DOCSLIB.ORG

TOXICOLOGICAL REVIEW of TOLUENE (CAS No

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
TOXICOLOGICAL REVIEW of TOLUENE (CAS No EPA/635/R-05/004 TOXICOLOGICAL REVIEW OF TOLUENE (CAS No. 108-88-3) In Support of Summary Information on the Integrated Risk Information System (IRIS) September 2005 U.S. Environmental Protection Agency Washington D.C. DISCLAIMER This document has been reviewed in accordance with U. S. Environmental Protection Agency policy and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. i CONTENTS —TOXICOLOGICAL REVIEW OF TOLUENE (CAS No. 108-88-3) LIST OF TABLES.............................................................v LIST OF FIGURES ........................................................... vi FREQUENTLY USED ABBREVIATIONS AND ACRONYMS ...................... vii FOREWORD ................................................................x AUTHORS, CONTRIBUTORS, AND REVIEWERS ................................ xi 1. INTRODUCTION ..........................................................1 2. CHEMICAL AND PHYSICAL INFORMATION RELEVANT TO ASSESSMENTS .....3 3. TOXICOKINETICS RELEVANT TO ASSESSMENTS ............................4 3.1. ABSORPTION .....................................................4 3.1.1. Oral Exposure ...............................................4 3.1.2. Inhalation Exposure ..........................................4 3.1.3. Dermal Exposure ............................................5 3.2. DISTRIBUTION ....................................................6 3.3. METABOLISM .....................................................6 3.4. ELIMINATION .....................................................9 3.5. PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODELS ....10 4. HAZARD IDENTIFICATION................................................11 4.1. STUDIES IN HUMANS .............................................11 4.1.1. Oral Exposure ..............................................11 4.1.2. Inhalation Exposure .........................................12 4.1.2.1. Acute and Case Studies ...............................12 4.1.2.2. Pre-chronic and Chronic Studies .......................15 4.1.2.3. Cancer Studies ......................................31 4.2. PRECHRONIC AND CHRONIC STUDIES AND CANCER BIOASSAYS IN ANIMALS - ORAL AND INHALATION .............................32 4.2.1. Oral Exposure ..............................................32 4.2.1.1. Prechronic Studies ...................................32 4.2.1.2. Chronic Studies .....................................38 4.2.2. Inhalation Exposure .........................................39 4.2.2.1. Prechronic Studies ...................................39 4.2.2.2. Chronic Studies .....................................42 4.3. REPRODUCTIVE/DEVELOPMENTAL STUDIES - ORAL AND INHALATION ...............................................................44 4.3.1. Studies in Humans ..........................................44 4.3.2. Studies in Animals ..........................................45 4.3.2.1. Oral Exposure ......................................45 4.3.2.2. Inhalation Exposure ..................................47 4.4. OTHER STUDIES ..................................................51 4.4.1. Acute Toxicity Data .........................................51 ii 4.4.1.1. Oral Exposure ......................................51 4.4.1.2. Inhalation Exposure ..................................52 4.4.2. Genotoxicity ...............................................53 4.5. SYNTHESIS AND EVALUATION OF MAJOR NONCANCER EFFECTS – ORAL AND INHALATION ........................................54 4.5.1. Oral Exposure ..............................................54 4.5.2. Inhalation Exposure .........................................55 4.5.3. Mode of Action .............................................57 4.6. WEIGHT-OF-EVIDENCE EVALUATION AND CANCER CHARACTERIZATION ...........................................60 4.6.1. Summary of Overall Weight-of-Evidence ........................60 4.6.2. Synthesis of Human, Animal, and Other Supporting Evidence ........61 4.7. SUSCEPTIBLE POPULATIONS AND LIFE STAGES ....................62 4.7.1. Possible Childhood Susceptibility ..............................62 4.7.2. Possible Gender Differences ...................................63 4.7.3. Other .....................................................64 5. DOSE RESPONSE ASSESSMENTS ..........................................64 5.1. ORAL REFERENCE DOSE (RfD) .....................................64 5.1.1. Choice of Principal Study and Critical Effect .....................64 5.1.2. Methods of Analysis .........................................67 5.1.3. RfD Derivation - Including Application of Uncertainty Factors .......68 5.1.4. Previous RfD Assessment .....................................70 5.2. INHALATION REFERENCE CONCENTRATION (RfC) ..................70 5.2.1. Choice of Principal Study and Critical Effect .....................70 5.2.2. Methods of Analysis .........................................83 5.2.3. RfC Derivation - Including Application of Uncertainty Factors .......84 5.2.4. Previous RfC Assessment .....................................86 5.3. CANCER ASSESSMENT ............................................86 6. MAJOR CONCLUSIONS IN THE CHARACTERIZATION OF HAZARD AND DOSE RESPONSE ........................................87 6.1. HUMAN HAZARD POTENTIAL .....................................87 6.2. DOSE RESPONSE .................................................89 6.2.1. Noncancer/Oral .............................................89 6.2.2. Noncancer/Inhalation ........................................90 6.2.3. Cancer/Oral and Inhalation ....................................90 7. REFERENCES ............................................................91 Appendix A1. Summary of External Peer Review and Public Comments and Disposition .................................................................. A1-1 iii Appendix A2. Summary of External Peer Review and Public Comments and Disposition .................................................................. A2-1 Appendix B1. Benchmark Dose Modeling Results for the Derivation of the RfD (NTP, 1990) ...................................................................B1-1 Appendix B2. Benchmark Dose Modeling Results for the Derivation of the RfD (Selected Immunotoxicity Studies) ...................................................................B2-1 iv LIST OF TABLES Table 1. Selected subset of occupational studies of neurological effects from toluene inhalation .......................................................74 Table 2. Summary of subchronic and chronic toluene inhalation studies in animals ....80 Table B1-1. Benchmark modeling summary for relative kidney weight, NTP 1990 .....................................................B1-2 Table B2-1. Results of BMDS analyses from Hsieh et al. (1989) study with maximum p for hypothesis 4, goodness of fit of means ..............................B2-5 Table B2-2. Results of BMDS analyses from Hsieh et al. (1989) study with minimum AIC for hypothesis 4, goodness of fit of means ..............................B2-6 Table B2-3. Results of BMDS analyses from Hsieh et al. (1989, 1990b) study with maximum p for hypothesis 4, goodness of fit of means ..........................B2-7 Table B2-4. Benchmark responses for the endpoints reported in Hsieh et al. (1989) .....B2-8 Table B2-5. Basic sensitivity analyses for BMDS results ..........................B2-9 v LIST OF FIGURES Figure 1. Proposed pathways for toluene metabolism .............................8 Figure 2. Summary of NOAELs/LOAELs for neurological endpoints for a subset of occupational studies of chronic inhalation exposure to toluene .............73 vi FREQUENTLY USED ABBREVIATIONS AND ACRONYMS [3H]TdR [3H]thymidine 5-HIAA 5-Hydroxyindoleacetic acid 5-HT 5-Hydroxytryptamine (serotonin) AACCI Alcohol intake-adjusted color confusion index ACGIH American Conference of Governmental Industrial Hygienists ACTH Adrenocorticotropic hormone AIC Akaike Information Criterion ALT L-alanine-aminotransferase anti-GBM Antiglomerular basement membrane antibody anti-LAM Antilaminin antibody ASPH Association of Schools of Public Health ATSDR Agency for Toxic Substances and Disease Registry BAEP Brainstem auditory evoked potentials BMD Benchmark dose BMDL BMD lower 95% confidence limit BMDS Benchmark dose modeling software BMR Benchmark response BTEX Benzene, toluene, ethylbenzene, and xylenes CAS Chemical Abstracts Service CASRN Chemical Abstracts Service Registry Number CATSYS Computerized test system for neurotoxicity CCI Color confusion index CDP Cubic distortion-product CH50 Number of cells necessary to lyse 50% of target cells CHO Chinese hamster ovary CI Confidence interval CIIT Chemical Industry Institute of Toxicology CNS Central Nervous System CoA Coenzyme A Con A Concanavalin A CYP Cytochrome P-450 DA Dopamine DCV Distribution of nerve conduction velocities DH Dehydrogenase DNA Deoxyribonucleic acid DOPAC 3,4-Dihydroxyphenylacetic acid ECG Electrocardiograph ELISA Enzyme-linked immunosorbent assay F0 Parent generation vii F1 First filial generation F2 Second filial generation FEP Flash-evoked potential FOB Functional observation battery GABA (-Aminobutyric acid GSH Glutathione (reduced) HEC Human equivalent concentration HVA Homovanillic acid IARC International Agency for Research on Cancer IgE Immunoglobulin E IgG Immunoglobulin G IgM Immunoglobulin M IL-2 Interleukin-2 IRIS Integrated Risk Information System LOAEL Lowest observed adverse effect level LPS Lipopolysaccharide LWAE Lifetime weighted average exposure MCV Maximal
Load more

Recommended publications
  • Insights Into the Molecular Basis for Substrate Binding and Specificity of the Wild-Type L-Arginine/Agmatine Antiporter Adic
    Insights into the molecular basis for substrate binding and specificity of the wild-type L-arginine/agmatine antiporter AdiC Hüseyin Ilgüa,b,1, Jean-Marc Jeckelmanna,b,1, Vytautas Gapsysc, Zöhre Ucuruma,b, Bert L. de Grootc, and Dimitrios Fotiadisa,b,2 aInstitute of Biochemistry and Molecular Medicine, University of Bern, CH-3012 Bern, Switzerland; bSwiss National Centre of Competence in Research TransCure, University of Bern, CH-3012 Bern, Switzerland; and cComputational Biomolecular Dynamics Group, Max-Planck-Institute for Biophysical Chemistry, D-37077 Goettingen, Germany Edited by Christopher Miller, Howard Hughes Medical Institute, Brandeis University, Waltham, MA, and approved July 26, 2016 (received for review April 4, 2016) Pathogenic enterobacteria need to survive the extreme acidity of Arg-bound states (10). The two outward-open, substrate-free the stomach to successfully colonize the human gut. Enteric bacteria structures are at the reasonable and moderate resolutions of 3.2 Å circumvent the gastric acid barrier by activating extreme acid- (8) and 3.6 Å (9), respectively, and the only ones available of wild- resistance responses, such as the arginine-dependent acid resistance type AdiC (AdiC-wt). The two other structures are with bound system. In this response, L-arginine is decarboxylated to agmatine, Arg and at 3-Å resolution, and could only be obtained as a result thereby consuming one proton from the cytoplasm. In Escherichia of the introduction of specific point mutations: AdiC-N22A (10) coli,theL-arginine/agmatine antiporter AdiC facilitates the export and AdiC-N101A (11). The N101A mutation results in a defective of agmatine in exchange of L-arginine, thus providing substrates for AdiC protein unable to bind Arg and with a dramatically de- further removal of protons from the cytoplasm and balancing the creased turnover rate compared with wild-type (11).
    [Show full text]
  • Separation of Isomers <Emphasis Type="Italic">L </Emphasis>-Alanine and Sarcosine in Urine by Electrospra
    SHORT COMMUNICATION Separation of Isomers L-Alanine and Sarcosine in Urine by Electrospray Ionization and Tandem Differential Mobility Analysis-Mass Spectrometry Pablo Martínez-Lozanoa and Juan Rusb a Institute for Biomedical Technologies-National Research Council, Milan, Italy b SEADM, Valladolid, Spain Sarcosine, an isomer of L-alanine, has been proposed as a prostate cancer progression biomarker [1]. Both compounds are detected in urine, where the measured sarcosine/alanine ratio has been found to be higher in prostate biopsy-positive group versus controls. We present here preliminary evidence showing that urine samples spiked with sarcosine/alanine can be partially resolved in 3 min via tandem differential mobility analysis-mass spectrometry (DMA-MS). Based on the calibration curves obtained for two mobility peaks, we finally estimate their concentration ratio in urine. (J Am Soc Mass Spectrom 2010, 21, 1129–1132) © 2010 American Society for Mass Spectrometry rostate cancer is a leading cause of death among the tive-ion mode at the DMA entrance slit. Our nanospray male population. Sarcosine, an isomer of alanine, parameters were: capillary 360 ␮m o.d., 50 ␮m i.d., length Pwas recently proposed as a prostate cancer progres- 22 cm, driving pressure 75 mbar, and 3.8 kV. The ions sion biomarker [1]. In particular, the sarcosine/alanine entered the separation region propelled by an electric field ratio was found to be significantly higher in urine derived and against a counterflow gas (0.2 L/min). Sheath gas from biopsy-positive prostate cancer patients compared flow was kept constant, and the classification voltage was with biopsy-negative controls.
    [Show full text]
  • Toluene Poisoning (Accidental Ingestion of Evostik) Summary
    Toluene Poisoning (Accidental Ingestion of Evostik) *Solarin A.U1, Aremu E.O1, Gbelee O.H1, Animasahun A.B1, Akinola A.O1, Ogunlana A.T1, Nwakpele O.T1, Olugbade O1 1. Department of Paediatrics, Lagos State University Teaching Hospital, Ikeja Lagos. Corresponding Author: Solarin A.U. Email address: [email protected] Summary INTRODUCTION Childhood poisoning is one of the causes of high morbidity and mortality especially among under-five children in low income countries. The home and its surroundings may harbour poisonous substances which might be ingested by adventurous children. Evo-stik glue is a modified silane (MS) polymer based high performance adhesive. It contains toluene, a colourless, sweet-smelling liquid with detrimental effects on virtually every organ in the body especially brain and kidneys. Toluene is a component of household items such as gasoline, shoe and nail polish. AIM / OBJECTIVES From a few reported cases of toluene poisoning worldwide there was need to create awareness on the possibility of toluene poisoning as well as its deleterious effects. This is a case report on exposure to the effects of toluene by accidental ingestion that set the platform to emphasize the importance of prompt and appropriate management of toluene poisoning. METHODOLOGY This case report is about a 2year old girl who accidentally ingested 15-20ml evostik glue stored in an attractive container in the home. QH was presented at the Lagos State University Teaching Hospital Paediatric Emergency Unit with a one day history of persistent spontaneous, non-projectile and non-bilous vomiting. On admission, she was conscious, moderately dehydrated with dry buccal mucosa.
    [Show full text]
  • Beta Alanine
    PERFORMANCE ENHANCERS FACTS AND BOTTOM LINE BETA ALANINE What is it? B-alanine is a naturally occurring amino acid (a non-essential amino acid) not used by the body to make muscle tissue. Rather, research has shown that B-alanine works by increasing the muscle content of an important compound – carnosine. In fact, the production of carnosine is limited by the availability of B-alanine. Carnosine is highly concentrated in muscle tissue where its role is primarily to soak up hydrogen ions. Does it work? B-alanine is one of the few dietary supplements that actually have good scientific evidence that it can possibly enhance performance. How does it work? When you exercise intensely the body produces hydrogen ions. The longer you exercise the more hydrogen ions you produce and this reduces the pH level in your muscles. Muscles work best in a very specific pH range and when the pH drops below that level then muscular performance also starts to decrease. Anything that helps to prevent or delay that drop in pH will help delay muscle fatigue. This is where B-alanine has proven to be very helpful. Beta-alanine increases the levels of carnosine in your slow and fast twitch muscle fibers and carnosine is a buffer that basically soaks up hydrogen ions and so reduces the drop in pH. By keeping your hydrogen ion levels lower, B-alanine allows you to train harder and longer. The bottom line is that B-alanine works by increasing the hydrogen ion buffering abilities of your muscles. What benefits does it offer? B-alanine has been shown to increase muscle strength, increase muscle mass, increase anaerobic endurance, increase aerobic endurance and increase exercise capacity.
    [Show full text]
  • Toxicological Profile for Toluene
    TOXICOLOGICAL PROFILE FOR TOLUENE U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Agency for Toxic Substances and Disease Registry September 2000 Additional Resources http://www.atsdr.cdc.gov/toxprofiles/tp56.html TOLUENE ii DISCLAIMER The use of company or product name(s) is for identification only and does not imply endorsement by the Agency for Toxic Substances and Disease Registry. TOLUENE iii UPDATE STATEMENT Toxicological profiles are revised and republished as necessary, but no less than once every three years. For information regarding the update status of previously released profiles, contact ATSDR at: Agency for Toxic Substances and Disease Registry Division of Toxicology/Toxicology Information Branch 1600 Clifton Road NE, E-29 Atlanta, Georgia 30333 TOLUENE vi *Legislative Background The toxicological profiles are developed in response to the Superfund Amendments and Reauthorization Act (SARA) of 1986 (Public law 99-499) which amended the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA or Superfund). This public law directed ATSDR to prepared toxicological profiles for hazardous substances most commonly found at facilities on the CERCLA National Priorities List and that pose the most significant potential threat to human health, as determined by ATSDR and the EPA. The availability of the revised priority list of 275 hazardous substances was announced in the Federal Register on October 21, 1999 (64 FR 56792). For prior versions of the list of substances, see Federal Register notices dated April 17, 1987 (52 FR 12866); October 20, 1988(53 FR 41280); October 26, 1989 (54 FR 43619); October 17, 1990 (55 FR 42067); October 17, 1991 (56 FR 52166); October 28, 1992 (57 FR 48801); February 28, 1994 (59 FR 9486); April 29, 1996 (61 FR 18744); and November 17, 1997 (62 FR 61332).
    [Show full text]
  • Targeting Glycine Reuptake in Alcohol Seeking and Relapse
    JPET Fast Forward. Published on January 24, 2018 as DOI: 10.1124/jpet.117.244822 This article has not been copyedited and formatted. The final version may differ from this version. TITLE PAGE Targeting Glycine Reuptake in Alcohol Seeking and Relapse Valentina Vengeliene, Martin Roßmanith, Tatiane T. Takahashi, Daniela Alberati, Berthold Behl, Anton Bespalov, Rainer Spanagel Downloaded from The primary laboratory of origin: Institute of Psychopharmacology, Central Institute of jpet.aspetjournals.org Mental Health, Faculty of Medicine Mannheim, Heidelberg University, Germany; at ASPET Journals on September 30, 2021 VV, MR, TTT, RS: Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, Heidelberg University, Germany; DA: Roche Pharma Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases, Roche Innovation Center Basel, CH-4070 Basel, Switzerland; BB, AB: Department of Neuroscience Research, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany; AB: Department of Psychopharmacology, Pavlov Medical University, St Petersburg, Russia JPET #244822 JPET Fast Forward. Published on January 24, 2018 as DOI: 10.1124/jpet.117.244822 This article has not been copyedited and formatted. The final version may differ from this version. RUNNING TITLE GlyT1 in Alcohol Seeking and Relapse Corresponding author with complete address: Valentina Vengeliene, Institute of Psychopharmacology, Central Institute of Mental Health (CIMH), J5, 68159 Mannheim, Germany Email: [email protected], phone: +49-621-17036261; fax: +49-621- Downloaded from 17036255 jpet.aspetjournals.org The number of text pages: 33 Number of tables: 0 Number of figures: 6 Number of references: 44 at ASPET Journals on September 30, 2021 Number of words in the Abstract: 153 Number of words in the Introduction: 729 Number of words in the Discussion: 999 A recommended section assignment to guide the listing in the table of content: Drug Discovery and Translational Medicine 2 JPET #244822 JPET Fast Forward.
    [Show full text]
  • Poly(L-Alanine) As a Universal Reference Material for Understanding Protein Energies and Structures TERESA HEAD-GORDON, FRANK H
    Proc. Nati. Acad. Sci. USA Vol. 89, pp. 11513-11517, December 1992 Biophysics Poly(L-alanine) as a universal reference material for understanding protein energies and structures TERESA HEAD-GORDON, FRANK H. STILLINGER, MARGARET H. WRIGHT, AND DAVID M. GAY AT&T Bell Laboratories, Murray Hill, NJ 07974 Contributed by Frank H. Stillinger, June 17, 1992 ABSTRACT We present a proposition, the "poly(L- alanine) hypothesis," which asserts that the native backbone geometry for any polypeptide or protein of M residues has a closely mimicking, mechanically stable, image in poly(L- POLY-L-ALANINE alanine) of the same number of residues. Using a molecular co mechanics force field to represent the relevant potential energy a: hypersurfaces, we have carried out calculations over a wide z range of M values to show that poly(L-alanine) possesses the w structural versatility necessary to satisfy the proposition. These w include poly(L-alanine) representatives of minima correspond- U- ing to secondary and supersecondary structures, as well as PROTEIN poly(L-alanine) images for tertiary structures of the naturally occurring proteins bovine pancreatic trypsin inhibitor, crambin, ribonuclease A, and superoxide dismutase. The suc- cessful validation of the hypothesis presented in this paper BACKBONE COORDINATES indicates that poly(L-alanine) will serve as a good reference FIG. 1. Topographic basis ofthe poly(L-alanine) hypothesis. Free material in thermodynamic perturbation theory and calcula- energy hypersurfaces are compared for a given protein and for tions aimed at evaluating relative free energies for competing poly(L-alanine) with the same number of residues. candidate tertiary structures in real polypeptides and proteins.
    [Show full text]
  • Alcohol Use Disorder
    Section: A B C D E Resources References Alcohol Use Disorder (AUD) Tool This tool is designed to support primary care providers (family physicians and primary care nurse practitioners) in screening, diagnosing and implementing pharmacotherapy treatments for adult patients (>18 years) with Alcohol Use Disorder (AUD). Primary care providers should routinely offer medication for moderate and severe AUD. Pharmacotherapy alone to treat AUD is better than no therapy at all.1 Pharmacotherapy is most effective when combined with non-pharmacotherapy, including behavioural therapy, community reinforcement, motivational enhancement, counselling and/or support groups. 2,3 TABLE OF CONTENTS pg. 1 Section A: Screening for AUD pg. 7 Section D: Non-Pharmacotherapy Options pg. 4 Section B: Diagnosing AUD pg. 8 Section E: Alcohol Withdrawal pg. 5 Section C: Pharmacotherapy Options pg. 9 Resources SECTION A: Screening for AUD All patients should be screened routinely (e.g. annually or when indicators are observed) with a recommended tool like the AUDIT. 2,3 It is important to screen all patients and not just patients eliciting an index of suspicion for AUD, since most persons with AUD are not recognized. 4 Consider screening for AUD when any of the following indicators are observed: • After a recent motor vehicle accident • High blood pressure • Liver disease • Frequent work avoidance (off work slips) • Cardiac arrhythmia • Chronic pain • Rosacea • Insomnia • Social problems • Rhinophyma • Exacerbation of sleep apnea • Legal problems Special Patient Populations A few studies have reviewed AUD in specific patient populations, including youth, older adults and pregnant or breastfeeding patients. The AUDIT screening tool considered these populations in determining the sensitivity of the tool.
    [Show full text]
  • Supranuclear and Internuclear Ocular Motility Disorders
    CHAPTER 19 Supranuclear and Internuclear Ocular Motility Disorders David S. Zee and David Newman-Toker OCULAR MOTOR SYNDROMES CAUSED BY LESIONS IN OCULAR MOTOR SYNDROMES CAUSED BY LESIONS OF THE MEDULLA THE SUPERIOR COLLICULUS Wallenberg’s Syndrome (Lateral Medullary Infarction) OCULAR MOTOR SYNDROMES CAUSED BY LESIONS OF Syndrome of the Anterior Inferior Cerebellar Artery THE THALAMUS Skew Deviation and the Ocular Tilt Reaction OCULAR MOTOR ABNORMALITIES AND DISEASES OF THE OCULAR MOTOR SYNDROMES CAUSED BY LESIONS IN BASAL GANGLIA THE CEREBELLUM Parkinson’s Disease Location of Lesions and Their Manifestations Huntington’s Disease Etiologies Other Diseases of Basal Ganglia OCULAR MOTOR SYNDROMES CAUSED BY LESIONS IN OCULAR MOTOR SYNDROMES CAUSED BY LESIONS IN THE PONS THE CEREBRAL HEMISPHERES Lesions of the Internuclear System: Internuclear Acute Lesions Ophthalmoplegia Persistent Deficits Caused by Large Unilateral Lesions Lesions of the Abducens Nucleus Focal Lesions Lesions of the Paramedian Pontine Reticular Formation Ocular Motor Apraxia Combined Unilateral Conjugate Gaze Palsy and Internuclear Abnormal Eye Movements and Dementia Ophthalmoplegia (One-and-a-Half Syndrome) Ocular Motor Manifestations of Seizures Slow Saccades from Pontine Lesions Eye Movements in Stupor and Coma Saccadic Oscillations from Pontine Lesions OCULAR MOTOR DYSFUNCTION AND MULTIPLE OCULAR MOTOR SYNDROMES CAUSED BY LESIONS IN SCLEROSIS THE MESENCEPHALON OCULAR MOTOR MANIFESTATIONS OF SOME METABOLIC Sites and Manifestations of Lesions DISORDERS Neurologic Disorders that Primarily Affect the Mesencephalon EFFECTS OF DRUGS ON EYE MOVEMENTS In this chapter, we survey clinicopathologic correlations proach, although we also discuss certain metabolic, infec- for supranuclear ocular motor disorders. The presentation tious, degenerative, and inflammatory diseases in which su- follows the schema of the 1999 text by Leigh and Zee (1), pranuclear and internuclear disorders of eye movements are and the material in this chapter is intended to complement prominent.
    [Show full text]
  • Amino Acid Chemistry
    Handout 4 Amino Acid and Protein Chemistry ANSC 619 PHYSIOLOGICAL CHEMISTRY OF LIVESTOCK SPECIES Amino Acid Chemistry I. Chemistry of amino acids A. General amino acid structure + HN3- 1. All amino acids are carboxylic acids, i.e., they have a –COOH group at the #1 carbon. 2. All amino acids contain an amino group at the #2 carbon (may amino acids have a second amino group). 3. All amino acids are zwitterions – they contain both positive and negative charges at physiological pH. II. Essential and nonessential amino acids A. Nonessential amino acids: can make the carbon skeleton 1. From glycolysis. 2. From the TCA cycle. B. Nonessential if it can be made from an essential amino acid. 1. Amino acid "sparing". 2. May still be essential under some conditions. C. Essential amino acids 1. Branched chain amino acids (isoleucine, leucine and valine) 2. Lysine 3. Methionine 4. Phenyalanine 5. Threonine 6. Tryptophan 1 Handout 4 Amino Acid and Protein Chemistry D. Essential during rapid growth or for optimal health 1. Arginine 2. Histidine E. Nonessential amino acids 1. Alanine (from pyruvate) 2. Aspartate, asparagine (from oxaloacetate) 3. Cysteine (from serine and methionine) 4. Glutamate, glutamine (from α-ketoglutarate) 5. Glycine (from serine) 6. Proline (from glutamate) 7. Serine (from 3-phosphoglycerate) 8. Tyrosine (from phenylalanine) E. Nonessential and not required for protein synthesis 1. Hydroxyproline (made postranslationally from proline) 2. Hydroxylysine (made postranslationally from lysine) III. Acidic, basic, polar, and hydrophobic amino acids A. Acidic amino acids: amino acids that can donate a hydrogen ion (proton) and thereby decrease pH in an aqueous solution 1.
    [Show full text]
  • Therapeutic Effect of Agmatine on Neurological Disease: Focus on Ion Channels and Receptors
    Neurochemical Research (2019) 44:735–750 https://doi.org/10.1007/s11064-018-02712-1 REVIEW PAPER Therapeutic Effect of Agmatine on Neurological Disease: Focus on Ion Channels and Receptors Sumit Barua1 · Jong Youl Kim1 · Jae Young Kim1 · Jae Hwan Kim4 · Jong Eun Lee1,2,3 Received: 15 October 2018 / Revised: 19 December 2018 / Accepted: 24 December 2018 / Published online: 4 January 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract The central nervous system (CNS) is the most injury-prone part of the mammalian body. Any acute or chronic, central or peripheral neurological disorder is related to abnormal biochemical and electrical signals in the brain cells. As a result, ion channels and receptors that are abundant in the nervous system and control the electrical and biochemical environment of the CNS play a vital role in neurological disease. The N-methyl-D-aspartate receptor, 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid receptor, kainate receptor, acetylcholine receptor, serotonin receptor, α2-adrenoreceptor, and acid-sensing ion channels are among the major channels and receptors known to be key components of pathophysiological events in the CNS. The primary amine agmatine, a neuromodulator synthesized in the brain by decarboxylation of L-arginine, can regu- late ion channel cascades and receptors that are related to the major CNS disorders. In our previous studies, we established that agmatine was related to the regulation of cell differentiation, nitric oxide synthesis, and murine brain endothelial cell migration, relief of chronic pain, cerebral edema, and apoptotic cell death in experimental CNS disorders.
    [Show full text]
  • Flavor Masking/Enhancement
    T,&YJJIVMRK %RMQEP*IIHW *PEZSV1EWOMRK)RLERGIQIRX 'LIQMGEP-RXIVQIHMEXI ® §%7MQTPI%QMRS%GMH [MXL'SQTPI\*YRGXMSREPMX] Glycine, also known as aminoacetic acid, is the simplest amino acid. Found naturally in many foods, glycine is also synthesized in the human body, where, among other functions, it helps improve glycogen storage, is utilized in the synthesis of hemoglobin, collagen, and glutathione, and facilitates the amelioration of high blood fat and uric acid levels. In addition to the important metabolic functions glycine &YJJIVMRKT,7XEFMPM^EXMSR performs, this versatile substance is widely used in With acidic and basic properties in the same molecule, a range of applications, such as flavor enhancers and glycine acts to buffer or stabilize the pH of those maskers, pH buffers and stabilizers, ingredients in phar- systems containing it. Many of the uses for glycine maceutical products, and as a chemical intermediate. depend on this ability. Glycine’s efficiency in stabilizing pH has resulted in %X,SQIMRE,SWXSJ%TTPMGEXMSRW its wide usage as a buffering agent in many pharma- ceutical products. Antacid and analgesic products are often formulated with glycine to stabilize the acidity *PEZSV1EWOMRK*PEZSV)RLERGIQIRX of the digestive tract and prevent hyperacidity. Glycine Glycine has a refreshingly sweet taste, and is one and a has been shown to promote the gastric absorption of half times as sweet as sugar. In addition to its sweetness, certain drugs, including aspirin. glycine also has the ability to mellow saltiness and bit- terness. The bitter after-taste of saccharin, for example, When formulated in an aluminum-zirconium is masked by glycine. Carbonated soft drinks and flavor tetrachlorohydrex complex, glycine buffers the high concentrates based on saccharin may contain up to 0.2 acidity of active ingredients in antiperspirants.
    [Show full text]