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i n(ik.<_ii uuiue tvsj, u ST0852892 HANDBOOK of ORGANIC INDUSTRIAL SOLVENTS Second Edition NATIONAL ASSOCIATION OF MUTUAL CASUALTY COMPANIES 20 N. WACKER DRIVE CHICAGO 6, IU. ST 0852893 Copyright 1961 by National Association of Mutual Casualty Companies ST 0852894 FORfWORD This publication was developed by the Industrial Hygiene Subcommittee of the National Association of Mutual Casualty Companies. Its need was suggested by the continued rapid development of new solvents, their increasing prominence in industrial operations, and the attendant health hazards. Since the safety engineer is usually one of the first to encounter the exposure, this Handbook has been pre pared primarily for his use. To assist the safety engineer in his analysis of these problems, the fundamentals of solvent exposure hazards and their control were considered. A list of the common solvents was compiled, along with pertinent data needed in evaluating hazards. In addition, a list of the effects of these solvents on humans is included. From these data the safety engineer can make his own general evaluations of potential solvent hazards, and from such evaluations he selects those exposures which should then be referred for further study. This Handbook is a compilation of the already existing data, except for the Evapor ation Rates which were determined as a part of a research project sponsored by the Association. The footnotes in the Table of Solvent Properties pertaining to the effects of solvents on humans are interpretations of published information. The first edition of the Handbook was published in 1958. This second edition is a revision of the text, and it also contains additional solvent data. I ST0852895 ACKNOWLEDGMENTS The National Association of Mutual Casualty Companies acknowledges the as sistance of the Industrial Hygiene Subcommittee, whose members gave freely of their time, knowledge, and experience in the development of this Handbook. They are: F. Freeland Chew, Senior Industrial Hygienist, Liberty Mutual Insurance Company, Chicago, Illinois James Lake, Manager, Industrial Hygiene Department, Michigan Mutual Liability Company, Detroit, Michigan E. G. Meiter, Ph.D., Director, Industrial Hygiene Division, Employers Mutuals of Wausau, Milwaukee, Wisconsin J. B. Shaw, Sr., Manager, Research Engineering Department, Utica Mutual Insurance Company, Utica, New York (deceased) J. B. Skinner, Chief, Industrial Hygiene Section, American Mutual Liability Insurance Company, Wakefield, Massachusetts H. T. Walworth, Director, Industrial Hygiene Division, Lumbermens Mutual Casualty Company, Chicago, Illinois F. H. Deeg, Committee Secretary, National Association of Mutual Casualty Companies, Chicago, Illinois The National Association of Mutual Casualty Companies also gratefully acknowl edges the assistance of: Lynn D. Wilson, Ph.D., Wilson Industrial Hygiene and Research Laboratories, Chicago, Illinois, who, through his literature research, and also by his determi nation of Evaporation Rates included in the Table of Solvent Properties, has coptributed both new and useful information. Warren A. Cook, Professor, Industrial Health and Hygiene, School of Public Health, University of Michigan, Ann Arbor, Michigan, for his comments on the physiological and toxicological effects of the solvents. J. A. Houghton, Supervisor, Industrial Chemical Service, Liberty Mutual Insurance Company, Hopkinton, Mass, for his contributions in gathering data and in the development of material for the first edition, most of which continues to be included. Ill CONTINTS ST0852896 FOREWORD ................................................................................................................ I ACKNOWLEDGMENTS........................................................................................... HI INTRODUCTION Solvents and Their Importance ...........................................................................1 The Handbook and Its Purpose ........................................................................... 1 SOLVENTS AND THEIR CHARACTERISTICS Solvent Properties ..................................................................................................3 Boiling Point Flash Point Explosive Limits Evaporation Rate Specific Gravity Vapor Volume Threshold Limit Values Chemical Classification.......................................................................................... 6 Solvent Action ..................................................................................................... 6 Chemical Stability and Reactivity ....................................................................... 6 Solvent Mixtures ..................................................................................................7 POTENTIAL HAZARDS Health .....................................................................................................................9 Dermatitis ............................................................................................................. 9 Fire and Explosion .............................................................................................. 10 EVALUATION OF SOLVENT EXPOSURES Estimating Degree of Health Hazard ................................................................11 Estimating Exhaust Ventilation Required to Control Explosion Hazard........... 12 CONTROL OF SOLVENT EXPOSURES GENERAL CONTROL METHODS ................................................................................15 Employee Education .................................................................................................15 Labeling ................................................................................................................. 15 Personal Protective Equipment...................................................................................15 Respiratory Protection.......................................................................................16 Protective Clothing .......................................................................................... 16 Eye Protection .................................................................................................16 Protective Creams..............................................................................................17 Housekeeping........................................................................................................... 17 ENGINEERING CONTROLS.......................................................................................... 17 Substitution.............................................................................................................. 17 Process or Equipment Enclosure................................................................................ 17 Ventilation .............................................................................................................. 17 Local Exhaust Ventilation................................................................................... 17 General or Dilution Ventilation......................................................................... 18 Make-Up Air.................................................................................................... 18 Elimination of Sources of Ignition.............................................................................18 Flame ............... 18 Static Electricity.................................................................................................18 Heat..................................................................................................................18 Electric Spark.................................................................................................... 18 V Use of Inert Gas ST 0852897 SOLVENT CONTROL CHECK LIST ........................................................................... 19 Large Volume User Suggested Check List Small Volume User Suggested Check List HEALTH PROGRAMS .......................................................................................... 21 EXPLANATION OF TABLE OF SOLVENT PROPERTIES .......................................... 23 TABLE OF SOLVENT PROPERTIES ............................................................................. 27 SYNONYM INDEX.........................................................................................................65 GLOSSARY..................................................................................................................... 71 REFERENCES References Cited in Text ......................................................................................... 72 General References ................................................................................................ 73 MEMBER COMPANIES ST 0852898 NATIONAL ASSOCIATION OF MUTUAL CASUALTY COMPANIES American Hardware Mutual Insurance Company P. O. Box 435, Minneapolis 40, Minnesota American Mutual Liability Insurance Company Wakefield, Massachusetts Automobile Mutual Insurance Company of America 10 Weybosset Street, Providence 1, Rhode Island Bakers Mutual Insurance Company of New York 75 Maiden Lane, New York 38, New York Central Mutual Insurance Company 800 South Washington Street, Van Wert, Ohio Chicago Ice Producers Mutual Liability Company B S. Dearborn --Room 711, Chicago 3, Illinois Employers Mutual Liability Insurance Company 407 Grant Street, Wausau, Wisconsin Exchange Mutual Insurance Company 741 Delaware Avenue, Buffalo 9, New York Factory Mutual Liability Insurance Company of America 1 0 Weybosset Street, Providence 1, Rhode Island Federated Mutual Implement and Hardware Insurance Co. 1 29 East Broadway, Owatonna, Minnesota Hardware Mutual Casualty Company 200 Strongs Avenue, Stevens Point, Wis consin Indiana Lumbermens Mutual Insurance Company 429 N. Pennsylvania Street, Indianapolis 9, Indiana Interboro Mutual Indemnity Insurance Company 270 Madison Avenue, New York 16, New York Iowa National Mutual insurance Company 518 Second Avenue, S. E., Cedar Rapids, Iowa Jamestown Mutual Insurance Company 110 East Fourth Street, Jamestown, New York Liberty Mutual Fire Insurance Company 175 Berkeley Street, Boston 17, Massachusetts Liberty Mutual Insurance Company 1 75 Berkeley Street, Boston 1 7, Massachusetts Lumbermens Mutual Casualty Company 4750 Sheridan Road, Chicago 40, Illinois The Lumbermens Mutual Insurance Company P. O. Box 459, Mansfield, Ohio Michigan Mutual Liability Company 2B West Adams Avenue, Detroit 26, Mich igan Mill Owners Mutual Insurance Company 2015 Grand Avenue, Des Moines 12, Iowa The Millers Mutual Fire Insurance Company of Texas 900 Monroe Street, Fort Worth 2, Texas Millers Mutual Insurance Association of Illinois 320 Easton Street, Alton, Illinois Security Mutual Casualty Company 309 West Jackson Boulevard, Chicago 6, Illinois Texas Employers' Insurance Association 423 South Akard Street, Dallas 1, Texas United States Mutual Liability Insurance Com pany 1400 Hancock Street, Quincy 69, Massachu setts Utica Mutual Insurance Company Utica, New York Utilities Mutual Insurance Company 291 Broadway, New York 7, New York The National Association of Mutual Casualty Companies is an organization of twentyeight of the nation's principal mutual casualty insurance companies. The oldest was founded in 1887, and was the first company organized in the United States to write liability insurance. These companies hold membership in the association because they are established and acknowledged leaders in the casualty insurance field. They write about half of all premiums written by mutual casualty insurance companies in this country, and are an especially im portant factor in the field of workmen's compensation insurance. In their many years of service to industry and to individuals, these companies have seen the mutual insurance principle-THAT PREVENTION OF LOSS IS BASIC IN THE EF FECTIVE ORGANIZATION OF INSURANCE PROTECTION - cease to be regarded as a novelty and come to prevail throughout America. Ever since its organization in 1917, a principal concern of the National Association of Mu tual Casualty Companies has been the improvement of loss prevention by every available means. This has meant close and helpful cooperation with other organizations concerned with such problems, and it has meant continuing emphasis upon research and application of sound safety engineering principles to the activities of the policyholders of the member mutual casualty insurance companies. The effects of this promotion of safety long since have spread beyond the circle of mutual insurance policyholders to benefit the public generally, and every effort is made to insure that they will continue to do so. ST 0852899 THE SCIENTIFIC BASIS OF TOXICITY ASSESSMENT Proceedings of the Symposium on The Scientific Basis of Toxicity Assessment held in Gatlinburg, Tennessee, U.S.A., 15-19 April, 1979. Editor HANSPETER R. WITSCHI 1980 ELSEVIER/NORTH-HOLLAND BIOMEDICAL PRESS AMSTERDAM *NEW YORK OXFORD ST0852900 1980 Elsevier/North-Holland Biomedical Press All rights reserved. No part of this publication maybe reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the copyright owner. ISBN for this volume: 0-444-80200-2 ISBN for the series: 0-444-80013-1 Published by: Elsevier/North-Holland Biomedical Press 335 Jan van Galenstraat, P.O. Box 211 Amsterdam, The Netherlands Sole distributors for the USA and Canada: Elsevier North-Holland Inc. 52 Vanderbilt Avenue New York, N.Y. 10017 Library of Congress Cataloging in Publication Data Syngjosium on the Scientific Basis of ToxicityAssessment, Gatlinburg, Tenn., 1979. The scientific basis of toxicity assessment. (Developments in toxicology and environmental science ; v. 6) Includes bibliographies and indexes. .1. Toxicity testing--Congresses. 2. ToxicologyCongresses. I. Witschi, Hanspeter. II. Title. III. Series. RA1199.S95 1979 615.9'05 ISBN 0-1*444-80200-2 79-28108 Printed in The Netherlands STO85290I PREFACE For more than 30 years the Biology Division of the Oak Ridge National Laboratory has sponsored an annual spring conference. Each of these symposia has covered an area In which significant and exciting new research was being done and which promised that even more knowledge of fundamental biological processes would be developed In the near future. In April 1979 the theme of the conference was "The Scientific Basis of Toxicity Assessment." During the last few years, the science of toxicology has received much attention. There Is an ever growing awareness that toxic hazards In our dally environment may be a threat to our well-being It Is the goal of toxicology, as a predictive science, to understand such hazards. Only then will we be able to deal successfully with both the real and the Imaginary hazards we face today and in all likelihood will continue to face in the future If we hope to maintain and to improve the quality of life. Research in toxicology will never guarantee us absolute safety. However, sound and responsible toxicology will help to make intelligent decisions and will assist us in weighing risks against benefits in the assessment of our increasingly complex chemical environment. In order for toxicology to be a truly predictive science, we need to explore and to understand how chemicals affect the structural and functional integrity of living organisms. Knowledge has to be acquired at each level of biological organization and the powerful tools of modern research must be fully exploited. The scope of the present meeting was deliberately a broad one. t The problems and issues in toxicology were defined first. A discussion followed which explored new avenues on how to detect and how to predict untoward interactions of chemicals with living systems. The pathways of chemicals through the environment, within animals and single cells, and their interaction with critical target molecules were described with vi ST0852902 selected examples, and the role of metabolism of foreign compounds In producing toxicity was explored. Of equal Importance was to learn how the organism reacts toward a chemical Insult. Finally, three most basic questions were discussed: how do we best use the Information we generate In experiments with animals to predict hazard for man, what can toxicology learn from the closely related discipline of radiation biology, and where has the basic approach to toxicological problems met with success. The papers In this volume hopefully will give us some Indication how close we have come to our goals and will help to Identify directions of future research. At this point It Is a pleasure to thank all my colleagues who helped to plan this meeting: Dr. Robert A. Neal, Vanderbilt University, Nashville; Dr. J. E. Gibson, Chemical Industry Institute of Toxicology, Research Triangle Park; Drs. S. I. Auerbach and C. W. Gehrs, Environmental Sciences Division, ORNL, and, from the Biology Division, Drs. R. J. M. Fry, R. F. Kimball, S. Mltra, J. K. Selkirk and T. J. Slaga. The success of even the best planned meeting depends upon enthusiastic speakers and a receptive audience; we were fortunate to have both. Particular thanks go to the then Director of the Biology Division, Dr. J. B. Storer, and to the Associate Director for Biomedical Sciences of ORNL, Dr. C. E. Richmond, for their continuing support. The meeting was sponsored by the Biology Division of the Oak Ridge National Laboratory (operated by the Union Carbide Corporation for the Department of Energy). Travel for speakers and chairpersons was supported .by a grant from the National Institute of Environmental Health Sciences. Finally, I would like to acknowledge the most competent and unfailingly enthusiastic help of Mrs. Mary Jane Loop, without whose experience and cheerfulness the meeting never would have gone as smoothly as it did. Hanspeter Witschl ST0852903 vii CONTENTS Preface Opening Remarks C.R. Richmond THE PROBLEMS AND ISSUES IN TOXICOLOGY Introduction M.S.Rose Problems and issues In toxicology R.G. Tardlff Toxic substances in retrospect and prospect R.l. Krieger Environmental toxicology: Issues, problems, and challenges S.l. Auerbach and C.W. Gehrs V 1 7 9 '5 23 NEW OUTLOOKS AND APPROACHES TO TESTING Introduction V.K. Rowe The appropriate use of genetic toxicology in industry J.L. Epler, W. Winton,A.A. Hardigree and F.W. Larimer Assays for in vitro carcinogenesis, initiation, and promotion C. Heidelberger Implications of the mechanisms of tumorigenicity for risk assessment P.G. Watanabe, R.H. Reitz, A.M. Schumann, M.J. McKenna, J.F. Quast, and P.J. Gehring Behavioral toxicology: A critical appraisal S. Norton A3 1*5 61 69 91 WHAT MAKES A CHEMICAL A THREAT TO HEALTH Introduction J.E. Gibson Critical pathways of polycyclic aromatic hydrocarbons in aquatic environments S.E. Herbes, G.R. Southworth,D.L.Shaeffer, W.H. Griest and M.P. Maskarinec Metabolic activation of carcinogens: An error in detoxification J.K. Selkirk, M.C. MacLeod and G.M. Cohen Metabolic activation of toxins in extrahepatic target organs and target ce 11 s M.R. Boyd, A.R. Buckpitt, R.B. Jones, C.N. Statham, J.S. Dutcher and N.S, Longo 111 113 129 vlH -ST0852904 The Interaction of platinum compounds with the genome: Correlation between DMA binding and biological effects R.O. Rahn, N.P. Johnson, A.W. Hsie, J.F. Lemontt, W.E. Masker, J.D. Regan, W.C. Dunn, Jr.,J.O.Hoeschele and D.H.Brown 153 MECHANISMS IN ORGAN AND TISSUE DAMAGE IntroductIon H.P. Vitschi Myocardial toxicity E.W. Van Stee Role of metabolism in hexacarbon neuropathy G.D. DiVincenzo,W.J. Krasavage and J.L.O'Donoghue Molecular mechanisms of toxic cell death J.L. Farber U1trastructural morphometric/biochemical assessment of cellular toxicity B.A. Fowler CHEMICAL STRUCTURE, METABOLIC PATHWAYS AND TOXICITY 165 167 183 201 211 Introduction R.C. Shank 2,3.7,8-tetrachlorodibenzo-p-dioxin: Studies on the mechanism of action A. Poland and E. Glover Metabolism and mechanisms of toxicity of compounds containing thiono-sulfur R.A. Neal The metabolism of xenobiotics: A study in biochemical evolution C.F. Wilkinson 221 223 24l 251 TOXICOLOGY AS A PREDICTIVE SCIENCE - THE FUTURE Introduction S. Norton The use of quanta I response data to make predictions J. Van Ryzin and K. Rai Radiation toxicology; Carcinogenesis R.J.M. Fry, J.B. Storer and R.L. Ullrich 271 273 291 Tf^e need to understand mechanisms W.N. Aldridge Concluding remarks W.N. Aldridge Author index Subject index 305 321 323 325 C 1990 Elsesler/North-Holland Biomedical Press The Scientific Basis of Toxicity Assessment H. WitscHi. editor. ST08529Qj5 NEW OUTLOOKS AND APPROACHES TO TESTING: INTRODUCTION V. K. ROWE Toxicological Issues, Health and Environmental Research, Dow Chemical U.S. A., Midland, Michigan 48640 The theme of this section of the symposium on "The Scientific Basis of Toxicity Assessment" is entitled "New Outlooks and Approaches to Testing." This title is one which always has been and always will be in tune with the times. Researchers are always searching for new, better and quicker ways to solve their problems. Through the years the techniques and approaches to toxicology testing and safety evaluations have continuously improved and will continue to improve. Many of the test procedures used in the past are viewed as crude and inadequate by today's standards and yet they provided much basic information useful today. It should be emphasized that merely because a test is old does not necessarily mean that it was the source of incorrect data. More likely the problem was not with the data but with the inadequacy of its interpretation, past and present. Many of the newer test procedures and concepts are merely refinements and extensions of proven older procedures made possible by technological advances such as have occurred in analytical chemistry. There is no doubt that the techniques viewed as sophisticated today will be commonplace in two or three years and some will be replaced with better ones in the next few years. The rate at which new and better approaches to testing will be devised and validated will be commensurate with the need and our ability to unravel the mysteries of biological systems. There is no question that there is a serious need for technology to rapidly test chemicals and mixtures of chemicals for their potential to cause serious adverse effects such as cancer, genetic aberrations and behavioral or neurological changes in human beings. A multitude of investigators are responding to these needs. Researchers have been studying the response of many ingenious biological systems to various types of chemicals in an effort to find a test or a battery of tests that will yield data in a short time from which reliable predictions can be made as to long term effects of a test material. Others are attempting to refine old techniques, develop new tests and describe the limitations of various animal models for detecting and measuring the capacity of materials to alter behavior and to determine by what mechanism the alterations occur. 44 ST0852906 Considerable effort is now being expended to elucidate the biochemical mechanisms through which chemical carcinogenesis develops. There is good reason to believe that differences between species and strains in susceptibility to particular chemicals may be attributable to differences in inherent biochemical capabilities. Mott certainly a better understanding of such basic mechanisms whether in monocellular organisms, tissue cultures or whole animals, will permit a far better interpretation of data from the various models and its extrapolation to the human being. The following four papers by recognized authorities in their fields present a comprehen sive review and evaluation of the state-of-the-art in several categories of testing. This insight should be very valuable not only to researchers in the particular fields but also to those in related fields of research, to administrators, to product planners and to regulators involved with safety evaluations.