Investigations of the Effect of Some Antibacterial Agents on a Bacteriophage

Total Page:16

File Type:pdf, Size:1020Kb

Investigations of the Effect of Some Antibacterial Agents on a Bacteriophage 1. INVESTIGATIONS OF THE EFFECT OF SOME ANTIBACTERIAL AGENTS ON A BACTERIOPHAGE. A THESIS submitted by WILLIAM ROBERT LAING BROWN for the degree of DOCTOR OF PHILOSOPHY in the UNIVERSITY OF LONDON. School of Pharmacy, University of London. April 1962. 2. ABSTRACT. The effects on coliphage T6r of 11 commonly used chemical antibacterial agents have been examined. The effect of the agents on the multiplication of the phage was shown by their effect on the mass lysis of fluid cultures of the host by the phage. Only aminacrine hydrochloride and sodium lauryl sulphate showed significant inhibition of the growth of the phage at concentrations below those inhibiting the host. For the examination of the effect of the agents on free phage particles, a method of assessment giving precise inactivation time estimates has been applied and two methods of interpreting the results have been compared. Large differences have been shown in the effectiveness of different antibacterial agents in inactivating the free phage. The effect on the inactivation time of changes in concentration of the antibacterial agent has been examined for five of the agents and the regression between log inactivation time and log concentration has been shown to be linear. The dilution coefficients for these agents fell into two distinct groups, those for ohioramine T and formaldehyde (about 2 and 3 respectively) being very much smaller than those for crystal violet, cetrimide and phenol (about 11,13 and 15 respectively). It has been postulated that this difference in dilution coefficients indicates different mechanisms of inactivation between the two groups and the possible nature of the mechanisms has been discussed. Methods of cultivation of the phage and its stability under different conditions of storage have been investigated. A method of plaque counting by surface drop plating has been developed and its reproducibility examined. 3. CONTENTS. Title 1 Abstract 2 Contents 3 Acknowledgements 6 PART I. INTRODUCTION Definitions 8 Inhibition of the interaction of phage and host 9 Inactivation of free bacteriophage 13 Assessing the inactivation of free phage 16 Counting methods 16 Extinction methods 17 Phage extinction methods 18 Bacterial extinction methods 20 The viricidal activity of specific antibacterial agents on phage 23 Chlorine compounds 23 Formaldehyde 25 Medicinal dyes 27 Triphenylmethane dyes 27 Acridine derivatives 28 Mercury Compounds 29 Phenol and its derivatives 31 Surface active agents 33 Quaternary ammonium compounds 33 Anionic surface active agents 34 Object of present work 35 4. PART II. EXPERIMENTAL TECHNIQUES AND RESULTS. A. Apparatus 37 1. Dropping pipettes 37 2. Volumetric apparatus 39 3. Automatic tilt measures 39 Miscellaneous containers 40 B. Materials 42 1. Water 42 2. Media 42 3. Antibacterial agents 43 C. The Bacterial Host 46 1. Characters 46 2. Maintenance of cultures 47 3. Stability of characters 47 4.. Viability of cultures 48 D. The Bacteriophage 51 1. Cultural characteristics 51 2. Counting of phage particles 52 3. Preparation of phage stocks 71 4. Storage of phage stocks 79 E. Inhibition of the action of the phage on its host 81 1. The effect of inocula size on the rate of action of the phage on its host. 81 2. The effect of antibacterial agents on the action of the phage on its host 84 3. The effect of size of phage inoculum on the rate of lysis in the presence of antibacterial agents. 90 5. F. Inactivation of free phage by antibacterial agarlia 94 1. Method of evaluation 94 2. Reproducibility of the method 98 3. Estimation of the Mean Single Survivor Time 98 h- Relation of Mean Inactivation Time to Mean Single Survivor Time 110 5. Two factors affecting the reproducibility of the 113 Mean Inactivation Time 6. The systematic examination of the antibacterial agents 116 PART III. DISCUSSION . The Bacteriophage 128 Phage plaque counting method 128 Cultivation of phage 129 Storage of phage 130 Inhibition of the action of the phage on its host 130 Inactivation of free phage 135 The method of evaluation 135 The precision and reproducibility of the method 139 The Mean Single Survivor Time 140 The relation of Mean Inactivation Time to the Mean Single Survivor Time. 141 The systematic examination of the antibacterial agents 1)i2 Phage reactions and other viruses 149 Suggestions for further work. 151 Bibliography. 151_ 6. ACKNOWLEDGEMENTS. I wish to record my gratitude to Dr. A.M. Cook for first suggesting the subject of this thesis and for his helpful and enthusiastic direction of the work presented here. I am also grateful for the technical assistance of Mr. A. Edwards and his staff in preparing the apparatus and materials used. 7. PART I. INTRODUCTION. J. DEFINITIONS. The term antibacterial agent may be used to describe any agent, physical or chemical, which inhibits the growth of or kills bacteria. Heat, sonic vibration, white light, ultraviolet and ionising radiations may all be classed as physical antibacterial agents while the term chemical antibacterial agent may be used to describe those chemicals having a bacteriostatic or bactericidal action and referred to variously as disinfectants, antiseptics and germicides. The investigations which are the subject of this thesis were concerned with examining the effect of chemical antibacterial agents on a baoteriophage and the term "antibacterial agent" will be used throughout the thesis as meaning this type of agent. The agents considered have been further limited to include only those which belong to the classes of compounds commonly used as disinfectants or antiseptics, namely chlorine compounds, formaldehyde, medicinal dyes, mercury compounds, phenol and its derivatives and surface active agents. The antibiotics and other chemotherapeutic agents have been largely excluded. The study of the action of antibacterial agents on bacteriophages has two main aspects. The first is the action of the agents on extracellOrm phages and the second is the interaction of phages and their bacterial hosts in the presence of the agents. The present work has been primarily concerned with the former aspect but any such study must include a consideration of the latter. This arises because the examination of antibacterial agents for possible viricidal activity 90 requires a clear distinction to be made between viristatic and viricidal effects. Tests for virioidal action. must therefore be so designed as to ensure that conditions are provided in which any phage particle surviving exposure to the agent can subsequently multiply, INHIBITION OF THE INTERACTION OF PHAGE AND HOST. Inhibition of the growth of phages by the presence of an antibacterial agent may result from inhibition of the growth of both the bacterial host and the phage. Alternatively, phage production may be arrested by a selective inhibition of phage growth with no effect on the growth of the host. Several surveys have been undertaken in which large numbers of substances have been examined for possible selective phage inhibitory action in the hope that compounds showing this action may have some application in the development of chemotherapeutic agents for viral infections in man. Notable amongst these surveys are those carried out by Asheshov and his co—workers (Hall et al, 1951; Asheshov et al , 1950, Bourke et a] (1252), Boyd and Bradley (1951), Chantrill et al (1952) Dickinson (1948), Graham and Nelson (1954), Mills (1955) and Wooley et a] (1952). From all these surveys the same general picture emerges; that, of thelundreds of compounds tested, the majority inhibit both bacteria and phage and only a very few show any selective phage inhibitory action. Of these the majority have proved to have no application as chemotherapeutic agents against animal viruses. In investigating the mechanism of selective inhibitors of phage growth 10. a wide variety of techniques, some relatively oomplex, are required to show the effect of the inhibitor on all or some stages of miltiplication, A useful, indication of whether or not a compound possesses phage-speoifio inhibitory activity can, however, be obtained by the relatively simple procedure of examining its ability to inhibit visible or mass lysis of a bacterial culture infected with phage. In preliminary screening programmes this effect is conveniently shown on a qualitative basis using phage cultures on solid media the agent under test being localised in the medium by use of the cup-plate and filter-paper disc teohnique (Jones and Schatz, 1946; Ball et a]., 1951; Asheshov et al, 1954). This type of procedure must then be followed by a quantitative determination of the concentration of phage inhibitor whioh will prevent mass lysis in fluid culture of the phage without affecting the growth of the host, the progress of lysis being followed by estimation of the turbidity of the culture. Finally, if the agent shows promise, the detailed examination already referred to may be undertaken using techniques such as the single-step growth curve (F1iis and DelbrUck, 1939; DelbrUckand Luria, 1949) or electronmicrographio and radiochemical examinations. A detailed examination of the mode of aotion of the few selective phage inhibitors known is outside the scope of the present work and the subject has been extensively reviewed by Gots (1959). Two examples of selective phage inhibition are, however, of particklar interest in the investigations to be reported here. The first example is the action of the acridine derivatives. Modern interest in the action of these compounds on phage was stimulated by 11. the demonstration by Fitzgerald and Babbit (1946) that a number of acridines, in sub-bacteriostatic concentrations, inhibited the lysis of Escherichia coli infected with phage. From the large number of reports on the subject subsequently published (cots, 1959),it became clear that - (a)not all acridines had a selective action in inhibiting all phages, (b) aoridines have little effect on free, mature phage00 (c)the inhibitory action of acridines can be reversed by the addition of ribonucleio acid (RNA) or desoxyribonuoleic acid (DNA), (d)the acridines act by blocking the final steps in the maturation of the phage particles.
Recommended publications
  • Comparison of Effectiveness Disinfection of 2%
    ORIGINAL RESEARCH Journal of Dentomaxillofacial Science (J Dentomaxillofac Sci ) December 2018, Volume 3, Number 3: 169-171 P-ISSN.2503-0817, E-ISSN.2503-0825 Comparison of effectiveness disinfection of 2% Original Research glutaraldehyde and 4.8% chloroxylenol on tooth extraction instruments in the Department of Oral CrossMark http://dx.doi.org/10.15562/jdmfs.v3i2.794 Maxillofacial Surgery, Faculty of Dentistry, University of North Sumatera Month: December Ahyar Riza,* Isnandar, Indra B. Siregar, Bernard Volume No.: 3 Abstract Objective: To compare disinfecting effectiveness of 2% glutaraldehyde while the control group was treated with 4.8% chloroxylenol. Each Issue: 2 and 4.8% chloroxylenol on tooth extraction instruments at the instrument was pre-cleaned using a brush, water and soap for both Department of Oral Surgery, Faculty of Dentistry, University of North groups underwent the disinfection process. Sumatera. Results: The results were statistically analyzed using Mann-Whitney Material and Methods: This was an experimental study with post- Test. The comparison between glutaraldehyde and chloroxylenol First page No.: 147 test only control group design approach. Purposive technique is showed a significant difference to the total bacteria count on applied to collect samples which are lower molar extraction forceps. In instrument after disinfection (p=0.014 < 0.05). this study, sample were divided into 2 groups and each consisting of 18 Conclusion: 2% glutaraldehyde was more effective than 4.8% P-ISSN.2503-0817 instruments. The treatment group was treated with 2% glutaraldehyde chloroxylenol at disinfecting lower molar extraction forceps. Keyword: Disinfection, Glutaraldehyde, Chloroxylenol, Forceps E-ISSN.2503-0825 Cite this Article: Riza A, Siregar IB, Isnandar, Bernard.
    [Show full text]
  • Comparative Analysis of Chlorhexidine Gluconate, Povidone Iodine and Chloroxylenol As Scrubbing Solution
    British Journal of Pharmacology and Toxicology 1(2): 93-95, 2010 ISSN: 2044-2467 © Maxwell Scientific Organization, 2010 Submitted date: May 20, 2010 Accepted date: August 21, 2010 Published date: November 15, 2010 Comparative Analysis of Chlorhexidine Gluconate, Povidone Iodine and Chloroxylenol as Scrubbing Solution 1A.S. Yakubu, 1A.A. Abubakar, 2M.D. Salihu, 1A. Jibril and 1I. Isah 1Department of Veterinary Medicine, Surgery and Theriogenology 2Department of Veterinary Public Health and Preventive Medicine, Usmanu Danfodiyo University, Sokoto Abstract: The study was carried out to determine the efficacy of stock concentration of the commonly used disinfectant as scrub solution for surgical site in goats. The evaluation of efficacy and safety of commercially available disinfectant and antiseptic (0.3% Chlorhexidine gluconate, 0.4% Chloroxylenol and 4% Povidone iodine) as scrub solution for surgical site, using stock concentration was assessed in thirty (30) Red Sokoto goats undergoing non elective surgical procedures at Usmanu Danfodiyo University, Veterinary Teaching Hospital and Zonal Veterinary Clinic, Sokoto. Colony counting was used to quantify skin bacteria Colony Forming Unit (CFU) at surgical site before and after skin preparation. Reduction of CFU before and after preparation was significant with all the three disinfectants compared (p<0.05) and the result shows that Povidone iodine and Chloroxylenol to be less effecacious than Chlorhexidine gluconate when mean colony forming unit after two minute of preparing the surgical sites.
    [Show full text]
  • Disinfection of Tonometers a Report by the American Academy of Ophthalmology
    Ophthalmic Technology Assessment Disinfection of Tonometers A Report by the American Academy of Ophthalmology Anna K. Junk, MD,1 Philip P. Chen, MD,2 Shan C. Lin, MD,3 Kouros Nouri-Mahdavi, MD,4 Sunita Radhakrishnan, MD,5 Kuldev Singh, MD, MPH,6 Teresa C. Chen, MD7 Objective: To examine the efficacy of various disinfection methods for reusable tonometer prisms in eye care and to highlight how disinfectants can damage tonometer tips and cause subsequent patient harm. Methods: Literature searches were conducted last in October 2016 in the PubMed and the Cochrane Library databases for original research investigations. Reviews, non-English language articles, nonophthalmology articles, surveys, and case reports were excluded. Results: The searches initially yielded 64 unique citations. After exclusion criteria were applied, 10 labo- ratory studies remained for this review. Nine of the 10 studies used tonometer prisms and 1 used steel discs. The infectious agents covered in this assessment include adenovirus 8 and 19, herpes simplex virus (HSV) 1 and 2, human immunodeficiency virus 1, hepatitis C virus, enterovirus 70, and variant Creutzfeldt-Jakob disease. All 4 studies of adenovirus 8 concluded that after sodium hypochlorite (dilute bleach) disinfection, the virus was undetectable, but only 2 of the 4 studies found that 70% isopropyl alcohol (e.g., alcohol wipes or soaks) eradicated all viable virus. All 3 HSV studies concluded that both sodium hypochlorite and 70% isopropyl alcohol eliminated HSV. Ethanol, 70% isopropyl alcohol, dilute bleach, and mechanical cleaning all lack the ability to remove cellular debris completely, which is necessary to prevent prion transmission. Therefore, single-use tonometer tips or disposable tonometer covers should be considered when treating patients with suspected prion disease.
    [Show full text]
  • Nomination Background: N-(3-Chloroallyl)Hexaminium Chloride
    • NATIONAL TOXICOLOGY PROGRAM EXECUTIVE SUMMARY OF SAFETY AND TOXICITY INFORMATION N-(3-CHLOROALLYL)HEXAMINIUM CHLORIDE CAS Number 4080-31-3 July 16, 1991 Submitted to: NATIONAL TOXICOLOGY PROGRAM Submitted by: Arthur D. Little, Inc. Chemical Evaluation Committee Draft Report • • TABLE OF CONTENTS Page L NOMINATION HISTORY AND REVIEW .................... 1 II. CHEMICAL AND PHYSICAL DATA ....................... 3 III. PRODUCTION/USE ................................... 5 IV. EXPOSURE/REGULATORY STATUS...................... .10 V. TOXICOLOGICAL EFFECTS ........................... .11 VI. STRUCTURE ACTIVITY RELATIONSHIPS ..................48 VII. REFERENCES ..................................... : . ......... 49 APPENDIX I, ON-LINE DATA BASES SEARCHED ............ .53 APPENDIX II, SAFETY INFORMATION.................... .54 1 ,, .• • • OVERVJEWl Nomination History: N-(3-Chloroallyl)hexaminium chloride was originally nominated for carcinogenicity testing by the National Cancer Institute (NCI) in 1980 with moderate priority. In March 1980, the Chemical Evaluation Committee (CEC) recommended carcinogenicity testing. Due to budgetary cutbacks in 1982, this compound was reevaluated and recommended for in vitro cytogenetics and chemical disposition testing by the CEC, and was selected for chemical disposition testing by the Executive Committee. The renomination of this chemical in 1984 by the NCI was based on potentialfor significant human exposure and concern that it may be carcinogenic due to structural considerations. This recent nomination was
    [Show full text]
  • Disinfection and Sterilization
    Disinfection and Sterilization William A. Rutala, Ph.D., M.P.H. University of North Carolina (UNC) Health Care System and UNC at Chapel Hill, NC Disinfection and Sterilization z HICPAC Guideline z Provide overview of disinfection and sterilization principles z Emerging pathogens and prions z Current Research Clostridium difficile Ophthalmic equipment (applanation tonometers) Infrared coagulation Microfiber mops Computer keyboards QUAT absorption Failure to follow disinfection/sterilization principles and patient exposures 1 disinfectionandsterilization.org Disinfection and Sterilization in Healthcare Facilities WA Rutala, DJ Weber, and HICPAC, “In press” z Overview Last CDC guideline in 1985 274 pages (>130 pages preamble, 21 pages recommendations, glossary of terms, tables/figures, >1000 references) Evidence-based guideline Cleared by HICPAC February 2003 Reviewed by OMB Publication in December 2006 2 Efficacy of Disinfection/Sterilization Influencing Factors Cleaning of the object Organic and inorganic load present Type and level of microbial contamination Concentration of and exposure time to disinfectant/sterilant Nature of the object Temperature and relative humidity 3 Disinfection and Sterilization EH Spaulding believed that how an object will be disinfected depended on the object’s intended use. CRITICAL - objects which enter normally sterile tissue or the vascular system or through which blood flows should be sterile. SEMICRITICAL - objects that touch mucous membranes or skin that is not intact require a disinfection process (high-level disinfection [HLD]) that kills all microorganisms but high numbers of bacterial spores. NONCRITICAL -objects that touch only intact skin require low-level disinfection. 4 Processing “Critical” Patient Care Objects Classification: Critical objects enter normally sterile tissue or vascular system, or through which blood flows.
    [Show full text]
  • Disinfectant and Antiseptics Pdf
    Disinfectant and antiseptics pdf Continue Antiseptics and disinfectants are very similar in that they are both used to kill microorganisms. They differ from each other, albeit in the composition of them, as well as their use. Antiseptics are used on living organisms, such as human skin, to kill any microorganisms living on the surface of the body. Disinfectants are used on non-living things such as countertops and handrails to kill microorganisms living on this inanimate surface. Antiseptics tend to have a lower concentration of a particular biocide, which is used in this product to clean the surface than that of a disinfectant. Since disinfectants are not intended for use on living tissues, but rather inanimate surfaces, they can use a higher concentration of biocide in the product, since there is no skin or tissue to worry about irritants. Antiseptics require a lower concentration of biocides, as too high concentrations of some biocides can cause a large amount of skin irritation. Some examples of antiseptics are mouthwash or hand sanitizer, both of which are safe for contact with your skin and also capable of being extremely effective in killing large numbers of microorganisms. Alcohol, bleach and formaldehyde are examples of various types of disinfectants used to kill microorganisms on the surface of any non-living objects. It is important that people know the difference between antiseptics and disinfectants, as they are both used for similar things, but in different ways. The use of disinfectant as an antiseptic is likely to irritate this tissue. In addition, the use of antiseptic as a disinfectant may result in less sufficient work to clean this surface due to the lower concentration of the biocide.
    [Show full text]
  • August 14, 2019 Docket Nos. FDA-1975-N-0012
    DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Silver Spring MD 20993 August 14, 2019 Docket Nos. FDA-1975-N-0012; FDA-2015-N-0101; and FDA-2016-N-0124 American Cleaning Institute Attention: Richard Sedlak Executive Vice President, Technical and International Affairs 1331 L Street, NW, Suite 650 Washington, DC 20005 Re: Benzalkonium Chloride, Benzethonium Chloride, Chloroxylenol, Ethanol, and Povidone- Iodine Dear Mr. Sedlak: This letter responds to American Cleaning Institute’s (ACI’s) March 12, 2019 request: (1) for a renewal of the extension of the deferral from final rulemaking under the OTC Drug Review on benzalkonium chloride, benzethonium chloride, chloroxylenol, ethanol, and povidone-iodine for use in nonprescription (often referred to as over-the-counter or OTC) consumer antiseptic wash, health care antiseptic, and consumer antiseptic rub drug products. In March 2016, FDA issued letters granting requests to defer three active ingredients—benzalkonium chloride, benzethonium chloride, and chloroxylenol—from inclusion in the final rulemaking for the December 2013 proposed rule for OTC consumer antiseptic washes (78 FR 76444). Similarly, in January 2017, FDA issued letters granting requests to defer six active ingredients—benzalkonium chloride, benzethonium chloride, chloroxylenol, ethanol, povidone-iodine, and isopropyl alcohol—from inclusion in the final rulemaking for the May 2015 proposed rule for OTC health care antiseptics (80 FR 25166). In October 2017, FDA issued letters granting requests to defer three
    [Show full text]
  • Environmental Health Criteria 242
    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY Environmental Health Criteria 242 DERMAL EXPOSURE IOMC INTER-ORGANIZATION PROGRAMME FOR THE SOUND MANAGEMENT OF CHEMICALS A cooperative agreement among FAO, ILO, UNDP, UNEP, UNIDO, UNITAR, WHO, World Bank and OECD This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the World Health Organization The International Programme on Chemical Safety (IPCS) was established in 1980. The overall objec- tives of the IPCS are to establish the scientific basis for assessment of the risk to human health and the environment from exposure to chemicals, through international peer review processes, as a prerequi- site for the promotion of chemical safety, and to provide technical assistance in strengthening national capacities for the sound management of chemicals. This publication was developed in the IOMC context. The contents do not necessarily reflect the views or stated policies of individual IOMC Participating Organizations. The Inter-Organization Programme for the Sound Management of Chemicals (IOMC) was established in 1995 following recommendations made by the 1992 UN Conference on Environment and Development to strengthen cooperation and increase international coordination in the field of chemical safety. The Participating Organizations are: FAO, ILO, UNDP, UNEP, UNIDO, UNITAR, WHO, World Bank and OECD. The purpose of the IOMC is to promote coordination of the policies and activities pursued by the Participating Organizations, jointly or separately, to achieve the sound management of chemicals in relation to human health and the environment. WHO Library Cataloguing-in-Publication Data Dermal exposure. (Environmental health criteria ; 242) 1.Hazardous Substances - poisoning.
    [Show full text]
  • Assessment of the Antibiotic Resistance Effects of Biocides
    Scientific Committee on Emerging and Newly Identified Health Risks SCENIHR Assessment of the Antibiotic Resistance Effects of Biocides The SCENIHR adopted this opinion at the 28th plenary on 19 January 2009 after public consultation. 1 Antibiotic Resistance Effects of Biocides About the Scientific Committees Three independent non-food Scientific Committees provide the Commission with the scientific advice it needs when preparing policy and proposals relating to consumer safety, public health and the environment. The Committees also draw the Commission's attention to the new or emerging problems which may pose an actual or potential threat. They are: the Scientific Committee on Consumer Products (SCCP), the Scientific Committee on Health and Environmental Risks (SCHER) and the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR), and are made up of external experts. In addition, the Commission relies upon the work of the European Food Safety Authority (EFSA), the European Medicines Evaluation Agency (EMEA), the European Centre for Disease prevention and Control (ECDC) and the European Chemicals Agency (ECHA). SCENIHR Questions concerning emerging or newly-identified risks and on broad, complex or multi- disciplinary issues requiring a comprehensive assessment of risks to consumer safety or public health and related issues not covered by other Community risk-assessment bodies. In particular, the Committee addresses questions related to potential risks associated with interaction of risk factors, synergic effects, cumulative effects, antimicrobial resistance, new technologies such as nanotechnologies, medical devices, tissue engineering, blood products, fertility reduction, cancer of endocrine organs, physical hazards such as noise and electromagnetic fields and methodologies for assessing new risks.
    [Show full text]
  • Antiseptics and Disinfectants: Activity, Action, and Resistance
    CLINICAL MICROBIOLOGY REVIEWS, Jan. 1999, p. 147–179 Vol. 12, No. 1 0893-8512/99/$04.0010 Copyright © 1999, American Society for Microbiology. All Rights Reserved. Antiseptics and Disinfectants: Activity, Action, and Resistance 1 2 GERALD MCDONNELL * AND A. DENVER RUSSELL STERIS Corporation, St. Louis Operations, St. Louis, Missouri 63166,1 and Welsh School of Pharmacy, Cardiff University, Cardiff CF1 3XF, United Kingdom2 INTRODUCTION .......................................................................................................................................................148 DEFINITIONS ............................................................................................................................................................148 MECHANISMS OF ACTION ...................................................................................................................................148 Introduction.............................................................................................................................................................148 General Methodology .............................................................................................................................................148 Alcohols ....................................................................................................................................................................151 Aldehydes .................................................................................................................................................................151
    [Show full text]
  • Chloroxylenol UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C
    United States Prevention, Pesticides EPA 738-R-94-032 Environmental Protection And Toxic Substances September 1994 Agency (7508W) Reregistration Eligibility Decision (RED) Chloroxylenol UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES CERTIFIED MAIL Dear Registrant: I am pleased to announce that the Environmental Protection Agency has completed its reregistration eligibility review and decisions on the pesticide chemical case chloroxylenol which includes the active ingredients chloroxylenol. The enclosed Reregistration Eligibility Decision (RED) contains the Agency's evaluation of the data base of these chemicals, its conclusions of the potential human health and environmental risks of the current product uses, and its decisions and conditions under which these uses and products will be eligible for reregistration. The RED includes the data and labeling requirements for products for reregistration. To assist you with a proper response, read the enclosed document entitled "Summary of Instructions for Responding to the RED". This summary also refers to other enclosed documents which include further instructions. You must follow all instructions and submit complete and timely responses. The first set of required responses are due 90 days from the date of this letter. The second set of required responses are due 8 months from the date of this letter. Complete and timely responses will avoid the Agency taking the enforcement action of suspension against your products. If you have questions on the product specific data requirements or wish to meet with the Agency, please contact the Special Review and Reregistration Division representative Yvonne Brown at (703) 308-8073. Sincerely yours, Peter Caulkins, Acting Director Special Review and Reregistration Division Enclosures SUMMARY OF INSTRUCTIONS FOR RESPONDING TO THE REREGISTRATION ELIGIBILITY DECISION (RED) 1.
    [Show full text]
  • 60474 Federal Register/Vol. 82, No. 243/Wednesday, December 20
    60474 Federal Register / Vol. 82, No. 243 / Wednesday, December 20, 2017 / Rules and Regulations DEPARTMENT OF HEALTH AND SUPPLEMENTARY INFORMATION: ingredients are benzalkonium chloride, benzethonium chloride, chloroxylenol, HUMAN SERVICES Table of Contents alcohol (also referred to as ethanol or Food and Drug Administration I. Executive Summary ethyl alcohol), isopropyl alcohol, and A. Purpose of the Final Rule povidone-iodine. Accordingly, FDA 21 CFR Part 310 B. Summary of the Major Provisions of the does not make a GRAS/GRAE Final Rule determination in this final rule for these [Docket No. FDA–2015–N–0101] C. Costs and Benefits six active ingredients for use as OTC RIN 0910–AH40 II. Table of Abbreviations and Acronyms health care antiseptics. The monograph Commonly Used in This Document or nonmonograph status of these six Safety and Effectiveness of Health III. Introduction A. Terminology Used in the OTC Drug ingredients will be addressed, either Care Antiseptics; Topical Antimicrobial Review Regulations after completion and analysis of ongoing Drug Products for Over-the-Counter B. Topical Antiseptics studies to address the safety and Human Use C. This Final Rule Covers Only Health Care effectiveness data gaps of these Antiseptics ingredients or at a later date, if these AGENCY: Food and Drug Administration, IV. Background studies are not completed. HHS. A. Significant Rulemakings Relevant to This rulemaking finalizes the ACTION: Final rule. This Final Rule nonmonograph status of the remaining B. Public Meetings Relevant to This Final 24 active ingredients intended for use in SUMMARY: The Food and Drug Rule health care antiseptics identified in the Administration (FDA, the Agency, or C.
    [Show full text]