 37397170
DOI: 10.2471/BLT.22.289232 -
Neurobiology of Disease Jan 2020The use of chemical warfare agents is an ongoing, significant threat to both civilians and military personnel worldwide. Nerve agents are by far the most formidable... (Review)
Review
The use of chemical warfare agents is an ongoing, significant threat to both civilians and military personnel worldwide. Nerve agents are by far the most formidable toxicants in terms of their lethality and toxicity. Nerve agents initiate neurotoxicity by the irreversible inhibition of acetylcholinesterase and resultant accumulation of acetylcholine in excitable tissues. The cholinergic toxidrome presents as miosis, lacrimation, diarrhea, fasciculations, seizures, respiratory arrest and coma. Current medical countermeasures can attenuate acute mortality and confer limited protection against secondary neuronal injury when given rapidly after exposure. However, there is an urgent need for the development of novel, add-on neuroprotective therapies to prevent mortality and long-term toxicity of nerve agents. Increasing evidence suggests that pathways other than direct acetylcholinesterase inhibition contribute to neurotoxicity and secondary neuronal injury. Among these, oxidative stress is emerging as a key therapeutic target for nerve agent toxicity. In this review, we discuss the rationale for targeting oxidative stress in nerve agent toxicity and highlight research investigating antioxidant therapy as a neuroprotective medical countermeasure to attenuate oxidative stress, neuroinflammation and neurodegeneration.
Topics: Animals; Antioxidants; Humans; Nerve Agents; Neuroprotective Agents; Neurotoxicity Syndromes; Oxidative Stress
PubMed: 31028872
DOI: 10.1016/j.nbd.2019.04.013 -
Toxins Jun 2021Marine biotoxins have been frequently implicated in morbidity and mortality events in numerous species of birds worldwide. Nevertheless, their effects on seabirds have... (Review)
Review
Marine biotoxins have been frequently implicated in morbidity and mortality events in numerous species of birds worldwide. Nevertheless, their effects on seabirds have often been overlooked and the associated ecological impact has not been extensively studied. On top of that, the number of published studies confirming by analyses the presence of marine biotoxins from harmful algal blooms (HABs) in seabirds, although having increased in recent years, is still quite low. This review compiles information on studies evidencing the impact of HAB toxins on marine birds, with a special focus on the effects of paralytic and amnesic shellfish toxins (PSTs and ASTs). It is mainly centered on studies in which the presence of PSTs and/or ASTs in seabird samples was demonstrated through analyses. The analytical techniques commonly employed, the tissues selected and the adjustments done in protocols for processing seabird matrixes are summarized. Other topics covered include the role of different vectors in the seabird intoxications, information on clinical signs in birds affected by PSTs and ASTs, and multifactorial causes which could aggravate the syndromes. Close collaboration between seabird experts and marine biotoxins researchers is needed to identify and report the potential involvement of HABs and their toxins in the mortality events. Future studies on the PSTs and ASTs pharmacodynamics, together with the establishment of lethal doses in various seabird species, are also necessary. These studies would aid in the selection of the target organs for toxins analyses and in the postmortem intoxication diagnoses.
Topics: Animals; Bird Diseases; Birds; Humans; Marine Toxins; Shellfish Poisoning
PubMed: 34209782
DOI: 10.3390/toxins13070454 -
Journal of Chemical Information and... Feb 2023We have previously applied our machine learning models for bioactivity and toxicity along with a generative algorithm to develop VX and tens of thousands of analogues....
We have previously applied our machine learning models for bioactivity and toxicity along with a generative algorithm to develop VX and tens of thousands of analogues. The publication brought attention to the ease of designing chemical warfare agents. In this Viewpoint, we discuss 10 recommendations to prevent future biochemical threats.
Topics: Organothiophosphorus Compounds; Chemical Warfare Agents; Machine Learning; Algorithms
PubMed: 36696568
DOI: 10.1021/acs.jcim.2c01616 -
Toxins Nov 2020Plant- and fungus-derived hepatotoxins are a major cause of disease and production losses in ruminants in Australia and around the world. Many are well studied and... (Review)
Review
Plant- and fungus-derived hepatotoxins are a major cause of disease and production losses in ruminants in Australia and around the world. Many are well studied and described in the literature; however, this is not the case for a number of hepatotoxicities with economic and animal welfare impacts, such as acute bovine liver disease (ABLD), brassica-associated liver disease (BALD) and , and toxicity. Additionally, significant overlap in the clinical presentation and pathology of these conditions can present a diagnostic challenge for veterinarians. This review summarizes the current and most recently published knowledge of common plant- and fungus-associated hepatotoxins affecting cattle in Australia, with a focus on the mechanisms of toxicity and distinguishing diagnostic features. Consolidation of the current understanding of hepatotoxic mechanisms in cattle provides insight into the potential mechanisms of lesser-known toxins, including cellular and subcellular targets and potential metabolic pathways. In the absence of specific etiological investigations, the study of epidemiological, clinical and pathological features of hepatotoxicity provides valuable insights into potential toxic mechanisms and is integral for the successful diagnosis and management of these conditions.
Topics: Animals; Australia; Cattle; Cattle Diseases; Chemical and Drug Induced Liver Injury; Fungi; Liver; Mycotoxins; Plant Poisoning; Plants, Toxic; Risk Assessment
PubMed: 33171661
DOI: 10.3390/toxins12110707 -
Environmental Toxicology and... Nov 2020Animal poisoning by chemicals (pesticides and household products) and drugs is a frequent occurrence and special attention should be paid to this phenomenon to improve...
Animal poisoning by chemicals (pesticides and household products) and drugs is a frequent occurrence and special attention should be paid to this phenomenon to improve prevention and treatment strategies and because of the fundamental role that animals may play as bioindicators. From January 2017 to March 2019 the Poison Control Centre of Milan (CAV) in collaboration with the University of Milan, collected and analyzed epidemiological data on animal poisoning. During this period, the CAV received a total of 442 enquiries on domestic animal poisoning episodes and, among these, 80.3 % were related to chemicals and drugs. Pesticides and drugs were the two major causes of poisoning (34.1 % and 33.5 %, respectively), followed by household products (29.3 %) and other causative agents (3.1 %, n = 11). In conclusion, these findings can provide useful information for the identification and monitoring of known and emerging toxicants, with positive repercussions on human, animal and environmental health.
Topics: Animals; Animals, Domestic; Household Products; Italy; Pesticides; Poison Control Centers; Poisoning
PubMed: 32818631
DOI: 10.1016/j.etap.2020.103471 -
Toxicology Mechanisms and Methods May 2021Highly toxic industrial chemicals that are widely accessible, and hazardous chemicals like phosgene oxime (CX) that can be easily synthesized, pose a serious threat as... (Review)
Review
Highly toxic industrial chemicals that are widely accessible, and hazardous chemicals like phosgene oxime (CX) that can be easily synthesized, pose a serious threat as potential chemical weapons. In addition, their accidental release can lead to chemical emergencies and mass casualties. CX, an urticant, or nettle agent, grouped with vesicating agents, causes instant pain, injury and systemic effects, which can lead to mortality. With faster cutaneous penetration, corrosive properties, and more potent toxicity compared to other vesicating agents, CX causes instantaneous and severe tissue damage. CX, a potential chemical terrorism threat agent, could therefore be weaponized with other chemical warfare agents to enhance their harmful effects. CX is the least studied vesicant and its acute and long-term toxic effects as well as its mechanism of action are largely unknown. This has hampered the identification of therapeutic targets and the development of effective medical countermeasures. There are only protective measures, decontamination, and supportive treatments available for reducing the toxic effects from CX exposure. This review summarizes CX toxicity, its known mechanism of action, and our current studies exploring the role of mast cell activation and associated signaling pathways in CX cutaneous exposure under the National Institutes of Health Countermeasures Against Chemical Threats program. Potential treatment options and the development of effective targeted countermeasures against CX-induced morbidity and mortality is also discussed.
Topics: Chemical Warfare Agents; Irritants; Oximes; Phosgene; Skin
PubMed: 33297803
DOI: 10.1080/15376516.2020.1861670 -
Free Radical Biology & Medicine Dec 2020In the long and intensive search for effective treatments to counteract the toxicity of the chemical warfare (CW) agent sulphur mustard (H; bis(2-chloroethyl) sulphide),... (Review)
Review
In the long and intensive search for effective treatments to counteract the toxicity of the chemical warfare (CW) agent sulphur mustard (H; bis(2-chloroethyl) sulphide), the most auspicious and consistent results have been obtained with the drug N-acetylcysteine (NAC), particularly with respect to its therapeutic use against the effects of inhaled H. It is a synthetic cysteine derivative that has been used in a wide variety of clinical applications for decades and a wealth of information exists on its safety and protective properties against a broad range of toxicants and disease states. Its primary mechanism of action is as a pro-drug for the synthesis of the antioxidant glutathione (GSH), particularly in those circumstances where oxidative stress has exhausted intracellular GSH stores. It impacts a number of pathways either directly or through its GSH-related antioxidant and anti-inflammatory properties, which make it a prime candidate as a potential treatment for the wide range of deleterious cellular effects that H is acknowledged to cause in exposed individuals. This report reviews the available literature on the protection afforded by NAC against the toxicity of H in a variety of model systems, including its efficacy in treating the long-term chronic lung effects of H that have been demonstrated in Iranian veterans exposed during the Iran-Iraq War (1980-1988). Although there is overwhelming evidence supporting this drug as a potential medical countermeasure against this CW agent, there is a requirement for carefully controlled clinical trials to determine the safety, efficacy and optimal NAC dosage regimens for the treatment of inhaled H.
Topics: Acetylcysteine; Chemical Warfare Agents; Glutathione; Humans; Iran; Mustard Gas
PubMed: 32980537
DOI: 10.1016/j.freeradbiomed.2020.09.020 -
Basic & Clinical Pharmacology &... Dec 2022The primary aim of this pilot study was to develop a machine learning algorithm to predict and distinguish eight poisoning agents based on clinical symptoms. Data were...
The primary aim of this pilot study was to develop a machine learning algorithm to predict and distinguish eight poisoning agents based on clinical symptoms. Data were used from the National Poison Data System from 2014 to 2018, for patients 0-89 years old with single-agent exposure to eight drugs or drug classes (acetaminophen, aspirin, benzodiazepines, bupropion, calcium channel blockers, diphenhydramine, lithium and sulfonylureas). Four classifier prediction models were applied to the data: logistic regression, LightGBM, XGBoost, and CatBoost. There were 201 031 cases used to develop and test the algorithms. Among the four models, accuracy ranged 77%-80%, with precision and F1 scores of 76%-80% and recall of 77%-78%. Overall specificity was 92% for all models. Accuracy was highest for identifying sulfonylureas, acetaminophen, benzodiazepines and diphenhydramine poisoning. F1 scores were highest for correctly classifying sulfonylureas, acetaminophen and benzodiazepine poisonings. Recall was highest for sulfonylureas, acetaminophen, and benzodiazepines, and lowest for bupropion. Specificity was >99% for models of sulfonylureas, calcium channel blockers, lithium and aspirin. For single-agent poisoning cases among the eight possible exposures, machine learning models based on clinical signs and symptoms moderately predicted the causal agent. CatBoost and LightGBM classifier models had the highest performance of those tested.
Topics: Humans; Infant, Newborn; Infant; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Poison Control Centers; Poisons; Pilot Projects; Acetaminophen; Bupropion; Lithium; Calcium Channel Blockers; Machine Learning; Diphenhydramine; Benzodiazepines; Aspirin; Poisoning
PubMed: 36181236
DOI: 10.1111/bcpt.13800