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ST 0852285 INDUSTRIAL TOXICOLOGY LAWRENCE T. FAIRHALL Scientirt Director, Public Health Service, Federal Security Agency, Chief, Induetrial Hygiene Laboratory, Indvetrial Hygiene Divieion. * 111^ BALTIMORE THE WILLIAMS & WILKINS COMPANY 1949 ST0852286 f/7/ QsOjO' m Lob, COPTBIQHT 1940 The Williams & Wilkins Company Made in the United States of America COKVOUD AX PjUSTBD AT TB WAVEELY PRESS, INC. FOB Tu William A Wiluib Comfant Mt'mim Ud., IT. 8. A. ST0852281 PREFACE This book has been written in response to many requests for information concerning the toxicity of new, as well as old, substances of industrial im portance. Its purpose is to serve as a bridge between the rapidly expanding fialrf cf toxicological investigation and the application of this knowledge of industrial poisons by the industrial hygienist. Many of the substances described are not poisons in the usual sense. Indeed, same are not toxic at all. These represent materials newly used in industry, however, and concerning which some doubt has existed. The industrial hygienist is occasionally compelled to search through may peri odicals and specialised books to acquaint himself with the current knowl edge concerning these substances. All too frequently the toxic effects of a substance are presented in case reports, which are often confusing and de tailed, and require careful study in order to define its toxicity. In the present manual this material has been surveyed and summarized with the object of relieving the industrial hygienist of much of thiB burden. Al though this has required the examination of the available literature regard ing each substance, only selected and pertinent bibliographical references are given, with such appraisal and interpretation as would serve to give the industrial hygienist an evaluation of toxicity without his having to digest a great mass of literature, or to seek out many obscure and difficultly obtain able publications. A short list of the more pertinent references is given at the end of each substance discussed. The references either relate directly to the subject matter, or are felt to be of general interest to the reader. No attempt whatsoever was made to append a complete bibliography--to do so would only expand the book without adding significantly to its value. It will be apparent that whatever merit this book may possess is due to the vast fund of information which the many researchers in this field have contributed during the last two or three decades. The author's task has been to examine and compare these investigations and to assess them criti cally so that the gist of current thought is presented for the toxicological evaluation of a given substance. The form in which the material is presented was arrived at after much consideration. It is largely based upon the needs of the industrial hy gienist and is as brief as was felt consistent with his requirements. Some disparity of space will be found in that certain substances whose toxicity is well recognized are treated in more summary fashion, in comparison with those substances of obscure toxicity or substances which currently are of great importance, which are discussed in more detail. The purpose in presenting the characteristics of the various substances v ST 0852288 Vi PREFACE under consideration is related to more than mere identification. The phys iological response to many substances depends to some extent upon their physical and chemical characteristics, such as volatility, solubility, solvent action, and stability. A knowledge of the outstanding characteristics of a substance is therefore often useful in defining a given occupational haaard. The chemical and physical constants are based upon the best information available for the pure substance and several may differ somewhat from those found in the usual tables. In all cases the most authentic values have been Bought for these constants. They are of course particularly useful to the chemist in the examination of materials. Under the section on industrial uses, an attempt has been made to gather from governmental and other sources such material as would indicate the extent of production and use. In many cases this will give a rough idea of the extent to which exposure may occur in industry. Because of the diversity of the substances discussed, no attempt has been made to classify these substances in groups based upon either chemical re semblance or similarity of physiological response. Furthermore, it was felt that a ample alphabetical arrangement would facilitate reference. For further simplicity, the substances are broken down into two main groups--inorganic substances and the carbon compounds. It has not been the author's intention to give detailed analytical instruc tion with reference to the various substances described in the following pages. Under the heading of analysis, reference is made to standard methods or to recently proposed methods. In a number of cases where no present method of analysis is available, the writer has suggested possible procedures. The writer is most grateful for assistance from his colleagues in the In dustrial Hygiene Division of the United States Public Health Service. However, he assumes full responsibility for the material as presented. Despite every good intention and every earnest and painstaking effort, imperfections and errors may occur; readers will confer a favor by reporting them so that they may be corrected in a future edition. ST0852289 CONTENTS Preface.................................................................................. Introduction......................................................................... Past I INORGANIC SUBSTANCES Alimdtinm............................................................................................... Alundum............................................................................... jlmmnnia................................................................................................. Antimony.............................................................................. Arsenle................................................................................... Asbestos................................................................................. Barium................................................................................. Beryllium............................................................................... Bismuth.................................................................................. Boron...................................................................................... Bromine................................................................................. fiHmiilin................................................................................................... Cerium................................................................................... Chlorine......................... ...................................................... Chromium.............................................................................. Cobelt..................................................................................... Columbium............................................................................ Copper.................................................................................... Fluorine.................................................................................. Gallium................................................................................... Germanium............................................................................ Glam fiber and mineral wool............................................... Hydrasoio add...................................................................... Hydrogen chloride................................................................ Hydrogen fluoride................................................................. Hydrogen nitrate.................................................................. Hydrogen sulfate.................................................................. Hydrogen sulfide................................................................... Indium..................... .............................................................. Iodine...................................................................................... Iron......................................................................................... TAnthfcniiTfi............................................................................................... Lead........................................................................................ Magnesium............................................................................. Manganese.............................................................................. Mercury.................................................................................. Mica........................................................................................ Molybdenum.......................................................................... Nickel.................................................................................... Nitrogen oxides..................................................................... Osmium................................................................... .............. vii v 1 15 17 19 21 25 29 32 34 38 40 43 44 49 51 53 56 60 61 64 68 70 72 75 77. 79 81 82 84 87 89 91 94 96 99 102 105 109 111 113 116 120 ST0852290 viii CONTENTS Osone........................................................................................................................... 122 Palladium.................................................................................................................... 126 Phosphine................................................................................................................... 127 Phoapboraa................................................................................................................. 129 Platinum..................................................................................................................... 132 Plutonium................................................................................................................... 134 Portland cement........................................................................................................ 137 Radioactive substance*............................................................................................. 140 Rubidium andcesium................................................................................................ 142 Selenium..................................................................................................................... 144 Silioa........................................................................................................................... 147 Silioones...................................................................................................................... 161 Silver........................................................................................................................... 163 Strontium................................................................................................................... 156 Sulfur................... 157 Sulfur ohloridee.......................................................................................................... 159 Sulfur dioxide............................................................................................................ 161 Sulfur hexafluoride..................................................................................................... 163 Talc............................................................................................................................. 164 Tantalum.................................................................................................................... 167 Tellurium.................................................................................................................... 169 Thallium..................................................................................................................... 171 Thorium...................................................................................................................... 174 Tin.............................................................................................................................. 176 Titanium..................................................................................................................... 179 Tungsten..................................................................................................................... 181 Uranium...................................................................................................................... 183 Vanadium................................................................................................................... 186 Zinc............................................................................................................................. 189 Zirconium................................................................................................................... 191 Past II CARBON COMPOUNDS Acetaldehyde.............................................................................................................. 197 Aeetio acid................................................................................................................. 200 Acetic anhydride........................................................................................................ 202 Acetone....................................................................................................................... 204 Acridine...................................................................................................................... 206 Acrolein...................................................................................................................... 208 Acrylonitrile............................................................................................................... 211 Allyl chloride and allyl bromide.............................................................................. 213 Amyl acetate.............................................................................................................. 215 Amyl alcohol.............................................................................................................. 217 Aniline........................................................................................................................ 220 Benzene....................................................................................................................... 223 Benzene hexachloride................................................................................................ 226 Bensoyl peroxide....................................................................................................... 229 Bromoform.................................................................................................................. 231 1,3-Butadiene............................................................................................................. 232 2-Butanone................................................................................................................. 234 ST085229 I >-r - CONTENTS ix ladtatyl acetate............................................................................................................ 238 Butyl aloohols.............................................................................................................. 238 -Batyl methyl ketone................................................................................................ 241 toBatyl methyl ketone............................................................................................... 243 Carbondioxide.-........................................................................................................... 244 OuioB diialfide........................................................................................................... 246 Carbon monoxide......................................................................................................... 248 Carbon tetrachloride................................................................................................... 250 Carbonyl chloride (phoegene).................................................................................... 253 Chlorinated diphenyls and chloronapthalenes......................................................... 255 Chlorinated mononitroparaffine..................... 257 Chlorobenaene........................................... 258 2-Cbloro-l, 3-butadiene (chloroprene)....................................................................... 261 Chloroform.................................................................................................................... 263 Chloronitrobensenes.................................................................................................... 265 Chloropiorin................................................................................. 267 Cxeaola--oreeylio aoid.................................................................................................. 270 Cyelohexane.................................................................................................................. 272 Cyolohexanol................................................................................................................ 274 Cyelohexanone.............................................................................................................. 276 C-yulohcxene.................................................................................................................. 278 Cyclopropane................................................................................................................ 280 Dibutyl phthalate........................................................................................................ 281 Diehlorobensene........................................................................................................... 283 Diohlorodiphenyltriohloroethane (DDT).................................................................. 286 Diohloroethanee............................................................................................................ 288 Diohloroethylene.......................................................................................................... 291 Diohloroethyl ether..................................................................................................... 293 Diehloromethane.......................................................................................................... 295 2.4- Diohlorophenoxyacetic acid.............................................................................. 297 1,2-Diohloropropane.................................................................................................... 299 Diethylene glycol monoethyl ether and related substances................................... 301 Diethyl ether................................................................................................................ 303 Di(2-ethylhexyl)phthalate.......................................................................................... 305 Dimethylaniline............................................................................................................ 306 Dimethyl sulfate.......................................................................................................... 308 Dinitrobeniene.............................................................................................................. 310 1.4- Dioxane............................................................................................................... 311 Diphenyl........................................................................................................................ 314 Ethyl acetate................................................................................................................ 316 Ethyl alcohol................................................................................................................ 318 Ethylbensene................................................................................................................ 320 Ethyl bromide.............................................................................................................. 322 Ethyl chloride............................................................................................................... 323 Ethylene chlorohydrin................................................................................................. 325 Ethylene glycol............................................................................................................ 328 Ethylene glycol mono-n-butyl ether......................................................................... 331 Ethylene glycol monoethyl ether............................................................................... 332 Ethylene glycol monoethyl ether acetate................................................................. 334 Ethylene glycol monomethyl ether........................................................................... 336 ST 0852292 X CONTENTS Ethylene glycol monomethyl ether acetate...................................... ...................... 338 Ethylene inline............................................................................................................. 340 Ethylene oxide..............................................................................................................841 Ethyl formate.............................................................................................................. 343 Ethyl silicate............................................ .................................................................. 345 Fluorocarbons.............................................................................................................. 348 Formaldehyde.............................................................................................................. 348 Formic acid.................................................................................................................. 351 Furfural........................................................................................................................ 353 Hydrocarbons, saturated--methane, ethane, propane, butane............................. 355 Hydrocarbons, saturated--pentane, hexane, heptane, octane............................ 357 Hydrocarbons, unsaturated--acetylene.................................................................... 359 Hydrocarbons, unsaturated--ethylene, propylene, butylene, amylene,hexylene.. 361 Hydrogen cyanide....................................................................................................... 363 Isophorone................................................................................................................... 366 Eletene.......................................................................................................................... 368 Mesityl oxide............................................................................................................... 869 Methanol...................................................................................................................... 371 Methyl acetate...................................................................................... .................... 874 Methyl bromide............................................................................................................ 376 Methyl chloride............................................................................................................ 378 Methylcydohexane...................................................................... ............................ 381 Methylcyolohexanol..................................................................................................... 382 Methyloyclohexanone........... : ........................................................ ....................... 384 Methyl formate........................................................................................................... 385 Methyl iodide............................................................................................................... 387 Methyl methacrylate................................................................................................... 388 Methyl n-propyl ketone (pentanone*2)..................................................................... 391 Metol............................................... ............................................................................. 392 Naphtha........................................................................................................................ 394 Naphthalene................................................................................................................. 396 Naphthylamine............................................................................................................ 397 Nitrobensene............................................................................................................... 399 Nitro derivatives of aniline....................................................................................... 401 Nitroethane.................................................................................................................. 403 Nitroglycerin............................................................... ............................................ 405 Nitromethane............................................................................................................... 407 Nitropropane............................................................................................................... 409 Oxalic acid................................................................................................................... 411 Pentachloroethane....................................................................................................... 413 Pentachlorophenol....................................................................................................... 414 Phenol........................................................................................................................... 416 Phenylenediamine........................................................................................................ 418 Phthalie anhydride...................................................................................................... 421 Picric acid..................................................................................................................... 422 Propyl acetates............................................................................................................ 426 n-Propyl alcohol.......................................................................................................... 427 tsoPropyl alcohol........................................................................................................ 428 isoPropyl benzene........................................................................................................ 430 isopropyl ether............................................................................................................. 431 ST 0852293 CONTENTS xi Pyridine..................................................................................................................... 433 Qtdnone and hydroquinone...................................................................................... 435 Styrene monomer...................................................................................................... 437 Tetraehloroethane..................................................................................................... 439 Tetraehloroethylene (perchloroethylene)................................................................ 442 Tetranitromethane.................................................................................................... 444 Toluene....................................................................................................................... 446 Toluidine................................................................................................................... 449 Triehloroethane......................................................................................................... 451 Triohloroethylene...................................................................................................... 453 TriortAoeresyl phosphate........................................................................................ 455 triethanolamine........................................................................................................ 458 Trinitrotoluene (TNT)...................................... 450 Turpentine................................................................................................................. 463 Vinyl chloride........................................................................................................... 465 Xylene........................................................................................................................ 467 Xylidine..................................................................................................................... 469 Index, 473 ST 085229U INTRODUCTION In an earlier period of our industrial development workmen were exposed to smoke, dust, fumes, and gases without regard to the possible injurious nature of many of these substances. Certain occupations, such as the fining of mercury, were formerly notorious in this respect. Furthermore, this condition was recognized in only very few instances and exposure to fumes or dusts of a deleterious type was generally recognized as a somewhat disagreeable and accepted condition of many occupations. The fact that pnme workers in mines, mills, or factories sickened, were forced to leave their occupation, and later died, did not always bring with it the realization that the nature of their work was a factor. In some occupations where industrial disease was prevalent there were often individuals who had been immersed in such an environment most of their working life and yet re mained apparently strong and healthy. Such cases would be cited as indi cating the general harmlessness of their occupation and those who sickened were regarded as weaklings. Many industrial diseases, such as phos phorus poisoning, were undetected for years, or, as in the case of manganese poisoning, were undetected for generations. The scrutiny of occupation as a factor in disease, although emphasized long ago by Ramazzini, is a comparatively modem development. Industrial physicians only a genera tion ago were largely concerned with the more external factors of employ ment--hernia, lumbago, cataracts in the case of glass workers, deafness in boilermakers--or in incidental disease, such as ankylostomiasis among miners or tuberculosis among cotton spinners. The latter were, of course, related to poor sanitation and poor nutrition, respectively, and were by no means peculiar to the occupation of the worker. Knowledge, however, of the existence of occupational disease became more and more evident and, although locally confined at first, gradually spread. Thus, such terms as "grinder's rot", "phossy jaw", "painter's colic", "chrome itch", and "miner's phthisic" gradually appeared in in dustry and in the literature. Within the past generation industrial physicians have been alerted to the danger of much of the Bmoke, dust, or gases to which workers were exposed, scientists have actively investigated the effects of many of these aerial contaminants on animal life, and engi neers have instituted control measures in industry to reduce the hazard of exposure. Poisoning familiarly occurs as the result of ingestion of toxic substances and this doubtless influenced much of the earlier industrial hygiene thought. As a result, stringent emitary measures were advocated and adopted in certain industrial processes in order to prevent possible entrance of indus- 1 ST0852295 2 intboduction trial poisons by mouth. These precautionary measures included such matters as a complete change of clothing on entering a shift, careful scrub bing of the hands and face before eating lunch, and a thorough washing and shower at the end of the work period. While excellent in themselves, these measures do not include the sanitation of breathing and instances of industrial poisoning have occurred where workers had observed strict cleanliness yet were exposed to dangerous concentrations of dust, fumes, or gases. Inhalation is now recognised as one of the most dangerous routes of entrance of industrial poisons. Gasbs, Fumes, and Dust While the greater part of industrial smoke consists largely of carbon and is relatively harmless, it frequently contains gases which are dangerous if continuously breathed or if breathed in high concentration and, in addition, it may contain noxious fumes or toxic dusts from certain processes. From the point of view of industrial hygiene a gas may be considered to be any aeriform or completely elastic fluid which does not become liquid or solid at ordinary temperatures. Fumes or vapors consist of material in the near-gaseous, or extremely fine particulate form which condense to liquids or solids at room temperature. Dusts, on the other hand, consist of larger particulate matter suspended in air. It must be realised that these definitions are not rigid and that they merely indicate somewhat roughly different stages of attenuation of matter. It is possible, for instance, to have mercury dust suspended in the air of a workroom, due to constant attrition of mercury spilled on the floor and carried into the air as extremely minute droplets following mechanical agitation. At the same time, mer cury fume may be present as the result of heating this substance and finally the vapor tension of mercury is such that true, gaseous mercury may also be present to a Blight extent. It is important for the industrial hygienist to keep these distinctions in mind. The detection and estimation of mercury gas in air by means of the photoelectric mercury detector depends upon the absorption of ultra violet light of a wave length of 2537 A and the degree of absorption is a measure of the amount of gaseous mercury present. How ever, thin instrument would not indicate the total mercury present in an atmosphere where particulate mercury or dust from any of its compounds was also present. While dusts have been classified as particles or aggregates of particles of from 150 microns to one micron in diameter, fumes of from one micron to 0.2 micron in size, and smokes as particles less than 0.3 micron in diameter, size alone represents at best only a rough separation of these three classes. The mode of formation must also be considered. Thus, dusts ordinarily result from mechanical attrition and distribution, while fumes and smokes INTRODUCTION ST0852296 ifOBDed and carried into the air usually as the result of chemical reaction |m dispersion of a chemically active substance by release of pres- ror.by explosion. ^disperse systems, or aerosols, in which the dispersion medium is a frTM" other disperse systems in the great disparity that exists between the density and structure of the disperse phase and the dispersion medtam. The mere fact that two Buch disperse systems contain amicrogpoplto particles gimil&r in magnitude does not necessarily mean that the properties of the two systems are identical, although they may have many pntwtn of similarity. In the case of dust, a great deal of work is required in Older to reduce a solid to fine dust, i.e., to overcome the forces of cohesion originally held the particles together in addition to the work required in distributing the particles throughout the dispersing medium. Even tfwgigVi a certain degree of uniformity finally is attuned by settling or other .means, dispersed dust of the finest order of magnitude is less uniform in [Structure than aerosols produced by the condensation of vapor. These factors have same weight in devising means of sampling and analysis of aerial contaminants. The evaluation of aerial contaminants is very frequently a matter of importance to the industrial hygienist and a knowledge of the properties of such disperse systems as those indicated above, as well as the properties of gaaes and vapors in relatively low concentrations, is of particular value >with reference to the analytical detection and determination of the con stituent contaminants. The composition of the aerial contaminant to which workmen in a given ' plant are exposed is of course of paramount importance to the industrial hygienist. This is usually known, or information may be obtainable from the management. In some cases, however, an unknown or unsuspected factor may be present and careful investigation may be necessary before the culprit is revealed. Cases have occurred, for example, where arsenic, cadmium, or selenium existing as unsuspected impurities in the material being fabricated have caused illness and death. An unrecognized by product of manufacture may cause difficulty, or a change in the formula of basic material used in manufacture may bring about an unhygienic situa tion. The industrial hygienist is required not only to ferret out the occu pational disease hazard but also--very necessarily--to know its charac teristics, a proper method of sampling, and the most reliable method of analytical evaluation in terms of air content. His study includes the weighted or average exposure of employees at various stations and occupa tions. Furthermore, he is required to know something regarding the toxicity of the aerial contaminant in order to define the conditions under which employees are to be permitted to work in such an environment. ST 0852297 4 INTRODUCTION The toxic effects of many hazardous materials in industry are well known and it is comparatively edsy to define safe working concentrations. There exist many substances in common use in industry, however, which are toxicologically not well defined. Unfortunately, toxicity cannot be evalu ated with the ease with which a chemical constant, such as a boiling point, melting point, or index of refraction, may be determined. Even with arduous investigation extending over many months, the toxicologist can at best give only a very general answer regarding the poisonous nature of a given substance. It would be of inestimable benefit of course, if one could--knowing the composition and molecular structure of such a sub stance--predict its physiological properties. Chemical Constitution and Physiological Response The possibility of relating chemical constitution and physiological ac tivity has long proved a fascinating field of speculation. The advantages of defining the toxicity of a substance from its constitution or structural formula are, as indicated above, obvious. Unfortunately, however, the matter is not simple. Certain relations exist, it is true, between structure and toxicity. For instance, ethyl and methyl alcohol, although differing in one important respect, are very similar in many of their other physio logical properties, and propyl, butyl, and amyl alcohols might be assumed to act similarly. These latter alcohols do, in fact, resemble the lower members but with a progressive increase in toxicity. An analogous in creasing toxicity might therefore be anticipated in the higher members of the alcohol series. This reasoning, however, is nullified by the changing physical properties of the higher members. In spite of a similar chemical structure, the higher alcohols become increasingly insoluble in body fluids and as a result there is an overall decreasing toxicity beyond a certain point. A similar increase in toxicity with an increasing number of carbon atoms is noted with sodium acetate, propionate, butyrate, and valerianate. Many other such relationships have been pointed out as more toxicological in formation has become available. The replacement of a hydrogen atom with chlorine in the saturated hy drocarbons results in an immediate change in toxicity; the entrance of such a halogen group in the organic sulfur compounds greatly intensifies the toxicity of the resulting compound. When one chlorine group is intro duced into ethyl sulfide, which is a weak poison, the resulting monochloroethyl sulfide, is found to be markedly toxic, while the introduction of a second chlorine atom results in dichlorodiethyl sulfide, or mustard gas, which is a very strong poison indeed. However, no such general rule can be applied in other cases. The successive replacement of hydrogens by chlorine in the methane molecule, which of itself is not toxic but merely INTRODT7CTION ST0852298 5 n an asphyxiant, results in monochloromethane, CHC1, dichloromethane, e CHtCli, trichloromethane, CHC1*, and tetrachloromethane, CCU, respec e tively. These substances, however, do not follow a pattern of increasing i- toxicity. For instance, chloroform with its excellent narcotic properties, as well as the attendant possibilities of liver and heart damage, is less toxic h in general than carbon tetrachloride on the one hand and much less toxic .t than methyl chloride on the other hand. Yet dichloromethane, which a occupies an intermediate position, is far less toxic than any of the other ie members of this group. It does not follow therefore that there is any >- direct correlation between the number of chloro groups and the toxicity. The relatively inert and inoffensive hydroxyl group when introduced into an organic molecule frequently results in an increase in toxicity. Thus, methanol, CH*OH, has pronounced toxic properties compared with the parent substance and monohydroxybenzene, CH*OH, or phenol, has 8 marked poisonous properties over and above those of benzene. Increas U ing the number of hydroxyl groups may also increase the toxicity of the .e aromatics. For example, the introduction of a second hydroxyl group in e the benzene ring yields resorcinol, C*H(OH)j, which is more toxic than g phenol, while the introduction of a third group yields phloroglycinol which >- is the most toxic of the three. J The entrance of an alkyl group into the molecule of a substance may also r intensify its poisonous quality. Dimethyl resorcinol, CtH*(OCHj)s, is more toxic than resorcinol, C*H(OH)*. On the other hand, an alkyl group may >f diminish the toxic effect in other substances. Dichloromethyl arsine, S Aa(CH)Cl, is very toxic, while the introduction of a second methyl group, .1 as in dimethyl chloroarsine, As(CH*)jCl, yields a substance of weaker B toxicity. While the introduction of a chlorine group in aliphatic hydrocarbons 3 increases the toxicity in general, this is not necessarily true in the case of Y the aromatic hydrocarbons. ThuB, monochlorobenzene is less toxic than benzene itself and has been of no particular significance as an industrial poison. It appears to be a general rule that iso compounds are somewhat less 1 toxic than normal compounds. tsoPropyl alcohol has a somewhat lower a toxicity rating than normal propyl alcohol; tsobutyl alcohol than normal butyl alcohol. A most interesting difference in toxicity has been found to exist in the benzene hexachlorides which have recently received attention 1 as insecticides. In this case, the gamma derivative of 1,2,3,4,5,6 hexa> chlorocyclohexane, CHCU, has been found to be especially lethal in action 1 compared with the other four known isomers (1). Woodard and Hagan / (2) found the gamma isomer to be as much as sixty times as toxic for certain T warmblooded animals as other isomers of benzene hexachloride. In the .s TO 8522 93 6 INTRODUCTION case of many other optically isomeric substances, great differences may also be found in toadcities. For instance, l-byoscyamine is twice as active physiologically as dl-hyoscyamine (atropine) and moreover the laevo compound is twelve to twenty times as active as the dextro compound (3). Usually, but not invariably, the laevo compounds are more active dextro compounds. Thus, Cushny found l-hyoscine to be sixteen to eighteen times as active as d-hyoscine and twice as active as dl-hyoscine. Similarly 1-adrenaline was twelve to fifteen times as active as d-adrenaline in its vasoconstrictor action and twice as active as dl-adrenaline. On the basis of rather indirect evidence, it is possible that the difference in physio logical behavior of such stereo-isomers is due to the ability of one or the other to combine with some protein or other constituent of the cell. How ever, sufficient quantitative data are not available to define clearly the mechanism of physiological activity and stereochemical configuration. The problem of relating chemical constitution and physiological action is even more confusing when it is recalled that substances of diverse pheminal nature may produce similar physiological effects. The aliphatic narcotics, for example, include a large variety of structural type, such as hydrocar bons, alcohols, ethers, amines, and sulfones. According to Ing (4), these substances appear to achieve their effect by modifying the physico-chemical conditions of the cells due to certain physical properties shared by all classes of these compounds and not by the presence of certain pharmaco dynamic groups. It will be apparent therefore that while the temptation to rationalise regarding the prediction of toxicities may be great, the evaluation of toxicities of new substances is fraught with considerable uncertainty. Since no great rational scheme is available to aid, except rather sketchily, in deciding upon the toxicity of a given substance, it is inevitably necessary to carry out experimental work with animals. Experimental Toxicology Experimental industrial toxicology does not differ widely from that of experimental pharmacology, since they both use the resources of chemistry, physics, physiology, and pathology to achieve their purpose. However, the pharmacologist is primarily interested in therapy rather than toxicity. Furthermore, he is interested in the effects of administration of a substance by mouth, or by intravenous or subcutaneous injection and rarely in the effects of inhalation, except in the case of inhalation anesthetics. The refinements of approach to certain physiological reactions adopted by the pharmacologist, however, often yield data of fundamental importance within a relatively short space of time. The toxicologist on the other hand may be compelled to follow an intricate procedure which is arduous and INTHODTTCnON ST0852300 7 " order to define a given physiological response. More over 'todoological studies frequently depend upon pathological changes following the administration of small amounts of such toxic materials as ip--t 0t dusts and these changes usually occur very slowly. : i Toadodogical investigations are in general based upon animal experi- nuwtutt**1 for Wim experimentation is, of course, indefensible. It is tnw experiments provide only indirect evidence of the probable action of toxic substances on man, yet they are none-the-lees of the greatest value. They not only afford information regarding upper toxic limitB, but by long-oontinued study, reveal changes in lower concentrations which are of the greatest importance. In experimental work of this character, a con siderable amount of interpolation is necessary and evaluation of the experi mental results requires both acumen and careful judgment. Moreover, there are many poisons which produce completely different effects in differ ent species of animals. Mice and guinea pigs, for example, are more sensi tive to poisoning by trichloroethylene (acetylene trichloride) than cats, while rabbits are less sensitive than cats. On the other hand, cats are more sensitive to lead poisoning than dogs and the latter more so than rats. Although such qualitative and quantitative differences may exist, never theless there can be no doubt that animal experiments are of value since they give an indication of the type of toxic action, as well as the relative toxicity of the substance under investigation. 1 The great advantage of animal experimentation is, first of all, the control of dosage and, secondly, the degree to which poisoning can be carried. This yields most useful information in tracing similar effects in humans accidentally poisoned and in warning against human exposure beyond a certain degree. Although the effects of exposure by inhalation are of paramount im portance, animal studies also usually include other formB of administration, such as ingestion, intravenous injection, intraperitoneal injection, and sub cutaneous injection. The latter form of administration is perhaps the least used as absorption is frequently slow and has less significance than the other forms. Intravenous injection provokes the most immediate response and is often useful in studying the immediate effects of substances upon the hemopoietic system. Intraperitoneal injection is one means of following the slow absorption of relatively insoluble substances, but is of particular value in studying the physiological response of various substances. For instance, when pure silica suspensions are intraperitoneally injected, a reaction occurs which is typical and fairly constant (5). Sayers and Miller found three types of reaction occurred with various dusts--absorptive, inert, and proliferative. The absorptive reaction occurs when fine dusts, suoh as calcite, limestone, gypsum, and cement, are injected. After suffi- ST0852301 8 INTRODUCTION dent time, this material disappears from the peritoneal cavity without the formation of any scar tissue. In the case of the inert reaction, the dust re mains distributed about the peritoneum by the action of phagocytes, some times forming flat nodules, which do not tend to progress or form fibrous scar tissue. Soapstone, carborundum, and cool dusts exhibit this inert reaction. In the proliferative reaction, nodules form which continue to increase in size with the formation of fibrous or scar tissue. Quartz, chert, and flint dust produce this reaction. These three types of reaction corre spond very closely with the results obtained by the inhalation technique. While this method perhaps requires further exploration, it is useful in the approximate classification of dusts. The inhalation technique with reference to dusts, fumes, and gases is by far the most useful method used in experimental toxicology. In the case of gases, the various concentrations to which animals are exposed may be regulated with accuracy. Hence, the exposure may be clearly and accu rately defined. With fumes and dusts, the concentration of fume or dust in the air may be determined by exact chemical analysis. Whether or not the animals always breathe in the amount in the atmosphere may not be so accurately defined in many cases as small animals, such as guinea pigs, tend to huddle together and may be able to filter out some of the dust or fume to which they are exposed. For the purpose of exposure, gas-tight or dust-tight exposure chambers of large size are usually used and animal cages may be placed directly in the exposure chamber. The gas may be introduced in known amounts and rapidly distributed throughout the exposure chamber by means of small fans. Substances which are sufficiently volatile, such as solvents, may be introduced in known amount into a constant current of air and the breath ing concentration may be accurately calculated. In addition, of course, samples of the exposure atmosphere may be taken in most cases and analyzed chemically. Fumes, such as metal fumes, may be generated by arcing between electrodes of the metal carrying 110 a.c. current and an appropriate re sistance. In order to prevent the formation of metallic oxide fume, it is usually necessary to generate this fume in an atmosphere of inert gas, such as nitrogen or helium, and "bleed" it into an incoming air current. Oxide fumes are readily formed by arcing in air or in an atmosphere of oxygen. Fumes of many organic substances may be formed by heating the material to the volatilization temperature in the incoming air stream. Dusts must be suspended in air in very finely divided form in order that they may remain in suspension as long as possible and so that the material is of sufficient degree of fineness to be carried deeply into the animals* lungs. An elutriating device is useful for this purpose (6), since it permits ST0852302 & INTBODUCnON flow of very finely divided dust of more or less uniform size. Ir exposures, it is difficult to control the amount of dust in th< .atmosphere and hence it is necessary to draw small samples from for analysis. Even though the dust concentration is accu- fcnown, the amount carried into the animals' lungs is questionable .invariable amount is removed by the filtering action of the nose, part oi thsidust remaining in suspension is removed before the air enters deeplj Into the The ciliated epithelium found throughout the extent of the air-passages and their prolongations constantly sweeps out air-borne par ticles and only the very finest material penetrates to the lung alveoli. ^ Description of the means of evaluating the effects of various industrial poisons will be found given in detail in the various publications referred to in ths ri<WM>^;nC text. It will be noted that a considerable latitude of experi mentation is necessary in order to study the effects of a given industrial poison. . Ths degree of exposure (that is, the total amount of substance to which an has been exposed for a given length of time) is, of course, only preliminary to the evaluation of the toxicity of the substance. The be havior of the animal must be observed for this is an index of the manner in which the poison acts. Some substances may cause death immediately or within a few minutes--for example, hydrogen cyanide, hydrogen sulfide, or carbon monoxide. Other substances may act as irritants with symptoms of pain, salivation, vomiting, and purging. Ammonia gas, cadmium oxide fume, and chloropicrin, respectively, produce these effects. Other sub- stanoes affect the central nervous system and produce characteristic symp toms, such as narcosis, convulsions, and paralysis. The various symptoms, in general, serve at best only as a rough classifi cation of toxic substances. The effects of poisons are often subtle and a variety of symptoms may be displayed. In chronic poisoning, or in the case of a cumulative poison, anatomical changes may be produced in cer tain organs or tissues which are characteristic for the poison. Blood changes may occur with an increase or decrease in hemoglobin, in red or white cells, and often with characteristic morphological changes in either or both the erythrocytes and leukocytes. All these and many other effects must be studied with care in the evaluation of the toxicity of a substance. It will be apparent therefore that the term toxicity does not refer to a fixed quantity, such as, Bay, a constant of nature. On the contrary, it is a de scriptive term and is often more clearly understood when applied in relation to other analogous substances. When the toxicity of a substance is evalu ated in the broad sense described above, however, the industrial toxicologist is able to advise somewhat definitely the limitation of possible exposure of human beings to industrial poisons. S T 0 8 5 2 303 10 rNTEODUCTION It should be clearly indicated that, while suoh procedures as those briefly indicated above serve to establish useful limits with regard to industrial poisons, the more fundamental aspects of toxicology involve far more exten sive and difficult physicochemical and physiological investigation. Vari ous physical factors such as surface activity, solubility, dispersibility, polarity, partition coefficient, particle sise, and electrophoretic properties may require study. The mechanism whereby many substances produce toxic effects in man is important and requires careful exploration. The fate of these substances in the body--the changes which organic compounds undergo and the metabolites formed--serves to indicate the means by which the body attempts to reduce their toxicity and thus protect itself against their poisonous effects. This is especially true of organic com pounds completely foreign to the body. In their passage through the ani mal organism these substances interact with the normal biochemical sys tems which they encounter. The enzymic systems which carry out the oxidations, reductions, hydrolyses, and syntheses in the body may be vari ously affected. The metabolic processes involved reflect an attempt to reduce or abolish the toxio action or damage to the organism. However, it is not true that the product or products formed are invariably less toxic than the parent substance. For example, Channon and his associates (7) found that 2,4,6-trinitrotoluene (a-TNT) iB partly converted in the animal organism to 2,6-dinitro-4-hydroxylaminotoluene which is excreted as such in the urine. Furthermore, the biological reduction produot of picric acid is picramic add. In both these cases the end-products are more toxic than the original substances. Nevertheless in the case of many other poisons the toxic substance is converted to harmless metabolites and elimi nated. Fundamental investigation of the toxicity of a given substance therefore includes study of the course of the toxic agent through the body, its effects on various organs and tissues during its passage, and the changes produced in the substance by the detoxicating mechanism of the body as indicated by the metabolites formed. RsraMNCBB 1. Slade, R.: The gamma isomer of hexaohlorocyclohex&ne (gammexane). The Hurter Memorial Leoture, Soc. Chem. Ind., March 1946. 2. Woodard, G., and Hagan, E. C.: Toxicological studies on the isomers and mixtures of isomers of benzene hexachloride. Fed. Proo., Soc. Pharm. Exptl. Therap. 6: 886 (1947). 3. Cuahny, A. R.: Biological Relations of Optically Isomeric Substances. Williams & Wilkins Co., Baltimore, 1926, p. 40. 4. lag, H. R.: Chemical constitution and pharmacological action. Trans. Faraday Soc. $9: 373 (1943). ST0852304 omtoDTJonoN 11 ___ , * uid Bayen, E. K.s Physiological reaponae of the peritoneal tiaaue . jatrodaoed ae foreign bodiea. TT. 8. Pub. Health Servioe, Pub. Health 4t: 80 (1984). L. x., and Sayan, R. R.: The relative toxicity of lead and aome of ita _____ n ^rnn^.. Pub. Health Bull. No. 253, U. 8. Pub. Health Bervioe, ^WaaUofton, D. C., 1940, P- 7. CbaBBOD, H. J., Mill*, G. T., and William*, R. T.: Metaboliam of 2:4:8-tnmtro- {ohwue (-T.N.T.). Bioehem. J. S3: TO (1944). f** ST0852305 Industrial Toxicology [ 29 ] asbestos 13. Lvrry, Q. A.: A study of sraine poisoning. Qusxt. J. Ezpar. Physiol. St: 47 (1047). 18. Ssndell, E. B.: Colorimetric miorodetermination of arsenio after evolution as arsine. Ind. Eng. Chem., Anal. Ed. H: 82 (1042). 14. Mell&n, I.: Organic Reagents in Inorganio Analysis. Blakiston Co., Philadel phia, 1041, p. 256. ASBESTOS Characteristics Asbestos, amianthus, earth flax, stone flax, mountain cork, is a charac teristically silky, fibrous mineral, the composition of which varies with its source. The form known as chiysotile is derived from serpentine and is a hydrous magnesium silicate containing from 12.5 to 14 per cent water of crystallisation. About 95 per cent of commercial asbestos is chiysotile. Chrysotile has the silkiest and strongest fiber and can be spun. The fibers may be as long as six inches in length. Asbestos derived from amphibole occurs as a variety of minerals consisting of iron, calcium, and magnesium with little water of constitution. The latter type of asbestos consists of short fibers and is usually inferior to that derived from serpentine. Am phibole asbestos (anthophyllite) while not so suitable for spinning is more stable chemically than chiysotile and more resistant to acids and heat. Canada has been an important source for the chrysotile asbestos used largely in the United States. The Canadian asbestos industry is centered in the Thetford Mines area of the Province of Quebec. A new source for chyrsotile type asbestos is a large quarry on the eastern shoulder of Belvidere Mountain in Vermont which was opened in the summer of 1944. This deposit is of importance because it represents the only large source of long-fibered chrysotile so far found in the United States. Deposits of amphibole asbestos are mined in Georgia and North Carolina. Industrial Uses Asbestos is an important substance in industry and consumption in the United States for 1945 amounted to 377,875 short tons (1). Due to its fibrous nature, flexibility and heat resistant properties, it is used extensively for valve packings, gaskets, boiler lagging, and pipe covering in industrial plants and as friction material in the automotive industry. A considerable market exists in the building industry for asbestos-cement products, heat insulation, and fire-proofing. The utilization of asbestos for fibers for spinning in the manufacture of asbestos clothing for fire fighting is an im- ST0852306 asbestos [ 30 ] Industrial Toxicology portant use for asbestos. The largest single outlet for asbestos in manu factured products in 1044 was for clutch facings, and next in quantity of output were brake linings. Asbestos roofing consumed the third largest amount of asbestos in that year. Industrial Injury The inhalation of asbestos dust produces a condition known as asbestosis. While certain other minerals of minor importance have been shown to pro duce lung fibrosis, asbestos is the only important silicate apart from talc and mica which does not contain free silica and yet produces pulmonary lung fibrotic changes leading to disability and death. Asbestosis occurs chiefly in industrial plants where asbestos is fabricated. The Bpinning and weaving of asbestos in combination with other textiles results in exposure of workmen to asbestos dust. The long continued inhalation of asbestos dust results in a form of pneumoconiosis. The primary effect of inhalation of asbestos dust is an interstitial pulmonary fibrosis. On an X-ray film the shadows cast by this type of fibrosis resemble ground glass in appearance and usually extend over the lower portions of the lung fields, frequently being heavier on the right side (2). Unlike silicosis, nodular fibrosis has not been detected in asbestos workers (3). A progressive dyspnea, vari able cough, substemal chest pains, decreased chest expansion, weakness, emaciation, clubbed finger tips, and curved fingernails are the chief symp toms of asbestosis, as in silicosis. A characteristic finding in asbestosis is that of asbestos bodies in the lungs and in the sputum (4). The so-called asbestos bodies are apparently formed only in the lungs and may be demon strated microscopically on sectioning lung tissue or in the sputum. The core of the body is an asbestos fiber which is surrounded by protein deposits. Unstained specimens are golden yellow or golden brown. They are not stained with ordinary histological stains but may be demonstrated by the Prussian blue staining procedure. The reaction to the fibrous needle in the tissue which becomes manifest in exudate cell infiltration is accompanied by numerous giant cells containing foreign particles and an increase of diffuse interstitial connective tissue and fibrosis. While the essential re action to asbestos particles is considered to be chemical by many investiga tors others consider the pathogenous of the disease to be mechanical (5) in nature. When the lungs are examined by the naked eye after death, they are large and densely fibrotic. Often the lung is completely adherent to the chest wall and, in advanced cases, to the diaphragm with the formation of a thick and extremely dense layer of fibrous tissue. Four main complica tions and sequelae of pulmonary asbestosis are purulent bronchitis, bron chial pneumonia, pulmonary tuberculosis, and emphysema (6). Several cases of asbestosis have been reported which progressed to a fatal terrains- ST 0852307 Induttrial Toxicology [ 31 ] asbestos tkm With heart failure and without evidence of infection or other complicat ing dir1**1** (7). Any appreciable decrease in the amount of asbestos dust will cause a decrease in the incidence and severity of asbestosis (8). It would appear that if the dust concentration in asbestos factories can be kept below five million particles per cubic foot, new cases of asbestosis would not arise (2). Analysis While the analysis of asbestos dust as an aerial contaminant is not of particular importance, its microscopy and above all the evaluation of the number of particles per cubic foot of air is of paramount importance. Air samples may be secured by the impinger method using 25-50 per cent al cohol as a collecting medium and dust counts made by the usual method. Microscopic examination of the dust reveals typical asbestos fibrous par ticles which may be accompanied also by cotton or other textile fibrous materials in samples taken from the air of weaving factories. The index of refraction being only slightly greater than that of Canada balsam, the relief is low. Other forms of asbestos than chrysotile have somewhat higher indices of refraction. Extinction is parallel except in the case of tremolite which has oblique extinction. The birefringence of chrysotile is moderate n, -- n = 0.013. The maximum interference color is bright yellow of the first order. The air sampling of asbestos dust both by the impinger method and by the electrostatic precipitator method is discussed in detail by Fehnel (9). Raraasma.. 1. Bowles, O., and Marsh, D. I.: Asbestos. Minerals Yearbook 1945. U. 8. Bur. Mines, Washington, D. C., 1947, p. 1457. 2. Dreessen, W. C., DaUaValle, J. M., Edwards, T. I., Miller, J. W., and Sayers, R. R.: A study of asbestosis in the asbestos textile industry. Pub. Health Bull. No. 241, U. 8. Pub. Health Service, Washington D. C., 1938. 3. Bayers, R. R., and Dreessen, W. C.: Asbestosis. Am. J. Pub. Health t9: 205 (1939). 4. Lansa, A. J.: Silicosis and Asbestosis. Oxford Univ. Press, New York, 1938. 5. Noro, L.: Histology of asbestosis. Aota pathol. miorobiol. scandinav., Kobenh. tS: 53.(1945). 6. Gloyne, 8. R., and Merewether, E. R. A.: Asbestos. Occupation and Health Supple. International Labour Office, Geneva, 1938. 7. Lansa, A. J., and Goldberg, J. A.: Industrial Hygiene. Oxford Univ. Press, New York, 1939, p. 387. 8. Page, R. T., and Bloomfield, J. J.: A study of dust control methods in an asbestos fabricating plant. U. 8. Pub. Health Service, Pub. Health Repts. St: 1713 (1937). 9. Fehnel, J. W.: Air sampling of asbestos dust: comparison of impinger and elcctrostatio precipitator methods. Ind. Med. 0: Ind. Hyg. Boot, t: 5 (1940). ST0852308 Industrial Toxicology [ 147 ] Silica 8.McConnell, E. P.: Respiratory excretion of selenium studied with the radio active isotope. J. Biol. Chem. lit: 65 (1942). 4. Dudley, H. C.: Toxicology of selenium. I. A study of the distribution of sele nium in acute and chronic cases of selenium poisoning. II. The urinary excre tion of selenium. III. Determination of selenium in air-gas-duet mixtures. Am. J. Hyg. MS: 169,181; Ml: 227 (1936). .IV. Effects of exposure to hydrogen selenide, by H. C. Dudley, and J. W. Miller. V. Toxio and vesicant properties of selenium oxychloride, by H. C. Dudley. U. 8. Pub. Health Servio, PubHealth Repta. BS: 1217 (1937); SS: 94 (1938). Reprint Nos. 1865, 1901. VI. Effeets of subacute exposure to hydrogen eelenide, by H. C. Dudley and J. W. Miller. J. Ind. Hyg. Toxicol. MS: 470 (1941). 5. Fitshugh, Q. G., Nelson, A. A., and Bliss, C. I.: The ohronio oral toxicity of selenium. J. Pharmacol. 80:289 (1944). 6. Dudley, H. C.: Selenium as a potential industrial hasard. U. 8. Pub. Health Servioe, Pub. Health Repts. 88:281 (1938). Reprint No. 1910. 7. Clinton, M., Jr.: Selenium fume exposure. J. Ind. Hyg. Toxiool. 89:226 (1947). 8. Buchan, R. F.: Industrial selenosia. Ooc. Med. 8:439 (1947). 9. Pringle, P.: Occupational dermatitis following exposure to inorganio selenium compounds. Brit. J. Dermatol. H: 54 (1942). 10. Duvoir, M., Pollet, L., and Herrensohmidt,.J. L.: Occupational ecsema due to selenium developing when work was resumed after a long interval. Bull. soc. franc, dermatol. syphilig. W 88 (1937). 11. Smith, M. I., Lillie, R. D., Stohlman, E. F., and Westfall, B. B.: Studies in ohronio selenosis. Natl. Inst. Health Bull. No. 174. U. 8. Pub. Health Serv ioe, Washington, D. C., 1940. 12. 8mith, M. I., Westfall, B. B., and Stohlman, E. F.: Studies on the fate of sele nium in the organism. U. S. Pub. Health Service, Pub. Health Repts. 88:1199 (1938). 13. Smith, M. I.: Chronic endemio selenium poisoning. A review. J. Am. Med. Assoc. 118:662 (1941). 14. Moxon, A. L.: Alkali disease or selenium poisoning. South Dakota Agri. Expt. Sta. Bull. (1937). 15. Challenger, F.: Biological methylation. Chem. Rev. 88: 315 (1945), (219 refer ences). 16. Moxon, A. L., and Rhiam, M.: Seleneum poisoning. Physiol. Revs. 88: 305 (1943), (196 references). 17. Painter, E. P.: The chemistry and toxicity of selenium compounds with special reference to the selenium problem. Chem. Rev. 88: 179 (1941). SILICA Silica (SiOt) or silicon dioxide, is the most abundant of all the minerals and rocks that form the earth's crust. It is characterized by its hardness and chemical resistance to reagents. It is slightly soluble in alkalies but the finely particulate material is only very slightly soluble in water (1, 2). ST085Z309 SHJCA [ 148 ] Industrial Toxicology Silica fractures into very minute angular particles. In the crystalline form it occurs as quarts but two other forms are also known which are tridymite and criatobalite and each of these exists in a number of modifications. Sand, flint, and agate are familiar forms of Bilica and diatomaceous earth, which is occasionally found in nature in large deposits, is composed of the silicious skeletons of diatoms. In view of what is known about the disease called "silicosis", it is important to distinguish between silica in the free state, as SiOi, and silica in the combined state, such as the various Bilicates. The silicates are still considered innocuous when inhaled as dust with the exception of talo, mica, and the fibrous silicates which are known as asbestos (3). The percentage of free silica in the various dusts which have been analyzed in connection with health studies of workers in dusty trades has been shown to range from 64 per cent to a trace (4). Silicosis is a chronic disease caused by the inhalation of particulate matter containing free or uncombined silica. It is Characterized anatomically by generalized fibrotic changes with miliary nodulation in the lungs. Clinical signs are shortness of breath, a lowered vital capacity, a lowered capacity for work, increased susceptibility to tuberculosis, and a characteristic X-ray appearance of the lungs. Silicosis is found to occur in such occupations as mining, the cutting of sandstone and granite, the coal industry, the smelting, refining, and grind ing of metals, the manufacture of certain abrasives, the pottery industry, and the processing Of the various forms of free silica. The number of work ers exposed to dangerous amounts of silica dust has been estimated at more than one million (5). Because of the disabling nature of silicosis (6), the extent to which ex posure occurs in industry and the number of workers involved, many sur veys have been made and these investigations have resulted in the Betting up of efficient protective measures in working establishments. Dust control measures, taking into consideration the chemical composition of the dust and the size of the silica dust particles, as well as the concentration of the dust in the air, have been instituted. There is more or. less general agreement that it is desirable to avoid concentrations of more than five million particles per cubic foot of air in working places where the dust con tains a high percentage of free silica. Granite dust, which contains about 35 per cent free silica, when in concentrations of ten to twenty million particles per cubic foot has been found not to cause disabling silicosis in a working lifetime, while anthracite dust, containing less than 5 per cent free silica, has been found not to cause anthracosilicosis in concentrations of less than fifty million particles per cubic foot (3). Because air-borne dust may differ markedly from that of the source material from which it arises, it is common practice in appraising dust hazards to determine the ST0852310 Industrial Toxicology (149 ] silica free silica content of samples. Furthermore, it has been indicated that toxicity increases sharply with silica dust below 3 microns in size (7). Since particles too large to be significant in silicosis production often con* tain a much higher percentage of free silica than fine particles of significant size, Holden and his associates (8) describe a procedure to eliminate the oversize particles before analysis. The mechanism and pathology of silicosis have been very adequately described. It is well recognized that very fine particulate silica is carried to the air sac or alveolus which represents the terminal dilatation of the bronchioles in the lungs. The alveoli are in intimate contact with blood vessels through which the oxygen-carbon dioxide interchange phenomena of respiration occur and they are also in contact with lymphatics which are important for the removal of foreign or irritant material. This defense mechanism is motivated by the activity of phagocytic cells which carry off the minute silica particles to the lymph nodes. There an ineffective ac cumulation of this material occurs and fibrotic changes take place resulting in areas which constitute the silicotic lung marking revealed by the chest roentgenogram. Just why the phagocytic cell is affected by the silica-- whether, in fact, silica has a direct toxic action, or whether it initiates other effects--is still in the realm of speculation. Certain substances, such as aluminum, iron, and magnesium dusts, when used with quartz, as well as coal and cement dusts, have apparently been found to decrease the pulmonary changes associated with free silica alone. Outstanding in this respect is the work of Denny, Robson, and Irwin (9), who have shown that small quantities of metallic aluminum powder almost completely inhibit the solubility of silicious material. While this work represents an interesting and significant development in silicosis research, Heffeman (10) has recently pointed out that the surface activity of the silica particles is the important factor in the production of silicosis rather than solubility of the silicon dioxide. Recent investigation of the use of aluminum and alumina has been made by Policard (11), who confirms the view that the aluminum dust itself is innocuous and by King (12), who, in a critical discussion of the solubility of silica, reports that a mixture of one per cent of aluminum hydroxide with the quartz fractions lowered their solubility but did not prevent the formation of fibrosis in animals. The phase of silicosis therapy indicated above, however, is still in the stage of experimental investigation. Since free silica or quartz is the important factor in causing silicosis, the identification of this substance and its quantitative evaluation as a dust constituent are of prime consideration. The microscopic examination of such dusts yields especially valuable information. Of the six distinct silica minerals, quartz, chalcedony, and opal are the more common. Tridy- silica ST08523II [ 150 ] Industrial Toxicology mite and cristobalite are more or less of volcanio origin and are also found as constituents of silica bricks, while lechatellierite is exceedingly rare. Quartz and chalcedony have refractive indices near that of Canada balsam and a birefringence of about 0.009. The other silica minerals have lower indices of refraction and weaker birefringence. The microscopic examina tion of such industrial dusts as are known to contain free silica can only be satisfactorily accomplished by the use of the petrographic microscope and a considerable amount of experience is necessary. Quantitative evaluation of the quartz content of a dust may be made microscopically by examining the dust and counting the dust particles in two different immersion media (13) having different indices of refraction. In one of these media all the particles are visible; in the other, having the same index of refraction as quartz, only the nonquartz particles are visible. The difference between these two estimations gives some approximation of the silica content of the dust. The method is not suitable for very fine particles and estimation based on particles of less than 10 microns in size is not good petrographic practice. Chemical methods for the estimation of free silica, such as the hydrofluosilicic acid method (14) and the fluoboric acid method (15), are tedious, time-consuming, and frequently yield information of no more quantitative value than less lengthy procedures. The X-ray diffraction method of dust analysis has become of increasing importance and is espe cially commendable from the point of view of speed, while it appears to yield results of as great accuracy as is obtainable by other methods of analysis. RxranHCEB 1. Titua, A. C.: Silica and silicate solubilities. J. Ind. Hyg. Toxicol. 19:138 (1937). 2. Kitto, P. H., and Patterson, H. S.: The rate of solution of particles of quarts and certain silicates. J. Ind. Hfg. Toxicol. H: 69 (1942). 3. Meller, H. B.: Silicosis and Allied Disorders. Med. Ser. Bull. No. 1, Air Hygiene Foundation of Am., Pittsburgh, 1937. 4. Bloomfield, J. J., and DallaValle, J. M.: The determination and control of indus trial dust. Pub. Health Bull. No. 217, U. S. Pub. Health Service, Washington, D. C., 1935, p. 62. 5. Bloomfield, J. J., Traako, V. M., Sayers, R. R., Page, R. T., and Peyton, M. F.: A preliminary survey of the industrial hygiene problem in.the United States. Pub. Health Bull. No. 269, U. S. Pub. Health Service, Washington, D. C., 1940. ' 6. Gardner, L. U., and Wright, G.: Disability in silicosis. Ind. Hyg. Foundation Am., Proc. Eighth Annual Meeting, Pittsburgh, 1943, p. 47. 7. Tebbens, B. D., Schuls, R. Z., and Drinker, P.: The potency of Bilica particles of different size. J. Ind. Hyg. Toxicol. 87:199 (1945). 8. Holden, F. R., Hemeon, W. C. L., and Hyatt, E. C.: Appraising exposures to silica dust. J. Ind. Hyg. Toxicol. 89; 285 (1947). 9. Denny, J. J., Robson, W. D., and Irwin, D. A.: The prevention of silicosis by metallic aluminum. Can. Med. Assoc. J. 37; 1 (1937); Ind. Med. 8; 133 (1939). 10. Heffernan, P.: Aluminum dust for silioosis. Brit. Med. J. 1:928 (1946). Industrial Toxicology [ 151 ] ST08523I 2 silicones 11. Polioard, A.: New data on the use of aluminum and of alumina in the prophylaxis and treatment of silicosis. Presse m6d. 55:006 (1946). 12. King, E. J.: Solubility theory of silicosis. Ooo. Med. 4- 90 (1947). 13. Boss, H. L. and Sehl, P. W.: Determination of free silica. Ind. Eng. Chem., Anal. Ed. 7:80 (1936). 14. Knopf, A.: The quantitative determination of quarts ("free silica") in dusts. U. S. Pub. Health Service, Pub. Health Repts. 45; 183 (1933). 16. line, W. R., and Aradine, P. W.: Determination of quarts in the presence of silicates. Ind. Eng. Chem., Anal. Ed. 9: 60 (1937). 18. Hamlin, L. E.: Industrial dust--the pneumoconioses. Ind. Med. IS: 223 (1944). THE SILICONES Characteristics Silicon forms a large number of compounds which are analogous to those of carbon. The amplest of these is silane, SilD, which corresponds to methane. While these compounds have been known for some time, they were, however, of academic interest only and received no practical ap plication until about 1940 when the unique properties of the silicones caused thn to assume considerable industrial importance. The silicones, R--SiO--R, correspond to the ketones but differ from the latter in most of their properties. Themethyl silicones occur as oiIb, resins, and elastomers or rubber-like substances. The methyl silicone oils are soluble in benzene and the lighter hydrocarbons but are only partially soluble in alcohol. Many very complex alkyl and aryl silicones have been reported and studied within recent years. Some of these substances, such as methyl silicone oil, are characterized by their chemical inertness, low temperature coefficient of viscosity, wide liquid range, and low freezing point. Their high boiling points and heat stability are important properties for many industrial applications. Industrial Uses The uses of the silicones are as varied as their properties. Certain of the liquids are used as damping fluids for instruments and machinery. Other liquids find application as special lubricants for high temperature instruments, while others are used as high viscosity heat transfer liquids and as heavy diffusion pump oils. Minute amounts prevent foaming in fuel oils--an important problem in Diesel engines--and also the foaming of aqueous solutions. The relative insolubility of methyl silicone oil in petroleum oil may account for the success of this substance in suppressing foam. Silicone greases are used as hot valve lubricants, as insulating ST0852313 Induttrial Toxicology [ 223 ] benzene 3. dark, B. B., Van Loon, E. J., and Morrizaey, E. W.: Aoute experimental aniline intoxieation. J. Ind. Hyg. Toxiool. 96:1 (1048). 4. Hamblin, D. O., and Mangeledorff, A. F.: Methemoglobinemia and its measure ment. J. Ind. Hyg. Toxiool. 90:623 (1038). 6. Lester, D., Greenberg, L. A., and 8hukovcky, E.: Formation of methemoglobm. IV. Limited importance of methemoglobinemia in the toxicity of certain aniline derivatives. J. Pharmacol. 30: 78 (1044). 6. Bass, A. D., Frost, L. H., and Salter, W. T.: 2-AniIinoethanol, an industrial hasard. Production of methemoglobinemia. J. Am. Med. Assoc. 198: 761 (1043). 7. Rosenberg, P. A.: Biochemical changes in blood and urine in severe acute aniiine poisoning. Farmakol. i Toksikol. 8: No. 4,23 (1046). 8. Rehn, L.: Ueber Blasentumoren bei Fuchainarbeitern. Arch. klin. Chir. 30; 688 (1806). 0. Hunter, D.: Industrial Toxicology. Clarendon Press, Oxford, 1044, p. 46. 10. Goldblatt, M. W.: Occupational cancer of the bladder. Brit Med. Bull. A' 405 (1047). 11. Schwarts, L., Tulipan, L., and Peck, S. M.: Occupational Diseases of the Skin. Lea A Febiger, Philadelphia, 1047, p. 277.,. 12. Graubarth, J., Bloom, C. J., Coleman, F. C., and 8olomon, H. N.: Dye poisoning in the nursery. J. Am. Med. Assoc. 198: 1165 (1046). 13. Henderson, Y., and Haggard, H.'W.: Noxious Gases. Reinhold Publ. Corp., New York, 1943, p. 228. 14. Elvove, E.: A method for the colorimetrio estimation of small amounts of aniline. Ind. Eng. Chem. 9:963 (1017). 15. Anon.: Methods for detection of toxio gases in industry. Aniline. Leaflet No. 11, Dept. Sci. Ind. Research. H. M. Stationery Office, London, 1039. BENZENE Characteristics Benzene, benzol, C*Ht, boiling point 80.094 C., melting point 5.51 C., density D 0.87895, and index of refraction n ^ 1.50124, is a colorless liquid with a characteristic odor. It is soluble in water only to the extent of 0.06 part per hundred at 20 C., but is miscible with organic solvents. Its flash point is from --12 C. to --10 C. and ignition may be caused by open flames or sparks from electrical appliances. The "light oil" from the fractional distillation of coal tar consists principally of the hydrocarbons-- benzene, toluene, xylene, and "solvent naphtha". On nitration, benzene yields both nitrobenzene with a boiling point of 209 C. and m-dinitrobenzene with a melting point of 90 C. On bromination, benzene yields bromobenzene, boiling point 157 C. and p-dibromobenzene, melting point 89 O. When heated with bromine plus iron catalyst, it yields mainly BENZENE [ 224 ] ST 0852314 Industrial Toxicology p-dibromobenzene. It forms a picrate of colorless needles, melting point 83.9 C. With C1S0H, it yields benzenesulfonyl chloride, melting point 14 C., boiling point 251 C., and diphenyl sulfone with a melting point of 128 C. It is slowly sulfonated with boiling concentrated sulfuric acid. Industrial Uses Domestic production of benzene has more than tripled during the past decade, chiefly due to the increased demand for the manufacture of phenol and for a motor fuel additive. The production of benzene amounted to 36,555,643 gallons for all purposes except motor fuel in 1940. Nearly three times as much (101,140,079 gallons) was produced for use as motor benzene alone in that year (1). During the war, however, the use of benzene for chemical purposes increased considerably, while its use for motor fuel dropped correspondingly. Thus in 1945, the total production of benzene for motor fuel amounted to 32,151,532 gallons, while the pro duction of benzene for all other purposes corresponded to 159,013,084 gallons (2). Apart from motor fuel, benzene is mostly used in manufac ture of rubber, chemicals, dyestuffs and intermediates, explosives, aniline, phenol, resorcinol, benzidine, picric acid, and miscellaneous organic prepara tions. It is used as a solvent for oils, fats, waxes, gums, natural and synthetic resins, cellulose esters and ethers, and a large variety of varnishes, airplane dopes, as well as in paint and varnish removers. Toxicity On inhalation in high concentration, benzene is narcotic in action pro ducing successively euphoria, hypermotility followed by sleepiness, and fatigue. The preliminary excitement is greater than with chloroform and as a general anesthetic, its action is more of a convulsive character. In concentrated form, it is especially toxic and may produce death. In dilute form, the vapors produce headache, vertigo, ataxia, twitchings, con vulsions, and coma. Chronic poisoning in industry is characterized by leukopenia and aplastic anemia. Bowers has recently described a chronic case of benzene poisoning with fatal termination characterized by an in tractable anemia, leukopenia, and thrombocytopenia following long con tinued exposure to benzene. In this case, the bone marrow was grossly hyperplastic with extensive areas of extramedullary hemopoiesis (3). It should be emphasized that blood changes alone cannot be accepted as evidence of benzene intoxication in the absence of estimations of benzene as an atmospheric contaminant (4). Benzene is absorbed through the skin but clinically detectable benzene poisoning has not been found from this source (5). However, absorption from the skin is of far less importance than absorption from inhalation. A test for detecting active absorption _1 ST 0852315 Industrial Toxicology [ 225 ] benzene of benzene may be made by determination of the ratio of the total urine sulfates to the inorganic sulfates (6). Since serious trouble may develop following exposure to benzene without any warning symptoms, the sig nificance of neglected disorders is often apparent when too late. Lambin (7) has indicated a procedure for the detection of benzene poisoning applica ble to large groups of individuals so exposed. The 1949 American Con ference of Governmental Industrial Hygienists has accepted 35 parts of benzene in air as a maximum allowable concentration in workrooms. Analysis Methods for the determination of minute amounts of benzene are at best, methods of approximation only. The chemical methods are colori metric in character and depend upon nitration and colorimetric evaluation of the reaction products. Various physical methods have been developed for the determination of benzene, such as the gas interferometer method and the combustible gas detector, and are useful when the air contaminant is solely benzene vapor. In contact with a nitrating mixture (equal parts of concentrated sulfuric acid and fuming nitric acid of d. 1.50) in the cold for 30 minutes, benzene is converted into a mixture of the ortho, meta, and para isomers of dinitrobenzene. The mixture contains about 95 per cent of the meta isomer. With aldehydes and ketoneB, the mixed dinitrobenzenes give a violet color in alkline solution. The meta isomer in par ticular gives a color with acetone. In low concentrations of benzene, the color develops within 30 minutes, is stable for three hours, and follows Beer's law. Schrenk and his associates (8) have adapted the nitration method to the determination of small amounts of benzene vapor as an air contaminant, using methyl ethyl ketone as reagent. A combined absorp tion nitration bubbler tube is used in which the benzene is converted to m-dinitrobenzene which is then estimated colorimetrically in saline solu tion with methyl ethyl ketone. Both Baernstein (9) and Dolin (10) have published methods for the determination of benzene in the presence of toluene and xylene, which depend upon oxidation of the nitro derivatives of the two latter substances. The oxidation products of the nitro deriva tives of toluene and xylene are colorless under the conditions described and therefore do not interfere with the benzene determination. RxrzasNCKs 1. U. S. Tariff Commission: Synthetic organic chemicals, 1940. Kept. No. 148, 1941. 2. Anon.: United States production of synthetic organic ohemioals. Chem. Eng. News It; 1556 (1946). 8. Bowers, V. H.: Reaction of human blood-forming tissues to chronic bensene ex posure. Brit. J. Ind. Med. 4:87 (1947). BENZBNis hexachloride [ 226 ] ST08523i6 Industrial Toxicology 4. Hunter, D., Milton, R., Perry, K. M. A., end Barrie, H. J.: Investigation for signs of benzene intoxication in workers using aeroplane dope and rubber sol vents. Brit. J. Ind. Med. 1:238 (1944). 5. Lehmann, K. B., and Fluty, F.: Toxicology and Hygiene of Industrial Solvents. Williams A Wilkins Co., Baltimore, 1943, p. 98. 6. Yant, W. P., Sohrenk, H. H., Sayers, R. R., Horvath, A. A., and Reinhart, W. A.: Urine sulfate determinations as a measure of benzene exposure. J. Ind. Hyg. Toxiool. 18:09 (1936). 7. Lambin, P.: Detection of poisoning due to benzene eompounds. Arch, beiges m6d. sociale et hyg. 4:25 (March 1946). 8. Schrenk, H. H., Pearce, S. J., and Yant, W. P.: A microoolorimetric method for the determination of benzene. U. S. Bur. Mines, Rept. Investigations No. 8287, 1935. 9. Baernatein, H. D.: Photometrio determination of benzene, toluene and their nitro derivatives. Ind. Eng. Chem., Anal. Ed. IS: 251 (1943). 10. Dolin, B. H.: Determination of benzene. Ind. Eng. Chem., Anal. Ed. 16: 242 (1943). Batchelor, J. J.: The relative toxicity of benzene and its higher homologues. Am. J. Hyg. 7:276 (1927). Division of Industrial Hygiene: Benzene (benzol): its toxicity and potential dangers. U. S. Pub. Health Service, Pub. Health Repts. SB: 519 (1941). Re print No. 2248. Schrenk, H. H., Yant, W. P., Pearce, S. J., Patty, 7. A., and Sayers, R. R.: Ab sorption, distribution and elimination of benzene by body tissues and fluids of dogs exposed to benzene vapor. J. Ind. Hyg. Toxicol. iS: 20 (1941). BENZENE HEXACHLORIDE (Gamma Hexachlorocydohexane) Characteristics Benzene hexachloride, hexachlorocydohexane, C|HC1, one of the newer insecticides also known as "BHC" or "666", exists in five isomeric forms-- the alpha, beta, gamma, delta, and epsilon. In the pure state, the isomere are well-defined colorless crystals, practically insoluble in water, soluble in organic solvents, and have a bitter taste and practically no odor. The melting points of the isomers are as follows: alpha, 157.5-158 C.; beta, 309 C.; gamma, 112.5 C.; delta, 138-139 C.; and epsilon (1), 218.5219.3 C. At 40 C., the vapor pressure of these isomers are alpha, 0.06 millimeter of mercury; beta, 0.17 mm. Hg.; gamma, 0.15 mm. Hg.; and delta, 0.09 mm. Hg. The solubilities of the isomers of benzene hexachloride have been determined in each of forty-five organic solvents and the con- ST 0852311 INDEX Detailed dizcuzaiona shown by bold faoed page numbers Abrasives, 18 Acetaldehyde, 197, 288. 812, 818, 828 Acetaldehyde phenylhydrasone, 197 Acetamide, 868 Acetanilide, 203, 222 Acetic acid, 800, 243, 860 Acetic acid, glacial, 200 Aoetic acid, synthetic, 200 Acetic anhydride, 303, 368 Acetic ether, 816 Aoetoacetio acid, 204 Acetone, 304, 311, 860, 860, 868, 889, 428 Acetone cyanohydrin, 864, 889 Acetone oxime. 204 Acetone phenylhydrasone, 204 Acetn-p-toluiaide, 203 4-Acetylamino-l-uopropyl bensene, 480 Acetyl chloride, 200 Acetylene, 202, 205, 291, 816, 859 Acetylene dichloriae, 391 Acetylene tetrachloride, 489 Acetylene trichloride, 7 Acetyl1 dee, 350 Acetylaalicylio acid, 203, 369 Acridine, 306 Acridine complexes, 208 Acridine Orange NO 207 Acridine Yellow, 207 Aoriflavine, 207 Acrolein, 308, 368, 378 Acrylonitrile, 311, 364 Adipio acid, 275, 277 Adrenaline, 6 Aerosols, 3 Aerosol insecticide bomb, 64 Agate, 148 Alcohol, 360 Alcohol, wood, 371 Alizarin, 100, 175, 181, 193 Alisarib red S, 17 Alkyd resins, 404, 464 Allanite, 49 Ally! alcohol, 209 Allyl bromide, SIS Allyl chlorde, 313 A nico alloy, 57 Aloxite, 17 Alpha rays, 140 Aluminnn, 17 A uminum, 15 Alum;num bronze, 15 Aluminum ethoxide, 316 Aluminum phosphide, 128 Alundum, 17 Americ'um. 134 Am anthus, 29 Aminobensne, 330 Am'nodimethylaniline, 86 Aminodimethylbensene, 469 o-(2)-Am:nodiphenyl, 814 f-Aminodiphenyl, 314 Am: no-4-nydroxyanthraquinone, 87 panz-AminophenoI, 392 Ammonia, 9,19 Ammonia, synthetic, 20 Ammonium ohioroplatinate, 133 Ammonium molybdate reagent, 28 Ammonium paratungetate, 182 Ammonium piorale, 423 Amphetamine, 406 Amphibole, 29 Amyl aoetate, 315 Amyl aleohol, 817 iio.Amyl aleohol, 218, 219, 220 Amylene, 861 Amyl hydroxide, 817 Amyl nitrite, 365 Anesthetics, 362 Angles! te, 96 Aniline, 203, 330, 306, 398, 422, 436 Ani ine dyes, 222, 376 2-AnilinoethanoI, 221 Ankylostomiasis, 1 Anode rays, 140 Anodizing, 64 Anthophyuite, 29 Anthracene, 206 Anthracoeihcoeis, 148 Anti-fouling paints, 62 Anti-freese, 372 Antimony, 31 Apatite, 64,129 Arbutin, 436 Argyria, 153 Ariatol, 89 Armor-piercing sheila, 423 Arochlor, 255 Arsenic, 3, 36 Arsine, 360 Asbestos, M Asbestos bodies, 30 Asbestos dust, microscopy of, 81 sampling of, 31 Asbeetoeis, 30 Aspirin, 203 Asthma, occupational, 420 Atebrin, 207 Atropine, 6 Aurintricarboxylio acid, 17 Automobile radiators, 412 Aviation fuel, 430, 432, 468 Axobenzene hydrochloride, 814 472 ST0852318 Industrial Toxicdogy [ 473 ] INDEX Aso dyes, 470 Asaimide, 75 Asophenol dyes, 418 Baeillut acetoelkyUeum, 204 BaeiUut clotlridtum aeeMnUyUctm, 236 BaciUut maetrant, 204. 239 Baddeleyite, 192 Bakelite, 468 BAL, 164,170 Barite, U Bar'um, 32 Barium carbonate, 82 Barium chloride, 32 Barium stearate, 32 Barium sulfate, 32 Barium sulfide, 33 Bauxite, 18 Belvidere Mountain, 29 Benaal chloride, 448 Bensaldehyde, 187,204,207,384,893,460, 465 Bensene, 228, 814,417,431JW8 Bensene hexachloride, 5, 226 Bensene monochloride, 269 Benxenwulfonyl chloride, 224 Bensidine. 51. 52, 84, 104, 173, 183, 199, 222,865,446,457 a-Beasil dioxime. 115 Bensoflsvine, 207 Benzoic acid, 187, 820, 421, 430, 438 Bensol, 228 n-Bensoquinone, 485 Bensotrichloride, 807 Bensoyl peroxide, 229, 291 Bensyl aniline, 207 Bensylpyridine, 433 Beryllium, 84 Beryllium alloys, 84, 62 Beryllium nitrate, 174 Beryllium oxide, 34 Beryllium sulfate^ 35 Beryllium sine silicate, 84 Beta rays, 140 BHC, 228 Biotite, 109 Bismark brown, 420 Bismuth, 88 Bismuth hepatitis, 89 Bismuth hepta-dieneearboxylate, 39 Bismuth nephritis, 39 Bismuth trioxide, 38 Bladder papillomata, 222 Blasting gelatine, 405 Blasting powder. 405 Blood changes, 9 Blood, vanadium in, 187 Bone oil, 433 Bone sarcoma, 135 Borax, 41 Boric acid, 40 Boron, 40 Baron carbide, 41 Boron fluoride etherate, 65 Boron phosphate catalyst, 202 Boron trifluoride, 41 Brass founder's ague, 190 Bread, furfural in, 854 Bromallyiene, 214 Bromine, 43 Bromine burns, 44 Bromobensene, 223, 806 Bromoethane, 822 Bromoethylamine, 840 Bromoform, 281 8-Bromo-l-propene. 214 Bromphenol blue, 44 Buna N, 211, 212, 238, 235, 257, 289, 299 Buna S, 211, 233, 438 Bush sickness, 57 Butadiene, 282, 854, 860 Butadiene manufacture, 168 Butane. 866 Butanol-1, 238 Butanol-2, 238 2-Butanone, 284 Butanone method for xylene, 469 0-n-Butoxyetkanol, 881 n-Butyl acetate, 286, 243 Butyl alcohol, 6, 288 uoButyl alcohol, 5 n-Butyl bromide, 240 n-Butyl 0-bromoethyl ether, 331 Butylcarbinol, 218 woButylcarbinol, 218 Butyl oeUosolve, 881, 835 n-Butyl 0-chloroethyl ether, 331 Butylene, 861 tsoButylene, 239 2,3-Buty ene glycol, 232 n-Butyl 0-hyaroxyethyl ether, 831 uoButyl methyl carbmol, 243 isoButyl methyl ketone, 248 n-Butyl methyl ketone, 241 n-Butyraldehyde, 240 isoButyrio acid, 243 Cable rash, 266 Cacotheline, 178 Cadion, 48 Cadmium, 3, 44,189 Cadmium alloys, 45 Cadmium hydroxide, 45 Cadmium oxide, 9 Calcium phosphide, 127 Carbinol, 871 Carbitol, 801, 335 Carbolio acid, 416 Carbometbene, 868 Carbon dichloride. 442 Carbon dioxide, 244 Carbon disulfide, 246 Carbon monoxide, 9, 123, 246, 364, 371, 411,453 polycythemia from, 249 Carbon tetrachloride, 260, 443,467 ST08523I9 INDEX [ 474 ] Industrial Toxicology Carbonyl chloride, 263, 454 Chromotropio acid, 298 Carbonyls, 248 Chrysaniline, 207 Carboxide, 842 Chiysotile, 29 Carinoma, bladder, 898 birefringence of, 81 Carnallite, 142 Cinchonine hydroohloride, 188 Caeale process, 20 Citric add, 849 Cataracts, 1,286 Claude jprocess, 20 Cateohol, 276 Clay, 137 Cathode rays, 140 Clostridium aettobutvlieum Weiimann, Celestite, 166 236, 239 Cellosolve, 882, 336 Coal tar naphtha, 394 Cellosolve aceUte, 296,884,886,868,886, Cobalt, 66 404, 413, 440, 468 Cobalt, allotropic forms, 66 Cellulose acetobutyrate, 404 Codeine sulfate, 146 Cellulose aoetopropionate, 404 Codling moth, 26, 286 Cellulose formate, 369 Collidine, 434 Cerite, 49, 94 Colonial spirits. 871 Cerium, 49 Columbian spirits, 871 Cerium nitrate, 174 Columbium, 60 Cerium oxalate, 60 Columbium oarbide, 60 Cerium oxide, 60 Columbium fluoride, 168 Ceruasite, 96 Columbium oxide, 168 Cesium, 142 Columbium potassium fluoride, 61 Chalcedony, 137 Contact acid, 82 \ Chemical constitution and physiological Contaminants, aerial, 8 action, 4 Copper, 61 Chemical pneumonitis, beryllium, 86 Copper acetylide, 289, 360 Chemical pneumonitis, delayed, 86 Copper fever, 63 Chemigum, 257 Copper naphthenate, 62,190 Chlor acne, 266 Corn borer, 286 Chlorallylene, 218 Corundum, 17 Chloramine, 63 Cosmetic preparations, 801, 302, 312 Chlorex, 298 Cotton boll weevil, 227 Chlorinated diphenyls, 266 Crane fly. 284 Chlorinated monomtroparaffins, 967 Creed, 270, 382 Chlorine, 61 Cresylio acid, 270 Chloroanilines, 267 Cristobalite, 160 Chlorobenzene, 221, 269 Cryolite, 64. 79 2-Chloro-l, 3-butadiene, 281 Cumene, 43d, 431 1-Chloro-2-(6ea-chloretnoxy)ethane, 293 Cupric acetoarsenite, 26 4-Chloro-l,2-dimercaptobensene, 178 Cupric araenite, 26 1- ChIoro-2,4-dinitrobensene, 266 Curcumin, 101 Chloroethane, 323 " Curium, 134 2- Chloro-ethanol. 826 Cyanide antidote, 365 Chloroethyl alcohol, 826 Cyanides, 376 Chloroethylene, 466 Cyanogen ohloride, 863 Chloroform, 205, 288, 878, 414, 443, 467 Cyclohexane, 272 Chloronaphthalenes, 266 Cydohexanol, 274, 279, 883 Chloronitrobensene, 266 Cyclohexanone, 276, 286, 884 1-Chloro-l-nitroethane, 268 Cyclohexanone oxime, 277 1- Chloro-l-nitropropane, 268 Cyclohexene, 278 2- Chloro-2-nitropropane, 268 Cyclohexene 1,2-dithiocyanate, 279 Chloropentane, 217 Cyclohexyl bromide, 279 Chloropicrin, 9, 253, 267, 376, 407 Cyclohexyl chloride, 275 Chloroprene, 261 Cyclopropane, 280 3- Chloropropene, 218 Cysteine, detoxicating action of, 68 Chrome notes, 64 Chrome itch, 1 2, 4-D, 297 Chromite, 63, 64 DDT, 166, 227. 260. 286 Chromium, 68 Decanydronapnthalene, 395 Chromium oarbide, 60 Decalin, 396 Chromium picrate, 423 Dental caries, 66 Chromium plating, 64 Dental erosion, 82, 83 ST0852320 Industrial Toxicology [ 475 ] INDEX Dextro a-pinene, 464 Diaoetone, 206 Diaoetone alcohol, 870 2,4-Di-(aoetylamino)-l-ethylbensene, 320 p-Diaminobensaldehyde, 220 Diaminobensene, 418 Diaminophenol, 393 Diamylpnthalate, 230 Diatomaoeoua earth, 148, 406 Diatoms, 148, 387 Dibensalacetone, 204 Dibensoyl peroxide, 229 p-Dibromobenxene, 223 1,2-Dibromocyclohexane, 279 2,6-Dibromoindophenol, 418 DDiibbruotmylopmhathloanlaylted,ib2r3o0m, 2id8e1,, 368 286, 421 Dibutvl sebacate. 282 Dicarboxylic acid. 411 Diohloraoetio acid, 201 Diohloroacetyl chloride, 463 8:3'-Diohloroasoxybensene, 287 4:4'-Diehloroasoxybensene, 267 Diohlorobensene, 288 ortAo-Diohlorobensene, 260 para-Dichlorobenxene, 260 Diehlorodiethyl sulfide, 4, 253 Dichlorodifluoromethane, 64, 261, 346, 847 Diehlorodipnheennyylltrichloroethane flDDT) 288 Diioohhlloorroethanes, 288 Dichloroethylene, 291, 369 Diohloroethyl ether, 293 0,6'-Diohlaroethyl ether, 293 Diohloroethyl sulfide, 4 Diohloromethane, 6, 895, 378 Diohloromethyl arsine, 5 1.1- Diohloro-l-nitroethane, 258 21..42-- Dichlorophenoxyaoetic Dichloropropane, 299 acid, 297 Dichlorotetrafluoroethane, 347 Diethanolamine, 458 Diethylamine, 247 Diethylcarbnol, 218 Diethyldithiocarbamate, copper, 247 1.4- Diethylene dioxide, 311 1,4-Diethylene ether, 311 Diethylene glycol, 328, 329, 335 Diethylene glycol monoethyl ether, 301, 328 Diethylene glycol monoethyl ether ci trate, 301 Diethylene glyool monoethyl ether laurate, 301 Diethylene glycol monoethyl ether phthalate, 301 Diethylene glycol monoethyl ether ri- cinoleate, 301 Diethylene glycol monoethyl ether stearate, 301 Diethyl ether, 303 Di(2-ethylhexyl)phthalate, 282, 305, 422 Diethyl oxide, 803 Diethyl sulfate, 318 2.2- Difiuoropropane, 347 1.4- Dihydroxyanthraquinone-2-sulfonio acid, 87 1.4-Dihydroxybensene, 436 2.7- Dihydroxynaphthalene, 412 1.8- Dihydrox^naphthalene 3,8-disulfon- Dihydroxyoctachlorodiphenyl, 315 Diiminoquinone, 420 Diketene, 869 2.3- Dimercaptopropanol (BAL), 154,170 Dimethylamine, 306 para-Dunethylaminobensaldehyde, 254 p-Dimethylaminobensalrhodanme, 164 p-Dimethylaminobenzylidine rhodanine, 126 p-Dimethylamlnophenylasobensenear- sonio acid, 193 Dimethylaniline, 269, 806, 388, 469 Dimethylbeniene, 467 Dimethylohloroarsine, 6 Dimethylene imine, 340 Dimethylethylcarbinol, 218 Dimethyl gallium borohydride, 68 Dimethylmyoxime, 115,126, 162 Dimethyl hexine <nol, 889 Dimethylketone, 204 Dimethylphenylamine, 306 Dimethyl-p-phenylenediamine, 52, 90 Dimethyl phthalate, 286, 421 1.1- Dimetnyl-l-propanol, 218 2.2- Dimethylpropanol, 218 Dimethyl resorcinol, 6 Dimethyl sulfate; 808, 332, 387 4.6- DinItro-2-ammophenol, 424 Dinitrobensene, 310, 400 m-Dinitrobensene, 223, 225, 278 3.6- Dinitrobensoyl chloride, 304 Dinitrohydroxylaminotoluene, 10 Dinitrophenol, 393 2.4- Dimtrophenylhydrasine, 206, 278, 356 2.4- Dinitrotoluene, 447 Dioctyl phthalate, 305 Dioform, 291 1.4- Dioxane, 311, 336 Dioxane peroxide, 312 Dipentene, 463 Diphenyl, 814 Diphenylamine, 207, 254 Diphenylaminechloroarsine, 354 Diphenylcarbaside, 55 Diphenylearbohydrasine, 255 Diphenylchlorarsine, 253 Diphenyloxide, 314 Diphenylsulfone, 224 Diphenylthiocarbazone, 39, 48, 63, 98, 107,154 Dipropylene glycol, 329 <. Diuopropyl ether, 481 o,a'-Dipyridyl, 93 ST 0852321 INDEX [ 476 ] Industrial Toxicology Disacryl, 200 Dithisone, 39, 48, 63, 88, 107, 164 Dithymol di-iodida, 88 Dolomite^ 100,165 Dowioido O, 414 Dow metal, 100 Dowtherm A, 314 Drehaohmidt capillary, 110 Dry oleanlng induetry, 400 Dry ice, 245 D-otoff, 808 Duprene, 261 Duralumin, 15 Duet, definition of, 2 Dusts, experimental exposure to, 0 reaction to, 7 Dynamite, 405 Earth flax, 28 Electrioul odor, 122 Electron metal, 16 Elon, 392 Emery, 17 Ensootio marasmus. 57 Eoein, 44. 232 Essence a'orient, 440 Ethane, 355 Ethane-diacid, 411 Ethanoio acid, 800 Ethano, 318 Ethene, 861 Ether, 301 Ethide, 258 Ethoxyaoetaldebyde, 832 2-Ethoxy-6,8-diaminoacridine, 207 Ethyl acetate, 818, 886, 426 Ethyl alcohol, 818, 862 Ethylamine, 840 Etbybenaene, 380, 438 Dow pruoese of, 320 p-Ethyf bensene sulfonamide, 821 Ethyl bromide, 822 Ethyl ohloride, 3tS, 418,467 Ethylcyelohexane, 438 Ethyl diethylene glycol, 301 Ethyl-3,5-dinitrobensoate, 804 Ethylene, 326, 881, 466 Ethylene acetal, 312 Ethylene bromonydrin, 842 Ethylene chloride, 324, 461 Ethylene oblorohydrin, 825, 828, 458 Ethylene oyanohydrin, 211 Ethylene cuohlonde, 288, 466 Ethylene glycol, 828, 832, 335, 349 Ethylene glycol mono-n-butyl ether, 331 Ethylene glycol monoethyl ether, 328, 332 Ethylene glycol monoethyl ether acetate, 334 Ethylene glyool monomethyl ether, 336 Ethylene glycol monomethyl ether ace tate, 338 Ethylene imine, 840 Ethylene oxide, 211. 832, 840, 341, 458 Ethylene tetrachloride, 442 Ethylene triohloiide, 451, 453 Ethyl ether, 80S Ethyl formate, 343 n-Ethyl -8-hydroxy-tetrahydroquinoline hydrochloride. 28 Ethylidene chloride, 824 Ethylidene diacetate, 202 Ethyl iodide, 318, 403 Ethyl polyglyool, 301 1-Ethyl-1-propanol, 218 Ethyl silicate, 345 Ethyl sulfide, 4 Ethyl sulfurio acid, 818 Fatigue resistance, metal, 34, 187 Fehling's solution, 197, 354, 436 Ferrochrome, 54 Ferron. 175 Ferrophosphorus. 129 Ferro-eilioon, 127 Ferrous phosphide, 127 Fiberglas, 74 Fire damp, 356 Fire extinguishers, 876 Fischer-Tropsch process, 67 Flexol plasticiser DOP, 306 Flint, 148 Flour, bleaching of, 229, 230 Flour mills, fumigation, 884 Fluorescein, 124, 232, 283, 323, 422 Fluorescein reaction, 306 Fluorescent bead test, 185 Fluorescent lamps, 36 Fluorine, 64 Fluorine burns, 65 Fluorite, 64 Fluorocarbons, 846 Fluoroform, 847 Formaldehyde. 348, 854, 372 Formamide. 864 Formic acid. 343, 351, 372 Formic aldehyde, 348 Formic ether. 343 , Formylio acid, 851 Freon, 251, 286, 847 Fruit, ripening of, 362 Fuchsin. basio, 44, 210 p-Fuchsin, 126 Fuel tablets, 198 Fulminate of mercury, 407 Fume, definition of, 2 generation of, 8 Furfural, 216, 363, 427, 429, 465 Furfural phenylhydrasone, 354 Furiuraldehyde, 863 a-Furil dioxime, 116 Furoic acid, 354 Furol. 363 Fused collars, 836 Fusil oil, 216, 217, 427 Industrial Toxicology Galena, 96 Gallic acid. 860 Gallium, 68 Gallium, borohydridee of, 68 Gallium hydroxide, 60 Gallium thermometer, 68 Gemma rays, 140 Gammoxsne, 227 Gasee, definition of, 2 Gae mantlee, 174 Gasolene, 804 Gasolene, easing head, 217 Gasolene, high octane, 70 Gelatine dynamite, 405 Gelignite, 405 Germanium, 70 excretion of. 71 oxides of, 70 Germanium hydride, 70 Germanium sulfide, 72 Germanium tetrachloride, 72 Glass fiber, 72 Glucuronic Mid, 888, 885 Giyoerol, 200. 828 Glyoerol triohlorohydrln, 214 Glyoery! trinitrate, 405 Glyool, 812, 828 Clyptal, 421, 468 Golf greena, 284 Grain aleohol, 818 Grain oU. 217 Granite dust, 148 Griess reagent, 110 Griees test, 406 Grinder's rot. 1 Guaiaeoldialdehyde teet, 420 Gun ootton, 405 Gutaeit teet, 27 Gyepy moth, 28 Haber process, 20 Hafnium, 103 Hafnyl phosphate, 193 Hair dye, 420 Halowax, 255 HCN disco'da, 863 Heavy naphtha, 394 Hematite, 91 Hematoxylin, 17 Hemoglobinuria, 201,331 Heptane, 867 Hexachlorobenzene, 227 HexMhlorocydohexane, 228 Hexahydrobensol, 272 Hexahydrocreeol, 882 Hexahydromethylphenol, 882 Hexahydrophenol, 274 Hexahydrotoluene, 881 Hexalin, 274 Hexamethyl disiloxane, 162 Hexamethyiene, 272 Hexamethylenetetramine, 170, 340 Hexane, 867 ST0852322 [ ATI ] INDEX Hexanone-2, 241 Hexone, 248 Hexylene, 881 Houseflies, 286 Hyoar O. R., 257 Hydrasine chloride, 170 Hydrasine hydrate, 76 Hydraioio Mid, 76 Hydrocarbons, saturated paraffins, 865, 867 Hydrocarbons, unsaturated, Metylene, 860 Hydrocarbons, unsaturated--olefins, 861 Hydrochinone, 436 Hydroohlorio acid, 77 Hydrochlorio etherL823 Hydrocyanic acid, 868 absorption of, 363 preparation of, 363 Hydroforming. 447 Hydrogen Hide, 76 Hydrogen chloride, 77 Hydrogen cyanide, 9, 868 Hydrogen fluoride, 78 Hydrogen nitrate, 81 Hydrogen phosphide, 127 Hydrogen selenide, 145,146 Hydrogen sulfate, 82 Hydrogen sulfide, 9, 84, 860, 865 Hydroquinone, 892. 417, 436 Hydroxyacetie acid, 849 Hydroxyanthraquinone, 42 SHydroxyben*aldehyde, 220 ydroxybensene, 5, 416 p-Hydroxybiphenyl reagent, 199 0-HydroxyButyric acid, 204 a-Hydroxy ssobutyrio Mid, 889 l-Hydroxy*2-chloroethane, 826 Hydroxylamine, 162 Hydroxylamine hydrochloride, 277 4-Hydroxy-5-metnoxyiophthalalde- hvde test, 429 8-HydroxyquInoline, 17, 39, 61, 69, 88, 95, 101. 104, 175. 191 Hydroxytoluene, 270 Hyoecine, 6 Hyoecyamine, 6 Hypophosphorous Mid, 129 Hypovanadic oxide, 186 Hvnnvenftdoiia nrina ISA Igelite plastic, 466 Ilmenite, 179 Incendiary bombs, detection of, 145 Indigo, 23), 872, 421 Indium, 87 Indulene dyes, 423 Infra-red radiation, 142 Inhalation, experimental, 8 Insect repellent, 421 Iodine, 89 Iodine pentoxide method, 319 lodobensene, 306 ST 0852323 INDEX [ 478 ] Industrial Toxicology p-Iodobensohydraride, 277 Iodoform, 206, 818, 428 7-Iodo-8-hydroxyquinoline-5-siiIfonio add (ferron), 176 Iodomethane, 887 Iron, 81 Iron, chilled, 169 Iron pierate, 423 Isoacetophorone, 866 Iaophorone, 866 Isoprene rubber, 383 Jamaica oncer. 466 Jet.propdled airplanes, 60 Kelene, 323 Ketene, 203, 888 Ketoetnylene, 868 Keto-hexamethylene, 876 g-Ketopropane, 804 Eieselguhr, 406 Laevo a-pinene, 464 Lanthanum, 94 Lanthanum hydride, 94 Lead, 96 Lead aside, 76 Lead phthalate, 422 Lead pierate, 423 Lead poisoning. 97 Lead tetraethyl, 98 Lechatellierite, 160 Lepidolite, 109 Leptynol, 126 Lighter flints, 60, 94 Limonite, 91 Lithopone,83, 190 Lucidfol, 229 Lucite, 389 Luminous paint, 140 Lutidine, 434 Magnalium, 16 Magnesium, 99 Magnesium perchlorate, 262 Magnesium phosphide, 127 Magnesium silicate, 164 Magnetite, 91 Malachite green, 307 Malarial control, 286 Maleic anhydride, 233 Malonie acid. 368 Manganese, 102 Manganese acetate, 197 Marcaaite, 91 Marsh gas, 366 Marsh test. 27 Mercuric chloride paper, 131 Mercuric sulfate, 197 Mercury, 2,106 Mercury-cadmium iodide paper, 128 Meroaiy detector, 2, 107 Mesityl oxide, 369 Mesothorium, 140, 174 Metaldehyde, 197 Metal fume fever, 190 Meta-styrene, 438 Methacrylate resins, 364 Methaerylio acid, 388 Methane, 866 Methanoic acid, 861 Methanol, 6, 364, 871, 374, 427 Methanol, synthetic, 372 Methemoglobinemia, 118, 221, 307, 402, 446 Methemoglobinuria, 221, 398 Methionine, 264 Methoxyaoetaldehyde, 336 p-Methoxyphenyl-iso-thiocyanate, 398 Methyl acetate, 371, 874, 386, 426 Methyl alcohol, 371, 386 Methylamine, 268 p-Methylaminophenol sulfate, 898, 393 Methyl&niiine, 308 Methyl anone, 884 Methyl bensene, 448 Methyl bensoate, 371 Methyl bromide, 876, 387 2- Methyl-l-butanol, 218, 219 3- Methyl-l-butanol, 218, 219 2-Methylbutanol-3, 218 2-Methyl-2-butanoi, 218, 219 Methyl tso-butenyl ketone, 869 Methyl isobutyl ketone, 867 1-Methyl-3-carbohydrasidopyridiniurn B-toluenesulfonate, 277 Methyl cellosolve, 336 Methyl cellosolve acetate, 338 Methyl chloride, 878, 387 Methyl chloroform, 461 Methyloyelohexane. 881, 383 Methylcyclohexanol, 888, 384 Methylcyclohexanone, 383, 384 4- Methyl-l,2-dimercaptobenxene, 178 Methylene blue, 61 Methylene ohloride, 896 Methylene di-fl-napnthol, 349 Methyl ethyl ketone, 834 Methyl formate, 364, 386 Methyl glyool acetate, 838 1- MethyT-9-hydroxy-4-nitrosobensene, 68 Methyl iodide, 371, 387 Methyl methacrylate, 230, 388 Methyl nitrite, 447 4-Methy!-3-pentenone-2, 869 o-Methyl phenol, 270 2- Methyl propanol-1, 238 2-Methyl propanol-2, 238 Methylpropylc&rbinol, 218 Methyhsopropylcarbinol, 218 Methyl n-propyl ketone, 311, 391 Methyl silicones, 161 Methyl eulfate, 393 9-Methyl-2,3,7-trihydroxy-6-fluorone, 24 Methyl violet, 268, 307 Metol, 398 S T 0 8 5232 U Industrial Toxicology [ 479 ] INDEX Mica. 109 Michler's ketone, 807 Mineral wool, 78 Miner's phthisio, 1 Misehmetall, 60 Molybdenum, 111 Molybdenum chloride, 300 Molybdenum trioxide, 113 Monel metal, 64 Monobromoethane, 888 Monobromomethane, 876 a-Monobromopropylene, 314 Monochlorobensene. 6. 869, 386, 417 Monoehloroethyl sulfide, 4 Monochloromethane, 6, 878 a-Monoohloropropylene, 818 Monoethanolamine, 468 Monofluorinated hydrocarbons, 346 Monofluorotrichloromethane, 847 Monohydroxybensene, 6 Monomtrobensene, 310 Mononitronaraffins, ohlorinated, 867 Monosite. 60, 94,174 Moth balls. 896 Moth proofing, 284 Motor fuel, 224 Mountain oork.29 Muriatic acid, 77 Muscovite, 100, 166 Mustard gas, 4, 862 Naphtha, 894 Naphtha, high flash, 894 Naphtha, wood, 371 Naphthalene, 187, 895, 897, 421 Naphthalene cataracts, 896 Naphthalene picrate, 396 Naphthalene-4-eulfonio acid-l-aio-6- orMo-hydroxyquinoline, 126 Naphthenio aoid, 190 a-Naphthol, 266, 897 0-Naphthol, 286, 849, 897 Naphthoquinoline, 48 1, 2-Naphthoquinone-4-eulfonio acid, 403 Naphthylamine, 897 <r-Naphthylamine, 119, 406 0-Naphthylamine, 222, 398 1,8-Naphthyleneaiamine sulfate, 146 Neoprene, 261, 273 Neoprene cement, 273 Neptunium, 134, 233, 258, 261 Nesaler's reagent, 21, 866 Neutrons, 41, 136, 184 Nickel, 118 Nickel oarbonyl, 114 Nickel picrate, 423 Nicotine, 166, 434 Nicotinic acid, 434 Nigrosine, 423 Niobium, 60 Nitric aoid, 81 Nitrio acid pneumonia, 81 Nitrio oxide, 117 Nitroaniline, 401 m-Nitroaniline, 810, 811, 401 o-Nitroaniline, 311, 401 p-Nitroaniline, 272, 401 p-Nitroaniline red, 402 o-Nitroanisole, 267 p-Nitroanisole. 267 o-Nitrobensaldehyde, 278 Nitrobensene, 220, 223, 899 p-Nitrobenxene-aso-chromo-tropio acid, 42, 71 p-Nitrobensene diasonium chloride, 21 Nitrobruciquinone hydrate (cacothe- Iine), 178 Nitrocellulose, 216, 301, 316, 333, 367, 370, 374, 404, 458 solutions of, 282, 426 Nitrodiphenyl, 314 o-Nitroaiphenylamine, 311 Nitroethane, 408, 407 Nitroform. 867, 444 Nitrogen dioxide, 117 Nitrogen oxides, 116 Nitroglycerin, 406 5-Nitro-4-hydroxy-l, 3-dimethyl bensene, 406 Nitromethane, 407 a-Nitronaphtnalene, 397 0- Nitrophenylaeetyl chloride, 427 Nitropropane, 409 1- Nitropropane, 407, 409 2- Nitropropane, 407, 409 p-Nitrosocumetnylaniline, 307 Nitroeo-2-hydroxynaphthalene-3,6-di- sulfonate of sodium, 68 Nitroso-0-naphthol, 68 a-Nitroso-0-naphthol, 68 0-Nitroso-a-naphthol, 68 Nitroeophenylhydroxylamine, 93 Nitroso-R-salt, 68 Nitrous oxide, 116 Nitroxylenes, 469 Nordhausen acid, 82 Novadelox, 230 Octane, 857 Oil of ants, 353 Oil of bitter almonds, artificial, 399 Oil of mirbane, 399 Oleic acid, 354 Oleum, 82 Opal, 149 Orcinol, 365 Orthomtrosocresol, 68 Osmium, 190 Oxalic acid, 411 orfho-Oxytoluene, 270 Osone, 122 Painter's colic, 1 Paint remover, 295, 410 Palladium, 125,133 Papillomatosis, bladder, 398 ST0852325 INDEX [4801 Industrial Toxicology Paraformaldehyde, 349 Paraldehyde, 197 Pane green, 26 Pariaite, 94 Parroline, 434 Patronite, 187 Peach tree borer, 284 Pearle, artificial, 440 Pellagra, 434 Pentabromorosaniline, 877 Pentabromotoluene, 881 Pentachloroethane, 418, 442 Pentachlorophenol, 414 Pentaerythntol, 349 Pentane. 8(7 Pentanol, 218, 219 Pentanone-2, 891 Peracetic acid, 200 Perbenaoio acid, 229 Perchlorethylene, 448 Peremeein, 60 Petroleum, 861.428,430, 447 Petroleum naphtha, 894 Petroleum refining, 293, 878 Phenol, 5, 416 Phenoldiaulfonie act'd; 82, 119 Phenol-formaldehyde industry, 417 Phenolic resins, 271 Phenolphthalein, 417 Phenol red, 44 Phenylamine, 880 o-Phenyibenaamide, 814 PbenylMocyanide, 222, 251, 264 Phenylenediamine, 418 m-Phenylenediamine, 199 o-Phenylenediamine, 811 p-Phenylenediamine, 402,418 Phenylethane, 880 Phenylethylene, 487 Phenylhycfraxine, 209, 259, 854 Phenylhydrasine hydrochloride, 850 Phenylmethane, 448 Phenylpyraioline, 209 Phlogopite, 109 Phloroglucmol, 437 Phosgene, 268, 807, 309,463 Phosphate rock, 120 Phosphine, 187, 130, 350 Phosphorous acid, 129 Phosphorus, 189 Phosphorus oxychloride, 131 Phosphorus pentaohloriae, 130 Phosphorus pentaaulfide, 131 Phosphorus, red, 130 Phosphorus, tetra, trisulfide, 130 Phosphorus trichloride, 130, 213 Phosphorus tri-iodide, 387 Phosphorus trieulfide, 130 Phosphuretted hydrogen, 127 Phoeey jaw. 1 Photoelectric cells, 142 Phthalanil, 422 Phthalic acid, 396, 421, 468 uePhthalic acid, 468 Phthalio acid esters. aM Phthalic anhydride, 187,883,895,417,481 Physiological response and chemical con stitution, 4 Pioooline, 434 Pickling of metals, 27,77 Pioramic add, 10, 424 Picric acid, 415, 488 Picric acid in drinking water, 424 Piorolonio acid, 175 Plcryl ohloride, 424 Plmelio add, 270 Pimelic ketone, 876 Pinene. 463 Piperidine, 460 Platinum, 188 Platinum black, 132 Platinum sponge, 132,133 Plexiglas, 889 Plutonium, 184 Pneumoconiosis, 138, 177, 188 Pneumonia, 139 Pneumonia, lobar, susceptibility to, 189 Pneumonitis, 145 Polycythemia, 50,. 57, 249 Polystyrene plastics, 438 Polytetrsfluoroethylene, 65 Polyvinyl chloride, 466 Portland cement, 187 Potassium beryllium sulfate, 85 Potassium di-thio-oxalate, 115 Potassium nitromethane, 407 Potassium picrate, 423 Potassium tantalum fluoride, 61 Potato spirit, 817 Potstone, 165 Proflavine, 207 Propane, 856 Propanol-1, 487 Propanol-2, 488 2-Propanone, 804 Propene nitrile, 211 Propyl acetates, 426 Propyl alcohol, secondary, 428 *o-Propyl alcohol, 5, 204, 428 n-Propyl alcohol, 5, 427 tte-Propy) bensene, 480, 438 Propyl bromide, 430 Mo-Propyl carbanilate, 429 uo-Propyl chloride, 429 Mo-PropyI-3,5-dinitrobeuoate, 429 Propylene, 280, 361. 428 Propylene dichloriae. 299 Propylene glycol, 828, 829 uo-Propyl ether, 4S1 Mo-Propylidene&cetone, 389 ito-Propyl iodide, 301 n-Propyl iodide, 280 Mo-Propyl-p-nitrobensyl phthalste, 429 Proetigmine bromide, 406 Prussian blue test, 365 Prussic add, 363 S T 0 852326 Industrial Toxicology [ 481 ] INDEX Pyrethrin, 227 Pyrethrum. 165. 286 Pyridine, lVo, 264, 831, 888,414, 488 Pyridine ethiodide. 485 Pyridine methlodiae, 485 Pyridine piorete, 485 Pyrite, 91 ___ Pyroeoetio ether, 904 - ..... Pjcocateohin, 417 Pyrocateohol. 181 Pyrorallol, 61 Pyroligneous acid, 200 Pyrolueite, 103 Pyromueie aldehyde, 858 Pyrophorio alloy, 50 Pyrophyllite, 165,166 Pyrrol, 146 Quarts, 137.148 C uinaorine hydrochloride, 207 ( uinaidinio acid, 191 C uinalisarin, 17, 42, 69, 71, 88, 95, 101 Culnol, 436 Quinone, 485 Radioactive subetanoes, 140 Radioaotivity, tolerance level, 136 Radio antimony, 23 Radio oobalt, 67 Radio elements, 140 Radium, 140 Radon, 140 Ramassini, 1 Rationite, 808 Refrigerants, 466 Resorcinol, 5, 61, 284, 268, 350, 422 Resorufin, 52 Rhodamine B, 24 Rhodiionio acid, 33 Rivanol, 207 Rotenone, 165 Rubber cement, 432 Rubber, synthetic, 212,370, 450,452,456 Rubidium, 142 distribution in tissues, 143 Rubidium, silico-tungstate, 143 Rutile, 179 8afetv glass, 316, 440, 486 8aftifume briquets, 363 8alicylio aldehyde, 220, 465 Salt sickness, 57 Sand, 148 Saran, 291 Sarcoma, osteogenic, 141 Soheele's Green, 28 Schiff's reagent, 44, 199, 373 Beekay, 255 8elenium, 3,144 8elenium, radioactive, 145 8elenium sulfide, 107 8erpentine, 29,165 Sesame oil, 286 Shale, 137 Shaver's disease, 18 Ships, fumigation of, 363, 364 Siderite, 91 Silane, 151 ___ Silica, 147. 845 .... -- Silicic acid, 345 Silicone greases, 151 Silioone robins, 152 Silicone rubber, 152 Silicones, 151 Silicosis, 148 Silver, 158 Silver acetylide, 359 Silver fulminate, 154 Silver nitrate paper, 128, 131 Silver permanganate, 128 Soapstone, 164 Sodamide, 75 Sodium acetate, 201 Sodium alisarin sulfonate, 67 Sodium anilide, 220 Sodium arsanilate, 51 Sodium aside, 75, 158 Sodium bensenesulfonate-p-diaxonium chloride, 399 Sodium chloride, electrolysis of, 52 Sodium diethydithiocarbamate, 63, 191 Sodium diphenylamine sulfonate, 82 Sodium fluoride, 64 Sodium formate, 371 Sodium formyl sulfonate, 269 Sodium nitrite, 865 Sodium nitromethane, 407 Sodium nitroprusside. 86, 206 Sodium pentaohloropnenate, 415 Sodium rhodizonate, 156 Sodium tellurite, 170 Sodium tetraborate, 40 Sodium tungstate, 182, 188 Soil disinfeatants, 227, 293, 294 Soil larvicide, 407 Solaesthin, 995 Solvay process, 245 Solvent naphtha, 223, 394 Sphalerite, 190 Spine cells, 23 Spirit, wood, 371 Spotting fluids, 409 Spray painting, 55 Stannous phosphide, 127 Steatite, 164 Steel, stainless, 54, 114, 160, 179 Stellite steels, 56 Stibine, 22 Stoddard Solvent, 394 Stone flax, 29 Strontianite, 155 Strontium, 155 Strontium, radioactive, 136, 156 Strontium saccharate, 156 Styrene, 320, 487 Styrene dithiocyanate, 438 ST0852327 INDEX. [ 482 ] Industrial Toxicology Styrene monomer, 437 Sugar eane SuTfur, 167 g. rub, 284 Sulfur dichloride,168, 202 Sulfur dioxide, 161 Sulfur hexafluoride, 163 Sulfuric acid, 62 Sulfuric ether, 308 Sulfur monochloride, 169 Sulfur, pneumoconiosis from, 168 Sulfur trioxide, 161 Sulfur trioxide manufacture, 187 Sulfuryl chloride, 169 Sulfuryl oxychloride, 159 Superphosphate, 129 Sylveetrene, 463 Talc, 164, 286 Tannic aoid, 61, 104, 183, 188 Tantalum, 167 Tantalum carbide, 168 Tantalum fluoride, 168 Tantalum oxide. 168 Tar camphor, 896 Teeth, mottled, 66 Teflon, 65 Tellurium, 169 Tellurium dioxide, 169 Tellurium hydride, 169 Terephthalic acid, 468 Tetrachloroethane, 439 1.1.1.2- Tetrachloroethane, 439, 440, 441 1.1.2.2- Tetrachloroethane, 439 -Tetrachloroethane, 291, 439, 453 Tetrachloroethane collodion, 440 Tetrachloroethylene, 413, 442 Tetrachloromethane, 5, 378 Tetraethylenepentamine, 63 Tetraethyl lead, 77, 98, 470 Tetraethylrhod&mine, 24 Tetraethyl ortAo-silioate, 345 Tetrahydrobenzene, 278 . Tetrahydronaphthalene, 395 Tetrahydroxyquinone, 33 Tetralin, 395 Tetramethyldiaminobensophenone, 807 Tetramethyldiaminotriphenylmetnane, 104 Tetranitromethane, 444 Tetranitromethanatee, 445 Tetryl, 307 Thallium, 171 Thallium oobaltinitrite, 173 Thallium iodide, 173 Thallium sulfate, 172 Thermionic valves, 142 Thermite incendiary bombs, 32 Thermometry, high temperature, 68 precision, 126 Thetford mines, 29 Thiocarbamid, 170 Thiocyanate excretion, 212 Thiodiethylamine, 340 Tbiokol, 289, 452 Thionyl chloride, 169 Thiourea, 122 Thorite, 174 Thorium, 174 Thorium-aliiarin lake method, 67 Thorium dioxide, 174 Thorium fluoride, 175 Thorium nitrate, 67 Thorium oxalate, 175 Throium-x, 175 Thoron, 140, 175, 176 Thorotrast, 135, 174, 175 Thylox process, 85 Tin, 176 Tinkal, 41 Tin tetrachloride, 178 Tin tetrahydride, 178 Tin tetramethyl, 178 Titanium, 179 . in human tissues, 180 Titanium carbide, 179,180 Titanium dioxide, 179 Titanium fluoride. 168 Titanium pigments, 180 Titanium tetrachloride, 180 Titan Yellow, 101 TNT, 469 excretion of, 460, 461 Tobacco reaction, 255 Tobacco. thiocyanate excretion from, 212 ortAo-Tolidine, 52, 90 TToolluleenn'es,re18a7g,e4n3t1, ,149476, ,345638 Toluene piorate, 447 Toluidine, orfAo, meta, and para, 449 p-Toluidine. 203 Toluidine blue, 460 Toluol, 446 m-Toluylene diamine, 207 a-p-Tofyl-pyrrolidine, 433 Topaz, 64 Tourmaline, 64 Toxicity, 9 Tracer bullets, 32 Transuranium elements, 134 Tremolite, 165 Tribromomethane. 231 Tribromophenol, 417, 418 Tributyl phosphate, 298 Triohloracetio acid, 2)1 Trichlorobenxene, 229 Trichloroethane, 451 Trichloroethylene, 7, 265, 413, 463 TTrriicchhlloorroometehtyhleannee,p5o,is2o63ning, 454 Trichloromonofluoromethane, 347 Trichloronitromethane, 267 Triohlorotrifluoroethane, 347 Tricresol, 270 TriortAocresyl' phosphate, 74, 282, 466 Tridymite, 149 Triethanolamine, 468 Industrial Toxicology 1 483 ] ST085232B INDEX Triethylene glyool, 828, 820 Triethjiene glycol di(2-ethyl butyrate), Trifluoroethane, 846 0./S',P'-Trihydroxytriethylamine, 458 Trimethylamine hydrochloride, 878 1,1,8-Tnmethyl-cyclohexanone-5-eul- fonic acid-3, 866 3,5,5 - Trimethyl - 2 - cyclohexene -1 - one, 866 Trimetnylene, 880 Trimethylene bromide, 280 Trimethyiphenylammonium iodide, 388 Trinitrobensene, 395 2.4.6-Trinltro-l-ethylbensene, 321 Trinitronaphthalene, 896 2.4.6- TrimtrophenoI, 416, 488 TYinitrophenylmethyimtramine, 307 Trinitrostilbene, 466 Trinitrotoluene, 10, 895, 444, 466 Trioxymethylene, 295, 849 Tropfoel, 266 Trypaflavine, 207 Tryptophane, 210 Tuberculosis. 1 Tumors, bladder, 398 Tungsten, 181 Tungsten carbides, 182 Turpentine, 468 Turpentine oil, 463 Vinylbensene, 487 Vinyl chloride, 305, 451, 485 vinyl oyanide. 811 Vinylidene chloride, 291 Vinylidine, 305 Vinylite, 466 Vinyl resins, 867, 404, 466 Vinyl resin solutions, 409 Vinyl trichloride, 451 Visoose, 211, 247 Vomiting gas, 268 Watoh dial painting, 175 Weed killer. 26, 297 Welding rod coating, 179 Welsbach mantle, 50 Wire worms, 294 Witherite, 32 Wood alcohol, 871 Xanthate reaction, 427 Xanthogenate test, 241 Xenylamine, 314 X-rays, 140 Xylene, 467 piorates of, 468 m-Xylenol, 406 Xylidene, 489 Xylol, 487 .< Uranium, 184,188 Uranium, hexafluoride, 65, 184 Uranium isotopes, 184 Uranium tetraSuoride, 184 Uranyl salts, 184 Urobuinuria, 216 Ursol asthma, 420 Ursol D, 419 MoValerio acid, 243 Vanadio oxide. 186, i88 Vanadium, 188 in blood, 187 Vanadium pentoxide, 188, 421 Vanadium-sulfide, 188 Vanillin, 307, 408, 465 Vinegar, 200 Vinegar naphtha, 816 Vinyl aoetala, 316 Vinyl acetate, 466 Vinyl acetylene, 261 Vinylamine, 840 Zapon lacquer, 219 Zine, 189 Zinc blende, 190 Zinc chloride fumes, 190 Zinc chromate, 55 Zino diethyldithiocarbamate, 191 Zino hydroxide, 190 Zino naphthenate, 190 Zinc nitroprusaide, 163 Zinc phosphide, 127 Zino sulfide, phosphorescent, 140 Zircon, 192 Zirconium, 191 Zirconium-alizarin method for fluorides, 80 Zirconium oarbide, 192 Zirconium dihydride, 193 Zirconium dioxide, 192 Zirconium phosphate, 193 Zirconium eilioate. 192 Zirconium triethyl phosphate, 193 Zyklon, 363 ST0852284 V RKCKIVED SEP 1 G1949 Bioaiem. lies, t/epti BIOCHEMICAL RESEARCH Tha Dow Cbamfcal Company H & ES Library