DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2011/0015273 A1 Kandhagatla Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2011/0015273 A1 Kandhagatla Et Al US 2011 0015273A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0015273 A1 Kandhagatla et al. (43) Pub. Date: Jan. 20, 2011 (54) STABLE PHARMACEUTICAL AQUEOUS (30) Foreign Application Priority Data COMPOSITIONS Jan. 17, 2008 (IN) ............................. 147/CHFA2008 (76) Inventors: Rajnarayana Kandhagatla, Hyderabad (IN); Srihari Raju Publication Classification Kalidindi, Hyderabad (IN) (51) Int. Cl. Correspondence Address: A6II 3/167 (2006.01) BLANK ROME LLP A6IP 29/00 (2006.01) WATERGATE, 600 NEW HAMPSHIRE AVENUE, N.W. (52) U.S. Cl. ........................................................ S14/629 WASHINGTON, DC 20037 (US) (21) Appl. No.: 12/863,317 (57) ABSTRACT PCT Fled: Jan. 12, 2009 The present invention refers to an parenterally administerable (22) aqueous formulation containing paracetamol. For enhancing (86) PCT NO.: PCT/IN09/00038 stability the formulation contains a Sulphur containing anti oxidant, preferably sodium metabisulfite. For making the S371 (c)(1), formulation more soluble it contains hydroxy propyl beta (2), (4) Date: Jul. 16, 2010 cyclodextrin. The composition is used as analgesic. US 2011/OO15273 A1 Jan. 20, 2011 STABLE PHARMACEUTICAL AQUEOUS the formulations comprise antioxidants selected from a group COMPOSITIONS of ascorbic acid, N-acetyl-L-cysteine and thiol group-con taining stabilizer compounds. FIELD OF THE INVENTION 0008. The use of organic solvents for the preparation of liquid formulations of paracetamol has also been reported 0001. The present invention relates to stable pharmaceu (WO 05053747, WO 0007588). However, the prior art stabi tical aqueous compositions, having analgesic activity com lized liquid formulation of paracetamol have the drawback of prising a therapeutically effective dose of paracetamol or its causing a potential irritant and/or allergic effect in certain pharmaceutically acceptable salts, Solvates, enantiomers or patients, because of the toxicity of either the antioxidant or derivatives thereof, the processes for preparing the same and the organic solvent present in the formulation. methods of use and treatment of Such compositions. 0009 Hence, the development of an aqueous parenteral formulation of paracetamol which does not contain a buffer BACKGROUND OF THE INVENTION system or an organic solvent and bypasses all the disadvan 0002 Paracetamol (Formula I) is chemically N-(4-Hy tages mentioned above would be a significant improvement in droxyphenyl)acetamide. It is an analgesic and antipyretic the field of medical practice. Thus the present invention fills a agent. The mechanism of analgesic action of paracetamol has highly desirable gap in medical art comprising stable aqueous not been fully determined. Paracetamol may act predomi formulations of paracetamol. nantly by inhibiting prostaglandin synthesis in the central nervous system and to a lesser extent through a peripheral SUMMARY OF THE INVENTION action by blocking pain impulse generation. The peripheral 0010. The objective of the present invention is to provide action may also be due to inhibition of prostaglandin synthe stable parenteral compositions of paracetamol, wherein the sis or inhibition of the synthesis or actions of other substances paracetamol formulation does not contain a buffer system. that sensitise pain receptors. In recommended therapeutic 0011 Further it is an objective of the present invention to dosage, it is usually well tolerated. However, acute overdose provide aqueous compositions of paracetamol, having anal may cause fatal hepatic damage. The potentially toxic gesic activity, which are formulated without any organic Sol metabolite is said to be N-acetyl-p-benzoquinoneimine. vent and hence to bypass any allergic, irritant or similar potential side effect caused by such solvents. (Formula I) OH DETAILED DESCRIPTION OF THE INVENTION 0012. The present invention relates to aqueous, parenteral paracetamol compositions which comprise a therapeutically effective dose of paracetamol. The paracetamol compositions as per the present invention are formulated without the addi tion of any organic solvent and do not contain a buffer system. NH-C-CH 0013. In an embodiment, stable pharmaceutical aqueous compositions as disclosed in the invention are formulated as O parenteral formulations, in particular infusible formulations, in a solvent. 0003 Formulating liquid compositions of paracetamol 0014. In another embodiment of the present invention, the has critical considerations. The paracetamol in aqueous solu preferable solvent is water. tion is liable to undergo hydrolysis to form p-aminophenol, 0015. In another embodiment, stable pharmaceutical which itself degrades to quinoneimine. Also, the stability of aqueous compositions as disclosed in the context of the aqueous formulations is dependent on variables such as present invention may optionally include a solubilising aid. removal of dissolved oxygen from carrier, optional further 0016. By solubilising aid is meant any compound that presence of antioxidant in the formulation and adjustment to may assist in Solubilising the active by accommodating the Suitable pH. Hence a composition comprising an aqueous active in a cavity formed in the solubising aid to form inclu formulation of paracetamol wherein the stability of the for sion complexes. mulation is achieved is highly desirable. 0017 Representative solubilising aids which may be used 0004 Perfalgan R is a commercially available formulation include but are not limited to cyclodextrins such as a cyclo which comprises a liquid formulation of paracetamol. The dextrin, B cyclodextrin, Y cyclodextrin; calixarenes and the formulation contains buffering agents. It is available from like as well as their pharmaceutically useful derivatives. Bristol Myers Squibb. Combinations of more than one of these solubilising aids in 0005 U.S. Pat. No. 6,992.218 reports a method for pre different ratios or proportions as required are covered within paring aqueous formulations with easily oxidizable active the scope of the invention without limitation. principles, notably phenols. The method comprises deoxy 0018. In an embodiment, a physiologically acceptable ? genation of the solution by bubbling it with at least one inert cyclodextrin derivative was found to be useful in the context gas until the oxygen content is below 2 ppm. of the present invention. 0006. The preparation of parenteral formulations of parac 0019. In another embodiment, hydroxy propyl beta cyclo etamol has been known in the art. However, the parenteral dextrin, herein referred to as “HPBCD', was found to be formulations of paracetamol utilize a buffer system to main useful in the context of the present invention. tain the pH to the required value (U.S. Pat. No. 6,028.222). 0020. In yet another embodiment, the w/w ratios of 0007 EP1752139 describes liquid formulations of parac HPBCD to the active can range from about 0.5:1 to about 2:1, etamol for infusion, without using a buffer system. However, particularly from about 0.75:1 to about 1.5:1. US 2011/OO15273 A1 Jan. 20, 2011 0021. In yet another embodiment, the present invention potentiate the effect of paracetamol, may optionally include a provides stable pharmaceutical aqueous compositions, hav solubilising aid and/or other pharmaceutically acceptable ing analgesic activity comprising a therapeutically effective excipients. dose of paracetamol with a solubilising aid with or without pharmaceutically acceptable excipients. 0035. The aqueous paracetamol formulation according to 0022 Antioxidants may be used in the present invention to the present invention can be used in the field of medicine as a protect the active (s) from oxidative degradation. The antioxi parenteral analgesic. dants or free radical scavengers or combinations thereofused 0036. The aqueous composition in the present invention in various ratios are exemplified by but are not limited to may be prepared by processes known to one skilled in the art sodium sulfite, sodium bisulfite, sodium metabisulfite, but is not limited to the following process: Sodium thiosulphate, Sodium formaldehyde Sulfoxylate and 0037 a) Dissolving either paracetamol or solubilising the like in various ratios and proportions. Combinations of aid or both in the solvent or mixture of solvents option more than one of these antioxidants in various ratios and ally with other pharmaceutically acceptable excipients proportions as required are within the scope of the invention optionally under inert atmosphere. without limitation. 0023. In an embodiment, sodium metabisulfite was found 0.038 b) Optionally adjusting the pH and/or the osmo to be useful in the context of the present invention. lality of the solution to suitable values. 0024. In another embodiment, sodium metabisulfite may 0.039 c) Subjecting the solution to sterilization option be used in amount from about 200 mg/l to about 1 g/l. ally using filteration sterilization. 0025. As an alternative or in addition to the use of antioxi 0040 d) Optionally deoxygenating the resultant solu dants, the antioxidant effect may be achieved by displacing tion using inert gas and/or optional terminal steriliza oxygen from the composition of the active(s). This may be tion. achieved by purging the composition with a water insoluble inert gas. Inert gases which are known to a person skilled in the art may be employed. These include but are not limited to EXAMPLES nitrogen, carbon dioxide and the like. 0026. In an embodiment, the pharmaceutical composition 0041. The following examples are
Load more

Recommended publications
  • PUBLISHED UNITED STATES COURT of APPEALS for the FOURTH CIRCUIT ZENECA, INCORPORATED, Plaintiff-Appellant, V. DONNA E. SHALALA
    PUBLISHED UNITED STATES COURT OF APPEALS FOR THE FOURTH CIRCUIT ZENECA, INCORPORATED, Plaintiff-Appellant, v. DONNA E. SHALALA, in her official capacity as Secretary of Health and Human Services; JANE HENNEY, M.D., Commissioner of the Food No. 99-2329 and Drug Administration, Defendant-Appellees, v. GENSIA SICOR PHARMACEUTICALS, INCORPORATED, Movant-Appellee. Appeal from the United States District Court for the District of Maryland, at Baltimore. William M. Nickerson, District Judge. (CA-99-307-WMN) Argued: April 5, 2000 Decided: May 17, 2000 Before NIEMEYER, Circuit Judge, HAMILTON, Senior Circuit Judge, and Roger J. MINER, Senior Circuit Judge of the United States Court of Appeals for the Second Circuit, sitting by designation. _________________________________________________________________ Affirmed by published opinion. Senior Judge Hamilton wrote the opinion, in which Judge Niemeyer and Senior Judge Miner joined. COUNSEL Anthony Craig Roth, MORGAN, LEWIS & BOCKIUS, L.L.P., Washington, D.C., for Appellant. Gerald Cooper Kell, Senior Trial Counsel, Office of Consumer Litigation, UNITED STATES DEPARTMENT OF JUSTICE, Washington, D.C., for Appellees Sha- lala and Henney; David Glenn Adams, VENABLE, BAETJER, HOWARD & CIVILETTI, L.L.P., Washington, D.C., for Appellee Gensia Sicor. ON BRIEF: Stephen P. Mahinka, MORGAN, LEWIS & BOCKIUS, L.L.P., Washington, D.C., for Appellant. David W. Ogden, Acting Assistant Attorney General, Office of Consumer Liti- gation, UNITED STATES DEPARTMENT OF JUSTICE, Washing- ton, D.C.; Barbara J. Stradling, Associate Chief Counsel for Enforcement, FOOD AND DRUG ADMINISTRATION, Washing- ton, D.C., for Appellees Shalala and Henney. James N. Czaban, VEN- ABLE, BAETJER, HOWARD & CIVILETTI, L.L.P., Washington, D.C., for Appellee Gensia Sicor.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • Sodium Metabisulfite Hypersensitivity in Urticaria
    Our Dermatology Online Original Article SSodiumodium mmetabisulfietabisulfi ttee hhypersensitivityypersensitivity iinn uurticariarticaria Beata Sadowska, Marlena Sztormowska, Marika Gawinowska, Marta Chelminska Department of Allergology, Allergology and Pneumonology Clinic, Medical University of Gdansk, Smoluchowskiego 17, 80- 214 Gdansk, Poland Corresponding author: Beata Sadowska, MD, E-mail: [email protected] ABSTRACT Background: Sodium metabisulfite is a recognized, but rare, trigger of urticaria, wherein the IgE mechanism has been sporadically proven. The aim of this study was to identify the potential reaction to sodium metabisulfite (MBS) based on a placebo-controlled oral challenge in patients with urticaria and suspected hypersensitivity to food additives. Materials and Methods: A total of 110 adult patients (76 females and 34 males with a mean age of 46 years) were included in the study between 2017 and 2019. All subjects underwent MBS skin prick tests (SPT) and patch tests (PT). Patients with a positive skin test or suspected MBS hypersensitivity were qualified for a placebo-controlled oral challenge (OC). Results: Skin testing was positive in 24 patients: SPT in 20% (n = 22), PT in 5% (n = 6). Out of 64 oral challenges, 13 positive results were obtained. Patients with a positive challenge typed sulfite foods twice as often as a culprit compared to those with a negative OC. Conclusions: In patients with urticaria, both the IgE and non-IgE mechanism of MBS hypersensitivity has been demonstrated. Skin tests with a detailed medical history of potentially guilty foods may be helpful in determining sulfite hypersensitivity. Key words: Sulfites; Sodium metabisulfite; Urticaria; Food additive hypersensitivity INTRODUCTION they are not obliged to disclose the total amount of the substance [5].
    [Show full text]
  • Safety Assessment of Sulfites As Used in Cosmetics
    Safety Assessment of Sulfites as Used in Cosmetics Status: Re-Review for Panel Consideration Release Date: August 22, 2019 Panel Meeting Date: September 16-17, 2019 The 2019 Cosmetic Ingredient Review Expert Panel members are: Chair, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D., Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Executive Director is Bart Heldreth, Ph.D. This safety assessment was prepared by Wilbur Johnson, Jr., Senior Scientific Analyst © Cosmetic Ingredient Review 1620 L Street, NW, Suite 1200 ♢ Washington, DC 20036-4702 ♢ ph 202.331.0651 ♢ fax 202.331.0088 ♢ [email protected] Distributed for Comment Only -- Do Not Cite or Quote Commitment & Credibility since 1976 Memorandum To: CIR Expert Panel Members and Liaisons From: Wilbur Johnson, Jr. Senior Scientific Analyst Date: August 22, 2019 Subject: Re-Review of the Safety Assessment of Sulfites The CIR Expert Panel first reviewed the safety of Sulfites in 2003. The Panel concluded that Ammonium Bisulfite, Ammonium Sulfite, Potassium Metabisulfite, Potassium Sulfite, Sodium Bisulfite, Sodium Metabisulfite, and Sodium Sulfite are safe as used in cosmetic formulations. The original report is included for your use (identified as sulfit092019orig in the pdf). Minutes from the deliberations of the original review are also included (sulfit092019min_orig). Because it has been at least 15 years since the safety assessment was published, in accordance with CIR Procedures, the Panel should consider whether the safety assessment of Sulfites should be reopened.
    [Show full text]
  • 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.
    [Show full text]
  • Chemical Pretreatment for RO and NF
    Chemical Pretreatment For RO and NF October 2013 Lenntech [email protected] Tel. +31-152-610-900 www.lenntech.com Fax. +31-152-616-289 There are a number of chemicals that can be introduced into the RO feed to enhance the operation of the RO system. Acids Caustic Dechlorination chemicals Antiscalants and Dispersants Acids: Acids, typically hydrochloric [HCl] or sulfuric [H2SO4], are injected into the RO feed to lower pH. Sulfuric acid is used more often than HCl acid. One reason for this is because sulfuric acid is relatively lower in operating cost than HCl acid. Another advantage to using sulfuric over HCl is the reduced fuming to the atmosphere, which means less corrosion to surrounding metal components. Sulfuric acid is sometimes preferred over HCl since there is a better membrane rejection of the sulfate ion than the chloride ion. Technical grade sulfuric acid, with no other additives, is suitable for use with a RO. Sulfuric acid is commercially available as a 20% and 93% solution. The 93% solution is also referred to as “66 0 Baume solution”. Caution is required in diluting 93% sulfuric acid, since the maximum heat of dilution of about 280 F occurs around 60%. It is critical that the concentrated acid is added slowly to the top of dilution water that is being agitated to minimize the buildup of heat and boiling of the makeup solution. Hydrochloric acid is preferred when calcium sulfate, barium sulfate, or strontium sulfate scaling is a concern. Sulfuric acid increases the sulfate ion level in the RO feed, which directly increases the potential for sulfate-based scaling.
    [Show full text]
  • Sodium Metabisulfite
    Sodium metabisulfite sc-203389 Material Safety Data Sheet Hazard Alert Code EXTREME HIGH MODERATE LOW Key: Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION PRODUCT NAME Sodium metabisulfite STATEMENT OF HAZARDOUS NATURE CONSIDERED A HAZARDOUS SUBSTANCE ACCORDING TO OSHA 29 CFR 1910.1200. NFPA FLAMMABILITY0 HEALTH3 HAZARD INSTABILITY1 SUPPLIER Company: Santa Cruz Biotechnology, Inc. Address: 2145 Delaware Ave Santa Cruz, CA 95060 Telephone: 800.457.3801 or 831.457.3800 Emergency Tel: CHEMWATCH: From within the US and Canada: 877-715-9305 Emergency Tel: From outside the US and Canada: +800 2436 2255 (1-800-CHEMCALL) or call +613 9573 3112 PRODUCT USE ■ Reducing agent. Reagent. Widely used in food as preservative; as Food Additive 223. Amounts in foods are subject to regulation. Usually only 0.01 to 0.10%. Used as a reagent and as a source of sulfur dioxide. Used to deactivate isothiazolone biocides. SYNONYMS Na2-S2-O5, "SBS powder", SMBS, "Food Additive 223", "disodium pyrosulphite", "pyrosulfurous acid, disodium salt", "sodium pyrosulfite", "disodium pyrosulfite", "sodium meta-bisulphite", "sodium meta-bisulfite", "anhydrous sodium bisulfite", "SMB POwder", APS, FOOD00004251, AR00000487, 04506808, 015705, "Redox SOMETA39", Nalco, "IONAC 140" Section 2 - HAZARDS IDENTIFICATION CANADIAN WHMIS SYMBOLS EMERGENCY OVERVIEW RISK Harmful if swallowed. Contact with acids liberates toxic gas. Risk of serious damage to eyes. Irritating to respiratory system and skin. POTENTIAL HEALTH EFFECTS ACUTE HEALTH EFFECTS SWALLOWED ■ Accidental ingestion of the material may be harmful; animal experiments indicate that ingestion of less than 150 gram may be fatal or may produce serious damage to the health of the individual. ■ Ingestion of sulfite salts may cause gastric irritation.
    [Show full text]
  • 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.
    [Show full text]
  • Free Radical and Drug Oxidation Products in an Intensive Care Unit Sedative: Propofol with Sulfite*
    Free radical and drug oxidation products in an intensive care unit sedative: Propofol with sulfite* Max T. Baker, PhD; Marc S. Gregerson, BS; Sean M. Martin, BA; Garry R. Buettner, PhD Objectives: Some propofol emulsion formulations contain EDTA The EDTA propofol emulsion remained white at all times. The or sodium metabisulfite to inhibit microbe growth on extrinsic absorbance spectra of the propofol dimer and propofol dimer contamination. EDTA is not known to react with propofol formu- quinone extracted from sulfite propofol emulsion showed that lation components; however, sulfite has been shown to support propofol dimer did not absorb in the visible spectrum, but the some oxidation processes and may react with propofol. This study propofol dimer quinone had an absorbance peak at 421 nm, compared the oxidation of propofol and the formation of free causing it to appear yellow. Electron paramagnetic resonance radicals by electron paramagnetic resonance analysis in EDTA analysis of the propofol emulsion containing metabisulfite and sulfite propofol emulsions during a simulated intensive care revealed that the sulfite propofol emulsion yielded a strong unit 12-hr intravenous infusion. free radical signal consistent with the formation of the sulfite ⅐؊ Design: Controlled laboratory study. anion radical (SO3 ). The EDTA propofol emulsion yielded no free Setting: University laboratory. radical signal above background. Measurements and Main Results: Propofol emulsions (3.5 mL) Conclusion: Sulfite from the metabisulfite additive in propofol were dripped from spiked 50-mL vials at each hour for 12 hrs. emulsion creates an oxidative environment when these emul- Two propofol oxidation products, identified as propofol dimer and sions are exposed to air during a simulated intravenous infu- propofol dimer quinone, were detected in sulfite and EDTA propo- sion.
    [Show full text]
  • Sulfate Salts in Gasoline and Ethanol Fuels – Historical Perspective and Analysis of Available Data Robert L
    Sulfate Salts in Gasoline and Ethanol Fuels – Historical Perspective and Analysis of Available Data Robert L. McCormick and Teresa L. Alleman National Renewable Energy Laboratory Janet Yanowitz Ecoengineering, Inc. NREL is a national laboratory of the U.S. Department of Energy Office of Energy Efficiency & Renewable Energy Operated by the Alliance for Sustainable Energy, LLC This report is available at no cost from the National Renewable Energy Laboratory (NREL) at www.nrel.gov/publications. Technical Report NREL/TP-5400-69001 September 2017 Contract No. DE-AC36-08GO28308 Sulfate Salts in Gasoline and Ethanol Fuels – Historical Perspective and Analysis of Available Data Robert L. McCormick and Teresa L. Alleman National Renewable Energy Laboratory Janet Yanowitz Ecoengineering, Inc. Prepared under Task No. VTOP.10335.04.01.03 NREL is a national laboratory of the U.S. Department of Energy Office of Energy Efficiency & Renewable Energy Operated by the Alliance for Sustainable Energy, LLC This report is available at no cost from the National Renewable Energy Laboratory (NREL) at www.nrel.gov/publications. National Renewable Energy Laboratory Technical Report 15013 Denver West Parkway NREL/TP-5400-69001 Golden, CO 80401 September 2017 303-275-3000 • www.nrel.gov Contract No. DE-AC36-08GO28308 NOTICE This report was prepared as an account of work sponsored by an agency of the United States government. Neither the United States government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights.
    [Show full text]
  • Interagency Committee on Chemical Management
    DECEMBER 14, 2018 INTERAGENCY COMMITTEE ON CHEMICAL MANAGEMENT EXECUTIVE ORDER NO. 13-17 REPORT TO THE GOVERNOR WALKE, PETER Table of Contents Executive Summary ...................................................................................................................... 2 I. Introduction .......................................................................................................................... 3 II. Recommended Statutory Amendments or Regulatory Changes to Existing Recordkeeping and Reporting Requirements that are Required to Facilitate Assessment of Risks to Human Health and the Environment Posed by Chemical Use in the State ............................................................................................................................ 5 III. Summary of Chemical Use in the State Based on Reported Chemical Inventories....... 8 IV. Summary of Identified Risks to Human Health and the Environment from Reported Chemical Inventories ........................................................................................................... 9 V. Summary of any change under Federal Statute or Rule affecting the Regulation of Chemicals in the State ....................................................................................................... 12 VI. Recommended Legislative or Regulatory Action to Reduce Risks to Human Health and the Environment from Regulated and Unregulated Chemicals of Emerging Concern ..............................................................................................................................
    [Show full text]