DOCSLIB.ORG

Toxicity of Formaldehyde in Experimental Animals -Concentrations of the Chemical in the Elution from Dishes of Formaldehyde Resin in Some Vegetables

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Toxicity of Formaldehyde in Experimental Animals -Concentrations of the Chemical in the Elution from Dishes of Formaldehyde Resin in Some Vegetables Keio J. Med. 24: 19-37, 1975 TOXICITY OF FORMALDEHYDE IN EXPERIMENTAL ANIMALS -CONCENTRATIONS OF THE CHEMICAL IN THE ELUTION FROM DISHES OF FORMALDEHYDE RESIN IN SOME VEGETABLES KENZABURO TSUCHIYA, YOSHIO HAYASHI, MITSUKO ONODERA and TAKAO HASEGAWA Department of Public Health and Preventive Medicine, School of Medicine, Keio University (Received for publication Oct. 16, 1974) ABSTRACT The study composes of the following experiments: 1) The first experiment was carried out in order to calculate the lethal dose (LD50) of formaldehyde and of formalin solution. 2) The second one was to examine the quantitative method and to measure the concentration of formaldehyde in solution eluted from plastic bowls made of formaldehyde resin. 3) In the final experiment formaldehyde in some foods was measured. Princinal results obtained were as follows: 1) LD50 of formaldehyde by oral administration was determined to be 500-800 my/ke for rats. 2) The maximum allowable concentration of the chemical for chronic poison ing was estimated to exist at the level of around 25 to 30 mg/day/50 kg for man. 3) However, it was conceivable that various kinds of food would contain formaldehyde as high as almost 20 ppm. More elaborate studies are required on this point. 4) It was confirmed that formaldehyde is eluted from plastic dishes and bowls made from a monomer of formaldehyde from the non-detectable con centration at 40•Ž up to 20 ppm at 90•Ž, and up to almost 400 ppm in solu tion of 4% acetic acid of 90•Ž, showing only 10 ppm at 40•‹ to 50•Ž, after leaving the solutions in the bowls for 15 minutes. Formaldehyde is used for various purposes in industry, and the manufactur ing industry of synthetic resin, deodorizer, sterilizing agent, antiseptics, dye, leather, rubber and synthetic fiber and the industry of water proofing and re 19 20 Kenzaburo Tsuchiya et al ducer are attended with the dangers of exposure to formaldehyde. The toxic action of formaldehyde was studied by Flury et al,1,2 using cats. The animals died chiefly of edema, hemorrhage and inflammation of the mucous membrane of the respiratory organs, and in cases where death did not occur, the symptoms being limited to irritation of the mucous membrane, they recovered without sequelae. The maximum allowable concentration in the atmosphere of the working environment ranges from 10 to 5 ppm1,3 but it seems unlikely up until the present that formaldehyde has posed a great problem in industrial medicine in Japan. However, since no research under actual conditions has been conducted, the real situation is uncertain. In accordance with the recent production of various kinds of plastic table ware made from synthetic resins, it was found that formaldehyde was eluted from the tableware made of formaldehyde resin, presenting a problem in food sanitation. Noted in particular was a study4 in which the toxic action of formal dehyde was found by chronic experiments with rabbits, though the number of cases was small. It was though that this problem required full examination from a public health point of view. The chronic toxic action of a substance is a very difficult problem, and in consideration of the period, concentrations, species of animals and method of medical observation, it is thought to be almost impossible to discover the limits sufficient to induce chronic toxic action experimentally. Therefore, the maximum limit possible to perform actually would be to administer the water which was actually used for the dish or bowl made of synthetic resin to animals of 2-3 species for 1-2 years for physiological, biochemical and pathological examina tions. However, since even such an experimental study requires great expense, effort and a certain period of time, the authors decided to first calculate the lethal dose as a preliminary study for an estimation of the rough dose for chronic intoxication in humans in order to contribute it as basic material for future experiments on chronic intoxication. In addition, the amount of formaldehyde in various foods which we eat daily was measured for comparison with the amount of eluted formaldehyde from the tableware made from synthetic resin commercially available. The problem of formaldehyde in the tableware made of synthetic resin seems to have been brought forward in the United States as well, and the dispute as a political problem between the Association for Ceramics and the Association for Resin is noted in the November 1951 issue of the Journal of Modern Plastics. Although we encountered the "Formaldehyde-Its Toxicity and Potential Dangers" in Supplement No. 181 of the Public Health Report for 1945 as litera Toxicity of Formaldehyde 21 ture, unfortunately, we were not able to obtain in journal concerned nor reprints in spite of all our efforts. Accordingly, it is not possible to introduce literature on chronic disturbances by the oral administration of formalin, but the present study is though to be contributory in the sense mentioned above. With this study as a basis, studies on chronic intoxication should be further developed in the future. EXPERIMENTAL METHODS 1) Calculation of the lethal dose. About 400 male rats were used for the experiments. Their body weight ranged from 100 g to 200 g, and animals of the same body weight and age were used in an experiment as long as possible. The rats were of the Wister strain, but because of the large number required they were purchased from animal dealers whose reliability was not necessarily high. The number of rats purchased each time was about 50, and those not showing a certain increase in the body weight or those with a poor increase rate were not included. The animals were raised in metal cages in groups of 5 each, fed on solid feed and placed in an animal room which maintained a temperature of 18•‹ to 20•Ž. Formaldehyde was administered in single doses through sonde, and included in the calculation were rats which died after one week of the administration. As will be stated later, most animals died within 24 hours of the administration, a few dying on the 3rd day. Those which survived lived until the experiments were finished. The LD5O was calculated from the formaldehyde solution prepared from the special-grade paraformaldehyde and the commercial special-grade formalin (in cludes methyl alcohol of more than 10%) according to body weight (age) and concentration (2% and 4%). The routinely adopted Litchfield's method was used for the calculation. 2) Measurement of formaldehyde in the eluate of plastic bowl of formaldehyde resin. As will be mentioned later, the method by Schiff's reagent with fuchsine or rosaniline added was examined in various ways, and the calibration curve was prepared every time. Combined was the method•‹ by chromotropic acid which is said to react specifically with formaldehyde. Using the dilute solution of formal dehyde of a known amount measured by iodimetry, recovery test was performed to confirm the advantages, disadvantages and confidence limits of the above-men tioned three methods (the details of this methodology will not be included here). Observed also was the relationship between the degree of coloration of the Rimini 22 Kenzaburo Tsuchiya et al reaction, qualitative reaction, and the value of quantitative analysis. The method for eluting plastic bowl will be found in the data to follow and will not be included here. 3) Measurement of formaldehyde in foods. Formaldehyde in foods was measured according to the literature mentioned below.7 However, some part still requires examination, and therefore, only a part of it will be reported as the results of a preliminary experiment. It was found necessary to examine the analytical method in the future so that formaldehyde should be measured for various kinds of food.8 EXPERIMENTAL RESULTS 1) Lethal dose. As mentioned previously, male rats were used for the measurement of the lethal dose. Table 1 and Fig. 1 shows the relationship between the dose admin istered orally of 2% of the commercial special-grade formalin and the mortality rate. The body weight was 184 g in average, and the variation was large (standard deviation= 31.7 g). Table 2 and Fig. 2 demonstrates the results of the administration of 2% solution of formaldehyde not containing methyl alcohol. The rats in this case weighed less than those in Table 1, being 103.4 g •} 13.5 g, Fig. 1 LD50 for 2% solution of for Fig. 2 LD50 for 2% solution of for malin. maldehyde. LD50 and 95% confidence lim LD50 and 95% confidence lim its: 460 (330-650) mgm/kgm its: 550 (423-715) mgm/kgm S and 95% confidence limits: S and 95% confidence limits: 1.52 (1.04-2.42) 1.6 (1.12-2.29) Toxicity of Formaldehyde 23 Table 1 Oral administration of 2% formalin solution LD50 460(330-650)mgm/kgm Mean of total body weight: 180.9g•}31.7 Table 2 Oral administration of 2% formaldehyde solution LD50 550(420-715)mgm/kgm Mean of total body weight: 103.4g•}13.5 q/, , Fig. 3 LD50 for 4% solution of for Fig. 4 LD50 for 4% solution of for maldehyde. maldehyde. Lll50 and 95% confidence lim LD50 and 19/20 confidence lim its: 590 (770-460) mgm/kgm its: 675 (803-560) mgm/kgm S and 95% confidence limits: S and 19/20 confidence limits: 1.65 (2.56-1.06) 1.36 (1.57-1.17) 24 Kenzaburo Tsuchiya et al Table 3 Oral administration of 4% formaldehyde solution LD50 590(460-770)mgm/kgm Mean of total body weight: 112.1g•}15 Table 4 Oral administration of 4% formaldehyde solution LD50 675(567-803)mam/kgm Mean of total body weight: 105.1g•}10 Fig.
Load more

Recommended publications
  • Four Patients with Amanita Phalloides Poisoning CASE SERIE
    CASE SERIE 353 Four patients with Amanita Phalloides poisoning S. Vanooteghem1, J. Arts2, S. Decock2, P. Pieraerts3, W. Meersseman4, C. Verslype1, Ph. Van Hootegem2 (1) Department of hepatology, UZ Leuven ; (2) Department of gastroenterology, AZ St-Lucas, Brugge ; (3) General Practitioner, Zedelgem ; (4) Department of internal medicine, UZ Leuven. Abstract because they developed stage 2 hepatic encephalopathy. With maximal supportive therapy, all patients gradually Mushroom poisoning by Amanita phalloides is a rare but poten- improved from day 3 and recovered without the need for tially fatal disease. The initial symptoms of nausea, vomiting, ab- dominal pain and diarrhea, which are typical for the intoxication, liver transplantation. They were discharged from the can be interpreted as a common gastro-enteritis. The intoxication hospital between 6 to 10 days after admission. can progress to acute liver and renal failure and eventually death. Recognizing the clinical syndrome is extremely important. In this case report, 4 patients with amatoxin intoxication who showed the Discussion typical clinical syndrome are described. The current therapy of amatoxin intoxication is based on small case series, and no ran- Among mushroom intoxications, amatoxin intoxica- domised controlled trials are available. The therapy of amatoxin intoxication consists of supportive care and medical therapy with tion accounts for 90% of all fatalities. Amatoxin poison- silibinin and N-acetylcysteine. Patients who develop acute liver fail- ing is caused by mushroom species belonging to the gen- ure should be considered for liver transplantation. (Acta gastro- era Amanita, Galerina and Lepiota. Amanita phalloides, enterol. belg., 2014, 77, 353-356). commonly known as the “death cap”, causes the majority Key words : amanita phalloides, mushroom poisoning, acute liver of fatal cases.
    [Show full text]
  • Clinical Biochemistry of Hepatotoxicity
    linica f C l To o x l ic a o n r l o u g Singh, J Clinic Toxicol 2011, S:4 o y J Journal of Clinical Toxicology DOI: 10.4172/2161-0495.S4-001 ISSN: 2161-0495 ReviewResearch Article Article OpenOpen Access Access Clinical Biochemistry of Hepatotoxicity Anita Singh1, Tej K Bhat2 and Om P Sharma2* 1CSK Himachal Pradesh, Krishi Vishva Vidyalaya, Palampur (HP) 176 062, India 2Biochemistry Laboratory, Indian Veterinary Research Institute, Regional Station, Palampur (HP) 176 061, India Abstract Liver plays a central role in the metabolism and excretion of xenobiotics which makes it highly susceptible to their adverse and toxic effects. Liver injury caused by various toxic chemicals or their reactive metabolites [hepatotoxicants) is known as hepatotoxicity. The present review describes the biotransformation of hepatotoxicants and various models used to study hepatotoxicity. It provides an overview of pathological and biochemical mechanism involved during hepatotoxicity together with alteration of clinical biochemistry during liver injury. The review has been supported by a list of important hepatotoxicants as well as common hepatoprotective herbs. Keywords: Hepatotoxicity; Hepatotoxicant; In Vivo models; In Vitro production of bile thus leading to the body’s inability to flush out the models; Pathology; Alanine aminotransferase; Alkaline phosphatase; chemicals through waste. Smooth endoplasmic reticulum of the liver is Bilirubin; Hepatoprotective the principal ‘metabolic clearing house’ for both endogenous chemicals like cholesterol, steroid hormones, fatty acids and proteins, and Introduction exogenous substances like drugs and alcohol. The central role played by liver in the clearance and transformation of chemicals exposes it to Hepatotoxicity refers to liver dysfunction or liver damage that is toxic injury [4].
    [Show full text]
  • The Effect of Bacillus Larvicidal Toxins on Mammals
    The effect of Bacillus larvicidal toxins On mammals By Nadia Adam Mohammed Ahmed B.Sc. of Veterinary Sciences University of Bahr-Elgazal ٢٠٠٠ Thesis submitted for the partial fulfillment of the requirements For the degree of Master of Science (M.Sc.) in microbiology Supervisor Professor: Mohammed Sulieman El-sanosi Department of microbiology Faculty of Veterinary Medicine University of Khartoum ٢٠٠٦ May To My lovely parents, My husband (M/Elmurtada) and my children (Reem&Rwan) To My brothers and sisters, And To Those who suffer from malaria, I dedicate this work. Nadia I would like to express my sincere thanks to my supervisor Prof. Elsanosi for his valuable supervision and encouragement. I also like to extend my thanks to Prof.Ahamed.A.Gameel for his great help in histopathological investigation of this study. Thanks also extend to all staff and technicians of the Department of Microbiology for their valuable advices and assistance. Iam also greatfull to my colleague and all my friends Special thanks to my family for their patience and continuous encouragement during this work. Abstract Mosquito control is the key for hopeful and sustainable eradication of different socio-economic as well as fatal viral, bacterial and parasitological diseases in the tropical and subtropical countries. In addition the safety of any pesticide should be assured before application. In the present study the susceptibility of arabiensis mosquito larvae to the toxin of two endo-spores forming bacilli strain was examined. Both Bacilli spp B. ٪١٠٠ thuringiensis and B. sphaericus were found to be highly toxic and fatal with was found to be tolerant to the (٤_Instar) ٤_mortality rate.
    [Show full text]
  • Research Article Presentations Related to Acute
    Hindawi Emergency Medicine International Volume 2019, Article ID 3130843, 7 pages https://doi.org/10.1155/2019/3130843 Research Article Presentations Related to Acute Paracetamol Intoxication in an Urban Emergency Department in Switzerland Natalia Piotrowska,1 Jolanta Klukowska-Ro¨tzler ,1 Beat Lehmann ,1 Gert Krummrey,1 Manuel Haschke,2,3 Aristomenis K. Exadaktylos,1 and Evangelia Liakoni 2,3 1Department of Emergency Medicine, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland 2Clinical Pharmacology and Toxicology, Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland 3Institute of Pharmacology, University of Bern, Bern, Switzerland Correspondence should be addressed to Evangelia Liakoni; [email protected] Received 25 March 2019; Accepted 22 November 2019; Published 6 December 2019 Academic Editor: $eodore J. Gaeta Copyright © 2019 Natalia Piotrowska et al. $is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Aim. To investigate the characteristics of Emergency Department (ED) presentations due to acute paracetamol intoxication. Methods. Retrospective observational study of patients presenting to the ED of Bern University Hospital between May 1, 2012, and October 31, 2018, due to a paracetamol overdose (defined as intake of >4 g/24 h). Cases were identified using the full-text search of the electronic patient database and were grouped into intentional (suicidal/parasuicidal) and unintentional in- toxications (e.g., patient unaware of maximal daily dose). Results. During the study period, 181 cases were included and 143 (79%) of those were intentional.
    [Show full text]
  • Ethanol and Tobacco Abuse in Pregnancy: Anaesthetic Considerations
    REVIEW ARTICLE Ethanol and tobacco abuse in pregnancy: Anaesthetic considerations K M Kuczkowski M.D, Assistant Clinical Professor of Anesthesiology and Reproductive Medicine, Co-Director of Obstetric Anesthesia, Departments of Anesthesiology and Reproductive Medicine, University of California, San Diego , USA Introduction The illicit drug abuse in pregnancy has received significant attention over the past two decades.1 However, far too little attention has been given to the consequences of the use of social drugs such as ethanol and tobacco, which are by far the most commonly abused substances during pregnancy. While the deleterious effects of cocaine or amphetamines on the mother and the fetus are more pronounced and easier to detect, the addiction to ethanol and tobacco is usually subtle and more difficult to diagnose.1, 2-4 As a result recreational use of alcohol and tobacco may continue undetected in pregnancy, significantly effecting pregnancy outcome and obstetric and anaesthetic management of these patients. This article reviews the consequences of ethanol and tobacco use in pregnancy and offers recommendation for anaesthetic management of these potentially complicated pregnancies. General considerations rette smoking.2, 17 The American College of Obstetricians and Substance abuse is defined as “self-administration of various drugs Gynaecologists (ACOG) has made multiple recommendations regard- that deviates from medically or socially accepted use, which if pro- ing management of patients with drug abuse during pregnancy. longed can lead to the development of physical and psychological Women who acknowledge use of illicit substance during pregnancy dependence”.5 This chemical dependency is characterized by peri- should be counseled and offered necessary treatment.
    [Show full text]
  • The Nervous System – Target Organ Into the Twenty-First Century
    The Nervous System – Target Organ into the Twenty-First Century R. Douglas Hamm MD, CCFP, FRCPC (Occ Med), FCBOM President, Canadian Board of Occupational Medicine CONTENTS 1. WHY NEURONS MAKE GOOD TARGETS FOR OCCUPATIONAL TOXICANTS 2. FROM CLASSICAL PLUMBISM TO BEHAVIORAL TOXICOLOGY 3. TOXICOKINETICS, COMPARTMENTS, AND PBPK MODELS 4. THE DIVERSE TOXICODYNAMICS OF THE NERVOUS SYSTEM 1. Peripheral Neurons (neuronopathy, axonopathy, myelinopathy) 2. Synaptic Neurotransmission (cholinergic pathways) 3. Special Senses (visual, auditory, olfactory) 4. Movement Disorders (parkinsonism, ataxia, tremor) 5. Neuroaffective and Neurocognitive Effects 5. NOTEWORTHY OCCUPATIONAL NEUROTOXICANTS 1. “Heavy metals” (Pb, Hg, Tl) and other elements (Mn, As, Al, Sb, Te) 2. Organic Solvents (toluene, xylene, styrene, C2HCl3, C2Cl4, CH3CCl3, CS2) 3. Gases (HCN, CO, H2S, ethylene oxide) 4. Pesticides (organophosphates, carbamates, organochlorines, pyrethroids, neonicotinoids) 6. CLINICAL NEUROTOXICOLOGY 1. Identification of Occupational Neurotoxic Disorders 2. Biomarkers of Exposure and Effect 3. Clinical Investigations of Neurotoxicity 1. WHY NEURONS MAKE GOOD 2. FROM CLASSICAL PLUMBISM TO TARGETS FOR OCCUPATIONAL BEHAVIORAL TOXICOLOGY TOXICANTS Hippocrates (c. 460-370 BC) has been cited as Neuroanatomical structures have large surface the first ancient author to describe a case of areas and receptor populations, e.g., the occupational neurotoxicity but this has been surface area of the brain’s 100 billion neurons shown to be erroneous (Osler, 1907; Waldron, totals hundreds of square metres. 1973, 1978; Skrabanek, 1986; Vance, 2007). The earliest report appears to be that of Neurons have high rates of metabolism, e.g., Nicander of Colophon (2nd cent. BC) who the brain at 2% body mass consumes 20% of observed that in “psimuthion” i.e.
    [Show full text]
  • Results of Liver Transplantation in Patients with Acute Liver Failure Due to Amanita Phalloides and Paracetamol (Acetaminophen) Intoxication
    Original paper Results of liver transplantation in patients with acute liver failure due to Amanita phalloides and paracetamol (acetaminophen) intoxication Maciej Krasnodębski, Michał Grąt, Wacław Hołówko, Łukasz Masior, Karolina M. Wronka, Karolina Grąt, Jan Stypułkowski, Waldemar Patkowski, Marek Krawczyk Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, Warsaw, Poland Gastroenterology Rev 2016; 11 (2): 90–95 DOI: 10.5114/pg.2015.52031 Key words: acute liver failure, Amanita phalloides poisoning, paracetamol poisoning, liver transplantation. Address for correspondence: Maciej Krasnodębski MD, Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 1 A Banacha St, 02-097 Warsaw, Poland, phone: +48 22 599 25 45, fax: +48 22 599 15 45, e-mail: [email protected] Abstract Introduction: Amanita phalloides and paracetamol intoxications are responsible for the majority of acute liver failures. Aim: To assess survival outcomes and to analyse risk factors affecting survival in the studied group. Material and methods: Of 1369 liver transplantations performed in the Department of General, Transplant, and Liver Sur- gery, Medical University of Warsaw before December 2013, 20 (1.46%) patients with Amanita phalloides (n = 13, 0.95%) and paracetamol (n = 7, 0.51%) intoxication were selected for this retrospective study. Overall and graft survival at 5 years were set as primary outcome measures. Results: Five-year overall survival after liver transplantation in the studied group was 53.57% and 53.85% in patients with paracetamol and Amanita phalloides poisoning, respectively (p = 0.816). Five-year graft survival was 26.79% for patients with paracetamol and 38.46% with Amanita phalloides intoxication (p = 0.737).
    [Show full text]
  • Transdermal Methyl Alcohol Intoxication: a Case Report
    Acta Derm Venereol 2015; 95: 740–741 SHORT COMMUNICATION Transdermal Methyl Alcohol Intoxication: A Case Report Burcu Hizarci, Cem Erdoğan, Pelin Karaaslan, Aytekin Unlukaplan and Huseyin Oz Department of Anesthesiology and Reanimation, Medipol University Medical Faculty, Istanbul, Turkey. E-mail: [email protected] Accepted Jan 8, 2015; Epub ahead of print Jan 9, 2015 Methyl alcohol (methanol) is a colourless, odourless visual disorder gradually improved during the period and bitter substance found in solvents, paint removers, he was observed in the intensive care unit. His cranial varnish es, antifreezes, cologne and grain alcohol (1). imagings revealed no abnormality. Bicarbonate infu- Methanol is a central nervous system depressant that is sion was discontinued after 24 h as metabolic acidosis potentially toxic after its ingestion, inhalation or transder- had normalised. After 72 h of monitoring, the patient mal exposure (1–4). Most of the patients have headache, was discharged after stabilisation. nausea, vomiting, weakness and vision loss during this period. As a result of high intake, the patient presents DISCUSSION with stupor, coma and even death. Although methanol in- toxication is most frequently reported due to oral intake, After oral intake methanol is converted to formalde- cases of inhalation and transdermal methanol intoxication hyde in the liver and oxidised to formic acid. Formic are reported as well (5). In this paper we report a rare acid is toxic for central nervous system and as a result, case of transdermal methanol intoxication. We suggest histological hypoxia, which is caused by axonal cell that transdermal toxication should be considered and death occurs (6). Percutaneous exposure of methanol questioned whilst taking the medical history of a patient.
    [Show full text]
  • Drug Metabolism: Phase I
    NEPHAR 305 Pharmaceutical Chemistry I Drug Metabolism: Phase I Assist.Prof.Dr. Banu Keşanlı Drug Metabolism ¾ Drug’s biochemical modification or degradation, usually through specialized enzymatic systems ¾ Xenobiotic: a chemical which is found in an organism but which is not normally produced or expected to be present in it ¾ Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products ¾ Duration and intensity of the pharmacological action of drugs is important ¾ Drug metabolism can result in toxication if the metabolite of a compound is more toxic than the parent drug or chemical ¾ or detoxication (process of preventing toxic entities from entering the body in the first place) by the activation or deactivation of the chemical A prodrug is a pharmacological substance (drug) that is administered in an inactive (or significantly less active) form. Once administered, the prodrug is metabolised in vivo into an active metabolite. Importance of Drug Metabolism Basic premise: Lipophilic Drugs Hydrophilic Metabolites (Not excreted) (Excreted) Water soluble increased renal excretion and Decreased tubular re-absorption of lipophilics Importance of Drug Metabolism Metbolism Termination of Drug - Bioinactivation - Detoxification - Elimination Metabolism Bioactivation - Active Metabolites - Prodrugs - Toxification Phase I or Functionalization Reactions Oxidative Reactions • Oxidation of aromatic moieties • Oxidation of olefins • Oxidation at benzylic, allylic carbon, carbon atoms α to carbonyl and imines •
    [Show full text]
  • Impact of Methanol Intoxication on the Human Electrocardiogram
    Cardiology Journal 2014, Vol. 21, No. 2, pp. 170–175 DOI: 10.5603/CJ.a2013.0053 Copyright © 2014 Via Medica ORIGINAL ARTICLE ISSN 1897–5593 Impact of methanol intoxication on the human electrocardiogram Zardasht Jaff1, William F. McIntyre1, Payam Yazdan-Ashoori2, Adrian Baranchuk1 1Division of Cardiology, Queen’s University, Kingston, Ontario, Canada 2McMaster University, Internal Medicine, Hamilton, Ontario, Canada Abstract Background: Methanol is a common commercial compound that can lead to significant morbidity and mortality with high levels of exposure. The purpose of this study was to describe electrocardiographic (ECG) changes associated with methanol intoxication. Methods: A retrospective chart review was conducted with data from Kingston General Ho- spital collected between 2006 and 2011. Patient data, including demographics, medications, and laboratory data were recorded. Twelve-lead ECGs were obtained and changes were noted in relation to timing and extent of methanol intoxication. Results: Nine patients with a mean age of 45 years were analyzed. All patients ingested methanol orally and presented to hospital between < 1 to 25 h after ingestion. The mean plas- ma methanol concentration on admission was 49.8 mmol/L. A lower pH and higher plasma methanol concentration were associated with multiple ECG changes. On admission, ECG changes included sinus tachycardia (44%), PR prolongation (11%), QTc prolongation (22%) and non-specific T-wave changes (66%). One patient developed a type-1 Brugada ECG pattern. During their course in hospital, 7 patients required dialysis, 3 required mechanical ventilation, 3 developed visual impairment, and 1 died. All ECG changes normalized while in hospital. Conclusions: Methanol intoxication can lead to several ECG changes with sinus tachycardia and non-specific T-wave changes being the most common.
    [Show full text]
  • Research Article Presentations Related to Acute Paracetamol Intoxication in an Urban Emergency Department in Switzerland
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Bern Open Repository and Information System (BORIS) Hindawi Emergency Medicine International Volume 2019, Article ID 3130843, 7 pages https://doi.org/10.1155/2019/3130843 Research Article Presentations Related to Acute Paracetamol Intoxication in an Urban Emergency Department in Switzerland Natalia Piotrowska,1 Jolanta Klukowska-Ro¨tzler ,1 Beat Lehmann ,1 Gert Krummrey,1 Manuel Haschke,2,3 Aristomenis K. Exadaktylos,1 and Evangelia Liakoni 2,3 1Department of Emergency Medicine, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland 2Clinical Pharmacology and Toxicology, Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland 3Institute of Pharmacology, University of Bern, Bern, Switzerland Correspondence should be addressed to Evangelia Liakoni; [email protected] Received 25 March 2019; Accepted 22 November 2019; Published 6 December 2019 Academic Editor: $eodore J. Gaeta Copyright © 2019 Natalia Piotrowska et al. $is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Aim. To investigate the characteristics of Emergency Department (ED) presentations due to acute paracetamol intoxication. Methods. Retrospective observational study of patients presenting to the ED of Bern University Hospital between May 1, 2012, and October 31, 2018, due to a paracetamol overdose (defined as intake of >4 g/24 h). Cases were identified using the full-text search of the electronic patient database and were grouped into intentional (suicidal/parasuicidal) and unintentional in- toxications (e.g., patient unaware of maximal daily dose).
    [Show full text]
  • NIDA Monograph 173, Pp. 106-127
    The Role of Iminium-Enamine Species in the Toxication and Detoxication of Cyclic Tertiary Amines Lawrence M. Sayre, David A. Engelhart, Durgesh V. Nadkarni, M.K. Manoj Babu, Ann Marie Flammang, and G. David McCoy INTRODUCTION AND BACKGROUND Aliphatic cyclic tertiary amines constitute a major class of naturally occurring and synthetic drugs directed at central biogenic amine receptors. Microsomal metabolism of these amines is known to be associated with low levels of covalent binding and/or suicide inactivation of the pertinent metabolizing P-450 isozymes; two of the more notorious examples are phencyclidine (1-(1- phenylcyclohexyl)piperidine) (PCP) (Hoag et al. 1984) and nicotine (Shigenaga et al. 1988). Covalent binding was initially believed to result from alkylation of protein-based nucleophiles by the respective endocyclic iminium metabolite arising from cytochrome P-450 mediated two-electron oxidation (Hoag et al. 1984; Nguyen et al. 1979; Overton et al. 1985; Shigenaga et al. 1988; Ward et al. 1982). These iminium species are generated in equilibrium with a carbinolamine, an endocyclic enamine, and a ring-opened aminocarbonyl compound (figure 1). In contrast to acyclic tertiary amines, where the iminium intermediates are readily hydrolyzed via carbinolamines to secondary amines and aldehydes (or ketones) (figure 2), iminium hydrolysis for cyclic tertiary amines remains reversible, ensuring the persistence of all equilibrium species in figure 1. This explains why covalent binding is seen only for cyclic tertiary amines. Support for the notion that the iminium electrophiles could be the covalent binding species is found in their ready formation of stable cyanide adducts and the fact that the presence of cyanide during metabolism of the parent amines protected against covalent binding (Hoag et al.
    [Show full text]