DOCSLIB.ORG

Absorption and Evaporation of Pesticides from Human Skin in Vitro

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Absorption and Evaporation of Pesticides from Human Skin in Vitro UNIVERSITY OF CINCINNATI Date:___________________ I, _________________________________________________________, hereby submit this work as part of the requirements for the degree of: in: It is entitled: This work and its defense approved by: Chair: _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ Absorption and evaporation of pesticides from human skin in vitro. A dissertation submitted to the Division of Research and Advanced Studies of the University of Cincinnati in partial fulfillment of the requirements for the degree of DOCTORATE OF PHILOSOPHY (Ph.D.) In the Division of Pharmaceutical Sciences of the College of Pharmacy 2007 by Varsha D. Bhatt B.Pharm., S.N.D.T University, Mumbai, 1999 Committee Chair: Gerald B. Kasting, Ph.D. ABSTRACT Estimation of penetration rates of compounds through skin is an important for assessment of either the efficacy of a topical formulation, its irritation potential, or its potential systemic exposure. Current risk assessment models often assume that 100 % of the applied dose is absorbed through the skin. This thesis provides experimental data to validate and calibrate a working diffusion/evaporation model for topically applied chemicals based on their physicochemical properties, the known biological properties of skin and principles of diffusion theory. Four compounds with varying physicochemical properties were studied under different conditions—benzyl alcohol (BA), diethyl-m-toluamide (DEET), tecnazene and malathion. Absorption of 14C – BA, a perfume ingredient, was studied at different doses (0.9 µg/cm2 – 10.6 mg/cm2) through human cadaver skin and silicone membrane. The disposition of BA was satisfactorily described by the diffusion model using a variable diffusivity coefficient. The absorption and evaporation of the insect repellent 14C – DEET (127 µg/cm2) was characterized at airflows ranging from 10 – 100 mL/min. The amount of DEET absorbed through the skin systematically decreased as the airflow increased. For tecnazene, a fungicide, and malathion, an insecticide, a Head space Solid Phase Micro Extraction technique was developed to analyze the receptor fluid following skin penetration experiments. The analysis was done using GC-MS. Absorption rate of tecnazene, was studied following application of 103 µg/cm2 and 864 µg/cm2 under open and occluded conditions. The absorption was much higher under occlusion and the overall recovery was also better for the occluded treatment. Additionally disposition of topically applied 14C – malathion (101, 0.5 and 0.1 µg/cm2) was studied under open and occluded conditions and compared to GC-MS results from 101 µg/cm2. A silicone membrane study was performed with all three doses of 14C – malathion. The model satisfactorily described the absorption of malathion and tecnazene through human skin in vitro. Key parameters that needed modification were kevap (evaporation mass transfer coefficient), Ksc (partition coefficient of the stratum corneum, SC) and Psc (permeability of SC). Future work entails conducting partitioning studies of lipophilic compounds to get better understanding of disposition of such compounds in the lower skin layers. To my Grandparents: Krishnalal Gopalji Bhatt and Sharda K. Bhatt & My parents: Dilip Krishnalal Bhatt and Charu D. Bhatt ACKNOWLEDGEMENT Cincinnati has been home away from home since September 2000. At the end of my graduate life, I would be remiss if I did not express my sincere thanks and gratitude to everyone who helped mould my life at both professional as well as personal level. Firstly, I would like to thank Dr.Kasting, or Dr.K as we fondly call him, for his mentorship, guidance, patience and support throughout my graduate life. I only hope to take on some of his virtues and do justice to his teachings wherever I go. I express my deepest regard for Dr. Wickett who admitted me into the program and from whose anecdotal tales; I’ve learnt not only science, but also ways of life. Collaboration with Dr. Soman came about at a time when options for furthering my research were dim and thanks to his support and guidance, I could see my doctoral work to completion. Dr. Talaska and Dr. Shenouda have been invaluable in both their input and suggestions for my research and I thank them both. I would also like to take this opportunity to thank University of Cincinnati for granting me Graduate Scholarship through out. I would also like to express my gratitude to College of Pharmacy, all professors and administrative staff especially, Marcie Silver, Sue Ryan and Donna Taylor. Along side academics, my involvement with extra curricular activities enriched my living experience at Cincinnati. I express my special thanks to the Office of International Student Services for providing a platform for cross cultural interaction. I will cherish the memories from ISSO events and Cultural Connections for life time! My involvement with Association for India’s Development (AID) and Graduate Association for Pharmaceutical Sciences Students (GAPSS) helped me foster my people skills and will always have a special place in my heart. During my stay at UC, I have come to know some wonderful people with whom I have developed a life long friendship. Among these are Andy, Arjun, Fair, Grettel, Hemali, Leena, Penpan, Rachna, Rucha, Shagun and Tarun. I have been extremely fortunate to have had my closest friend, Namrata, with me from undergraduate to graduate days. I want to thank her and all my friends for the unwavering support and kindness! Others, with whom I interacted with over the course of time at UC, I thank you for the friendship and a sense of belonging, especially the entire group of Cosmetic Sciences. Finally, my family, without their love and direction and faith I would not be here. My Grandparents, parents, uncles, aunts, siblings and extended family have continuously blessed me with good wishes and I cannot thank you enough! All I can say is that I love you all. A special thanks to my sister, Kavita, who was patient with me during the hectic and sometimes chaotic behavior towards the end of the graduate life. Last but not at the very least, I thank the Almighty for showering his kindness and giving me the strength to face challenges in life. TABLE OF CONTENTS Page No. Abstract Acknowledgement Table of Contents 1 List of Tables 2 List of Figures 4 List of Abbreviations 8 List of Symbols 12 Chapter 1 Introduction 13 Chapter 2 Objective 27 Chapter 3 Experimental methodology 29 Chapter 4 Working diffusion model 44 Chapter 5 Dose & airflow dependence of benzyl alcohol disposition on skin 49 Chapter 6 Airflow dependence study of DEET: Results 81 Chapter 7 Absorption of tecnazene through human skin in vitro 97 HS-SPME/GC-MS study Chapter 8 Dermal absorption of malathion in vitro: GC – MS results 127 Chapter 9 Dermal absorption of malathion through human cadaver skin and silastic membrane: Radiochemical results 153 Chapter 10 Summary and future directions 180 Chapter 11 References 184 1 LIST OF TABLES Table 1.1 Literature studies of dermal absorption of pesticides 17 Table 1.2 Physiochemical properties of compounds of interest 26 Table 3.1 Recent SPME pesticide studies 42 Table 5.1 Appearance of radioactivity in the receptor solution for dose- dependence skin disposition study with 14C-benzyl alcohol 63 Table 5.2 Cumulative disposition of radioactivity at 24 h for the study reported in Table 5.1 64 Table 5.3 Regression parameters for diffusion models of benzyl alcohol disposition on skin. 68 Table 5.4 Physical properties and auxiliary skin permeability data for benzyl alcohol 76 Table 5.5 Derived diffusion model parameters for benzyl alcohol. 77 Table 5.6 Percentage absorption of benzyl alcohol after 24 h estimated by three different methods 79 Table 6.1 Physical Properties of DEET 87 Table 6.2 Mean cumulative evaporation of 14C- DEET from human skin in vitro 88 Table 6.3 Mean absorption of 14C- DEET from human skin in vitro 89 Table 6.4 Appearance of radioactivity in the vapor trap for airflow-dependence skin disposition study with 14C- DEET from human skin in vitro 90 Table 6.5 Appearance of radioactivity in the receptor solution for airflow-dependence skin disposition study with 14C- DEET from 2 human skin in vitro 91 Table 6.6 Mass balance of 1% w/w solution of 14C-DEET from human skin in vitro as a percent of dose applied 92 Table 7.1 Figures of merit for tecnazene method development 109 Table 7.2 Correction factors for predicted absorption flux of tecnazene 124 Table 7.3 Mass balance of topically applied tecnazene from human skin in vitro as % applied dose 125 Table 8.1 Figures of merit for malathion method development 133 Table 8.2 Mass balance of topically applied malathion from human skin in vitro as % applied dose 150 Table 9.1 Appearance of radioactivity in the receptor solution: Skin disposition study with 14C-malathion through human skin in vitro 160 Table 9.2 Mass balance of disposition of radioactivity associated with 14C- malathion from human skin in vitro, expressed as the percent of dose applied 162 Table 9.3 Physical properties and input parameters of malathion 170 Table 9.4 Calculated model parameters for malathion absorption through human skin in vitro 171 Table 9.5 Appearance of radioactivity in the receptor solution: Skin disposition study with 14C-malathion through silicone membrane in vitro 172 Table 9.6 Mass balance of disposition of 14C-malathion from silicone membrane in vitro as a percent of dose applied
Load more

Recommended publications
  • Federal Register/Vol. 70, No. 216/Wednesday
    Federal Register / Vol. 70, No. 216 / Wednesday, November 9, 2005 / Notices 68037 OPP–2005–0173. The official public TABLE 2.—REGISTRANT OF AMENDED effective date of the order to terminate docket consists of the documents PRODUCT use. The order issued in this Notice specifically referenced in this action, includes the following existing stocks any public comments received, and EPA Company Company Name and Ad- provisions. other information related to this action. No. dress Products in the United States that have been packaged, labeled, and Although a part of the official docket, 2596 The Hartz Mountain Cor- the public docket does not include released for shipment prior to the poration, 400 Plaza effective date of the order terminating Confidential Business Information (CBI) Drive Secaucus, NJ or other information whose disclosure is 07094–3688 use on cats and kittens may be sold or restricted by statute. The official public distributed by Hartz from its facilities until December 31, 2005. After docket is the collection of materials that III. Summary of Public Comments December 31, 2005, Hartz may not sell is available for public viewing at the Received and Agency Response to or distribute product labeled for use on Public Information and Records Comments cats and kittens. Products labeled for Integrity Branch (PIRIB), Rm. 119, During the public comment period use on cats and kittens may be sold or Crystal Mall #2, 1801 S. Bell St., provided, EPA received no comments in distributed by persons other than the Arlington, VA. This docket facility is response to the July 20, 2005 Federal registrant until March 31, 2006.
    [Show full text]
  • Polydimethylsiloxane Emulsion
    DMS-T31M50 - POLYDIMETHYLSILOXANE EMULSION POLYDIMETHYLSILOXANE EMULSION Safety Data Sheet DMS-T31M50 Date of issue: 04/28/2016 Version: 1.0 SECTION 1: Identification of the substance/mixture and of the company/undertaking 1.1. Product identifier Product form : Mixture Physical state : Liquid Product name : POLYDIMETHYLSILOXANE EMULSION Product code : DMS-T31M50 Synonyms : POLY(DIMETHYLSILOXANE), TRIMETHYLSILOXY TERMINATED, emulsion; SILICONE OIL EMULSION Chemical family : ORGANOSILOXANE 1.2. Relevant identified uses of the substance or mixture and uses advised against Use of the substance/mixture : Chemical intermediate For research and industrial use only 1.3. Details of the supplier of the safety data sheet GELEST, INC. 11 East Steel Road Morrisville, PA 19067 USA T 215-547-1015 - F 215-547-2484 - (M-F): 8:00 AM - 5:30 PM EST [email protected] - www.gelest.com 1.4. Emergency telephone number Emergency number : CHEMTREC: 1-800-424-9300 (USA); +1 703-527-3887 (International) SECTION 2: Hazards identification 2.1. Classification of the substance or mixture GHS-US classification Not classified 2.2. Label elements GHS-US labeling No labeling applicable 2.3. Other hazards No additional information available 2.4. Unknown acute toxicity (GHS US) No data available SECTION 3: Composition/Information on ingredients 3.1. Substance Not applicable 3.2. Mixture Name Product identifier % GHS-US classification Polydimethylsiloxane (CAS No) 9016-00-6/63148-62-9 45 - 50 Not classified Water (CAS No) 7732-18-5 45 - 50 Not classified Polyoxyethylene(20)sorbitan monooleate (CAS No) 9005-65-6 1 - 5 Not classified Sorbitan monolaurate (CAS No) 1338-39-2 1 - 5 Not classified SECTION 4: First aid measures 4.1.
    [Show full text]
  • Synthesis of Functionalized Poly(Dimethylsiloxane)S and the Preparation of Magnetite Nanoparticle Complexes and Dispersions
    Synthesis of Functionalized Poly(dimethylsiloxane)s and the Preparation of Magnetite Nanoparticle Complexes and Dispersions Kristen Wilson O’Brien Dissertation submitted to the Faculty of the Virginia Polytechnic Institute and State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy In Chemistry Approved by: ____________________________ Judy S. Riffle, Chair ____________________________ ____________________________ Alan Esker Jack Lesko ____________________________ ____________________________ Timothy E. Long James E. McGrath August 21, 2003 Blacksburg, Virginia Keywords: Polymers, iron oxides; steric stabilization; magnetic fluids Copyright 2003, Kristen Wilson O’Brien Synthesis of Functionalized Poly(dimethylsiloxane)s and the Preparation of Magnetite Nanoparticle Complexes and Dispersions Kristen Wilson O’Brien (ABSTRACT) Poly(dimethylsiloxane) (PDMS) fluids containing magnetite nanoparticles stabilized with carboxylic acid-functionalized PDMS were prepared. PDMS-magnetite complexes were characterized using transmission electron microscopy, elemental analysis, and vibrating sample magnetometry. PDMS-magnetite complexes containing up to 67 wt% magnetite with magnetizations of ~52 emu gram-1 were prepared. The magnetite particles were 7.4 ± 1.7 nm in diameter. Calculations suggested that the complexes prepared using mercaptosuccinic acid-functionalized PDMS (PDMS-6COOH) complexes contained unbound acid groups whereas the mercaptoacetic acid- functionalized PDMS (PDMS-3COOH) complexes did not.
    [Show full text]
  • (PDMS) Properties for Biomedical Micro/Nanosystems
    Biomedical Microdevices 7:4, 281–293, 2005 C 2005 Springer Science + Business Media, Inc. Manufactured in The Netherlands. Characterization of Polydimethylsiloxane (PDMS) Properties for Biomedical Micro/Nanosystems Alvaro Mata,1,2 Aaron J. Fleischman,2 and Shuvo Roy2,∗ 1Department of Chemical and Biomedical Engineering, Cleveland State University, Cleveland, OH 44115 2BioMEMS Laboratory, Department of Biomedical Engineering, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44120 E-mail: [email protected] Abstract. Polydimethylsiloxane (PDMS SylgardR 184, Dow Corn- search and development of MEMS-based devices in the ing Corporation) pre-polymer was combined with increasing biomedical arena for a variety of applications ranging amounts of cross-linker (5.7, 10.0, 14.3, 21.4, and 42.9 wt.%) and from diagnostics (Fujii, 2002; Mastrangelo et al., 1998; designated PDMS1, PDMS2, PDMS3, PDMS4, and PDMS5,respec- tively. These materials were processed by spin coating and subjected Paranjape et al., 2003; Wu et al., 2001) to therapeutics to common microfabrication, micromachining, and biomedical pro- (Borenstein et al., 2002; Chung et al., 2003; Ferrara et al., cesses: chemical immersion, oxygen plasma treatment, sterilization, 2003; Santini et al., 1999; Tao and Desai, 2003). However, and exposure to tissue culture media. The PDMS formulations were the development of these applications through established analyzed by gravimetry, goniometry, tensile testing, nanoindenta- MEMS manufacturing approaches is hindered by inherent tion, scanning electron microscopy (SEM), Fourier transform in- frared spectroscopy (FTIR), and X-ray photoelectron spectroscopy characteristics of traditional silicon-based processes such (XPS). Spin coating of PDMS was formulation dependent with film as high costs and limited access to clean room environ- thickness ranging from 308 µmonPDMS1 to 171 µmonPDMS5 ments (Roy et al., 2001; Whitesides et al., 2001).
    [Show full text]
  • Chapter 6 Ecological Health
    Integrated Mosquito Management Program │ Programmatic EIR Table of Contents 6 Ecological Health ..........................................................................................................6-1 6.1 Environmental Setting ...................................................................................................... 6-1 6.1.1 Hazards, Toxicity, and Exposure in the Environmental Setting ........................ 6-1 6.1.2 Pesticides and the Environment ....................................................................... 6-3 6.1.3 Regulatory Setting............................................................................................. 6-4 6.2 Environmental Impacts and Mitigation Measures ............................................................ 6-7 6.2.1 Evaluation Concerns and Criteria ..................................................................... 6-7 6.2.2 Evaluation Methods and Assumptions ............................................................ 6-10 6.2.3 Surveillance Alternative .................................................................................. 6-14 6.2.4 Physical Control Alternative ............................................................................ 6-15 6.2.5 Vegetation Management Alternative ............................................................... 6-16 6.2.6 Biological Control Alternative .......................................................................... 6-19 6.2.7 Chemical Control Alternative .........................................................................
    [Show full text]
  • Nufarm Product Guide
    NUFARM PRODUCT GUIDE FOR VEGETABLES HERBICIDES NUFARM ACTIVE Asian Brussels Asparagus Beans Beetroot Broccoli Cabbage Capsicum Carrots Cauliflower Celery Corn Cucurbits Garlic Ginger Lettuce Mushrooms Onions Parsnip Peas Potatoes Radish Rhubarb Shallots Spinach Squash Tomatoes Turnips PRODUCT INGREDIENT Brassicas Sprouts Amitrole 250g/L and Ammonium thiocyanate 220g/L Atrazine 900g/kg Sweet corn Glufosinate- ammonium 200g/L ® S-Metolachlor Sweet Sweet 960g/L corn potatoes Fluroxypyr 400g/L Sweet corn Chlorthal dimethyl Potatoes & sweet 900g/kg potatoes Diuron 900g/kg Sweet SELECTIVE PRE–EMERGENT EPTC 720g/L HERBICIDE corn Glyphosate 450g/L For weed control prior to sowing crop Glyphosate 680g/L For weed control prior to sowing crop Glyphosate 540g/L For weed control prior to sowing crop Clethodim 240g/L Carfentrazone For weed control prior to sowing crop ethyl 600g/L Prometryn 900g/kg Propachlor 480g/L Sweet corn ® Paraquat 135g/L For weed control prior to sowing crop and Diquat 115g/L ® Paraquat 250g/L For weed control prior to sowing crop Simazine 900g/kg Oxyfluorfen 240g/L Metribuzin 750g/kg Trifluralin 480g/L Glyphosate 540g/L For weed control prior to sowing crop Glyphosate 470g/L For weed control prior to sowing crop Glyphosate 360g/L For weed control prior to sowing crop PLANT GROWTH REGULANTS NUFARM ACTIVE Asian Brussels Asparagus Beans Beetroot Broccoli Cabbage Capsicum Carrots Cauliflower Celery Corn Cucurbits Garlic Ginger Lettuce Mushrooms Onions Parsnip Peas Potatoes Radish Rhubarb Shallots Spinach Squash Tomatoes Turnips
    [Show full text]
  • Hollow Polydimethylsiloxane (PDMS) Foam with a 3D Interconnected Network for Highly Sensitive Capacitive Pressure Sensors
    Kim et al. Micro and Nano Syst Lett (2020) 8:24 https://doi.org/10.1186/s40486-020-00127-8 LETTER Open Access Hollow polydimethylsiloxane (PDMS) foam with a 3D interconnected network for highly sensitive capacitive pressure sensors Dong Hwan Kim1, Young Jung1,3, Kyungkuk Jung4, Dong Hwa Kwak1, Dong Min Park1, Myung Gyu Shin2, Hyeong Jun Tak1 and Jong Soo Ko1* Abstract We propose a highly sensitive capacitive pressure sensor made of hollow polydimethylsiloxane (PDMS) foam with a three-dimensional network structure. The stifness of the foam is adjusted by the viscosity of the PDMS solution. The fabricated PDMS-30 (PDMS 30 wt%) foam shows extremely high porosity (> 86%) approximately 19 times that of bare PDMS (PDMS 100 wt%) foam. Capacitive pressure sensors fabricated using the foam possess high sensitivity, good compressibility (up to 80% strain), and consistent output characteristics in a 2000-cycle test. Keywords: Capacitive pressure sensor, Hollow PDMS foam, Porosity Introduction εr and the distance between the electrodes d are the key Over the last decade, fexible pressure sensors for a vari- factors afecting the performance capabilities of sensors ety of wearable applications, such as electronic skin [1], such as those designed to measure pressure responsive human health monitoring [2, 3], and human–machine sensitivity levels [17]. interfaces [4, 5], have received signifcant attention. Many To ensure the fabrication of high-performance capaci- researchers have concentrated on the development of tive pressure sensors, recent studies have reported that various types of fexible and wearable pressure sensors, microstructured or patterned polydimethylsiloxane including piezoresistive [6, 7], capacitive [8–10], piezo- (PDMS) dielectric layers represent the most efective electric [11, 12], and triboelectric types [13, 14].
    [Show full text]
  • Lindane Bioremediation Capability of Bacteria Associated with the Demosponge Hymeniacidon Perlevis
    marine drugs Article Lindane Bioremediation Capability of Bacteria Associated with the Demosponge Hymeniacidon perlevis Stabili Loredana 1,2,*, Pizzolante Graziano 2, Morgante Antonio 2, Nonnis Marzano Carlotta 3,4, Longo Caterina 3,4, Aresta Antonella Maria 5, Zambonin Carlo 5, Corriero Giuseppe 3,4 and Alifano Pietro 2 1 Istituto per l’Ambiente Marino Costiero, Unità Operativa di Supporto di Taranto, CNR, Via Roma 3, 74123 Taranto, Italy 2 Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Via Prov.le Lecce Monteroni, 73100 Lecce, Italy; [email protected] (P.G.); [email protected] (M.A.); [email protected] (A.P.) 3 Dipartimento di Biologia, Università di Bari Aldo Moro, 70125 Bari, Italy; [email protected] (N.M.C.); [email protected] (L.C.); [email protected] (C.G.) 4 CoNISMa, Piazzale Flaminio 9, 00196 Roma, Italy 5 Dipartimento di Chimica, Università di Bari Aldo Moro, 70125 Bari, Italy; [email protected] (A.A.M.); [email protected] (Z.C.) * Correspondence: [email protected]; Tel.: +39-0832-298971 Academic Editors: Vassilios Roussis, Efstathia Ioannou and Keith B. Glaser Received: 23 January 2017; Accepted: 27 March 2017; Published: 6 April 2017 Abstract: Lindane is an organochlorine pesticide belonging to persistent organic pollutants (POPs) that has been widely used to treat agricultural pests. It is of particular concern because of its toxicity, persistence and tendency to bioaccumulate in terrestrial and aquatic ecosystems. In this context, we assessed the role of bacteria associated with the sponge Hymeniacidon perlevis in lindane degradation.
    [Show full text]
  • Oral, Ultra–Long-Lasting Drug Delivery: Application Toward Malaria Elimination Goals
    Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Bellinger, Andrew M. et al. "Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals." 8, 365 (November 2016): 365ra157 © 2016 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. As Published http://dx.doi.org/10.1126/scitranslmed.aag2374 Publisher American Association for the Advancement of Science (AAAS) Version Author's final manuscript Citable link https://hdl.handle.net/1721.1/128845 Terms of Use Creative Commons Attribution-Noncommercial-Share Alike Detailed Terms http://creativecommons.org/licenses/by-nc-sa/4.0/ HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Sci Transl Manuscript Author Med. Author Manuscript Author manuscript; available in PMC 2017 November 16. Published in final edited form as: Sci Transl Med. 2016 November 16; 8(365): 365ra157. doi:10.1126/scitranslmed.aag2374. Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals Andrew M. Bellinger1,2,3,*, Mousa Jafari1,*, Tyler M. Grant1,3,*, Shiyi Zhang1,*,†, Hannah C. Slater4, Edward A. Wenger5, Stacy Mo1, Young-Ah Lucy Lee1, Hormoz Mazdiyasni1, Lawrence Kogan1, Ross Barman1, Cody Cleveland1,6, Lucas Booth1, Taylor Bensel1, Daniel Minahan1, Haley M. Hurowitz1, Tammy Tai1, Johanna Daily7, Boris Nikolic8, Lowell Wood5, Philip A. Eckhoff5, Robert Langer1,9,10,‡, and Giovanni Traverso1,6,11,‡ 1Department of Chemical Engineering and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. 2Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.
    [Show full text]
  • Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act
    Updated June 07, 2021 Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act Three categories of bulk drug substances: • Category 1: Bulk Drug Substances Under Evaluation • Category 2: Bulk Drug Substances that Raise Significant Safety Risks • Category 3: Bulk Drug Substances Nominated Without Adequate Support Updates to Categories of Substances Nominated for the 503B Bulk Drug Substances List1 • Add the following entry to category 2 due to serious safety concerns of mutagenicity, cytotoxicity, and possible carcinogenicity when quinacrine hydrochloride is used for intrauterine administration for non- surgical female sterilization: 2,3 o Quinacrine Hydrochloride for intrauterine administration • Revision to category 1 for clarity: o Modify the entry for “Quinacrine Hydrochloride” to “Quinacrine Hydrochloride (except for intrauterine administration).” • Revision to category 1 to correct a substance name error: o Correct the error in the substance name “DHEA (dehydroepiandosterone)” to “DHEA (dehydroepiandrosterone).” 1 For the purposes of the substance names in the categories, hydrated forms of the substance are included in the scope of the substance name. 2 Quinacrine HCl was previously reviewed in 2016 as part of FDA’s consideration of this bulk drug substance for inclusion on the 503A Bulks List. As part of this review, the Division of Bone, Reproductive and Urologic Products (DBRUP), now the Division of Urology, Obstetrics and Gynecology (DUOG), evaluated the nomination of quinacrine for intrauterine administration for non-surgical female sterilization and recommended that quinacrine should not be included on the 503A Bulks List for this use. This recommendation was based on the lack of information on efficacy comparable to other available methods of female sterilization and serious safety concerns of mutagenicity, cytotoxicity and possible carcinogenicity in use of quinacrine for this indication and route of administration.
    [Show full text]
  • Polydimethylsiloxane Containing Block Copolymers
    POLYDIMETHYLSILOXANE CONTAINING BLOCK COPOLYMERS: SYNTHESIS AND CHARACTERIZATION OF ALTERNATING POLY(ARYLENE ETHER PHOSPHINE OXIDE)-b-SILOXANE AND SEGMENTED NYLON 6,6 –b-SILOXANE COPOLYMERS by W. David Polk Dissertation submitted to the Faculty of the Virginia Polytechnic Institute and State University In partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in Chemistry Dr. James E. McGrath, Chairman Dr.JudyS.Riffle Dr.AllanR.Shultz Dr. John G. Dillard Dr.PaulA.Deck July 2, 2001 Blacksburg, Virginia Keywords: Polydimethylsiloxane, Polyarylene Ether, Phenyl Phosphine Oxide, Polyamide, Nylon 6,6, Block Copolymer, Fire Resistance, Optical Materials, Nanoparticles Copyright 2001, W. David Polk POLY(DIMETHYLSILOXANE) CONTAINING BLOCK COPOLYMERS: SYNTHESIS AND CHARACTERIZATION OF ALTERNATING POLY(ARYLENE ETHER PHOSPHINE OXIDE)-B-SILOXANE AND SEGMENTED NYLON 6,6-B- SILOXANE COPOLYMERS W. David Polk (ABSTRACT) Two novel classes of siloxane containing, organic-inorganic block copolymers were prepared using different synthetic approaches. The first copolymers were alternating poly(arylene ether phosphine oxide)-poly(dimethylsiloxane) systems, prepared via oligomeric silylamine-hydroxyl reactions. Secondly, segmented nylon 6,6- poly(dimethylsiloxane) block copolymers were synthesized via a non-aqueous adaptation of the “nylon 6,6 salt” hydrolytic polyamidization, using bis(aminopropyl) dimethylsiloxane oligomer as a co-reactant. Three series of “perfectly” alternating block copolymers were produced from well characterized hydroxyl-terminated poly(arylene ether phosphine oxide) and dimethylamine-terminated poly(dimethylsiloxane) oligomers, in order to investigate both block length and chemical composition effects. Copolymerization in chlorobenzene resulted in high molecular weight materials capable of forming optically clear, nanophase separated films, which displayed unusual morphologies and good mechanical strength.
    [Show full text]
  • Polydimethylsiloxane-Titania Nanocomposite Coating: Fabrication and Corrosion Resistance
    Polymer 138 (2018) 203e210 Contents lists available at ScienceDirect Polymer journal homepage: www.elsevier.com/locate/polymer Polydimethylsiloxane-titania nanocomposite coating: Fabrication and corrosion resistance Xiaokun Cui a, Guiyu Zhu a, Yufeng Pan a, Qian Shao b, Cindy (xinxin) Zhao c, * ** Mengyao Dong c, d, Yue Zhang a, , Zhanhu Guo c, a Institute of Material Science and Engineering, Ocean University of China, Qingdao, Shandong, 266100 PR China b College of Chemical and Environmental Engineering, Shandong University of Science and Technology, Qingdao 266590, PR China c Integrated Composites Laboratory (ICL), Department of Chemical Engineering, University of Tennessee, Knoxville, TN 37996, USA d National Engineering Research Center for Advanced Polymer Processing Technology, Zhengzhou University, Zhengzhou 450002, PR China article info abstract Article history: Titania (TiO2) nanoparticles were added to polydimethylsiloxane (PDMS) matrix to form nanocomposite Received 9 December 2017 coating via spin coating method on the AA 2024 (one of the aluminum alloys) to improve the anticor- Received in revised form rosion ability of metal. The microstructures of the PDMS/TiO2 composite coating were detected by 11 January 2018 scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectrometry to verify the Accepted 22 January 2018 structure of composite coating. The corrosion properties of PDMS/TiO composite coating was evaluated Available online 3 February 2018 2 by the electrochemical tests. The results showed that the anticorrosion ability of the composite coating has been significantly affected by the TiO2 content. For example, the impedance modulus value reached Keywords: 6 2 10 Ucm of the composite coating with 8 wt % nano-TiO2 fillers. Meanwhile, the corrosion current PDMS/TiO2 Corrosion resistance density (Icorr) of the coating was smaller than that of bare aluminum.
    [Show full text]