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Sulfite: Here, There, Everywhere
Sulfite: Here, There, Everywhere Max T. Baker, PhD Associate Professor Department of Anesthesia University of Iowa Inadvertent Exposures Combustion of fossil fuels, Air pollutant Large quantities as sulfur dioxide are expelled from volcanos Kilauea on the Big Island Small quantities endogenously formed in mammals from sulfur-containing amino acid metabolism Deliberate Exposures As Preservative- Wine, Beer (dates to Roman times From burning sulfur candles) Fruits and Vegetables (reduce browning, extend shelf-life) Pharmaceuticals1 Reductant - Antioxidant - Antimicrobial What are Sulfites? Oxidized Forms of the Sulfur Atom Sulfur Dioxide, MW = 64, bp = - 10oC (gaseous) Sulfur (IV) - Oxidation state of 4 S = Atomic number 16 – electrons/shell, 2,8,6 Sodium Dioxide Readily Hydrates2 Sulfur Carbon Dioxide Dioxide (irritant) H O H2O 2 Sulfurous Unstable Carbonic low acid species acid pH high pH Bisulfite Bicarbonate anion anion Sulfite Carbonate dianion dianion Forms radical Doesn’t form radical Bisulfite Can Combine with SO2 to form Metabisulfite + excess Bisulfite Metabisulfite (disulfite, pyrosulfite) “Sulfite” usually added to drugs as sodium or potassium salts of: Sulfite, Bisulfite, or Metabisulfite Endogenous to Mammals Small quantities formed from sulfur-containing amino acid metabolism - cysteine, methionine3 + - + H2O + 2H + 2 e Sulfite Sulfate Rapidly detoxified by sulfite oxidase (SOX) to form sulfate – a two electron oxidation, molybdenum dependent Two Confirmed Sulfite Toxicities Neurological abnormalities from genetic sulfite oxidase deficiency3 Allergic reactions from exogenous exposure4 Oral, parenteral, inhalational exposure: dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhea to life- threatening anaphylactic and asthmatic reactions “The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people." - FDA Prevalence – 3-10% are sulfite sensitive among asthmatic subjects. -
Sodium Chlorite Neutralization
® Basic Chemicals Sodium Chlorite Neutralization Introduction that this reaction is exothermic and liberates a If sodium chlorite is spilled or becomes a waste, significant amount of heat (H). it must be disposed of in accordance with local, state, and Federal regulations by a NPDES NaClO2 + 2Na2SO3 2Na2SO4 + NaCl permitted out-fall or in a permitted hazardous 90.45g + 2(126.04g) 2(142.04g) + 58.44g waste treatment, storage, and disposal facility. H = -168 kcal/mole NaClO2 Due to the reactivity of sodium chlorite, neutralization for disposal purposes should be For example, when starting with a 5% NaClO2 avoided whenever possible. Where permitted, solution, the heat generated from this reaction the preferred method for handling sodium could theoretically raise the temperature of the chlorite spills and waste is by dilution, as solution by 81C (146F). Adequate dilution, discussed in the OxyChem Safety Data Sheet thorough mixing and a slow rate of reaction are (SDS) for sodium chlorite in Section 6, important factors in controlling the temperature (Accidental Release Measures). Sodium chlorite increase (T). neutralization procedures must be carried out only by properly trained personnel wearing Procedure appropriate protective equipment. The complete neutralization procedure involves three sequential steps: dilution, chlorite Reaction Considerations reduction, and alkali neutralization. The dilution If a specific situation requires sodium chlorite to step lowers the strength of the sodium chlorite be neutralized, the chlorite must first be reduced solution to 5% or less; the reduction step reacts by a reaction with sodium sulfite. The use of the diluted chlorite solution with sodium sulfite to sodium sulfite is recommended over other produce a sulfate solution, and the neutralization reducing agents such as sodium thiosulfate step reduces the pH of the alkaline sulfate (Na2S2O3), sodium bisulfite (NaHSO3), and solution from approximately 12 to 4-5. -
Reregistration Eligibility Decision (RED) for Inorganic Sulfites
Reregistration Eligibility Decision – Inorganic Sulfites May 2007 Reregistration Eligibility Decision Inorganic Sulfites Special Review and Reregistration Division Office of Pesticide Programs U.S. Environmental Protection Agency 1801 South Bell Street Arlington, VA 22202 Introduction The Environmental Protection Agency (EPA) has completed its Reregistration Eligibility Decision (RED) for the inorganic sulfites case, which includes the chemicals sulfur dioxide and sodium metabisulfite. This assessment provides information to support the issuance of a Reregistration Eligibility Decision for inorganic sulfites. EPA’s pesticide reregistration process provides for the review of older pesticides (those initially registered prior to November 1984) under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) to ensure that they meet current scientific and regulatory standards. In this document, EPA presents the results of its review of the potential human health effects of dietary, drinking water and occupational/bystander exposure to inorganic sulfites, as well as its ecological risk findings. Evaluations performed by the World Health Organization (WHO), the International Agency for Research on Cancer (IARC), and the Agency for Toxic Substances and Disease Registry (ATSDR) were relied upon for this assessment, in addition to peer-reviewed evaluations performed by the Cosmetic Ingredient Review (CIR), the Organization for Economic Cooperation and Development-Screening Information Data Set (OECD-SIDS) and from other open literature sources. Based on this assessment, the Agency has determined that products containing sulfur dioxide or sodium metabisulfite are eligible for reregistration provided the necessary label changes are made. As a result of this assessment, one tolerance has been reassessed. I. Use Information The inorganic sulfites reregistration case includes the chemicals sulfur dioxide (CAS No. -
“Inactive” Ingredients in Pharmaceutical Products: Update (Subject Review)
AMERICAN ACADEMY OF PEDIATRICS Committee on Drugs “Inactive” Ingredients in Pharmaceutical Products: Update (Subject Review) ABSTRACT. Because of an increasing number of re- bronchospasm from antiasthmatic drugs, aspartame- ports of adverse reactions associated with pharmaceutical induced headache and seizures, saccharin-induced excipients, in 1985 the Committee on Drugs issued a cross-sensitivity reactions in children with sulfon- position statement1 recommending that the Food and amide allergy, benzyl alcohol toxicity in neonates Drug Administration mandate labeling of over-the- receiving high-dose continuous infusion with pre- counter and prescription formulations to include a qual- served medications, dye-related cross-reactions in itative list of inactive ingredients. However, labeling of inactive ingredients remains voluntary. Adverse reac- children with aspirin intolerance, lactose-induced di- tions continue to be reported, although some are no arrhea, and propylene glycol-induced hyperosmola- longer considered clinically significant, and other new lity and lactic acidosis. Although many other excipi- reactions have emerged. The original statement, there- ents have been implicated in causing adverse fore, has been updated and its information expanded. reactions, these are the most significant in the pedi- atric population. ABBREVIATIONS. FDA, Food and Drug Administration; MDIs, metered-dose inhalers ANTIASTHMATIC MEDICATIONS It is readily appreciated that some percentage of asthmatic children will develop a “paradoxical” Pharmaceutical products often contain agents that bronchospasm after they inhale their medication. Be- have a variety of purposes, including improvement cause many of these reactions were attributed to of the appearance, bioavailability, stability, and pal- sulfite, which had been highly publicized as a caus- atability of the product. Excipients (substances ative agent, it was often first suspected. -
Sulfur Dioxide and Some Sulfites, Bisulfites and Metabisulfites
SULFUR DIOXIDE AND SOME SULFITES, BISULFITES AND METABISULFITES 1. Exposure Data 1.1 Chemical and physical data 1.1.1 Synonyms and structural and molecular data Sulfr dioxi Chem. Abstr. Serv Reg. No.: 7446-09-5 Replaced CAS Nos.: 8014-94-6; 12396-99-5; 83008-56-4; 89125-89-3 Chem. Abstr. Name; Sulfur dioxide IUPAC Systematic Name: Sulfur dioxide Synonyms: Sulfurous acid anhydride; sulfurous anhydride; sulfurous oxide; sulfur oxide (S02); sulfur superoxide; sulphur dioxide 0=8=0 S02 MoL. wt: 64.07 Sodium sulfte Chem. Abstr. Serv Reg. No.: 7757-83-7 Altemate CAS No.: 10579-83-6 Replaced CAS No.: 68135-69-3 Chem. Abstr. Name: Sulfurous acid, di sodium salt IUPAC Systematic Name: Sulfurous acid, disodium salt Synonyms: Anhydrous sodium sulfite; disodium sulfite; sodium sulphite o 1/ Na · 0 - 8 - 0 · Na Na2S0J MoL. wt: 126.04 Sodium bisulfe Chem. Abstr. Serv Reg. No.: 7631-90-5 Replaced CAS Nos.: 57414-01-4; 69098-86-8; 89830-27-3; 91829-63-9 Chem. Abstr. Name: Sulfurous acid, monosodium salt IUPAC Systematic Name: Sulfurous acid, monosodium salt -131- 132 lARe MONOGRAPHS VOLUME 54 Synonyms: Hydrogen sulfite sodium; monosodium sulfite; sodium acid sulfite; sodium bisulphite; sodium hydrogen sulfite; sodium sulfite (NaHS03) o Il HO - S - a · Na NaHS03 MoL. wt: 104.06 Sodium metabisulfte Chem. Abstr. Serv Reg. No.: 7681-57-4 Altemate CAS No.: 7757-74-6 Replaced CAS No.: 15771-29-6 Chem. Abstr. Name: Disulfurous acid, disodium salt IUPAC Systematic Name: Pyrosulfurous acid, disodium salt Synonyms: Disodium disulfite; disodium metabisulfite; disodium pyrosulfite; sodium disulfite; sodium metabisulphite; sodium pyrosulfite oIl Il0 Na · 0- S - a - S - a · Na .Na2S20S MoL. -
Synthetic and Biosynthetic Approaches to Cherylline and Related Compounds Richard Duane Shaffer Iowa State University
Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1972 Synthetic and biosynthetic approaches to cherylline and related compounds Richard Duane Shaffer Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Organic Chemistry Commons Recommended Citation Shaffer, Richard Duane, "Synthetic and biosynthetic approaches to cherylline and related compounds " (1972). Retrospective Theses and Dissertations. 5277. https://lib.dr.iastate.edu/rtd/5277 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. INFORMATION TO USERS This dissertation was produced from a microfilm copy of the original document. While the most advanced technological means to photograph and reproduce this document have been used, the quality is heavily dependent upon the quality of the original submitted. The following explanation of techniques is provided to help you understand markings or patterns which may appear on this reproduction. 1. The sign or "target" for pages apparently lacking from the document photographed is "Missing Page(s)". If it was possible to obtain the missing psge(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting thru an image and duplicating adjacent pages to insure you complete continuity. 2. When an image on the film is obliterated with a large round black mark, it is an indication that the photographer suspected that the copy may have moved during exposure and thus cause a blurred image. -
Coei-1-Potanh: 2000
INTERNATIONAL ŒNOLOGICAL CODEX Potassium Anhydrous Sulfite COEI-1-POTANH: 2000 POTASSIUM ANHYDROUS SULFITE Potassium pyrosulfite Potassium disulfite Potassium metabisulfite Kalii metabisulfis K2S2O5 = 222.3 SIN No. 224 (Oeno 34/2000) 1. OBJECTIVE, ORIGIN AND SCOPE OF APPLICATION Potassium anhydrous sulfite, commonly called potassium metabisulfite, is used because of the sulfur dioxide it makes available. Potassium metabisulfite, which is sold in powdered form, contains 52- 55% by weight SO2. There are regulatory limits restricting the sulfur dioxide content of wines. 2. LABELING The label should indicate the product's purity as well as its safety and storage conditions. 3. CENTESIMAL COMPOSITION Sulfur dioxide 57.63 Potassium 35.17 4. SOLUBILITY Water at 20 °C 454.5 g/l Alcohol, 95% by vol. insoluble 5. IDENTIFYING PROPERTIES 5.1. 5 ml of aqueous 10 pp 100 (m/v) solution treated with 5 ml of 1/10 diluted sulfuric acid (R) releases sulfur dioxide and reduces iodine and potassium permanganate. 5.2. The 10 pp 100 (m/v) aqueous solution is acidic as indicated by methyl red (R) of (pHapproximately 5). E-COEI-1-POTANH 1 INTERNATIONAL ŒNOLOGICAL CODEX Potassium Anhydrous Sulfite COEI-1-POTANH: 2000 5.3. The 1 pp 100 (m/v) aqueous solution produces potassium- based reactions. 6. TESTS 6.1. Preparing the Test Solution in a Concentration of 10 pp 100 Prepare a solution in a concentration of 10 pp 1000 (m/v). 6.2. Preparing a Test Solution in a Concentration of 1 pp 100 Prepare a 1 pp 100 (m/v) solution by diluting the previous solution (6.1) to 1/10. -
Website Exposure May Cause Bronchitis to Develop with Coughing, ( Or in Your Facility’S RTK Phlegm, And/Or Shortness of Breath
Right to Know Hazardous Substance Fact Sheet Common Name: SODIUM BISULFITE Synonym: Sodium Hydrogen Sulfite CAS Number: 7631-90-5 Chemical Name: Sulfurous Acid, Monosodium Salt RTK Substance Number: 1685 Date: August 1998 Revision: April 2008 DOT Number: UN 2693 (Solution) Description and Use EMERGENCY RESPONDERS >>>> SEE BACK PAGE Sodium Bisulfite is a white, crystalline solid with a slight odor Hazard Summary of rotten eggs. It is often in a liquid solution. It is used in Hazard Rating NJDOH NFPA making paper and leather, as a food preservative and in dye HEALTH 2 - and chemical production. FLAMMABILITY 0 - REACTIVITY 0 - CORROSIVE POISONOUS GASES ARE PRODUCED IN FIRE Reasons for Citation f Sodium Bisulfite is on the Right to Know Hazardous Substance List because it is cited by ACGIH, DOT, NIOSH, Hazard Rating Key: 0=minimal; 1=slight; 2=moderate; 3=serious; 4=severe IARC and EPA. f This chemical is on the Special Health Hazard Substance List. f Sodium Bisulfite can affect you when inhaled. f Contact can severely irritate and burn the skin and eyes. f Inhaling Sodium Bisulfite can irritate the nose, throat and lungs. f Sodium Bisulfite may cause a skin allergy and an asthma- like allergy. SEE GLOSSARY ON PAGE 5. f Sodium Bisulfite is CORROSIVE when in a liquid solution with water. FIRST AID Eye Contact f Quickly brush off excess chemical from the face. Immediately flush with large amounts of water for at least 60 Workplace Exposure Limits minutes, lifting upper and lower lids. Remove contact NIOSH: The recommended airborne exposure limit (REL) is lenses, if worn, while flushing. -
Substance Evaluation Report 2014 – Disodium Disulphite
SUBSTANCE EVALUATION REPORT 2014 – DISODIUM DISULPHITE SUBSTANCE EVALUATION REPORT Public Name: Disodium disulphite EC Number(s): 231-673-0 CAS Number(s): 7681-57-4 Submitting Member State Competent Authority: National Institute of Chemical Safety, Hungary H-1097 Budapest, Nagyvárad tér 2. tel: +36 1 476 1195 Year of evaluation (as given in the CoRAP): 2014 VERSION NUMBER: 1 DATE: 30.10.2015 Conclusions of the most recent evaluation step* Tick relevant box(es) Concern not clarified; Need to request further information from the Registrant(s) with the draft decision Concern clarified; No need of further risk management measures Concern clarified; Need for risk management measures; RMO analysis to be performed Other: Concern clarified; need for risk management measure (proposal for X harmonized C&L), but no need for RMOA *Include details in the executive summary. 1 SUBSTANCE EVALUATION REPORT 2014 – DISODIUM DISULPHITE DISCLAIMER The Substance evaluation report has been prepared by the evaluating Member State as a part of the substance evaluation process under the REACH Regulation (EC) No 1907/2006. The information and views set out in this document are those of the author and do not necessarily reflect the position or opinion of the European Chemicals Agency or other Member States. The Agency does not guarantee the accuracy of the information included in the document. Neither the Agency nor the evaluating Member State nor any person acting on either of their behalves may be held liable for the use which may be made of the information contained therein. Statements made or information contained in the document are without prejudice to any further regulatory work that the Agency or Member States may initiate at a later stage. -
Safety Data Sheet SODIUM BISULFITE
Safety Data Sheet SODIUM BISULFITE Section 1 - Product and Company Identification Product Name: Sodium Bisulfite Chemical Formula: NaHSO3 CAS Number: 007631-90-5 Other Designations: Sodium Bisulfite Solution, Sodium Hydrogen Sulfite Solution. General Use: Food and pharmaceutical preservative, waste water dechlorination agent, laboratory reagent, reducing agent, dietary supplement, and color preservative. Manufacturer: INEOS Calabrian Corporation 5500 Hwy. 366 Port Neches, Texas77651 Telephone: 409-727-1471 Fax: 409-727-5803 Emergency Contact: CHEMTREC 800-424-9300 Section 2 - Hazards Identification Emergency Overview Target Organs: Respiratory system, eyes, skin GHS Classification: Acute Toxicity, Oral (Category 4) Acute Toxicity, Dermal (Category 5) Serious Eye Irritant (Category 2A) GHS Label Elements: Signal Word – Warning Pictogram Corrosive Irritant Hazard Statements: H302 – Harmful if swallowed H313 – May be harmful to skin H319 – Causes serious eye irritation Precautionary P280 – Wear protective equipment for hands, eyes, face and respiratory tract Statements: P305, P351 and P338 – IF IN EYES: Rinse with water for several minutes. Remove contact lenses if present and continue rinsing. Other Hazards: Contact with acids liberates toxic sulfur dioxide gas. HMIS Classification: Health Hazard 2 Flammability 0 Physical 0 1 Safety Data Sheet SODIUM BISULFITE NFPA Rating: Health Hazard 2 Fire 0 Reactivity 0 Potential Health Inhalation: Irritant to respiratory tract Effects: Eye: Irritant Skin: Irritant Ingestion: Harmful if swallowed Aggravated Medical Condition: Capable of provoking bronchospasm in sulfite sensitive individuals with asthma. Section 3 - Composition / Information on Ingredients Composition CAS Number % Wt Water - 50 – 70 Sodium bisulfite 007631-90-5 30 – 50 Sodium Sulfite 007757-83-7 < 1.0 Sodium Sulfate 007757-82-6 < 3.5 Section 4 - First Aid Measures Exposure Route Symptom Treatment Inhalation: Sore throat, shortness of Remove from exposure to fresh air. -
The Most Reactive Position of a 1,2,4-Triazine
1378 Vol. 35 (1987) Chem. Pharm. Bull. 35( 4 )1378-1382(1987) Studies on as-Triazine Derivatives. IX.1) Synthesis of 5-Substituted 1,2,4-Triazine Derivatives through an Addition Reaction and Subsequent Oxidation SHOETSU KONNO, SETSUYA OHBA, MATAICHI SAGI, and HIROSHI YAMANAKA* Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980, Japan (Received July 31, 1986) The addition reactions of various nucleophiles to 6-methyl-3-phenyl-1,2,4-triazine (1) were investigated and a practical preparation of 1 was developed. The reactions showed many similarities to those of quinazoline (at the 4-position) and acridine (at the 9-position). The hitherto unknown compounds 5-cyand- (3), 5-carbamoyl- (5) and 5-phenacy1-6-methyl-3-phenyl-1,2,4-triazines (11e) were synthesized. Keywords •\ 1,2,4-triazine; nucleophilic addition; aromatization; active methylene com- pound; catalytic reduction The most reactive position of a 1,2,4-triazine (as-triazine) ring is position 5, where nucleophiles can attack very easily.2) For example, 3,5,6-trichloro-as-triazine reacts with 1 mol eq of sodium methoxide to give 3,6-dichloro-5-methoxy-as-triazine exclusively.3) Further- more, the combined electron-attracting effects of three ring nitrogen atoms suggest posi- tion 5 to be highly susceptible to nucleophilic addition, when there is no leaving group at this position.4) The present paper deals with the synthesis of 5-substituted as-triazine derivatives from 6-methyl-3-phenyl-as-triazine (1). The reaction of 1 with nucleophiles came up to our expectation, as shown in Chart 1. Compound 1 reacted with sodium bisulfite in methanol to give 6-methy1-3-phenyl-2,5- dihydro-as-triazine-5-sulfonic acid (2). -
The Catalytic Hydrogenation of Benzodiazines
THE CATALYTIC HYDROGENATION OF BENZODIAZINES: I. PHTHALAZINE II. QUINAZOLINE A Dissertation Presented to the Department of Chemistry Brigha~ Young University In Partial Fulfillment of the Requirements for the Degre~ Doctor of Philosophy by Danny Lee Elder August 1969 This dissertation, by Danny Lee Elder, is accepted in its present form b y the Department of Chemistry of Brigham Young University as satisfying the dissertation requirement for the degree of Doctor of Philosophy. ii . , TO Lynette, David, and Douglas iii ACKNOWLEDGEMENTS Deep appreciation is expressed to Dr. H. Smith Broadbent, without whose friendly association, patient help, and kindly ex- · tended advice this research problem could not have been carried out. Gratitude is also expressed £or the many extra-academic endeavors Dr. Broadbent has made on my behalf. Appreciation is extended to the Department of Chemistry of Brigham Young University for financial support in the form of teaching and research assistantships. My wife deserves special thanks for her encouragement, patience, understanding, and especially, for making it all worth- while. Finally, sincere thanks go to a great group of fellow-graduate students--Craig Argyle, Weldon Burnham, Vic Mylroie, Wes Parish, and Walter Sudweeks--for helpful discussions, comrade- ship, and most of all, for the memorable hours spent at such places as Anderson Lake, Four-Lakes Basin, Klondike Bluff, and of course, "Organic Pass, 11 (Grosebeck Pass). iv TABLE OF CONTENTS Chapter Page I. INTRODUCTION • • • • • • • • • • • • • • • 1 II. LITERATURE REVIEW • • • • • • • • • • • • 4 Phthalaz~ne • • • • . 4 Structure and properties • • • • • • • • • · 4 Synthesis of phthalazine • • • • • • • • • 8 Reduced phthalazines • • • • • • • • • • 10 Quinazoline • • • • • • . 12 Structure and properties • . • 12 Synthesis of quinazoline • • • • • 15 Reduced quinazolines • • • • 18 Catalytic Hydrogenation of Benzoazines and Benzodiazines • • • • • • • • 20 Quinoline .