Document zo5kGLbJYvnaKX8R8q6J0NLJm

FILE NAME: Metropolitan Life (ML) DATE: 1955-1960 DOC#: ML256 DOCUMENT DESCRIPTION: Met Life's Influence on Others' Writings Asbestos-Cancer 72 Asbestos: Medical and Legal Aspects in individuals first exposed afterwards. While the latter could have been unrelated to occupation in the regulated era, Smith acknowledged that people starting their employment in the 1930s "are only now reaching the mean age at which tum ors might be expected to a p p e a r."'"1" In the pualished discussion of one of Smith's papers, Dr. A.J. Lanza offered this incredible critique of M erewether's data:15" I think it is im portant to distinguish between cases of clinically recognizable and fatal lung cancer, on one hand, and cases in which the diagnosis of lung cancer has been made as more or less of an incidental finding at autopsy, on the other. The English claim for an association between lung cancer and asbestosis has been based, it seems to me, on data obtained from lungs that a pathologist has searched with a microscope. I wonder how many cases of lung cancer would be found if lungs from any sort of population were subjected to the same m inute scrutiny? Smith responded that the British Pneumoconiosis Board han dled silicosis cases the same way as asbestosis cases, and so the silicotics could serve as a ontrol group. In fact, the silicotics had an almost identical incidence of lung cancer as the general population, one tenth the incidence of lung cancer in asbestotics. In addition, many of the pathologists reporting excess lung cancer in asbestotics had done thousands of autopsies of the general population, and cited them as a comparison or "control" group. Further, no autopsy series of asbestotics was reported as having a "normal" rate of lung cancer. A nother person who commented after Dr. William Smith's report on European research on occupational cancer was Dr. Paul Cartier, of the Thetford Industrial Clinic in Q uebec.155 Cartier reported that his clinic had detected "eight cases of prim arv cancer of the lung" among an asbestos mine and mill working population of 4000. O ther cases were suspected, but only those cases confirmed by an autopsy (or biopsy) were included. Of the eight cases described. :wo were called "pleural mesothelioma." The degree of concomitant asbestosis c h ic a i o *o. U *> * .. J. iMMtf rv*t * m cm vcs ot Industrial Hygiene and Occupational Medicine <-ll> tU'l. (<!> O f t i W A t M * U l | , C I M I ! , CAD. O'illi. Watt. M R. (attui f !> J * 9 t i M. I U I M I " ' r t 1014 N. Broodivay, Cincinnati 2, Ohio, Januaxy 20, 1958 Dp* Daniel C. Braun IMXpal Bixvctor In d u stria l Hygiene Foundation o f America, In c. Ballon Institute, 4400 F ifth Pittsburgh A13v,enPueennsylvania Dear Dr. Braunj 00th Dr. P rlnci and I , having reviewed your paper, "An EpldomLolosical Study o f Lung Cancer in Asbestos Miners" are pleased tP accept i t fo r pu blication in the AUk Archives of In d u stria l H ealth. We fin d the report not only o f excep tion al in te r e st hut a model o f the epidexalologic method in d iseasea of tN lp g f; ' Qsy on ly c r itic ism was th at in pursuing the epidem iologic a t r i f l e long and one g o t the im pression toward tfcf end th at one had read th is before. I , m yself, was p a rticu la rly pleased to learn the main con clu sio n o f th e paper was a gain st the a sso cia tio n o f lung cancer w ith sa b esto a la , fo r I had come to a sim ila r conclusion on ob v io u sly f# r la s s inform ation but was afraid to say so fo r th is reason. I am en closin g a review which contains a few sentences th at I have m sr k e d in th is connection th a t appears in the Annual Review o f Medicine, Volume 7 , 1956. You w ill r e c a ll a t th is time evidence g rea tly favored the p o a itiv o co rrela tio n o f lung cancer on exposure to a sb estos. Sincerely yours, Enclosure Herbert E. StocAnger, Ph. D. "Acting' E ditor, AHA Archives o f In d u stria l Health ARE A review of what toxicologists and industrial hygienists are doing to develop threshold limits for concentrations of substances in the air, corresponding biological threshold limits, pretoxicosis tests, and pro phylactic and antidotal agents . . . and a discussion of recent de velopments in the techniques of air sampling and air analysis. Standards for Safeguarding tlie Health Of the Industrial Worker By HERBERT E. STOKINGER, Ph.D. THE EP1TOMICAL STATEMENT n in th some years ago by Dr. James A. Sterner, now medical director of Eastman Kodak Co. and past president of the American Industrial Hygiene Association, announced a chnnpe of attitude nmonp industrial hvpienists which to day is the keynote of onliphtened occupational health practice: "No substance is so toxic that it cannot be used if su/licient knowledge of its action has been made available; similarly, no substance is so nontoxic that it should be used without repard to caution." Currently, several effective means by which such a concept may be implemented are avail able: (a) threshold limits for concentrations of Dr. Stokingrr is chief toxicologist, Occupational Health Program of the Public Health Service, Cin cinnati, Ohio. Hr is a member pf the Subcom mittee on Toxicology, National Research Council; the Committee on Threshold Limits, American Con ference of Governmental Industrial Hygienists; and the board of directors, American Industrial Hygiene Association; and a liaison member of the American Standards Association. Formerly, Dr. Stokingcr mas chief of the Industrial Hygiene Section, Atomic Energy Project, Rochester, N. )'. Vnl. 70, N o . 1, Jnntiiirv 1955 injurious agents in the workroom air, (b) threshold limits of concentrations of injurious aponts or their metabolic products in biolopical fluids corresponding to the threshold limits for air (biolopical threshold limits), (c) tests of protoxicosis to screen persons for early signs of injury from exposure to hazardous agents, and (d) prophylactic and antidotal agents. Occupational hj'gienestandnrds in this coun try have been given various names, the most fa miliar of which is maximal allowable concen trations. Another designation *is threshold limit values, the name used by the American Conference of Governmental Industrial Hy gienists. Still another term is industrial hy giene standards, a designation recently adopted by the American Standards Association. All these terms refer essentially to the same con cept of permissible contamination of workroom air bv dusts, fumes, mists, vapors, or gases, although the bases on which the limits for certain substances are set may differ somewhat in the. different lists. The follow ing discussion will be confined chiefly to the list of threshold limit vnlues, writh which the author is most familiar. This list is prepared by the American Conference, of Governmental Industrial Hygienists' Committee on Thresh old Limits, winch is composed of persons work- 1 ingiii StHto and local industrial hygiene depart ments iinl in Federal industrial hygiene units, nnd members of (lie armed services in ibe F idled States and Canada. Only the Vnited Stales nnd linssin nppcnr to be currently developing stieli lists ns die tbresbold limits list, oilier countries preferring to use those already developed. Tartly because of ibis, but more especially because the ab breviated preface to (Ik*list only briefly refers to its application, tbe following paragraphs discuss in some detail tbe nature of the list and its purpose, methods by which the values are developed, and interpretation and proper usage of the values. Nature end Purpose of the List Tbe threshold limits list includes those nat ural minerals and oils and chemical substances, including economic poisons but excluding ra dioactive materials, in the form of dust. fume, mist, vapor or gas. which are in sutlicient ly wide use industrially to warrant control of their concentration in the breathing zone of Ibe in dustrial worker. ( 1'ermissible levels of expo sure to radioactive materials are independentlv set by various radiation protection commit tees throughout tbe world. Values for many radioactive substances may bo found in tbe Na tional Ihireau of Standards Handbook No. fr2.1 Heenuse of the rapid development nnd applica tion of certain choiyiirnl substances, often a timelng occurs between the industrial use of a substance nnd the appearance of the thresh old limit value. This interval, however, is becoming shorter as a result of increasing at tention of tbe chemical industries to the de velopment of data on the toxicity and hazards of their products prior to use. Limiting values assigned to each substance in the list represent the maximal atmospheric concentration to which workers may be exposed repeatedly day after day without injury to health. The purpose of the list is to provide a limit ing value of air concentration for injurious snbstnnces for use by plant engineers, indus trial-hygienists, and others concerned with the health nnd comfort, of the workers. The list, is intended to be a guide foe the co n tro l of w o rk ing atmospheres and to provide management, 2 labor unions, and the worker alike an nssurunee of healthful conditions on the job. Development of Threshold Limits A value for a toxic substanve is assigned on tbe basis of data accumulated from animal inhalation toxicity studies ami on tbe basis of industrial experience. Together, these repre sent, of course, ideal reipiircmcitts not always fulfilled for each substance in Ilie*list but ap proximated as far as possible. Of tbe two. industrial experience is the test on which (In validity of a value must ultimately vest. lte-t cause reliable information from industrial ex-! jMwieitee is frequently dillicult to obtain, tbe Committee on Threshold Limits is often forced to ivlv on opinion oi industrial hygienists, ratber than on factual information, or some times. merely on animal data. Such opinions, however, are based on specific experience with various substances and come from occupational hygienists throughout the country. The cur rent loxicologtrnl ^terntnre is also sentied continually for usable information.'"When the need for (he assignment of a value serins urgent, a tentative value is assigned on the basis of the 1ms< information available at the time. Originally, preventing impairment of health was virtually the only consideration in the selec tion of the proper limiting air concent rat ion of an injurious substance. Now. however, with the increasing emphasis in occupational health on the "total man," more subtle "effects on health, such as the efleets of annoying or irri tating agents, arc also considered. Thus, whereas a threshold limit value o f o r >1p.p.m. for chlorine would insure no impairment of workers' health, this value is reduced to 1 p.p.m. in die interest of greater freedom from irritant effects. The levels of oilier gases and vapors with irritant or other discomforting effects on the workers have heen similarly adjusted. The rapid growth in the number and diver sity of industrial substances to which workers are exposed and the increasing attention being given to occupational health in diis country have given rise to a very real problem of main taining the threshold limits list current. To meet, this problem, tbe Committee oii Tbresbold Limits reviews the lists annually, considering IV,Mir llrn tlti HrjM trl, 4gned on in animal /ir basis of hese repronot always list but n|). 'f the two. which tin rest. Bobistrinl oxobtain, tbp 'fton forced hygienists, i. or sonio1 opinions. icncc with <upnti>nn! The curo scnnnpd When tltp m s urgent, basis of tlie* if. '< of health ni theselec"centrntion ever, with Mini health effects on ng or irri- <1. T im s, or 4 p.p.m. lirment of to ] p.p.m. "m irritant 'ini vapors g effpets on nstpd. and diverli workers 'lion being is country oi of mninITPIlt. To Threshold onside.rinp Uli Itsp o rl- carefully encli vnbie and any new information essentially nonhnzardous or not inrnpacif nting. pertnininiT to a change in level. When n value Numerous reports from various countries make is changed. it is so designated. it nil too apparent that, many dusts formerly In the threshold limits list for 1UM. a fur considered inert, are rnpnble of producinp pul ther necommodation has been made in an at monary ehanpes flint are oftentimes disabling tempt to keep pure with the ever-increasing use ( / - / ) . It would therefore seem that, all in of new industrial chemicals. This is the addi soluble dusts of whatever lint tiro should he tion of a tentative list separated,from 1lie list l of established values. Henceforth the tenta bold suspect until proved otherwise. (^). Un fortunately, the assignment of a specific level tive list wiTl include all substances not pre- for each mineral dust is impossible at. present. viotislv listed. Because of the lesser certainty Mineral dusts are commonly of complex and sometimes associate! with these tentative val inconstant composition, often varying ncoord- ues. they should provide only general guidance inp to locality, and thus are potentially capable in the control of exposure and should carry no of caiisinp a variety of physiolopicnl response"?. lepal weiplit. The tentative list is looked upon As n rase, in point, pulmonary carcinoma is n* providinp levels under trial and test, to he commonly associated with the long-term in revised when new information justifies. Sub halation of nsliestos in Enplnnd. but. not in stances in the tentative list will not. be incurporated in the main list until the values have lieen Aismalesroicdaiff(i.cVu)l.t beAcsasuispenmpuclnmt oonfarsypecchiafincgelsevdeels r proved lv experience to be acceptable. It is rive! from the inhalation of mineral dusts imped that the. tentative list will stimulate a commonly reipiirc years to ass*ss. beenuse sound preater nnmlcr of yearly additions than in information j'i'latinp exposure to response is the past, as well as the critical evaluation if not. for the most Jart. available, because ex these values by preater numbers of industrial posures are not uniform owing to changes in hygienists. the industrial process ami jh changes, and be cause dusts from operations involving the same Overall Maximal Upper Limits materials often differ in size and surface area. Th*refire. it is believed that flit? validity of It is now considered desirable by a majority (lie present standards for dust should be re of the persons concerned with occupational viewed and onsideration given to the follow health to assipn a maximal upper limit of 1.000 ing suggestions. In the absence of informa p.p.m. for most, although not. all. of the gases tion and in view of th> poor prospect of ob and vapors that are apparently imntoxic or taining any in the near future, the conclusion nonhnzardous. Such a limit has l>eeu set for seems iimscapnblc that if protection from dusts certain Freons and other apparently innocuous is to be guided by hygienic standards, an overall substances, althouph it is known that neither limit value should be selected. Actually, two health nor safety are endanpered by expo.-nre values appear lesirable. one for lusts contain to far hipher levels under ordinary conditions. ing fr*e silica, and another for nonsilicooiis In favor of this practice is the argument that d u sts. it will prevent excessive or wanton exposure , For silica-bearing dusts, a limit of from il to air contaminants. It is recognized that all too million particle per cubic foot (m.p.p.c.f.) the facts needed to assure safety are seldom at is suggf'sted. It would be applicable to those hand. Physiologically inert substances, such substances containing free silica of any ap as certain Freons and sulfur hexafluoride, in preciable percentage (10 percent or morct. unlimited concentration may suddenly become Such a level appears justifiable on the basis hazardous, in the presence of weldinp or plumb- of usage and experience, ns shown in table inp operations, throuph decomposition bv beat 1, and tacitly assumes no other mineral is more to hiphly toxic products. hazardous than silica and/or any combination A similar concept is developing with respect of a mineral witli silica. Actually, this value to dusts that in the past have been considered represents a rather low level of exposure when Vol. 70. No. 1, Jnnim ry 1955 3 expressed in terms of milligrams of substance per cubic meter of nir. Depending upon par ticle size, ft m.p.p.c.f. silicon dioxide (SiO-) with n density of 2.2 might range from 0.0] or 0.02 milligram to several milligrams per cubic foot, assuming the general size distribu tion of industrial dusts thus far recorded by optical methods (.9); with dusts differing in density from SiO,, corresponding differences in weight, concentrat ion, of course, would occur. The. question then arises of how best, to express the dustiness of an atmosphere. Although this concerns matters too involved to be entered into here, it would seem that, with an absolute method now available for the measurement of industrial dusts, the limiting concentrations should be expressed in terms of cither millions of panicles per cubic foot or milligrams per cubic meter, or both, but within a definite size range, this range to be 0-3 n diameter. Other wise, dust counts, as well as expressions bused on weight per volume of air, become meaning less. Particles of the size 3 n and below can now be sampled and measured nnd arc believed to be the only ones of hygienic significance. Whether the value approximating 5 m.p.p.c.f. will be found to hold when the submicroscopic particles arc included is n very important proj ect for future investigation. Table 1. Recommended permissible limits of some silica-bearing d u sts1 Industry or source I Report <<) pcrceni five Si(V Iteeom- iiicnded concen tration m.p. p. c. f. Svdnev sandstone___________ Silica brick.... ......................... __ Gold mining (Union of South A fric a !..________________ Granite.......... .............................. Pottorv........ ................................ Gold mining (Ontario, Canada) Pyropbvllite................................ Anthracite (haul r o c k ) ........... Nonferrous mines....................... Anthracite (haulageways)......... C e m e n t.......................'_______ <10 so so so ao-40 ao 20-40 la <> i 0 2 3 0-20 4 * s. s 10 -10 r>-io 1(1- is 20 1 From a table prepared by Theodore F. linteh. professor of industrial hygiene, University of Pitts burgh. * Values are approxim ate.. * Owens Counter. * Konimt-lcr. 4 A practical threshold limit value for nonsiliccous dusts would appear to be ft nig./m.* This value has been in satisfactory use for some years for controlling hematite dust and fume in at. least one. American plant (JO). It would seem to represent a reasonable level of dusti ness for all other presently considered "inert" nonsilicoous inorganic dusts. More Specific Designations W ith increasing industrial hygiene knowl edge and experience, refinements in designating specific substances to wbicli values are assigned will assuredly follow. As yet, however, only n licginning has lieen made in this respect. Fov chromium, the designation specifically refers to chromic acid or to chromates. The highly poi sonous arsine gas has a threshold limit- value of O.Oft p.p.in., whereas the value for arsenic and its compounds is 0.5 nig./m.3 Differences in toxic action of- uranium compounds have been recognized by individualizing the soluble and insoluble compounds. It would appear that mangnnesc dioxide would be a desirable designation for manga nese, because manganese dioxide is the most common industrial hazard of this element. Mercury at 0.1 mg./m.5should refer to mercury vapor and its inorganic compounds and should not imply inclusion of the more toxic organic1 mercurials. Similarly, for fluorides the newer organic fluorides which vary widely in toxicity and hazard should be explicitly excluded, and for selenium, the threshold limit, should apply only 1o selenium compounds which are highly toxic, not to elemental selenium dust, which is essentially nontoxic. The value of 0.1 mg./m.' for cadmium should refer specifically to the cadmium fume, for use of this limit for most of the insoluble cadmium compounds imposes far too severe a restrict ion. Different levels for lead and its compounds should be specifically defined according to information accumulated in tin* lead industries in this couiitry over the past JO years. Data show that, whereas there is no reason to alter the value, of 0.1ft mg./m.* for lead f ome or fo r lead dust of subniicroseopic size, this value is unrealistically severe when applied to the more, insoluble lead salts, nnd probably too lenient if applied to certain or- Publie Heolth Iteporl* )o. know]Hgjiftting ' assigned or, only ft eot. For refers to iplilv poiiiiit value nrsenic rt*ronces in have been luble and r dioxide >r manga tlie most element. 0 mercury >nd should ic organic Hie newer in toxicity 'titled, and >uld apply are highly which is 1 mg./m.* llv to the for most Is imposes t levels for peeifically 'umnlated y over the `I.Treamspt.h/ienre.3 licroscopic vere when salts, and certnin or- lili Report* ' '; ffnnic lead comjoumls. Tliese ami other de sirable refinements in the list will undoubtedly lie nmdc in the near future. Biological Threshold limits One new feature of occupational hen1th standards that appears destined to piny a use ful role in evaluating personnel exposure in industry is wlnit might, he called biological threshold values, for want of n better term. These values refer nt the present time to the greatest permissible content of an air con taminant or its metabolic deriviitives in the. Iiodv fluids, usually in blood or urine, al though changes in other bodily const ituents tnnv in time serve also ns measures of exposure. A list of biological threshold values, which eorivsjsiiid to the threshold limits for concent ra tio) of the substances in air, is given in table 2. The values given for some of the substances are tentative, having been derived from limited experience; for others, such as lead and fluorine, the values are well founded. For still others, such as arsenic and mercury, there is considerable disagreement- among indus trial hygienists as to the usefulness of urinary determinations. It is probable that the biological thresh old limits of only a few selected substances will ultimately And an accepted place in occupational hygiene standards, since all sub stances are not amenable to accurate analysis in Iiodv fluids (complex organic molecules) by reason of wide individual variation in metabo lism. interferences from dietary sources (arsenic), or simply the relative absence of constituents in easily obtainable body fluids (chromium, manganese, silver, and probably beryllium). For biological values to be serv iceable, repeated determinations must be made on each person exposed, and preexposure con trol determinations are desirable. When bio logical threshold limits are used, they should supplement determinations of air concentra tions, not replace them. In effect, these biolog ical limits substitute diagnosis for the control or prevention of injury provided by air nmdysis. t urrently, in the lead industry, considerable enthusiasm is being expressed over the ap- T a b le 2 . B io lo g ic a l t h r e s h o ld lim it s ' S u b sta n c e i b lo n d (m g ./ !1 0 0 m l.) b r in e ( m g ./ Id I iiu r g n t iie e m is i it i t e li A r s e n i c _______ __ _ . I * (0 .5 fu r a r s in e o r le w is ile l. H e r v l l i u m ................. ( ' a d n u u n i ______ . C o p p e r ...................... _ C h r o m i u m ________ L e a d ...................................... M e r c u r v ......................... ___ __ _ ... . 0. 1 :............. ; . o k 1 0 .0 0 2 . 0 .1. A n v d e le c lu b le 0 .2 . 0 . 2 5 . lim o n ili M a n g a n e s e *.. T h o r i u m ......................... 0 .0 0 1 . N o t e l i m i n a t e d in e l i c n e ~ ie a lly m e a s iir n b le n u m m i . V a n a d i u m .................. 0 .0 5 .* C r a n iu m ... C h lo r id e . . . . . S e l e n i u m ................... T e llu r iu m . . . . i. . . 1 0 .0 1 . 4. 0 .0 7 . 0 .0 1 . Organic constim eli benzene......... . . . . . . J 10 percent below liornml ! sulfate ratio of inor- panic to total sulfate. Itroiniile............... . . .iltltl ('arlm ti disulfide__ . . . . . . . 0.J5. D initro-o-eresol....... .................. M ethyl aleoliol......... ........... , AA-.7. M ethyl acetate.......... Analyzed as methyl al- Toluene (as hippurir i............. 3,0r0o0li.ol. acid). Triclilo ro rth ylcn e I ............... 70. (us trichloracetic ! acid). 1 Many of the values given here are found in or have been revised from Chemistry of Industrial Toxicology by II. U. Elkins, New York City, Wiley, 1950, anti in Analyses ol biological Materials a Indices of Exposure to Organic Solvents by Elkins, A. M. A. Arch. Indnst. Jlyg. and Oceup. M. 9: 212-222, March 1954. - 11. 11. Schreiik, in New Information on Arsenic Trioxide, Ind. Eng. ('hem. 45: 11A (1953), stales that urinary arsenic values of 4-0 m p./l. are commonly not associated with signs of arsenic poisoning. Use of urinary values is considered of doubtful worth because of great variation in normal values. Dietary arsenic, Mich a* that obtained from seafoods, would greutly niter the urinary arsenic picture; moreover, arsenic is excreted chiefly in the feces. 5 lTinary values may not always be reliable in long term exposures owing to |iossibility tjf development of lower nephron nephrosis and for ither reasons. 4 Inasmuch us manganese is eliminated chiefly via the intestine, urinary determination is not a particularly valuable indicator of cx)x>surc-. 1 Tentative value. \o l. 70, No. 1, January 1955 :w:!2M--nr,------ parent 1y successful use of urinary lend values with or without prior screening by urinary coproporphyrin determinations. 'Die argulnont. in favor of tlit*usoof urinary values is that in prm-t it-omost industrial oxposnros aro neither uniform nor simple, hut aro mixed, and, there fore, that. the. laxly serves as a lx*tter sampling dovioo and indicator of this type of exposure than do air samples, Biological determinat ions also oiler a guide in the diagnosis of illness not provided by air analysis. Whether it is a wise decision to allow the individual to serve as his own indicator of exposure is debatable: De rangement of metabolic function or excretion for various causes is not. uncommon among working populations, especially in older age groups, and concomitant exposure to other sub stances or other stresses may deflect normal metabolic pathways. It. would appear reason able. for the present at least, that biological values should be accompanied by one other in dependent method of evaluating the working environment. Interpretation and Use A fter the threshold limits have been accepted, it is most important that they be properly in terpreted and used. Because there is some lack of agreement among industrial hygienists ns to the use of the"vnlues, it might he worthwhile to consider what is jncnnt l>v threshold limit or maximal allowable concentration. Confusion appears to center on the precise meaning of the term "threshold" or what- constitutes "maximal allowable." These are brief terms used to ex press a rather complex and abstract concept which may he explained philosophically and operationally. Philosophically, the threshold limit repre sents a level to which a normal healthy worker may lx* exposed for 8 hours each workday with out harm to his physical or mental well-Wing. Because, in practice, most situations involve in termittent or varying exposures, the concept of the limit is that the summation of physiological effects of such exposures shall not lx* greater than the effect of exposure to a constant con centration at the level of the limit. Operationally, the word limit refers to the highest, permitted averaged values of an agent in (lie workroom air that have been obtained in a complete cycle of operations during the day. Proper averaging of concentrat ions should take into consideration the duration of exposure at each concentration: this is referred to as a "weighted average." ('onccntrations far above the limit for periods of :to minutes or more and prevailing sporadically throughout the day, although possibly ei|iialing the jhreshold limit, are not within the intended meaning of the term. Such levels come under the classification of acute, high exposures, and suitable measures should he taken to bring such levels in line with the accepted limit. Threshold limit values are not Imscd on high, acute levels superimposed on a persistent lower level irrespective of what value their average is. Threshold limit values should lie used as guides in the control of health hazards and should not lx* regarded as line lilies between safe and dangerous concentrations, that is, a point above which injury is lMumd to occur and below which complete safety may lx* ex]x*cted for all exposed persons, ('omjx'tent judgment, is re quired here ns in the interpretation of any standard. Misuse of Limits The threshold limit .vulues should lx* used only for control of exposure atmospheres for repealed 8-hour working days. They should not he used in the. following ways*. 1. For brief acute exposures. (The thresh old limit, values have Wen set. on the basis of chronic exposures, not on the. basis of brief acute exposures.) 2. For mixtures of substances. (There is no assurance, that, mixtures may not have potenti ated and enhanced effects greater than the summated effects of each component.) 1. As levels for community air pollution or for levels to lx* derived theivfrom by simple extrapolation. (The threshold limits have been set on the basis of an 8-lionr exposure day with the assumption that a subsequent 38-hour jx*riod of noiiexposure will aid distribution and elimination of the toxic agent, from the body; therefore, they ennnot apply to 24-hour continuous exposures common in air pollution conditions.) f> Public Health Itrjiorl*. fill Jny. ` #/takc Are ut ns h nr aliovc non* and he tiny, Id limit, t lit*term, ation of measures line with allies arc *posed on of wlmt -f1' . >* ` - -. ' t'\X ^ '4 . As levels of permissible concentrations in community wafer supplies or for substiinees in solution. *(Appropriate levels have been fixed sjiecifienllv for severnl toxie elements in potable waters.) As the basis for selectin': dangerous eoin- pnumls for labeling. (Hazards involved in handling ebetnienls frequently rise from routes other than inhalation, which is the lmsis for threshold limits.) f,. As safe limits for flight personnel in avia tion. t Higher standards of safety and per formance are required, and degree and duration of exposure at flight altitude differ front the degree and duration at sea level.) used ns aids timi ween safe s. n ]M)int and below 'ed for all lentr is reai of any d lu* used plieras for iey should he threshhe basis of s of brief There is no )ve potenti ni the sum- -'ollntiou or bv simple imits have \1 insure day 'eut lC-hour distribution it. from the to 24-hour 1 sir ]K>llution Pretoxicosis Tests Closely related to the biological threshold values are tests of pretoxicosis, the detection of subtle metabolic ehnnges in the body before in jury of serious proportions has developed. The idea is not new, the first, reported test of this *ort. having been applied to the hematologic re action:- of presaturnism by Heim de llalsac in Hmi> (77). Although the determination of pretoxir reaction is unquestionably one of the highly desirable goals of the industrial toxicol ogist. few such tests have been developed mainly liecause the mechanism of action of most toxic agents on which such tests are based is not gen erally known. A pretoxicosis test for carbon disulfide lias been reported by Bourguignon (72). This test is based on the change in chronaxia, which, in turn, depends upon the knowledge of the vas cular and neurologic changes caused by carbon disulfide during the early stages of injury. Chronaxie, by definition, is the minimal time bat au electric current of standard strength is required for the excitation of the tissue. Uourguignoivs report, indicates tlint after men lead been exposed to carbon disulfide for only 2 months and before any clinical signs of disease "ere manifest, their clironaxie changed. Ac cordingly, this test permitted early detection of intoxication by carbon disulfide. Another test of preto.vieosis that is promis ing although it is still in the developmental stage is the lowered cystine content of finger nails of individuals exposed to vanadium. The !ridili Itrport** ^1. TO, ISu. ) , Jnnuarv 1055 lowered content occurs in the absence of any ob jective or subjective signs or symptoms in the workers, and it bus been experimentally demon strated in tin* Jiair of animals ingesting vana dium compounds in amounts tlmt caused no demonstrable signs of toxicity d o ) . When used in combination with urinary vanadium determinations, the test npjienrs to be high!)' suggestive of early metabolic changes result ing from exposure to vanadium. The well-known urinary coproporpliyrin H I screening test for lead poisoning might well be classed as a pretoxieosis test. Used in com bination with urinary lead values, it is now considered a reliable guide to incipient damage by lead (7.J). At potentially harmful body levels, lead is believed {l) to convert, more of the normally occurring colorless precursor to the ebrojiiogen while increasing the total copro porphyria of the urine. The relative paucity of such procedures at tests to the extreme difficulty of their develop ment. Investigators should he encouraged to develop this aspect of preventive medicine, however, liecause its value obviously transcends that of diagnostic tests of established disease. Prophylactic and Antidotal Agents As the realization of the importance of toxi cology in the development and safe use of im dnstrial chemicals has widened, more diversi fied groups of scientists have become attracted to its problems. Such attraction lias resulted in the development of a metal eomplcxing agent, the calcium salt of ethylene, diamine tetraacetic acid (CaEDTA), for the treatment of lead poisoning (JO). This chelating ngent has been given good evidence of effectiveness in mimerons clinical trials (77,7<S), and it gives promise of considerable versatility. It lias been found, for example, to be a satisfactory antidote in experimental vanadium poisoning (Iff) and to give promise in the treatment of essential hypertension (JO). Further use of CaEDTA for the more rapid elimination of other toxic metals having the capacity to com plex firmly with this chelating agent lit body pll conditions will undoubtedly be made. Since the advent of UAL (2. ff-Dimercaptopropanol) for combating arsenic poisoning, no other orpin- complexing agent Inis proved of Kiu'h value., although others, siu-h tis nnrin tri carboxylic. acid for the elimination of beryllium (" /), Juive been su rested from time to time. An ingenious and novel use of a complexing agent for combat ing cyanide poisoning lins been recently reported (.'yanidoless vitamin Ili;. (vitamin H,A hydroxo-eolmlamin) is capable of tightly coordinating with the cyanide ion in experimentally poisoned animals and thus preventing toxic symptoms and death. Well-known reducing agents, such as ascorbic, acid, have been reported experimentally at least to be effect iveprophylactieally against a variety of toxic agents. For example, vitamin 0 was shown to function as effectively as CaEPTA against vanadium poisoning in animals and this vitamin is reported (~J) to reduce substantially fat.nl pulmonary edema and hem orrhage in animals inhnling ozone or nitrogen dioxide. Essentially eoinplete protection against fatal ozone exposing? in animals was afforded by a mixture of sueb reducing sub stances as glycuronatc, cystine, and other sim ilar substances that include vitamin ( \ Two-carbon- fragments administered as etlumoi, acetate, and propanol lutve been re ported \o be capable of combating the highly toxic fhiorncetate (1080) in animals ( - j) , and they give promise of successful therapy for this poison. Cystine, methionine, and other sulfur- containing amino acids have been suggested as more general aids to the detoxifying capacity of the liver for protecting animals against the toxicity of 1,2-dichloroctliane (L'o) and methyl- chloride (2G). Within the last few years, atropine has proved an effective antidote for parathion and other closely related organic phosphorous insec ticides. Air Sampling and Analysis The development of valid threshold limitvalues goes hand in hand with the development of accurate procedures for sampling and analysis of the industrial atmospheric con taminants. The .1fi/fi/iorc F ilter Unquestionably, the greatest boon in recent years to such a development has been the in troduction into the field of industrial hygiene of the Millipore filter known also as the membrane filter or molecular lilter. This filter has an ellicieney of sampling airborne particulates approaching 100 yercont for all particle sizes of hygienic significance. The ];>() (i thick paper of cellulose acetates and ni trates with SO to 8 percent voids possesses n high dielectric constant and effectively attracts even nonelnirged particles of infinitely small size to its surface despite a mean pore size of (i.8 /i. Tims, the puper possesses a collection efficiency independent of the particle size of the nenisul. A limitation of the paper is that oils and tars clog the lilter in n very short period of time, making it. useless as a sampling medium for these materials. Valuable use may he made of the property of the membrane to become transparent upon the addition of a limited amount of solvent (ace tone, acetates, alcohols). This transparency permits the collected air sample to be directly counted under the optical microscope over a circumscrilied, known area of the filter, thus providing a permanent dust mount that, mnv he <piantitali vely analyzed. Further advantage, has l>een taken of the solubility characteristics of the Millipore filter by Fraser (29), who combined the high sam pling efficiency of the paper and its solubility properties with electron microscopy to develop for the first time an absolute method of sam pling and analyzing solid airborne, part enlates. In outline, the. procedure consists of {a) col lecting a sample of airborne particulates on the Millipore filter, {b) effecting transfer of the particles to a prepared electron microscope spec imen screen after solution of the paper, (e) photographing the particles, and {d) deter mining the size distribution of the particles by visual measurement, from their projection on a screen. ]l is st rongly urged that industrial hygienists take advantage of this powerful technique to explore the heretofore unsampled and u n se e n particles of industrial atmospheres and use. such information to aid in the determination of their 8 I'tihlir Hcultli ltf|vnrl rut ;* ingicne ,-llsO us /. Tliis airborne t. for all The s ami nissesses a v attracts 1y small e size of Hcction ize. of the flint oils rt period .r medium 'party of upon tin* out (aceosparcncy e directly :e over u Iter, tlius it may be n of the pore filter high samsohibility pdevelop d of samrt iciilates. f (<i) ool ites on the fer of tlie 'ope spec^nper, (c) >?) deter*rl ides by t ion on a hygienists hniqne to *id nnscen d list* such 'ti of their *ili Itrp o rl industrial henltli significance. The results of such a study could well revise some of our con cepts of the effective number of particles re quired to produce, pneumoconiosis. In the light of tliis and other recent develop ments, the Engineering Section of the Occupa tional Health Field Headquarters, Public Health Service, lias undertaken an extensive reinvest igation of the entire field of dust, sam pling and measurement, with the objective of developing improved generally acceptable methods that incorporate the advantages of these advances. Already the investigation lias led to a promising use of the. transparent prop erties of the Milliporc filter, referred to above, as a dry. permanently fixed, dust, sample, for on-thc-sitc use in plant or factory. An automatic instrument which continuously records the mass concentration of dust in the atmosphere lias recently been introduced (30). This instrument is based on the photoelectric measurement of forward-scattered light from solid or liquid aerosols and lias a range, from JO-3 to 10'=Mg./l. in terms of dioctyl phthalate as 0.;5 n diameter droplets. A further modificalion of this device is being undertaken hv Da vid Sinclair of the Johns-Manvillo Uesearch renter in the development of an instrument which will indicate the size of the particulates a- well as their concentration bv electronically computing the ratio of backward and forward scattered light from the particles. Another development in dust analysis tech niques is the use of the electron microscope as an electron diffracting instrument. This tech nique is capable of exploring the surface of particles to the depth of approximately 0.05 p in respect to their crystallinity or lack of it. In conjunction with X-ray diffraction techniques which determine similar properties within the core of the particle, it may provide, much useful information concerning the relation between the physical structure of dust ami its physiolog ical effects. At the Occupational Health Field Headquarters, such work is beitig done on tho various forms of diatomaceous earths,.and in Scotland, on various types of silica (SI). E f forts along this line arc expected to go far in helping elucidate the etiology of various types of pneumoconiosis. Vaporn anil (timi Developments in sampling and analysis in the highly individualized lield of vapors and gases during recent years have yielded no new principle or device, but rather they have found application for many of the methods long used in other Helds. The study of air pollut ion lum given a sudden impetus in this direction. Among the recent innovations used in the. air pollution Held are the portable Venturi scrub ber {>'), which lias jroved satisfactory for sampling ammonia, nitrogen oxides, aldehydes and sulfur dioxide, five/.e-out trains, large* capacity plastic bags, silica gel, nml other solid absorbents (.>'/). For the analysis of organic pollutants, the in frared analyzer and the mass spectrometer arc being explored rather widely. Chromatographic procedures have also aided in the confirmation of many often closely related organic sub stances present in the nir. Automat mTappcurs to he the only really new basic development in this Held in recent, years. This principle has been most successfully ap plied to the measurement of sulfur dioxide in the form of the Thomas Autonieter (<?.{) This instrument is especially useful in situ ations where round-the-clock measurements are needed, or with further- attachments for sig naling added, it may be used successfully for control of gaseous concentrations. Automatic analyzers have also been developed for halogen analysis, for carbon monoxide (3o), and for other substances. It should be emphasized that such automatic recorders in their present state of development require careful standardization and repeated attention and maintenance to assure, faithful recording of actual concentra tions. Commercially available, recorders vary widely in this respect. I f original design has been good and the. instrument carefully stand ardized and maintained, the saving to industry over the years far outweighs the relatively high initial cost. Increasing automation is foreseen for the coming years in this and related fields of analysis and control of nir concentrations of conlaininants. It may seem unfortunate that many of the recent, developments in the industrial hygiene. Held often involve the use of equipment that is ^ol. 70, Mo. 1, Jnmiury 1955 9 (xpcuMvc ami imu purl nlilp. Jmnmhilil y, Inn not expense. is fust lieitijr overcome when tin* n m l (li'iiininls. A moliilt- infrnm l analyzer Inis lit`i`ii tlesipietl ('Ml) mid n pnrtnlilr muss spec trometer iis well (.;?). ] Ij^li cost, n f net or necessarily nssorinleil with increased complexity mid sensitivity, will ho slower to ho overcome. Copies mental o / f the Ame m l listno/ 11rican Confe /t/ie lists' renc Jixt e o o f f t dovernhreshold limit value? 111111/ he obtained from Allan L. (,'airman, chairman o f the Committee on Threshold Lim ils, Connecticut State Depart ment o f Health, H artford <i. Conn. REFERENCES ( / ) 1'llliner. 1... unit Hicks, M. S .: lliondihil carcinoma mint piicuinot-oniosis) in dusty occuimtions; ( ihservalinns in holler scnlcrs nml grain dockers. Itril. .7. Tuhorr. -I": 14i>--1-ti*. July 1953. (2) Ituttner, J. I t.: Foundry workers' imeunniconiosis in Switzerland (nnlliraeosilieosis). A. >1. A. Arch. Intlusl. H.vp. nml Oecup. M. !: 297-305. April 1954. 1 1 imliii. ( itliee ol <'liief Adviser Fartm-ies : SilirosN in mien milling ill liilinr. UepoU No. New Delhi, The Otiice, lir a . 1 J1 Mnrclinn, I>. M.: l'lieuinoconiosis wiihout tihrosis. Arch. hig. ruilu 4 : ill-' 111153). |5 ) Martin, J. Jr.: Coal millers' pneumoconiosis. Am. J. l'uh. Health 44 : GS1-591 (1954 1. 1Hi Ahrunis, II. K .: liiniomneeous earth pneu moconiosis. Am. J. l'uh. Health 4-1: 592-599 (1954). (7) Smart. It. II.. nml Anderson, \V. M.: Pneu moconiosis due to dintomaeeous earth. Indust. Med. & Surg. 21: 509-518, November 1952. im Lanza, A. J . : Asbestosis. In Pais-rs presented 111 the Fourth Conference of the McIntyre Re search Association on silicosis mid aluminum therapy. Norando, Canada, Norando Mines. Ltd., Jan. 1952. t.'M Hloomlield. J. J., nml Dnlln Valle, J. >1.: Deter mination and control of industrial dust. Puh. Health Hull. 217. Washington. D. ('.. F. S. (iovernmeut Printing Oilier, 1955. i in 1 Weher, 11. .1.: Threshold limits of metnl fumes. Purl of a panel discussion at the annual meet ing of the American Industrial Hygiene Associa tion, Chicago, Apr. 27,1954. ( / l i Ileim de llalsnc el Agasse-La Font : Le dcpistnpc On salurisiiie Inlcnl par rrxnmi-n do sang. Hull. Acad. Med., 1908, p. 14(19. </2i ltourguignon, (.: Apparition d'alli'-rntions de lu ehroninxie nvant toute munlfestation elinhpu- IO lans un ras irintovirntion sulfo-rnrhniiri- pio. l'esslouelle. Ini Ioduri Ioli il rlmle des prf`loxii-oscs. Unii. Acmi. imi. nn'-d. 134: 2x7, 2SP ( 1950). I /.fi Mouiilaiu. .1. T., Ddki-r, 1,. 1... and Stoklnger, Il li.: Stiiilles in viinnditiui toxieology. I. ltedurllon in die eystine eonteut of th rat lialr. A. ,M. A. Ardi. Imitisi. H.vp. A Oeeup. SI. S: 400411, Nnvemlier 1953. 1 / ) 1 lliirold. (. C,, Slt-ek. S. F,, ami Padden, D. A. : A eoproiHirphyrlii III test iis 11 tneiisure of lead daiuage. Considerine lead dust of relatively largo pnrticlr sino. A. SI. A. Ardi. Imitisi, live, ami ( li-rup. SI. tl : 24-31. .luly 1952. 1 /'<1 UriteaIli. 1,.. and trandi-s, C. : Sulla preseu/.a ilt-un-preeursore eterosoluhlle lid ie prollrine nelle urlili- di nildeii alla Inimriiziime con piouiho IPresem-e of elher sol olile pri-cnrsor of Imrphyrin In urlile III workers cx| mihi>i1 Io lead). Sled. lavoro 44: 113-123. Slareli 195:!. 1 /i-'i ltnliin. SI., (igiim-, S., llessniaii, S. P., and lielknnp. li. L. : Knhaiieenieiit of lead exeretlon in humatis hy disodium ealdtiin elhylem-diamiuilelriiaeelate. Sdi-nee 117 : ti5'.Miltl. .lune 12. 1953. t 11 1 Cutter, 1jt- II.-, Treiilinenl of lem) imisoning hy i hi-lalion. .1. A. SI. A. 155; tHNt-HIS (1!I54). 1 / 1 Hardy, H. L.. lilkins, II. li.. lUiatola, li. P. \V.. and (Julnh.v, .).: Use of uioiiocalciuui disodium i-ihyli-ne diamine tetra-aeetate in lead poisoniug. .1. A. SI. A. 154 : 1171-1175, Aprii 3. 1954. ilt'i .Miteheli, W. (!., and Floyd, li. P .: Asoorhic acid and ethyli-m- dianiiiii- tetra-aeetate as antidotcs in px)ieriim-ntul. vanadiuiu ]misoning. Prue. Soc. lixper. Itiol. S5': 2(M!-208, Fehrttary 1954. i - ' " i l-opoviei, A. Ci-sdiiektei-. C. S.. nml Kulan. SI.: Treatment of csscntinl hy|iertensioii hy magnesium cheilite soluiion. liull. (eorgetown l'niv. Sled. Center 5: Itis-IHI, Oetoher-NovemlM*r, 1951. (2 /1 Whlte, SI. H.. Finkel, A. ,1.. and Sehuhert, J. : Pr<>teetlon against ex|N-riimuital la-ryllium polsoning hy. mirili trlearhoxylie ueid. .1. Piuminieoi. A lixper. Thernp. 102: 8S-93 (1!i51), <22i Mushelt. C. W., Kelley,-K. L., lloxer, C. K., and Itichards, J. C. : Antidotal etlieaey of vittimili P-i:` IhydroxiK-ohalnmin 1 in ex|ierimeutul eyatilde poisoning. Prue. Soi-. Kxts-r. Bini. A Siisi. SI : 234-237. Octotier l!i.V2. (-'fi Stokinger, 11. li., ami others: Toxieiiy of ozoni-, lteport delivi-red al th annulli nieetiiig of UnAim-ricaii Industria) Ilygieiie Associaiion. chi cago, Aprii 27, 1954 1 2 } ) Fawnz. U., and Fiiwaz. li. N. : KITei-t of nirtal-oliti-s 011 ai-eumutalioii of eli rie acid in (Inoro, nei-tate-poisolied rats. Prue. Sia-, li\|H-r. liol. 84:0x0-0X4 no.VII. 1 25 1 Hep)id, L. A., Porlerlii-ld. V. T., and Klmrpless. N. li. : Toxicology of 1,2- didiloroethani- lelhyli-iii- didiloride) : lts di-toxieation hy i.-i-ysllne. Puh!ir Health lte|Miri< kliippr, 11. I. Hcdur- !< riti linlr. i|>. M. K: 400- idei, 1>. A. ; A o f leud uf relntlvcly i. llllllIKt. H>'R . ' `rc tt'iim <lt u n rollrlnp nelle eoli piumini >ir(>euror o oseil to len ii]. l',, nuil lUdk: exeretion in 'ly l e n e d l n n i i i i e uto, .lim e 12. pniKiuiiiiK liy -uos O lirei). . II. r . W., nini 'ini {lKodiuni < lenii poisimApril :i. 1954. Ascorbic ueid iir an tid o ti'* <>ninp. Proc. tirn a ry 1954. } lenitili, M .: ni liy amplio.inowii l'n iv . Novenilier. Iirrt, .1. : l'i'o!Iuni poisoii- .1. P linrinnM951 ). l. 11., inni v nf viinmin .-xtirriinoiiffl! \m-v. Bini. A 11\ n f ozono. ini; nf tlie "l iiHiiili, O li- <1 n f inotill'- <-id iu Onorol'A|H>r. Ki"). ni Sluirplo**. illune (etlivll<y l.-oysliiio, Itllll K eporl *i-r tr ;; * lu.-nietldimlne "<1 eertnln utlioi Millin' ooiiliiliiinr eoiniK'iindH. <1. l 'fim'imirol. A Kxpor. Therap. 01: 385-3!1, Dem iiber 3017. 6) Sm ith, IV. IV.: lteliith m slil|i between protein nml sulfur-eiintiiilllnp limino iieids in plnloellon aenliiKt HiPlhylelilorlde jm IkonIiip (uM rncf I. Federation Proc. 0:20(1 (3947). ('71 (ioelZ. A.: A]i;>Jlcil!inll of liinleeilliil' titter mene brilli'* to the nmilynis of iierosnls. Am. .1. Puli, lleiiltli 43 : 150-157 (19.53). (/M First, M. IV., unii Sllvermiin. 1..: Air Minipllnp with uiemhrune tillers. A. >1. A. Ardi. Jinlust. U tk. und Uceup. M. 7:1-11, .litiimiry 1953. <201 Fnoicr, U. A.: Ahsulnte method of siiiiiplinp inn) measurement of solid iilr-horne piirlieuhites: Combined use of the moleenhir tiller memhrnne nml electron mieroscopy. A. M. A. Arch, lmliist. Hyp. and Oecup. >1. 8: -11- --lit, October 1953. 13 0 1 Sinclair, 1>.: Lipht senilerinp iiiKlriiineiits ns mi aid In nir pollution nieiisuremeiits. Air Itcpnir 3: 51-56, Anpust 1953. <31) (Sititi, J. G., Bitchle, 1*. 1).. and Sharp. .1. IV.: Physiocliemiciil studies on dust*. VI. Ulootronopticnl exiiinination of finely proli ml silica. J. Appi. Chem. 3:1113-218, May 1953. (32) Maplll, I'. ),., nini others: Snnitdlnp ceriuIn utniosplierle coiitiimlniints h.v kiiiiiII-nciiIc Veni uri scriihher. Annlyt. Cliem. 22:1174-1177. Septemher 19511. (33) Stinifonl Iteselireli liislltule. Stilofori! Univer sity ; The siimi: prniilein in l.os Anpeles County, 1115(1. Thlril interim repnrl. i.os Anpeles. West ern OH and Gns Associatimi, 1951, Apiieudlx A. (.V/) Wnshhiirn, II. IV., unii Austin, It. It. : Continomi* mensureinent of solfar dloxlde alni hydropen Milititi* coiiccnl in lino* hy nutomiille tllriillon. hi Urne. 1'. s. Teehnlenl Confercnec oli Air I'olltitlou. New York, McGrnw-ltllI, 1950, pp. 5S0 ; 550, 507. (33) ltiiniliill, It. A., (imi llunstiid. N. A. : Itelinlilllly of eomlnistilile pus nl.'irin*. lte)iort ilellvered ut th immuti .......tini; of th Amerieiin Industriili 1lypielie Assodilihm, Chieiipo, Aprii 27.19fi4. ((() CIin)itmi11. It. 1,.. nml Torle.v, lt. K. : Mollile infrared speciromoier fr rapili on-tbe-S|nt milysi*. Annlyt. Chem. 22:9s7-990, Aupust 1950. (37 Miller, ]'.. nml others : Alveolo!' ventilntlon studio* uslnp th innss *| motromei or. Prin-. Sue. P.spi'r. Bini. 74 :J3 (1950). Community Health W eek, March 21-27 Community Health Week programs are recommended for Mareli Jl-iiT, li)f>f, by the United Stales Junior ('handier of ( 'oiiunerce in cooperation with the National Health Council. Chapters of the .Junior Chamber of Commerce have been asked by their national ollicers lo name program chairmen for Community Health Week and to seek the aid of local health leaders. The pro gram theme is "Know Your Community Health Kesoiirecs." Voluntary organizations are recommending that their afliliates pro vide the programs with coo]>eration and guidance. Husk- health services will figure in programs where local public health units work with interested members of the organization. Interested chapters will obtain a kit of aids from the national oilier. Suggested activities include health fairs and forums, special news paper coverage, television andj'adio programs, exhibits, and school health projects. Program leaders may wish toeonsull Guide to Health Organizations; in the United Slates. ]!>51, by Joseph W. Mountin and Evelyn FJook. Public Health Service Publication No. l!Hi. Available from the Su perintendent of ] iocmnents, Washington ifif, 1>. ('. .10 cenls. '*1. 70. No. I, January 1955 n TOXICOLOGIC ASPECTS OF OCCUPATIONAL HAZARDS* By Heibert E. Stokjngbr Department of Health, Education,, and Welfare, Public Health Semite, Cincinnati, Ohio Within very recent years control of industrial hasards in the United States has become an integral part of plant operation. If the common indus trial materials such as heavy metals and solvents still prove troublesome hare and there, certainly it is the fault of application rather than the means of prevention, for these are now well defined in most instances. The accent ta.indeed on prevention; thoughts are being directed to tests of pretoxicosis rather than of injury. Considerations of comfort, rather than merely health, are being woven into the threshold limits of industrial exposure. The concept th at the "total" man should be considered has brought into the fold many fields of study that have never gained consideration before. Toxicology has pl*yed no small role in the broadening of these concepts. Serious attention if being given to what were formerly fringe endeavors: psychology, psychia try, effects of radiations, heat, light, vibration, noise, fatigue, color, and the defifio of machines fitted to the comfort of man. These enlarged and fore- lighted concepts have been recognized in the recent change of name from industrial health to occupational health, and have served to expand the realm of toxicologic activity. For the same reason, the number of fields that might be included in a review of this type is so large as not to permit the in clusion of alt. Prominent among the topics omitted are discussions on occu pational dermatoses, toxicology relating to pesticides, plastics, water quality, food, drugs and cosmetics, and methods of sampling and analyzing air-borne constituents. rA (ttw volumes (la) have been added to the toxicologic literature in the ! pM M *o years: Toxicology 0/ Industrial Organic Soloenit, by E. Browning; Toxicology, by the Aero Medical Association; The Halogenated Hydrocarbons, Their Toxicity and Potential Dangers, by W. von Oettingen. A few limited reviews on toxicology* have appeared within the year; the one by Goldblatt on "Research in industrial Health in the Chemical Industry" (lb ) expresses a decidedly English point 01 view. Also in England there ap peared a critical review of experimental methods in determining chronic pgicy by Barnes & Denz (2). An incisive address by Seevert titled "Per- iPBCSive vs. Caprice in Evaluating Toxicity ol Chemicals in Man" (3) de- serves attrntion. The Manufacturing Chemists' Assn., long a leader in the !field ol labeling dangerous chemicals, has published a third revision of to manual L-l, "Warning Labels;" New Jersey has recently developed a state code for labeling based on these recommendations. The Subcommittee on The survey of literature pertaining to this review was completed in July, 1935. 177 id Toxicology of (he National Research Council is planning to establish a toxi cologic center where information may be obtained; presently, limited toxi cologic information is obtainable from the Chemical Biological Coordination Center. Washington, D. C. The Threshold Limits Committee of the Amer ican Conference of (Governmental Industrial Hygienists has been active in adding many ncu- chemicals yearly to the original list. A series of Hygienic (uides on Hazardous Industrial Chemicals, useful for plant supervisors, is living prepared by the American Industrial Hygiene Association, and an En cyclopedia on instrumentation for Industrial Hygiene has been compiled jointly by the Occupational Health Field Headquarters and The Institute of Industrial Health, University of Michigan. Oi'st Diseases op the Lung Although during the last few years reports have appeared on more than a score of rather unusual inorganic dusts that have caused pulmonary in jur}' in workmen, major research emphasis has still been centered on a rela tive few. chiefly, on silica in its various forms and associated substances, coal, cement, slate, etc.; on asliestos. and, to a leaser degree, on beryllium and vanadium. In the United States in 1952, 5211 deaths were recorded (4) from pulmonary tuberculosis associated with occupational diseases of the lung; pneumoconioses, including silicosis, amounted to 1423; similar figures for England rc|>orted by Merewethcr (5) showed 1300 died of pneumoconioses In 1931. Tulierculosis was not the sole disease associated with pneumoco niosis for 16 per cent of 300 workers dead of asbestosis over the years had primary lung cancer also. It is of more than passing interest that the higher 14 rale of cancer in asbestos workers in England is not paralleled in the United 11 States or in Canada, according to Lanza (6). The cause for this difference *t may lie in the type of asbestos; asbestos is a fibrous form of several differ` :jrnt species of minerals, a point often disregarded. ' A symposium held in ItoMtnn in October 1953 was devoted to occupational diseases of the lung, and laid chief emphasis on silicosis and asbestosis. The pathology of asbestosis (7) was presented, roentgenologic aspects of both diseases (8). clinical observations on asbestos workers (9), its differentiation from other pneumoconioses (10) and the functional abnormalities of indus trial pulmonary fllwosis (11). Current study of the tibrotic diseases of the lung related to occupation may be divided into three areas: (a) contributing factors; (b) mode of de velopment of the silicotic nodule; (c) treatment. Because the literature is so voluminous, both here and abroad, on most of these areas, only the more gen erally informative reports have been selected. In a review of factors now believed essential to the production of silicosis. Dautrcbaiidc (12) discusses, as important, particle size, amounts of free crystalline silica, the presence of associated dusts and fumes, and breathing patterns. I*articies of 3 p and below in diameter, with special attention to those of 1 m size, are now generally considered the most injurious from evi- ictire im kU on human autopsy material ami dust-settling characteristic*. The electron iuicrosro|H' permits arruratc visualization of particles below 1ji Wd heretofore |xhilili* with littitt optical systems. Dnutrehandc. on review 'Trout'll evidence. considers silicosis a probability if the number of particles itj.'greater than 1.7 nip cu. ft.;* in rontrast to this opinion, the current limit hp|ievcd safe in the t'nited States is 5 mp/cu. it. (1.1) as measured optically. Aftu h evidence has now accumulated to indicate that the nature of the suit* stances associated with silica and even extraneous substances may influence Kljeatly the onset and nature of the ensuing silicosis. and cs|wcially the partitular crystalline structure of the silica itself. King el al. (14) have presented evident on intratradically injected rats to indicate that, of the various crystalline form*, tridymite was most rapid in producing a tissue reaction, fujlbwed by rrikiohalite, quartz, and fused silica, in that order. The more rg|)|d reaction of the crystalline forms has yet to he explained. In this eon(lection a limited French report (15) on possible pneumoconiosis from silica of fossil origin (amorphous) confirmed the findings of many previous authors who have found no nodular silicosis from untreated diatomarcous earth. A stqdy of the I'nitcd States diatomite industry by the Public Health Service (1 0 in co-operation with state health departments of California, Nevada aa*) Oregon. moiling five plants and 869 workers, showed, in agreement with past findings, that only one of 25 employees who had worked more than five years exclusively exposed to amorphous silica in the quarry had diato m ic pneumoronituiis. hut 22 per cent of 286 employed more than five years and working in mill* exposed to high temperature calcined, or fluxcalcincd. diatnmite. showed findings consistent with pneumoconiosis. Calcining diato mite with or without dux (sodium carbonate) converts the far less active variety to rritol>alitc. a crystalline form, which is believed responsible for the increased res|K>nse. It was not possible to draw the conclusion that there were an)' dilTvrences in the response to fresh and salt water forms of diatomite There is increasing evidence that the onset of silicosis ran Iw hastened by (lie inhalation of other substances along with silica. The alkalinity as sociated with sand in a scouring preparation was reported (17) to have caused silicosis in from 20 to 26 months ("galloping'* silicosis) in a small group of exposed individuals; the silica dust concentration was tremendously high as far as can be gathered from the original report. Rapidly progressive silicosis has been previously reported in this country (18) from the same cause. Talcosis of unusually rapid development (16 to 24 months) was re ported (19) also under circumstances of excessively high talc concentrations. Fluoride, in the form of fluorspar, in mixture with quartz has also been refiortod (2U) experimentally to induce more intense fibrosis than quartz alone, although the latter may lie present in only minute amounts (1 per cent) in the mixture. * Million particles per cubic feet of air. Isolated reports continue to appear with increasing frequency to in* criminate many dusts, formerly considered inert, in the production of pneu* moconiosis, such as sepiolite (21), corundum (22), feldspar (23). graphite (24), porcelain (25), barita (26), cement (27), mica (28), slate (29), kaolin (30, 31), and a substance to which gas workers are exposed (32). Several reports in the last few years from the U. S. and England (33, 34, 35) are in agreement that coal miners' pneumoconiosis is an entity dis tinct from silicosis. Some unknown factor other than inhalation of coal dust, probably an infectious agent, is believed necessary, however, for the develop ment of confluent lesions. The reports indicate a need for reinvestigation of the entire problem of soft coal mining (36). A study of the emotional aspects of respiratory diseases of coal miners has been made by Ross, Miller, Leet and Princi (37); psychoneurosis was the most significant diagnosis in onethird of 40 miners who had been referred to them for special study. Mtckanism.--The solubility theory (38) as an explanation for the formation of the silicotic nodule now appears to be weakening under more critical study. Almost as soon as it was enunciated, much evidence was pro duced that cast doubt that solubility alone could account for the developmcnt of the silicotic reaction. Among the first were experiments contrast ing the reactions of the amorphous and crystal forms of silica, which show that highly soluble amorphous varieties were responsible for the toxic reac tion. whereas the less soluble quarts produced the fibrogenic reaction (39). I t is, of course, commonly known that the tissue reactions produced by amorphous and crystalline forms differ markedly, although the product of solution of each is the same, silicic acid. If silicic acid were solely responsible for the silicotic reaction, then silicosis should develop equally well from amorphous as from crystalline forms. Certainly, if solution of silica occurs, it must be either very' limited in amount or localized in area, because no sig nificant differences could be detected, with especially sensitive chemical methods, in the blood or in the urine of silicotics and of normals (40,41, 42). Values in the urine varied with the acidity; no exact relation between blood and urine values was found, so that silica values could not be contillered of either diagnostic or prognostic value. These facts have led to modi fied solubility theories. Experiments with silicic acid and proteins by Holt fit Bowcott (43) showed, indeed, adsorption a t the isoelectric points through amino groups chiefly, it had already been shown by German workers (44) that quartz particles become coated with serum constituents with no sign of dissolution, and Scheel ti oi. (45) have shown that the rate of solution of quartz is depressed by protein in such a way as to make it improbable that a simple solution of silica can account for its toxicity as manifested by sili cosis. In a further study (46), these authors believed.the toxicity may be due to a foreign protein reaction developed from the alteration caused by ad sorption on quartz of normal serum proteins a t shown by immunologic reac tions. This important conclusion would appear to render less significant the opinions of Holt tl al, (47) that the action of silicic a d d in silicosis is a process III: of aggregation and disaggregation, depending upon pH, which altera the permeability of tissue membranes, liolsapfct (48) likewise inclines toward the view of the combination of silica with tissue constituents, but has shown specific adsorption with a galactose complex; a galactan, containing only D~galactow, has been isolated from beef lung (49). Similarly, Heffernan (50) rejects the solubility theory, and propounds the surface-valency theory whereby freshly fractured silica surfaces fix large masses of organic material; asbestos acts similarly. Whatever the final answers to the mechanism may be, the most convinc ing evidence now favors specific chemical combination of crystalline silica particles with certain tissue constituents, with consequent structural altera tion from normal to produce local disturbance and typical silicotic response. Somp crucial experiments are needed to confirm these views; (a) actual meas urement of crystalline silica particles after many months' residence in the lungs, to determine whether solution occurs, (b) the demonstration that crystalline silica specifically combines with some pulmonary tissue com ponent and can then produce the typical silicotic nodule. rrautment.--The value of aluminum treatment, and especially the pre vention of silicosis, after 10 years of trial, chiefly in Canada, is still open to final appraisal. Unfortunately, good control studies in man are almost non existent. Publications on the subject may be obtained from the McIntyre Research Foundation, Toronto, Canada. Dautrebande has proposed a treat ment: procedure, using a fine aerosol spray of sodium chloride to aggregate $ e ailica particles (51). Animal experiments with this aerosol haw shown excellent protective effects; whether field trials now in progress will prove the method of prophylactic value is yet to be reported. In Germany a recent form of treatment of silicosis (52) depends upon the use of electroaerosols conaiating of unipolar mists of a calcium-sodium salt solution charged nega tively and kept in suspension in an electric field before inhalation by the ppiientsl Claims for effective treatment also have been made for an electro- Ip lp o l produced from sea water (53). Intermittent, positive-pressure breath- i q | #ppeara to be the most promising method of affording relief and control df ymptoms in the majority of cases of emphysema and fibrosis with dysp* ofascoording to Motley (54). Studies to assess the benefits of the method, htwgver, were reported (55) to be complicated by the use of bronchodiiator 4#$$. When this factor was tested, it was concluded that administration of miypea and nebulized bronchodilators with improved breathing technics |g ^ m '# M t cases, aa good as intermittent positive-pressure breathing. ' Organic The capacity of organic as well as inorganic dust to pro duce lung changes has been documented in several reports. p-Dichloro- btnxcoc was reported to have produced pulmonary granulomatosis in a middle Offd woman (56). Examination of excised lung tissue by polarized light re- vcfled crystals believed to be p-OCB. The woman had been using p-DCB profusely for from 12 to 15 years on upholstery, carpets, and in dothes-cup- bogfds as an insecticide. Caution has been voiced on the inhalation of resin It dust 1>> Child & Clancy (57); during grinding and |xmilcring of the synthetic resin, dryness of the mouth and nasal mucosa, coughing and sneezing, and other signs of respiratory irritation were in evidence. Experiments in aid* mais produced wheezing, rales, blocking of major bronchi with distended resin granules, and salivation and atelectasis; the most prominent effects were caused from the loosely cross-linked resins. Dust and jiowder of Teflon (tctralhiorocthylcnc polymer) have been known for neural year* to produce respiratory condition akin to metal-fume fever (58); more recent investi gation of the inhalation hazards of heated Teflon (50) showed the evolu tion of highly toxic fluorine-containing decomposition products. "Printers' asthma" has Iwen re|xirtcd from England (60) to arise from inhaling a sprayed fluid containing gum araria. Although considerable study has been given to eottnn dust in relation to byssinosis (61). it is not yet dear which of the two structurally related components of cotton dust and associated mold are res|ionihlc for the "early" and "late" reactions. In bagassusi* the endutoxin of Aerobacter cloacae had been promised as a factor in its etiology (62). Pulmonary disability from the inhalation of grain dust is marked bv dyspnea, chronic hronrliitis. recurrent bronchial obstruction leading to clinically apparent emphysema, and was reported to occur among those working with seeds and grains for 10 or more years (65). This all-too-brief review of lung diseases from inhaled (tartirulatcs makes it difficult to escape the conclusion that all dusts, irrespective of their nature, if breathed in sufficient quantity and for sufficient time, may cause profound damage to the lung, and emphasizes the desirability of the physician's obtaining an accurate and thorough occu|iational history on individuals suspected of pulmonary disease. Beryllium.--A number of cases of both acute and chronic beryllium poisoning continue to appear, despite the (act that one of the major sources of exposure. U-ryllium phosphor in fluorescent lights. h;u been eliminated, in addition, an extremely low air standard of 2 ug.De/m1 for continued daily exposure, and no higher than 25 ug. for brief exposures, has long been Suggested by the Atomic Energy Commission, one of the greatest users of beryllium. To our knowledge, no cases have a piwared to date from the rigid use of these standards which have often been designed into production plants. Because of the peculiarly long latent period fur the onset of beryllium disease, only time can tell whether the recommended figure for chronic ex posure is a reliable une. The rases that arise are partly from exposures lung ppst. but also partly from beryllium put to new uses such as glass, glazes, and alloy, and a crrtaiu number from beryllium production. Partly on the basis of the recent case inridenre. Van Ordstrand (64). who was one of those who originally called attention to beryllium disease .in the United States, has written of berylliosis as a real but preventable disease. Diagnosis cuntinues to lie a difficult and controversial matter, however. Lieben & Jackson reported (65) that at least one case of their six. formerly diagnosed as berylliosis, was silicosis. Three new cases, two positively identififd- one doubtful, have appeared in their factory since their earlier rc|>urt , t ;i! ...... r .oinit *i\c nccn luiptcttd, but none conclusively demon*tr.i led. according to Stolen tt at. (66) in a study of beryllium extraction, reduction, and alloy fabrication covering a period of t0 year; bcr> Ilium concentrat inn in the plant air through the yearn ha* ranged from a few microgr.im to 600 pg. 'nd. A nummary survey of all clinical ty|tc* of berylliosis observed in a 12-year period ha been given by DeNardi rt at. <67): a total of 4.11 patients were nbst-rved and treated for acute her)Ilium intoxication. Curtis (Ml) states that dermatitis due to beryllium is of an allergii-.ee/emat<>us type, with the beryllium ion believed to lie the sem-iiiaing allergen. The patch test has been used with success in a limited number of cases as a diagnostic test of beryllium granuloma of the lung: a positive test was always found with true beryllium involvement, bile negative result were obtained in Knock's sarcoid and in normal beryl lium U'orkers. A registry to collect and correlate data on cases with lierytlium p<Honing is being arruntulatrd by Ur. Harriet Hardy at the Massachusetts General Hospital. Boston. Work is continuing by Schubert and co-workers (|S9) on the mechanism of protection <( aurin tricarl>\ylic acid in beryllium poisoning! ACT!I treatment has prtivided ntt lasting beneficial effect, but Hardy (70) believes that either adrvnocnrticotrophin or cortisone is of real value in controlling symptom though not in curing the disease. Vanadium.--The study *>i vanadium compounds in relation to respira tory disease has In-en given serious attention since 1652 for two reasons: find, the mining and milling of unprecedented quantities of carnotite ore ( H / M W V*t- HjU) in this eminir)' in connection with securing uranium fur atomic energy pur]Hie has increased the number of e x ite d individuals: and second, the finding of n-spiratory illness among workers producing vanadium compound* for high-grade steel and other pur|>oscs. by Sjoherg (7J) and by Knchin (72). as well 3is among workers cleaning Imilcrs fired with vanadium-bearing oil, by William (73), Sjobcrg (74), and by Fallentine fit Frost (75). and from gas turbines [Browne (76)1. Sjoiierg has written a monograph i77) in Kngiish on the health hazards in the production, of vanadium prntnxide. The responses to air-bocne vanadium dust are: slight MHdiiM! of the conjunctivac; slight or copious rhinitis, with acute or chronic hyperplastic changes in the uasal mucosa; dryness or irritation of the throat, with chronic atrophic, and sometimes also acute, changes; hoarseness; only mddattU* Changes in the mucous membrane of the larynx, and a cough as the.muff outstanding symptom, often with many rhonchi. although brim* choecopie examination shows only mild bronchitis. Pneumonia lias been diagnosed in several cases and was considered to be of chemical-bacterial origin ("vanadium pneumonitis"). The responses arc thus acute, not chronic, temporarily incapaciting, but not fatal. Dermatitis is not a common feature of vanadium exposure. Ecperimcntal research on the systemic effects of vanadium compounds carried out in lalmratories of the Occupational Health Program, United States Public Health Service, has shown that vanadium is capable of in ducing at extremely low tiasue concentrations (t pg/g of tissue) derange- 1iH* menu of basic metabolic processes which are not manifest clinically or felt by the worker, it has led to a highly sensitive test of pretoxicosis and to con clusions of practical value in the management of the health of vanadium workers. The critical feature of the pretoxicosis test is that the cystine con tent of the nails is depressed following chronic low-grade exposures to va nadium (78). Amounts of urinary vanadium resulting from exposure may amount to no more than 20 to 30 pg per I. when cystine depression occurs, according to a sensitive analytic method developed in these laboratories and reported by Talvitie & Wagner (79). Another important observation was that diet plays a deciding role in the toxic response. Complete, wellfortified diets have been shown experimentally to counteract the potentially toxic effects of vanadium, whereas borderline dieu failed to do so, suggesting the value of nutritious and well-balanced dieu for vanadium workers. The basic cause of the dietary differences has not yet been determined; metal an tagonism, vitamins, or other factors may be responsible. Ceruinly vitamins exert a beneficial effect, for it has been shown (80) that ascorbic add can counteract the effect of lethal doses of vanadium compounds in animals, if administered in small repeated doses within a short period after the faul vanadium dose. Vanadium has also been shown capable, a t nontoxic vana dium levels, of redudng elevated plasma cholesterol in rabbiu fed high cholesterol dieu (81). Reduction in arterial plaque formation "as associated with this response. The significance of the role of vanadium in atherosclerosis requires further elaboration. Possibly the most interesting aspect of this entire research is that vanadium is merely one of a number of similar sub stances to which man is continually being exposed, through conttminated air, water and food, from which trivial amounu of materials may cause deepseated metabolic alterations in the body. EOATBAMIL tV MSTAL POISONIMG Poisonings from a variety of meuls are stilt being reported, although the proportion of cases occurring in the United States in relation to worker exposure is decreasing; this does not appear to be the case in foreign coun tries. Of the meuls, lead is now receiving renewed interest. The surge of in terest arises for three reasons: (a) several cases of lead poisoning, some fatal, among children eating painted lead surfaces have been recognised in many of our larger United States cities; (b) a new and effective method of treat ment has been found in a chelating agent, ethylene diamine tetraacetate. (EDTA) which has been given the generic name of Edathamil, by the Coun cil on Pharmacy of the American Medical Association; (c) case of lead in toxication a rt atill being teen in some smelting operations, brass foundries, auto-body shop*, lead storage-battery plants, and printing csublishments. Reported cases of infant morulity from lead are sa high as 30 per cent, increaamf to 5 per cent when complicated by encephalopathy (82). Stim ulated by facta like these, the American Sundards Association has drawn Up specifications to minimise hazards to children from residual surface- costing materials; this activity was sponsored by the American Academy of Pediatrics. It is small wonder, therefore, that early reports of the effectiveoe*> of CDTA in children (83. 84. 85) were rerieved enthusiastically. The more recent excellent report of its use in adults by Sidbury (86) would seem tp leave little doubt of the value of EDTA in lead poisoning. This report presents a renew of the action of EDTA with reference to papers showing itf distribution and excretion in man and in animals, dosage-schedules, and case reports with Icad-cxcrctinn curves following therapy. The value of a chelating agent such as EDTA is its capacity to combine with metals so as m render them tin-ionized. The combination often has reduced toxicity and allows an increased rate of excretion via the kidneys. EDTA is used as the calcium salt because this form eliminates the development of low-serumealdum tetany. Aa with most drugs, there may be obvious dangers from prolonged, wanton or excessive use. Dudley ttal. (87) have already described toxicologic changes associated with the use of EDTA in treating hypercalccmia: "At autopsy, unexpectedly severe damage occurred to the renal tubules with engorgement of the reticuloendothelial cells with gross eosino philic granules and hemorrhagic manifestations." Kehoe (88) has con sidered as unwarranted the continued use of EDTA as a prophylactic meas ure for lead workers as a substitute for reduced lead air levels in the work room. Preparations for such use would be orally administered where ab sorption has been shown to lie minimal (89); hypotheses, and not proof, have been offered to explain EDTA's action by the oral route. Edathamil has been experimentally tested in mice for its effectiveness in manganese poisoning (90): it prevented the disease from progressing, but did out reverse the serious effects of manganese on the nervous system. Edatlianul has been reported (91) to accelerate the excretion of plutonium in matt, especially directly after plutonium intake and "offers promise in a situation formerly considered hopeless." CaEDTA was reported (92) to drereaserthu excretion of mercury in a single case of combined mercury and leiul exposure in which the patient was successively treated will) dimerraprol and HUTA. Fatal doses of vanadium administered to experimental animals woes successfully counteracted by later treatment with CaEDTA (93). Kdathamil has also iieen shown experimentally to increase excretion of yttrium and americium (94) and zinc (95). CaEDTA. combined in an oint ment, baa been reported by Malnof (96) to be of value in the treatment of chrome ulcers; EDTA loosens and permits easier removal of the ulcer base in f t must two or three applications. EDTA has also been recommended in the treatment of lime burns of the eye (97). Solvent* The last few years have witnessed a gratifying trend generally in the ap proach tp the development, marketing, and use of the safer solvent. The contact of industrial workers with solvents is probably the greatest of any tingip group of substances; their injurious effects range from extreme hazards % a*  - .... v-..- .mw mm iu ucrmautis. I no awareness of the hazards of solvent use has greatly increased in recent years because of the increase in toxicologic information and education on the risks involved. This knowledge has served to curtail the use of many of the more hazardous solvents: the highly flammable solvent is now less commonly used without admixture with a nonflammable component; the serious))' toxic benzene is restricted to limited and controlled uses, and the less hazardous toluene or xylene substituted for it; several safer chlorinated hydrocarbon solvents are now substituted for carbon tetrachloride. The hazards of carbon tetrachloride are considered so great that some companies have forbidden its use, or, if permitted, require experienced supervision, or usage limited to small quantities. Unauthorized or flagrant use stilt persists, however, as two recent excellent reviews testify (98, 99). Supportive treatment of severe CCU intoxication now emphasizes, in addition to attention to the liver in jury, the management of renal tubular damage with its possibilities of pul monary edema and potassium intoxication. Death frequently results from the last. It is now dear also that many of the severe and fatal cases of poison ing involve chronic alcoholics or individuals who have ingested alcohol prior to, during, or after CCU exposure. Despite the known potentiation of toxicity of haiogenated hydrocarbons by alcohol, the chief approach to safer sol vents is the use of chlorinated hydrocarbons of lesser toxicity than CCU. namely, trichloroethylene (TCE) (100), pcrchlorocthylcne (101) and, more recently, methyl chloroform (102); the threshold limit values for these agents are, respectively. 200, 200 and 500 p.p.m. in comparison with 25 p.p.m. for CCU. These threshold limits provide a rough indication that some hazard remains even with the use of these substitutes; indeed, cases of fatal ex posure to TCE have been reported (103), but exposures were far in excess of the threshold limit, presumably several thousand p.p.m. Study is being given the excretion products of TCE. especially trichloroacetic acid (TCA) (104) as a measure of exposure, but the results and interpretations are com plicated by the variability o{ the liver's capacity to metabolize the TCE. Some authors conclude that TCA cannot be used as a simple test of exposure to TCE (105). Another solvent, methylal (dimethoxymethane). of relatively low toxicity with a threshold limit approximating 1000 p.p.m. (106), ap pears to have received less attention and use, possibly because of its high volatility and flammability. Other approaches have been made toward so-called "safety" solvents. One such approach is the use of the azeotropic mixture (107) whereby a con stant b.p. for all components is achieved. This has the practical advantage that the vapor from the misturc has the same composition as the original mixture, thus permitting a more exact knowledge of the composition of the exposure vaimrs and preventing the disproportionate build-up of vapor con centrations of the more volatile substances. The use of solvent mixtures as a substitute for the single solvent is now common with all producers, the com ponents of the mixture being selected for their nonflammability and lowered toxicity. A typical solvent mixture now on the market is methylene chloride 25percent, perchlorocthylene 5 percent, and Stoddard Solvent 70 per cent, having a threshold limit approximating 500 p.p.m. Associated with the use of solvent mixtures is the <|ui>uon of the synergistic effect of the combi nation wherein the total toxicity may be greater than the sum of that of each component. Such effect is believed to occur from mixed exposures to methyl alcohol and methylene chloride, or carbon monoxide and many of the halogenatcd hydrocarbons, and there are others. LaBelle (108) hat shown that particulate substances may enhance, decrease, or have no effect on the toxicity of a vapor, depending on ita nature. The same worker (109) showed also that the toxicity of a solvent mixture of eight components waa essentially that of its chief (55 per cent) component, methyl ethyl ketone, likewise. McCollistrr (110), working with various fumigant mixtures of ethylene dichloride and dibromide and CCI, showed that the toxicity of the mixture could be mathematically predicted from the composition, i.e. no synergistic effect. Thus, whereas one should always be mindful of the possi bility of synergistic effects of mixtures, synergism is by no means a necessary consequence 0f mixtures. ' A new group of "OXO" solvents is now being marketed, so-called from the process that adds oxygen to unsaturated olefins to make a series of unsaturated aldehydes and alcohols that will have large application as paint and varnish solvents, components in safety glass, vitamin intermediates, and many othcr uses. Price margin* in this field being small, and purification being cosily, mixtures of these "OXO" solvents may be customary in the coming years. A number of solvents are used as vaporizing liquids for fire extinguishers. CCI* is by far the must common and important; however, other halogenatcd hydrocarbons arc being introduced as replacement for, or in combination with, CCl (111). Of the newer agents chlorobromomethane has received the widest usage; the haaards of this liquid arc somewhat less than that of C P i (112), the main advantage in firefighting being that CHjCllir can be uifd a t lower temperatures and is not as corrosive on metal extinguishers. Aix Pollution The increasing importance of this subject to occupational health would appgar to justify greater space than has been heretofore allotted it (113). Noif, after six years of research and study and an overabundance of discus* siufti and symposia, three major areas of accomplishment appear to have etwtfXed. Much is now known of the nature and amounts of solid particulates coqtributiog to the air pollution of many cities, both in the United States and abroad (119). The total particulate load in the air over many Unjtcd States cities ranged from 200 pg/m* in residential areas to 500 pg/m1 in the air over induatriai areas, of which identifiable metallic constituents accounted for front 5 to 10 |>er cent; the bulk of the remainder was carbo naceous material. Considerable uniformity of the particulate matter in the iii I \ -- >i*ui >.**./ ivuty wiit iouna, ana tne more toxic elements, sucli as 1'Ij, Mn. Cr, As, Be, etc. were invariably less than I /ig/ni* on the average. and al though unquestionably contributing to over-all body burden, these levels were well below those usually considered hazardous. Recently, however, new importance has been attached to the water-soluble fraction of these par ticulates by liemeon (120), to which he ascribes the capacity of respiratory irritation, fn this connection, it should be noted that the particulates over cities with little or no industry were similar in nature and only somewhat smaller in amount than over areas with high industrialization (121). This is expected, as many elements (Ti. Mg, Si, Al, Fe, Ca, Pb. etc.) are common to oil. rock, cement, and paint that find their way into the air by attrition. In the continuing March for evidence, that still proves elusive, of the long term elTccts of air pollutants on human health, a second possibly im portant area was developed in the demonstration, first in England (122, 123), and later in the United States (124), of atmospheric carcinogens; a large number of the commonly recognized polycyclic aromatic carcinogens have been identified in the atmosphere and in gasoline engine exhausts. Whether the amounts found in the genera) atmosphere (less than 1 ug/m*) are sufficient to induce lung cancer in man is still to be demonstrated. They have been shown, however, capable of causing skin cancer in mice (124). Other types of air-borne carcinogens such as printing inks (123) have also been implicated as causing bronchial carcinoma (Stockholm); and rubber tire dust, also carcinogen-containing, has been found in appreciable quanti ties in the air of our largest city. Rather detailed inventories of automobile gases have been made (126), and the distribution of these gases in city air estimated (127). It is estimated that of the more than 2000 tons of total hydrocarbons evaporated into the air of Los Angeles each day, 440 tons are unsaturated hydrocarbons, of which 220 tons arise from autos and service stations, and the remainder from gasoline production: smoke particulates from auto exhausts are estimated at 50 tons per day. The third major contribution to the understanding of air pollution is the demonstration of certain basic reactions of aerosols, by Haagen-Smit and co-workers (128), for Los Angeles air, namely that oxidants are the chief con tributors to eye irritation and crop damage. Potential oxidants arise in the air from natural and man-made sources through a complex set of chemically and photochemically catalyzed reactions involving oxygen, nitrogen oxides, and hydrocarbons. Among the products detected, and they are numerous, ozone and oxygenated hydrocarbons (peroxides) are considered to be the serious offenders. More recently Haagen-Smit has demonstrated that ozone may lie photochemically generated from auto exhaust gases (129). It has long been known (130) that combustion engines .are capable of forming ni trogen oxides by fixing the nitrogen in the air and, like unburned hydrqcarbons and ozone, the quantities formed depend upon operating variables (131). This, and related information (132), has provided speculation on the possibility of either better engine design for more complete burning of fuel. !i;l4 % or the uc of elected ty p o of fuel that will not yield oxidizable, potentially eye-irritating hydrocarbon derivatives in the exhaust. It is hoped that a greater proportion of future research on air pollution will consist of the study of the basic reactions of aerosols (synthetic ap proach). for it is wholly possible that the conventional methods of sampling and analysis of the atmosphere will completely (ail to detect or identify the mote highly reactive and transitory types of pollutants that will prove ulti mately to be the worst offenders. It is probable also that still more potent, elusive, aud unusual types of air pollutants are yet to be discovered (133). By a combination of both approaches, however, greater assurance of ob taining the objectives will be had. The question of the chronic effects on health is still awaiting develop ment of tissue function tests specific enough to differentiate between the effects of air pollutants and those of tobacco amoke. infectious processes, aging, e tc Epidemiologic surveys are suitable for indicating the areas for in vestigation, but final proof that air pollutants cause injury to organ systems must rest on direct objective evidence from teats of functioning of the af fected organ. s OzONK AND OXIDKS OF NtTftOGKK Because ozone has an essentially "dean" odor, ozoaizers are periodically recommended for their air-deansing value in hospitals, homes, offices, and garages. Ozone also is found associated with many industrial activities, such as welding, electrostatic precipitators, or other electric-generating devices. Because of ozone's powerful oxidizing action it it now being used in the fine organic chemical industry, in water purification, and in cheese storage rooms. These uses have led to an increased number of potentially serious exposures to a substance long known for its toxidty. Moreover, the role of ozone in Los Angeles smog has lately assumed major proportions. Recently, however, a new note in the toxicity picture of ozone was injected by Thorp (134), who cfejlptett that the oxides of nitrogen associated with ozouc production were rmpongible for the observed toxicity. Refuting evidence was recorded by Weaver (133) in a brief review on ozone toxicity. Because of the danger that Thorp's statement could be misinterpreted and misapplied (and,, in deed. each statements have found their way into recent toxicology texts (I3fi), the present author undertook a review and study of the problem of tjfe iielatiou of oxides of nitrogen to ozone toxicity. The review (137) showed ^convincing evidence to support the contention that the oxides of nitro gen would account for ozone toxicity, chiefly because, under usual circumStance* of ozone generation, only small amounts (usually 1 or 2 per cent or fe fe M nitrogen oxides are produced. Animal studies (138) further showed that addition of oxides of nitrogen to ozone up to 50 per cent failed to alter the toxfeity of ozone, the LD* of which for mice approximated 4 p.p.m. for fifer* exposures, in support of these findings, Cray, in a series of studies (130) oh the oxides of nitrogen (chiefly NO) produced from red fuming U,. > - ......... . iiic i. i>h lor rats to he approximately 75 p.p.m., and sug gested the safe level (or daily exposure for man to be 5 p.p.m.; this latter value has been incorporated into the threshold limits of the American Con ference oi (Governmental Industrial Hygienists. The matter, however, ap pears still unsettled, for reports from England by Digglc & Gage (14U) claim a toxicity for nitrogen protoxide somewhat greater than that of ozone; the importance of N|Ot is that it is the product resulting from NOi in the pres ence of excess ozone. The experiments of Diggie & Cage were complicated by a variety of factors, and seen to this reviewer not to support the con clusions of the authors; certainly, more work must he done to attempt to re resolvv this controversial and difficult problem. Part of the difficulty has undoubtedly lain m the inadequate sampling and analysis procedures. To overcome these difficulties Dyers et at. have critically evaluated and modi fied the method of Smith and Diamond (142) for ozone, and Saltzman (141) has developed a highly sensitive and accurate method of sampling and ana lyzing nitrogen dioxide. Other difficulties may also stem, as suggested else where in this review, from varying conditions of humidity, or the presence of as yet undemonstrated free radicals of a highly toxic nature, and these may prove responsible for the differences in the present experimental con clusions. LITERATURE CITED la. Drowning, E., Toxicology oj Industrial Organic Soioenlt (Her Majesty's Sta tionery Office, Loudon, England, 411 pp.t 1953) Aero Medical Association, Aviation Toxicology (The Blakiston Co., Philadel phia, Pcnna., 120 pp.. 1053) W. von Oettingen, The Halogenated Hydrocarbons, their Toxicity and Potential Dangers (Government Printing Office, Washington, D. C., 430 pp., 1955) lb. Goldbiati. M. W., Brit. J. Ini. hied., 12, 1-20 (1955) 2. Barnes J. M,, and Dcnz, F. A., Pharmacol. Revs., 6, 191-242 (1954) 3. Servers, M. H., J. Am. hied. Assoc., IS1, 1329-33 (1953) ^ 4. .Yoi Ojue Vital Statistics, Washington, D. C.. 5. Mcrewclhcr, E. R. A., .telit. Hig. Rada., 4, 365-82 (1953) 6. Lanza, A. J., Asbrstmu (Read before FourthConf. of McIntyre Research Foun dation on Silicosis, Jan., 1952) 7. Lynch. K. 3ft, 3 n l. M ust. Health. 11, 185-9 (1955) 8. Bristol, L. j . . Arch. Indutt. Health, 11, 189-96 (1955) 9. Cartier, P , .4rrA. M ust. Health, U, 204-8 (1955) 10. Sander, O. A.. -4rri. M ust. Health. 11,208-12 (1955) 1). Wright. G. ., Arch. Indutt. Health, 11, 196-204 (1955) 12. Dautrcbande, L., Bull. Hyg., 28,635-6 (1953) 13. "Threshold Limit Value," Am. Con}. Coo. Ini. Hygienist* (Buffalo, N. Y,, 1955) 14. Kiug, E. J,, Mohanty, G. P., Hamson, C. V., and Nagelschmidt, G., Brit. J . Ini. hied., 10, 9-17 (1953) 15. Lccocq, J., Guyot-jeanniii, C., and leLay, J. Arch, maladies presets, med. travail el tdeuriU tonale, 13, 363-5 (1952) 16. Unpublished Preliminary Report, "Study of Pneumoconiosis Hassid in the 17. Detoille, II.. Tar*, 5., Ddplace, V,,and Cavigneaut, A.. Attk. maladiu profits. mtd. Irani! rt stcuritt social/. 14, 279-8.1 (195.1) 18. Rittcrhoff. R. J., Am. Rtf. Tubtrt., 43, 117-31 (1941) 19. AliviutM. C. P.. Pontikaki, A. E., and Terri*. B., Brit. J. Ini. Mtd., 12,4.1-49, <1933) 20. Poiicard, A., and Collet, A., Arth. malaiiu profess. mid. Irani!it stcnritt social/, 14, 117-22 (1935) 21. Panda. A., Mtd. Stgur. Trab., 2, 11-14 (1454) 22. Hagen, J., 2. get. inn. Mtd. u. Hut Grtnug/bi/t/, 5, 51-5-1, (1950); Gartner, H.. Arch. Ind. Hyg. and Occupational Mtd., 6, .159-43 (1952) 25. Rotter, \V., and Gartner, H.. Ztntr. Arbtthmed. a. Arbtitschuu, 4, 55-40 (1954) 24. Boevt, P., Schveit. t. allgtm. Pathol, u. Baht/rial., IS, 548-32 (1955) 25. Kirch, E., Beitr. Silihott-Forsch., 23, 1-29 (1953) 26. Fendergraaa, E. P., and Greening, R. R., Arrh. Ind. Hyg. and Occupational Mtd. 7,45-48 (1455) 27. Manctoli, G.. Rut. mtd. ind., 23, 7-16 (1954) 28. Ramaawamv, A. S.. Venkatetb, O. S., and Rama Rao, R., J. Indian Inti. Sd. IS, Sect. A. 319-51 (1953) 29. D'Onofrio, V., R ut. mtd. ind., 21.544-6 (1952) 50. lynch, K. M., and Mclver, F. A., Am. J. Pathol., 30, 1117-27 (1954) 31. Poiicard, A,, and Collet, A., Sdneoit, 2. aUgtm, Pathol, a. BahUriol., 17, 320-5 (1954) 52. Tyler, F. 11., Gregory, J., and Canon, M. B., Trans. Autc. Indian Mtd. Officers, i t 246*9 (1935) 33. Martin. J. E.. Jr., Am. J. Public Health, 64. 581-91 (1954) 34* Heppleeton, A. G.. J. Pathol. Bacteria!., 66,255-41 (1955); J. Pathol. Barttriol. 67, 51-55, (1954) 35, Flinn, R. II., Seifert, H, E., Brintou, II. P., Jone* J. L., and Frank*, R. \V., Public Health Butt. (V.S.), 270, HS-pp., (1941) 56. Hannon, J. \V. G., Arth. Indus!. Health, 12, (1955) 37. Roe, \V.D., Miller, L. II., Leet, II. H.,and Prind, F., J. Am. Mtd. Astoc., 186, *484-7 (1954) 38. King, E. J., Wist, fortch., 00, 212-30 (1950) M m m , K W., and Kkatcrkotter, W.. Arth. Ryg. it. Bohlmol., 136, 1-4 (1952) 40. Yodtaka. T.. Matauura, T., Mattuda, G., Nuhioka, Y., and Okumura, Y., Hcguahi Igahhai Zasst, 29,404-22 (1954) 41. Worth, C., and Gaoipen. G., 2. physiol. Chtm., 288, 155-64 (1951) 42. Gohr, von H., and Bonniger, \V., 2. get. tea. Mtd. u. thee Crtntgtbicte, 7,455-9, (1952) 45. Holt, P. F.. and Bonxott, J. E. L., Biothtm. J., St, 471-5 (1954) 44. Kflcuth, W., and Sddipkoter. H. \V,, Arth. Hyg. u. Baht/rial., 157,53-60 (1953) 43. Schcel, L. D.. Fkbhar, E., and Klemperer, F. VV.. Arth. Ind. Hyg. and Occupa tional Med.. 8, 564-73 (l5.t) 41 Schce). L. O., Smith. B., Von Riper, J., and Fieuhcr, E., Arth. lad. Hyg. and Occupational Mtd., 9, 29-36 (1954) 47. Holt, P. F.. and Qiborac. S. C.. Brit. J. Ind. Mod., 10, 152-5 (1955) <*. Wolfram, M. L., Sutherland, G., and Schlamowits, M,, J. Am. Cbm. Soc., 74, 45SJ-S6 (1952) 50. Hcffernan. P., Tubercle, 54, 246-9 (1953) 51. Dautrcbande, L., VanKcrkom, J,, and Ceregheitl, A.. Ettai d Pmention it U Silicate (Union Miniere du Haut-Katanga. Belgium, 177 pp., 1954) 52. Rosenthal. E., Colliery Guardian, 185, 561-4 (1952) 53. Cauer, H., and Neymann. S., Staub, 55, 293-307 (1953) 34. Motley, H. L , and Tomasbcftki, j. F., Arch. ni. Hyg. uni Occupational hied., 5.(1952) 55. Wu, N,, Miller, W. F., Cade, R., and Richburg, P.. Am. Ret. Tubtrc., 71,693-701 (1955) 56. Weller. R. \V,, and Crellin, A. J., Arch. Intern. Med.. 91,408-13 (1953) 57. Child, G. P., and Clancy, C. Federation Prt., 12, 311 (1953) 58. Stokingcr, H. E.. Octupaticmol Health Hem. 15, 88 (1955) 59. Zapp, J., Toxicity oj Pyrolytit Product* of "Tean" (Presented at Ind. Health Coni., Buftaln, N. Y., April 23, 1955) 60. Fowler, P. B. S., Lancet, n, 7SS-7 (1952) 61. Cayton, H. R., Fume, C., Jackaon, D. S., and Maitland, 11. B., Brit. J. Ini. hitd., 9, 138-45; 146-53; 303-8 (1952). 62. Schneller, R., Reinhart, W. H., and Caroinita, B. H,, J. ind. Hyt. Toxicol., 50, 238-45 (1948) 63. Cohen, V. L., and Otgood, H., / . AUergy. 24, 193-211 (1953) 64. Van OnUtrund, H. S.. Ank. Iniutl. Health, 10, 232-4 (1954) 65. Lieben, J., and Jackaon, A. \\\, ind. hied, and Surg., 22, 507-9 (1953) 66. Sbilen, J., Koppenhaver, F. B,, Qelaud, J. G., Lutz, L. R., and Vougbt, V. M., Ind. hied, and Surg., 25, 291-9 (1954) 67. DeNardi, j. M., Van Ordstrand, H. S., Curtw, G. H., and Zielinski, J., Arch. ind. Ityg. and Occupational hied., 8, 1-24 (1953) 68. Curtis, G. H., Arch. Dermatol, and Sypkilal., 64, 470-82 (1951) 69. Schubert, J,, and White, M. R., .-Irr4. Biochtm. and Biophyt., 52, 143-7 (1954) 70. Hardy, H. L . Arch, induit. Health, II, 273-9 (1955) 71. jSjobcrg, S. G , Arch, Ind. Hyg. and Occupational Med., 5, 631-6 (1951) 72. " Roechin, I. V., Cigiena i SaniL, 11, 49-53 (1953) 73. Williams, S .. Brit. J. Ini. Med., 9 ,50-55 (1952) 74. Sjoberg. S. G., Arch. Induit. Health, 11, 505-12 (1955) 7$, Fallentine, B., and Fmat, J., AW. Hyg. Tidtkr., 3,58-64 (1954) 76. Browne, R. C , Brit. J. Ind. Med.. 12,57-59 (1955) 77. Sjoberg, S. G., Vanadium Pcntoxide Duii, Stockholm, Sweden, 188 pp., (1950) 78. Mountain, J. T., Stockeil, F. R., Jr., and Stokinger, H. E., Arch. Ind. Hyg. and Occupational hied. (In press) 79. Talvitie, N. A., and Wagner, W. D.. ,4rck. Ind. Hyg. and Occupational Med.. 9, 414-22 (1954) 80. Mitchell, W. G.. and Floyd, E. P.. Proc. Soc. Exp. Biol. hied. 85,206-8 (1954) 81. Mountain. J. T., Stockeil, F. R., Stokinger, H. E. (Unpublished reaulu) 82. Ennis, J. M.. and Uarrison, H. E., Pediatrict, S, 853-67 (1950) 83. Rubin, M., Gignac, S , Ikuman, S. P., and Beikuap, E. L., Science, 117,659-60 0953) 84. futcJkr, L. A., Uht. H. S. M., aud Orem, J.r Nta Unit. J. Med., 232, 458-40 (1955) AS. Byers, R. K.. and Msloof, C. C , Am. J, Dictates Children, 8?,359-62 (1954) 6. Sidboiy, j. B.. Am. J. Mtd.. IS, 943-7 (1955) 7. Dudley, H. R., Ritchie, A. G, Schilling, A., and Baker, W. H., N m Engl, J. Mod., 352,431-7 (1955) 55. Kehoc. K. A., J. Am. Med. Aw*.. 137, 411-3 (1955) 59. Crutcher, J. G, and Peters. J. H., Clin. Rutarek free., 4, SO-R2 (1955) 90. Rodier, J., Mallet, R., and Rodi, L., Artk. maladitt project. mtd travail at dturitt coeialt, 13, 210-25 (1954) 91. Forenun, K., Fuqua, P. A., and Norwood, W. D., Arch. Induet. Haaltk, 10, 226-41 (1954) 92. Bell, R. F., Gilliland, J. C., and Dunn, W. S., Arch, Induct. Health 11, 2J1-J (1955) 93. Mitchell, W. G., and Floyd, E. P,, Prat. Sot. Exptl. Biol. Mtd., 55,206-8 (1954) 94. Foreman, H. H., .-IrrA. Ind. Hyg. and Occupational Mod., 7, IJ7-47 (1954) 95. Miliar, >1. J., Fischer, M. I., Mawson, C A., and Elooate, P, V., Nature, 174, SSI (1954) 96. Maloof. C. G . Arch, induil. Health, 11, 124-5 (1955) 97. Oksala, A., Klin. MonattbL Augtnhtilk., 125,99-102 (1954) 98. Hardin, B. L., Jr., Ind. Mtd. and Surg., 24, 94-105 (1954) 99. Myatt, A. V., and Salmons, J. A., Arek. Ind. Hyg. and Occupational Mtd., 6, 74-82 (1952) 100. Adams, E. M., Spencer, 11. C., Rowe, V. K., McCollister, D. 0., and Irish, D. D., Arch. Ind. Hyg. and Occupational Mtd., 4, 469-81 (1951) 101. Adams, E. M., Spencer, H. G, Rowe, V. K., McCollister, D. D,, and Irish, D. D., Artk, Ind. Hyg., 5, 5o6-579 (1952) 102. Adams, E. M., Spencer, H. C., Rowe, V. K., McCollister, D. D., and Irish, D. D., Arek. Ind. llyg. and Occupational Mtd., 1, 225-46 (1950) 104. Kleinleid, M., and Tabenhaw, I. R-, Artk. Ind. Hygitnoand Occupational Mtd., 10,144-41 (1954) 104. Ahltnark, A., and Forstmann, S., Artk. Ind. Hyg. and Occupational Mtd., 5, - 486-98 (1951) 105. Soucek, B., and Pavelkova, E., Pracevni Ltkarctei 5, 62-68 (1954) 106. Weaver, F. L., Jr., Hough, A. R., Highman, B., and Fairhalt, L. T., Bril. J. Ind. Mtd., 8, 279-83 (1951) 107. Moore, J. B,, An Approach to Soletut Saftiy (Address delivered to Safety Eng. of Electric Power Industry, New York, N. Y., April, 1954) 108. LaBelle, C. W,, Long, J. E.. and Christofano, E. E., Artk. Induct. Health, 11, 297-405 (1955) 109. LaBrile, C. \V,, Long, J. E-, and Christofano, E. E., Vapor Toxicity of Mixed Satoeut (Presented at Ind. Health Coal., Buffalo, N. Y., April, 1955) 110. McCollister, D. O., Hollingsworth, R. L , Oyeu, F.. and Rowe, V. K., Comparo- tim Toxicity of fumigant Mixture* (Presented before Ind. Health Cool., Buffalo, N.Y., April, 1955) 111. Fawcett, H. H,, Arch. Ind. Ilyg. and Occupational 3/sA, 6, 455-40 (1952) 112. Tka Hatatds i f Vapoeitmg Liquid Extinguishing Agents (Nad. Fire Protection Assoc, Boston, Maas., 4 pp., May, 1955) II.'. Smyth. H. F., Jr. Ann. Rev. Strd., J, .149-62 (1934) 114. Stokinger. H. E.. Am. J. Putin Health, 4J, 742-51 (195.1) 115. Kcvnan, H. and Byers, I). H., Arch. M , Ityg. and Occupational .1fed., 6, 220-.10 (1952) 110. Chulak, J,, Schafer, L ]., Younker, W. J,, and Yeager, D., ArrA. M utt. Utalik, U, 280-90 (19551 117. Cholak, J,, Schafter, I.. J.. and Holier, R. F., Arch. Ind. Hyt- and Occupational Med.. 0,514-19 (1952) 118. Air Pollution Study Projat, (Cali/. Stale Dept. Health, 1955) 119. Beaver, II. and Associates,.1rck. Ind. llealtk, 11, 513 (1955) 120. Hemeon, W. C. L., (Prevented at 126th Natl. Meeting of Am. Chcm. Soc., New York, N. V.. Sept. 14. 1954) 121. Bloomfield, B. 1).. .4m. M . Hyt. Assoc. Quart. 16, 141--31 (1955) 122. Waller, U. .. licit. J. Canter, 6, 8-21 (1952) 123. Cooper, R. L., Chcm. Week. Dec.. 1564-5 (1953) 124. Kotin, P., Falk, H. L., and Thomas, M., Arch. Ind. Hyt. and Occupational Med., 9, 164-77 (1954): Auk. Indust, lltaitk, 11, 115-20 (1955) 125. Ask-Upmark, E., Diseases of the Chest, 27, 357-65 (1954) 120* Hutchison, !>. H., aud Holden, F. R. (Presented at S. A. E. Golden Anniv. Ann. Meeting, Detroit, Mich., January 14,1955) 127. Larson, G. P., Chipman, J. C., and Kauper, E. K.. (Presented at S. A. E. , Golden Anniv. Ann. Meeting, Detroit, Mich., January 14, 1955) 128. Haagen-Smit, A. J., Ind. Eng. Chcm., 44 1542-6, (1952) 129. Haagen-Smit, A. J.,and Fu, M. M., Air Pollution (Presented at S. A. . Golden Anniv. Ann. Meetiag, Detroit. Michigan, January 14, 1955) 159. Egerton, A. C.. and Hanon, T. K., Proc. Roy. Soc., London, (A)163,90-95 (1957) 131. Spindt, R. S., Wolfe, C. 1... and Stevens, D. R., Science, 121,856 (1955) 132. Haagen-Smit, A. J., Eng. and Sri. Dee. (1954) 153. llewchbcrgcr. W. IX. Mur,ware Method as a Tool in Studying Ike Composition of Air (Air Pollution Kynipmuun, Pasadena, Calif., April, 1955) 154. Thorp, C. E.. M . Med. and Surg., 19,49-54 (1950) 135. Weaver, E. R., U. S. Dipt. of Commerce, Kat'l. Bureau of Standards, Rapt. .Vs. - U2S (1951) H6. Aero Medical Aaii., Aviation Toxicology (The Blakiscon Co., New York, N. Y., 120 pp,, 1953) 137. Stokinger, H. E., Arch. Ind. llyg. ond Occupational Med., 9, 366-85 (1954) 138. Stokinger, H. E., Byers, D 11., Suiuman, B. E., Hyslop, F. L , and Wagner, W. D,, Tonicity ofOtont (Presented at Ind. Health Conf., Chicago, IU,, April, 1954) 139. Gray, E. LeB., Goldberg, & B., and Patton, F. M., Arch. M . Hytand Occupa tional AM.. 10, 409-25 (1954) 140. Djggle, W. M.. and Gage. J. C., Brit. J. M . Med., 11, 140-4, (1954): Brit. J. ind. Mod., 12, 0-64 (1955) 141. Saluman, B. E.. Anal. Ckem., 26, 1949-55 (1954) 142. Smith, R. G., and Diamond. P,, Atn. M. Hyg. A tm . Quart., 13,233-8 (1952) ps Jtff .flF?R-i7-1992 10:28 FROM TO 13014521039 . P.,01 - V / /' V I n d u s tr ia l M e d ic in e t .Sr s k- -.i, V. R u th e r fo r d T . J o h n sto n e , M , O . CONSULTANT IN INDUSTRIAL MEDICINE. .Tv CALNIDNICCAULNIPCRAOLFEPSRSOOFRESOSFOPRROEFVEMNBTDIV1CE1NMBE,DICINJL\AND FUSUC HEALTH UNIVERSITY OF CAUFORNU AT LOS ANOELE ' \ , v>. Sew ard E. D, ; DIRECTOR, INSTITUTE OF INDUSTRIAL HBALTH PlOFfi&fiR OP XlltnWMWP, WlirMsfAL CCMOL pftonssox OF l^DUSTRIAI. HJEajlTM, JttMlVti nv Mini 1 UNIVERSITY Or MldUOAN, ANN ARBOR - ' /' v M l - : r ... A'-' ' ' iw y . \ W B. Saunders Company !*;?/ -\ .. & e. 1'7-1992 1'0.:28 FROM % Chapter 13 Occupational Cancer lherr a n many diverse forms of neoplastic growths constituting a group of disorders rather than a specific disease entity. Ewing, years ago. defined a neo plasm as an a ltonomous new growth of tissue. Cowdry offers this definition of cancer: "Canctr is a condition manifested by a wide variety of cells of the body from before birth to the point of death in more or less remote response to the action of hundreds of influences. . . The over-all incidence of cancer has been increasing steadily for more than a ccntuty. Despite tremendous amounts of study and research, the etiology of cancer remains a mystery. Such diverse agents as the various ferms of ionizing radiations, ultraviolet light and a few chemicals ranging from rompUm organic Hirurtumi to metallii' run iniriare the develop ment of cancer in man. Exposures to cancer-producing agents occur in many occupations and are not limited to manufacturing industries. The farmer, sailor and outdoor worker suffer a high incidence of skin cancer from exjtosurc to the ultraviolet portion of sun light. W ithin industry, there is exposure to chemical cancer-producing agents and to some types of tomztng radiations. Cancer-producing agents ate called car cinogens. Most occupational cancers occur in the skin and the respiratory system, since they are directly exposed to the various carcinogenic agents (oils, waxes, coal tar, pitch soot and asphalt). Inhalation of chromium dust, nickel dust and nickel carbonyl, coal tar fume, "isopropyl ori" vapors, and radioactive dusts and gases may cause cancel of the icspiiaiuiy tiait. In addition, inhalation and ab sorption of 0 naphchylamine ot benzidine dust or vapors cause cancers of the urinary bladder, the tissues affected being those undergoing the greatest intensity of exposure to the carcinogenic material. Cancer does not appear at ance upon exposure to carcinogen nor among all individuals exposed. In general, it is Itelicvcd tha: the greater the intensity of P ageW the expo Apparcn discontir who hav jobs, hav no signs some tin been dcr As i dinarily, is impos vironme tertstics. alence ir in an en occupatii non. In \ tional a is not as In 19S4, tional ca exposure cancers, skin can H istory Air) among t Percival cancer. I phasued asse m b le dates, re] Eck much la< skin can as adequ carcinog She the wint  APR-17-1992 10:29 FROM TO 13014521039 uing a group efmed a neodcfinition of of the body ponsc co the cer has been mb or atudjr se agents as w chemicals the develop- and arc not vorkcr suffer li u i l o f Mill* icing agents c called Car roty system, oils, waxes, cel dust and re dusts and :ion and abncets o f the est intensity nor among intensity of O C C U P A T IO N A L C A N C E R * 323 the exposure and the more potent the carcinogen, the sooner cancer will develop. Apparently, once sufficient exposure lias been incurred in a susceptible individual, discontinuing die exposure docs not p r e v a i l ilic dcvclupmcm o f tautci. Wuikc who hive been exposed a few or a number of years to a carcinogen and then dunged jobs, hs.ve been known to develop cancer m a n y ye ar s later. In the intervening years, no sigr s or symptoms appeared. Perhaps a microscopic cancer in situ existed for some l ine prior to the development of overt cancer, but such lesions never have been deinonsnaicd in connection with an occupational exposure to a carcinogen. As with all occupational diseases, occupational cancer is poorly reported. Or dinarily, the establishment of a specific case of cancer as occupational in origin is impossible unril a rarr inogenk substance has been identified in the work en vironment. Mnrrnvcr, rhi occupational cancer has no specific identifying 'charao- ccristicn. The problem of skin cancer is particularly difficult because of its prev alence in the general population. Scrotal cancer and bladder cancer, developing in an employee who hat. been exposed to a carcinogen, readily are recorded as occupational because of the low incidence of diese cancels in die gctinal popula tion. cancer and In view of the inherent difficulties in tional the paucity of materials eessttaabblliisshheindgaas diagnosis of carcinogenic an to occupa men, it is nor iistonishing that the total iccuidcd cases of occupational cancers is small. In 1934, Hueper collected all such cases. He has recorded 730 cases of occupa tional cancer in the United States. About halif of these arc bladder cancers from A JfV h U t t u U iA A ItfW t**. ^ i i i i t i t . r i i a l I i i n I J #*!< a i V A < t A N * e l 1 1 ft cancers, chromates for 73 lung cancers and a few heavier petroleum oils for 70 skin catcers. H istoiy Although in 1331 Paracelsus noted the prevalence of a deadly lung disease K f x ( M a i W a e 0 mlnsaxe, If In It li^ >t i Q Percivtl Pott, in 1773, identified and described the first recorded occupational cancer. His description of scrotal cancer from soot among chimney sweeps em phasized both Severe prolonged exposure and the latent period. Eckardt (1939) has assembled the historical data on a world-wide basis in an interesting table including dates, re p o rte d u ge n t, site a n d number of cases re p o rte d (T a b le 1 3 .1 ). Eckardt properly points out that the actual number of cases is undoubtedly much larger due to inadequate reporting and lack of recognition. Particularly in skin cancers is this true. W e have not accepted arsenic, saltpeter, and asbestos U g4s.v3vljr ^swvwJ dki'Ctn^enf *r4 Iwlicw *kst eliry prrtkjtkty tkCWAftl)' flfi CO carcinogens. Siuxplieidcis in ilic Balkan* and outdocr workers in Kashmir, who during the winter tally beneath ihcil clothing, next to the skin, pots of coals (O keep ftPR-17-1992 10:30 FROM TO 13014521039 P.04 V I 1 34 T H E O C C U P A I I I J N A I . n iA E A fiE S TulAi 13.1 Historical Out* on Occupiitivnol Oman* FIR ST REPORTED YEAR REPORTED BY AGENT OR PROCESS SITE PROBABLE' TOTAL NUMBER OF CASES REPORTED TO DATE 1775 Pott 1822 Paris Soot Arsenic Scrotum stun 1875 Volkmann Crude Wax from Coal Skin 1876 Voikmann Coal Tar Skin 1876 Bell Shale Oil Skin 1879 Halting 8c Hesse Ionizing Radiation Lung 1894 Unni Ultraviolet Radiation Skin 1895 Rebn Aromatic Amines Bladder 1898 Mackenzie Creosote Skin 1906 Fricbcn X-rays Skin 1910 Wilson Shale Oil and Skin Mineral Oil Lubricants 190 254 >3000 >200 >300 Unkncwn >1200 20 >125 2C00 1911 Pfcil Chromate Produci ng Lung 140 1917 Leymanu Crude Anthracene Skin 20 (coal tar?) 1926 Prunes Saltpeter Skin 17 1929 MartUnd Radium Bnnp 9 1932 Grenfell Nickel Refining Lung 6: .35 Sinuses 1935 Lynch BeSmith Asbestos Production Lung 59 with Asbestosis 1952 Weil et a l. Isopropyl Alcohol Sinuses 10 Manufacture *,ly permission. from Ineuwrial GiidnoRens. M>km Mm u p uj.li n In Ju m l Median. Grunt & Stratton, New York. WV. w . iff fhmnic burnt. and squamous cell carcinomas have developed in the skin of the abdomen and thighs. Whether the radiant hen and chronic bums atone ate the Cliologic factor, or w lm lin u)ii<,riiU, perhap* tar*, from the #m*ld**ing caolt, charcoal, or leave* may he rhe sptet itic* exciting factor is not known. In Kashmir, these are known as Kangri cancers. Kangri being the name given the pot vsed for carrying die coals. Radiant heat also is probably a cocarcinogen. Etymmmtal Work Despite knowledge of the carcinogenic action of certain agents, the precise native uf uccupttiolwl cancer remain* a* tlutiv# at that of other cancers. Experi ment al work ro drrrrmine the carcinogenic ability or potency of a material uti- nnn iv 1 o o zi io * 3 i rnoM TO 1301-4^21030 I PROBABLE TO T A L _ 4UMOER O F CASES WEFORTED TO DATE 190 <25 254 >3000 >200 >500 Unknown >12 0 0 20 >U5 2000 140 20 17 9 135 59 10 industrial Medicine. \ k * w l v ^ b J ill iliv nfrdomchrrhoensicmobludmers- is nut known. In : name given the cocarcinogen. tents, the precise r cancers. Experiaf a material uti- OCCU PA TIO N A L CANCER Ii7.cs animals that ire lirtrtwn ro he luKepiibU to cint, The tuuuu^cnk pu- toncy vents of a and other material ordinarily is materials have shown greater with been hasten increased concentration.-Certain to the action or increase sol the patency of carcinogens; these arc called cocatdnugcus. It is not dearly understood just how carcinogens act upon nrlU to alter their type of growth to a malignant pattern. Attempts have been made to explain this diangc in tetms of cellular metabolism. Moreover, it was hoped that a relationship Cbcte.octnsweveererhsnifotcinnhVeomff ihacaasnlobsretmreunacltpucrroeevileatdno.d Cacaamcrccaiulnitwgonggaecnuncitcdosancmetiavayintdybeictodsueslducbribbseeecdfjouauesnnttdh.gerNoperwoittchheestrsoouaff bdte-tfeoctfarbrllUe ttuhmatorh.aHveowunedveerrg, ownheemthaerligtnuamnotrstrudnevfenlrompfrriomn dauseintoglaecrormll moronasuutumse. is u Ofnknown the . thousands of chemicals tested in vnnmi animals, hundreds have proved to as be carcinogenic. However, only a L * of possible occupational carcinogens. Th eofetxljpi.esreimsiecnutaseldwiollrkinhdautstermy pthhaussisseerdvtihneg necessity repeated exposures and the relatively long latent period. Moreover, ex- prri'm r n n have Substantiated the b e lie f that th e tissue p ilu .,. ily ,,<Tcittvi ! liie u u e whicMh ahtaesrigaulsttearbetdotbiheedminotost tnhemlboondayedmacoynbteacmt ewtaitbhotlihzeediarnridnnaafaenw metabolites h a re b een d c m o iis u a ic U to be carcinogenic. Thus, /J-naphthylammt is metabo lized to 2-amino- 1-niphfhol that is eliminated rapidly by the kidneys. After ad ministering /3-naphchylamine, the ratio of 2-amino-l-naphthol found iin the urinr to that found in the blood serum is about 200:1. Dogs who readily develop blad- Jv tw m uru fro m f t n a p h th y in m la v u i .ial<v/iU c 7 0 p c i ce n t o f such m a te ria l CO 2- anino-l-naphthol. while ratawho ordiniu-ily odof not develop bladder tumors fium this chemical only metabolise 1.5 per cent the material to the carcinogenic bmerernabesotiaitbel.isFherodmaxththise acanrdciontohgeerniwcoargke.nrth.<I-t t.pirmodinucce-st-cnaunyceiur liinvtthme eutarinbaorlyiteUhaaus iorbecause gest it is in c period of ontact time. with These threesseeartcishsufien*diinngtsh e highest concentration for the have added significance because of :he possibility ofthe body forming this mcubulite from relatedrhemiral*. Epidemiology Cancer is more difficult tu establish as occupational in origin chan any other occupational disease. Silicosis, for example, does not occur in the adult popula tion from non-work connected causes. All forms of cancer resulting from the oc octhucepcauatrviioenrngaag"leceaanngvceierorofnrimtshesesn. wtAoaprskepcienoagnrdpinfoaptchutoelartgwioehnniecirnhaclrmeaaadskueelsst, prtehocepouignlnactiitidiooennn.coIenfooafcd'cdnuiaptitaoutinroa,nlalaysl canters difficult is the long latent period or inrervai between exposure and the TO 13014521039 P.06 32.6 THE OCCUPATIONAL DISEASES development of overt cancet In the intervening period of year*, the worker may have chmged jobs or the Industrial processes may have been altered changing the mrpn'un completely. The latent period in mule-spinner's cancer of the scrotum is exceptionally long. A Study of 300 cases in Great Britain indicated (hat the in terval between a mule-spinner* first day in a textile factory and the devclojiment of trrnttl -anrer varied between 16 and 63 years. O f these patients, 67 per cent were b<tween 33 and 34 years of age. Because of low incidence in the general p opulation, tw o types o f cancer-- crotal and bladder end potsiM y third, nasal sinus esneer--should be considered occupational in an industrial employee until proved otherwise. Because of the difficulties in establishing the diagnosis of occupation^ can* cc t in a single ease, g ro u p stu d ie s seeking an in cre a se d in c id e n c e o f cancer in the work group constitute a fruitful approach. Unless it is excessive, an increased u u m b e t of cancers in a papulation group o rd in a rily is n o t self-evident. Painstak ing statistical Studies of mottality by occupation u su a lly are re q u ire d to establish a specific type of cancer as occupational in origin. Hueper has expressed this well. "The dmonitration of an o c c u p a iiiin x l iiiigin of ca n ce rs d e p e n d s mainly on sta tistical evidence which often shows an excessive incidcnrr nf a certain type or types of cancer in a restricted group of worker* . . At present only the most potent snd obvious cancers and carcinogens have been discovered while tliose of lo w incidence fate caused by carcinugi-nN o f low potency have n o t yet been m u g niaed." In (he epidemiological method of study, rhe amount o f cancer in the popu lation under study is determined, and expressed as an incidence, prevalence, or mortality rate. Basic material for such taiUi.ii.al stu d ie s is o b ta in e d chiefly from public health or insurance company records. Such studies may indicate an inci dence of cancer higher than expected in a population. P h y s ic ia n s may d isco v e r that an unusual amount of cancer prevails among a certain work group. Once rhis *u!picion ariu-s, immediate study of the medical records of that wuik group it imperative. Here it w h e re good industrial medical records are most helpful while poor records, lacking in follow-up or final diagnoses, arc practically useless. F o r details o f the stru c tu re o f epidemiological stu d ie s, the reader is referred to Eckard'i'a monograph, " in d u s t r ia l C a rc in o g e n s , o r a publication by rh e C o u n c il on Ind'istrial Health of the American Medical Association entitled "Occupational ClMttuK, *' J.A.M.A., 166.-2171 li>S6. Su>h p\rMi/-n-nr,'. excellent material on how to conduct epidemiological studies. In this connection, Cramer's hypothesis makes interesting speculation. Cra mer suggested that the susceptibility to cancer might be determined by intrinsic factors, perhaps genetic. The effect c>f environmental carcinogenic agents might be only to determine the site at which cancel would appear. However, the mate rial collected in occupational cancer studies docs not bear this out for, with an in crease of occupational cancer occurring at a particular site, ihctc should be less cancer of other sites and this does not appear co be the case. i APR-17-1992 10:33 FROM TO 13014521039 P.07 {BASES die work may jd changing the of the scrotum ted that the inie development its, 67 per cent in the general y a third, nasal employee until cupational can>f cancer in the e, an increased dent PiinHjk. red to establish essed this well, mainly on siacertain type or only the most while those of rer been recog- r in the popuprevalence, or d chiefly from dicatc an incimay discover group. Once it w vn k g ro u p most helpfiil tically useless, is referred to f the Council Occupational llent material -Illation. CM 1 by intrinsic igents might et, the mate%with an in* ould be less O C C U P A T IO N A L C A N C E R 527 Oci'ufia/JofiaJ Carcinogens T h e re are th re e c a te g o rie s o f c a rc in o g e n ic m a te ria ls to co n sid e r. -F irs t, th e e sta b lish e d o c cu p a tio n a l c a rcin o g e n s th a t fia v c been p ro ve d b eyo n d d o u b t as ca u s in g o c c u p a tio n a l ca n cer. S e co n d , m a te ria ls th a t are su sp e cte d o f c a u s in g o ccu p atio r a l ca n ce r b u r n o t p ro v e d . T h ird , m a te ria ls in u se in in d u stry th a t h a v e been tr.w ahljehr-d a t rs rc in o p e ric fo r com e ty p e s o f n im e l in il ic la b o ra to ry b u t W h ich hav: not been implicated as producing occupational cancer in man. Agents hill ing into the first two categories ate presented in Tables 13.2 and 15.3. Table 13.2 presents the generally accepted and established carcinogens and the sites character istically affected. Table 15.2. Established Occupational Cancer Producing Agents, with Site* AGENT 4 -A rrin o d tp h s n y l (x e n y la m in e ) Anthracene, crude Asphalt B e n i id in c and derivative* Chrc mates Creosote Ionising radiation (all types) Isopropyl oil Mineral oil, crude Naph rhylamine-beta Nickel and nickel carbonyl Paraflin, crude Pitch Shale oil Soot Spindle oils, aromatic Tar. coal Ultraviolet rays Wax, crude from coal TISSUE Dladdct Skin Skin Bladder, lirrrer, Vidrw-y Hespiratory system Skin Lip Skin Lungs Blood forming organs Bone Eye Larynx and sinuses Skin Bladder, uicict, kidney R e sp ira to ry tract Skin Skin Skin Skin Skin Up Skin Skin Eye Skin * M odified from O ccupational Cancer, a Challenge to the Physician, N ew Y o rk Scars Occupa tional Cancet Com m ittee. , APR-17-1992 10:33 FROM TO 13014S21039 P.08 THE OCCUPATIONAL DISEASES Smpected Occupational Cancer Producing Agents, with Sites* AGENT TISSU E Aromatic organic chemicals Arsenic Asbestos Benzol Beryllium Carbon black Chlorinated hydrocarbons Estrogens Isopropyl oil Mineral oil, crude Naphthylaminc-alisha Pitch Radiant heat Sodium nitrate, crude Tar, coal Liver Skin Liver Respiratory system Lung Blood forming organs Lung Skin Liver Breast (male) Lung R e sp ira to ry system Lip B la d d e r, u re te r, k id n e y tip Bladder Skin Skin Respiratory jystem Bladder R IaxmJ ip or^una * Modified from (krcupstional Cancer, * Challenge to the Physician. New York State Otvupj- tionai'Canrer Committee. Table 15 3 presents those materials that have been suspected of'producing occu- t>9 t i o m l C tlW e r b u r I K i n d i a p u r e t>, Imv- ,,> l T n pv>vrr.J u . p v t i t i c Several points should b e n o te d c o n c e rn in g Table 15.1 a n d 15.5. In Table 15.2, the potency of the established carcinogens is n o r in d ica te d . P a rtic u la rly -a m o n g the oils is this impc ream. For example, shale oil is n much more potwnt curcmogm than etude mineral oil. Also, despite the high incitlence of mule-spinner's cancer of the scrotum in the textile industry in Great O titu iiv , none has occurred in the United T tn * / t i 4 VHn; i n ek * M e A U .s^ v n '4 v f i l n o i l lii u a c i> i l k ' t k | ( ca* planation. In the United Suic, particularly since the stud es of Braun and Truan, ' there is considerable conviction that asbestosis docs not predispose to the develop ment of lung canctr- Until further evidence is forthcoming, we have arbitrarily placed asbestos in (ho unproved or doubtful giuup and arsenic in the suspected group. Finally, some substances appear on both lists. This comes about because a suhstance may be a proved carcinogen for one site, skin h i example, but nor hr established as a cardnogrn for another site, such as the lung. Aniline ilmr* not appear on either list since it now has brm established that it is non-carcinogenic despite rep arc Probib xpo The U terials test. P.H.S. Pub referred to C hief Site. A s ind tissue it rea words, it is that, of the tory tract--: tract, partic carcinogen it TH* Asnth leukemia w, l#ait the skin, wii cancer lesior cancer o t oc cases occur ii ic reared fc ui- p ic d o m ii istics from n tions of the 1 results from vapors direct Pigmen cinogenic oil if skin . APR-17-1992 10:34 FROM TO 13014521039 ES 1 Silts9 ______ State Occupi- ucingoccucarcinogen. I. in Tabi Nrljr wiiutig caiciuogcii :*scancer o f the United he best exand Truan, he develop : arbitrarily c suspected it because a but not be te does not uiiiijogcuic OCCUPATIONAL CANCER 329 despite reports to the contrary iti the older literature. Some emiics in Table 15.3 arc probably only cocarcinogens. Numerous materials have been established in the laboratory as carcinogens. Sven potent ones in the laboratory, although appearing in some occupational Cnvironmtnts have not been incriminated as causing occupational cancer in man; J, 4-bcntpyrcnc is one cxi.tnple. It is known to be present in the exhaust vapors of motor vehicles. yet no increased incidence of cancer among garage workers or other exposed groups has been demonstrated. The U.S. Public Health Service lias compiled and published a survey o f ma terials tsited for carcinogenic activity. The second edition appeared in 19)1, P.H.S Publication 149. The student desiring to look up any specific material is referred to this voluminous publication. C ij/cf i'itts A s in d ic a te d earlier, the site of action o f on o c c u p a tio n a l c a rc in o g e n is th e tissue it reaches in greatest concentration for the longest period of time. In other w o rd s , it is th e tissue s u ffe rin g the g re a te st e x p o su re . T h u s it is n o t a s ro n is h in g that, of the four major sites of occupational cancer, two--the skin and respira tory tract--are tissues of primary contact by carcinogens. The third site, the urinary tract, particularly the urinary bladdci, is the body M93U1. imm lApuavJ * hen 4 carcinogenic material rapidly is removed from the blood by action of the kidneys. T h e fourth and last chief site, the hematopoietic system, is the sice of origin of leukem ia w hich is vauavd by various forms o f ion isin g radiations and benxol. Skin. Eck&rdt states that over 7) per cenr of occupational cancers are of the skin, with co a l tar am.1 shale o il b rin g the 1h it-f carcinogens. Fortunately, skin c a n c e r le s io n s tUe tc u d ily u p p u rvlU and th e re fo rt cu re s are m o re e a s ily e ffe cte d S k irt cancer o f occupational prigtn is particularly poorly reported. It is believed that ra v e s n i-r n r in g a m o n g fa rm e rs ant? o u td o o r w o rk e rs d u e to u liu v iu lc t la C ia lio i'i * fir by bvii^' practxrionvr* lun nflili.it* n*|v<its*l OiiiijtuiMMiti) kLiii I'litcerfi Aar rli Ke>tA^ nst cHar** is r ic s fre tn n o n -o c c u p a tio u a l s k in can ctrts. A s tn ig ltt be e xp e cte d , d ie e xp o se d p o r tio n s o f th e b o d y -- th e h e a d , n e c k , h a n d s an d a rm -- in c u r m o st su ch ca n ce rs. T h is re s u lts fio ir i d ire c t c o n ta c : w ith th e c a rc in o g e n ic m a te ria ls o r d e p o sitio n o f su ch vap o rs d ire c tly u p o n e xp o se d s k in surfaces. Pigmentary changes in the skin have been reported from exposure to car cinogenic oils but are not believed to be a prccancerous skin response. However, areas of s k in hypertrophy and atrophy occurirg o n skin e xp o se d ro carcinogenic o il* are aw v ia r e d w ith s k in ca n c e rs s k in c a n c e rs d e v e lo p in g under such condi tio n s ar- co n sid e re d occupational. Unexposed portions of the body also ate sub ject ro ' Win ra n re r, particularly if the clothing becomes saturated with the car c in o g e n ic m a tu ris !. T K u # , 11 n a W tro u e v tc < n n v # j' ah* o il to th e it r a tm n ftPR-17-1992 10:35 FROM TO 13014521039 P.10 MO T H E O C C U P A T IO N A L D IS E A S E S provoking muJe-spinner's type scrotal cancer. Generally the latcnr period in skin n cancer is long. 20-40 years or longer, thus years of exposure ordinarily arc requi a: site for the development of such cancers. In this connection, tegular clear sing of the skjn certainly must play a part in delaying or preventing the occurrence of li skin cancer. a Several materials produce skin cancer and chvrc are probably others that have ai not bom identified. The presently accepted kin cancer agents include ulcaviolet la ltchc', ionieine radiations, alpha, b e t a and ^ a i u i t n i . u n i i t . m , p i n - h . r r w \ r r , 1.1 crude anthracene, and crude waxes; shale oils and crude shale paraffin oils, petro- h |truJuer, ftaJ snl* fwul wala, iaui piiklit 1C a n d ca rb o n b la c k . T h e c h ie f g ro u p s e xp o se d to th ese a g e n ts are; Sc U l t r a v io l e t L ig h t . Farmers, ranchers, construction workers and espe* dally outdoor workers are exposed, with greater risk in the south and at high b elevations where the intensity of light is greater. b. lO M ia m t. R atsiatiom.. T h eta agentt affect r t lie U g im , Icn tittt, veteri St narians, chiropractors, x-:ray technicians, and scientists and technicians in various p* nuclear energy industries. p. C o a l PRODUCTS. Work groups exposed to coal tar. pitch, soot, creosote ft or crude anthracene include workers engaged in handling these materials iv* a1 St Gas works B riq u e tte w o rk s ti Coke oven* R o a d b u ild in g a n d re p a irin g ta nhisr furnaces C o a l-ta r-p itc h p ip e m a k in g T a r d is tille rie s Dutiny miiktttg (3 Patent fuel manufactories Cord making L e n s in d u stry d u rin g p o lis h in g P a in t m a k in g or Building and allied trades electrical equipment works, making w Roiling h it preparation and cables, carbon brushes, carbon elec- ad: handling crock,' and insulation Flooring materials Work of seamen and fishermen w< Weatherproofing materials C m w ir c nr rar prrcrrvartisn n f wrwvt Sweeping roads Working with impermeable paper Making of tel and cardboard Caulking of ships it ac Sh a le Pro d u cts. W o r k g ro u p s e n g a g e d in th e p ro d u c tio n o f shade o ils a n d slu t v p a ra ffin o ils , E u ro p e a n m u le -sp it itie i . t iia e liin is t s a n d o th e rs w h o w o rk e d or continuously with shale oils. Little or no shale oil presently is being produced lil i l l th is u u tiu y a n d it ap p e a rs rh s r lir r lr Is h e n g u sed in A m e ric a n in d u s try . ra P e ' RO LEU M P r o d u c t s . Those exposed to these agents are workers en th gaged 1 the primary production and refining of petroleum products, as veil as * Tab ic modified trom Goal T a r anc Cutaneous Carcinogenesis in Industry. F. C Com bes, Charles C Thom as, l$04. W * PPR-17-1992 10:36 FROM TO 13014621039 P.ll EASES period in skin arily are regul ar cleansing o f occurrence of hers that havr ude ultraviolet itch, creosote, fin oils; pettoasphalt, pitch, kers and espeh and at high enlists, veterian in various soot, creosote terials in:* i making bonelec- nen of wood c paper i of shale oils who worked ng produced industry. workers ents, as well as F. C . Combes, O C C U P A T IO N A L C A N C E R 331 mul :*spinners, gunsmiths, paraifin pressmen, and a large number of varied metal and tool industrial workers. T he C arcinogenic Factors, The precise mode o f action o f ultraviolet lighi in the production of cutaneous cancer is unknown. The same is true of ioniztnjr radiation. However, in both infrtc.n, intnniry and duracin of cXpOSuic arc important. Alsu, absorption of these forms of energy by the basal proliferating laye: of the skin cells appears to be necessaiy. In coal products, carcinogenic prop- ertiet arc found chiefly in the heavy oils and anthracene oil. Pure anthracene itself is net carcinogenic but t, 2-bcnzanihraccne and 3 .4-benzpyrene are among several identified carcinogens in coal-tar and coal heavy oils. Coal products are the richest sources of carcinogenic agents yet discovered. The carcinogens in petroleum products are closely related carcinogens to die benzanthracene and bcnzpyirnc found in coal products, the bvrtccnoid hydtocar- bons. Petroleum oils vary greatly in rheir carcinogenic ability depending upon the Source, with shale oils being the more potent- Arranged in wider of carcinogenic porer cy, depending upon their source arc oils hum: Venezuela, Borneo. Rumania, Pcrsit, California, Mexico, Mid-continent, Texas, Pennsylvania and Russia. Re fined oils are the least carcinogenic and the sulfonated oils used as detergents are hirmless. Pure mineral oil and vegetable oils are innocuous. In the United State, carcinogens are not found in the mineral oil fraction of lubricating or cut ting oils. The chlorinated hvdrtv-.irhon present in lubricating and cutting oils can cause a folliculitis but never produces cancer. Suspected Skin Carcinogens. These include arsenic, sodium nitrate (saltpeter), radiant heat, chemical and physical trauma. Among those exposed to arsenic are workers engaged in mining and refining ores containing arsenic and workers engaged in the production of and working with arsenic alloys. Nursery and agriculture workers using arsenical insecticides also a/c exposed. Arsenical skin cancers are exceedingly rare, if they exist. Such a diagnosis would depend upon: 1. History of prolonged exposure 2. Characteristic arsenical skin manifestations. 3. D e m o n stra tio n o f a rse n ic in d ie s k in , h a ir and u rin e . I t is th e firm b e lie f o f th o se w h o h a v e stu d ie d th e e v id e n te c a re fu lly that arsenic acts essentially as a cocarcinogen but is not in itself carcinogenic. An excessive rate of skin canec has been reported among the sodium nitrate or saltjjeter workers in Chile. However, it is believed by many that this high rate likely is due to some factor other than the sodium nitrate, possibly ultraviolet radiation. Radiation hear, chemical and physical traumas are not carcinogens, at the most they act only as cocarcinogens. Respiratory TVact Cancers. Soluble gases and particulate matter from inhaled air are deposited in the thin film of fluid covering the respiratory tract. W ith tontinuous respiration, these materials accumulate on the walls of the re- TO 13014521039 P.12 332 THE OCCUPATIONAL DISEASES spiratuty ti4ii fiuui ilit nose to the terminal alwoli. Should cifcinogrnir mi. tcrial be present in the air, ir is easy to sec bow the respiratory tract tissues would suffer the greatest exposure b u ili in d u ra tio n a n d in te n sity . I o n iz in g R a d ia t io n . The first occupational respiratory tract cancers o ccu rre d i.mong miners in (He now fa m o u s Schneebcrg and Joacbimsthal mines, hirst arsenic, then cobalt, were blamed rut Uic cM.es!. im.iUvu.. vf Ung bur now it is agreed that ionizing radiation from both radioactive dust and gases (ra d o n ) w ere the carcinogenic agents. Tr is o f interest that these mines provided the ore fiom which the Curies isolated radium. It is believed that between 40 and 70 pet cent of the miners died of lung cancer. Neither the daily nor the total dosage of ionizing radiation received by these miners can be calculated at this time because of the great change in working conditions and ventilation of the mnes. Radon gas is short lived but its daughters are radioactive. The amounts of radio active gaies and dusts present in these mines over the centuries arc unknown. Mines producing radioactive o res in the United States usually have some radon gas and curiously enough some mines producing non-radioactive ores also have been found to have radon gas. As yet, uranium miners in this country, Canada and Africa have not shown any evidence of increased incidence of lung cancer. Nevertheless, a lung term study of the uranium m in e rs in western United States and die levels of ionizing radiation in the mines is being conducted by the Pub lic Health Service. in the production of lung cancer from ionhdng ra d ia tio n s, gicat hazard from inhalation of radioactive dust is possible because of the accumulation, deposition, storage and long retention of dust particles in the lung. C h r o m a t e s . Machle and Gregorius, by an epidemiological study in 1.948, firs t e sta b lish e d the increased incidence of lung cauvci u m u n g wirlc<-r e n g a g e d in the m; nufacture of chromates, The Public Health Service study of seven dirom at p la n ts in H its tc rf r h 'ir '.jlv in t ">? 1 in n it' th e d e a th s a m o n ch ro m a te v /u ik - ers were ;au$ed by cancer of die lung. T h e m u iiu lin from o th e r types of ameer was about the expected amount. It is estimated that the number of lung cancer deaths a m o n g the ch ro m a te w o rk e rs w as a b o u t ;(0 tim e s that e xp e cted in r h r gen eral p o p u la tio n . D e ra ile d stu d y o f th e w o rk e n v iro n m e n t in th e c h ro m a rr p la n ts h a s n o t identified a specific fo rm c f c h ro m iu m as r h r a g e n t. D r . Anna Bitetter has engaged in much laboratory experimental work with animals using chromates, but has filled to produce lung cancer. Hueper has produced bone sarcomas in rats by intrafimoral injection o;f c a lc iu m cIuoiimic. 7 u llu w iu g analysis of <hc e n v iro n im w iw I -,i wd<s i n ( h a h ra iM a f# p l a n n , t k * < w m >vf r k r n R i i i i m / 'a n t ing lung cancer is believed to be an acid soluble, water insoluble compound and probably trivalent. The carcinogenic form of chromium dues not appear to exist in the or iginal ore so the mining of chromium and its handling until the refining process in started bears nb known risk of lung cancer. Also, machining and work ing with the finished elemental chromium arc not attended by a risk of lung can cer, fur jiuic metallic chromium is non-carcinogenic. come cino sinus lung has s calcii upon supp in th smal pro fined of ni atoic cent: fortr one Wit cane and bie t cons poly 4CCO uu-u ploy and sufl'c hori with tic t mus oni) Ion; posi lml repc APR-17-1992 10:38 FROM TO 13014521039 P.13 BASES C(lIU^ClUL 111** : tissu e s w o u ld y ua.t cancers imsthal mines, of lung cancer dust and gases .lines provided between 40 y nor the total ed ar this time o f the mines. junta o f radioarc unknown, vc some radon ores also have untry, Umsda >f lung cancer. . United States xi by the Pub- at hazard from on, deposition, study in 1SK8, >rkers engaged of seven chrohtomate work7 pi u f cancer o f lu n g ra n rrr ted in the gen* hromarc plants . Anna fiaetjer ing chromates, arunnas in rats at*the environ tjivuiiuin causcompound and appear to exist til the refining *Afvi w ork- >k of lung can- O C C U P A T IO N A L C A N C E R m NlCKEL. First from Grpar Rrirain. and rrnw rcvv-mly frrim Kvn-way, have come reports and convincing studies implicating nickel as a respiratoiy tract car cin ogen . T h e evidence for i n b ein g the agent ru yu u n lU i. Cot m i c e , o f tin im u ! sinuses is o v erw h elm in g . Also, th e ev id en ce iihIuhc* w ith certainty that r tv a lung cancer carcinogen. Study of the w otk population in a Mond process plant has shown that the groups suffering the greatest exposure are those engaged in cakining the ore and those engaged in the extraction process using sulfuric acid upon the calcined m-.cccial. In yeurs past, much dust was produced and good dust suppressive measures were not used. However, the gas nickel carbonyl produced in the Mond process of refining nickel originally was believed to be the only tfn r-tn n g e n ic agnr. P>ctuly cuava wf lu u ^ vmvr Uiiv k e e n rc p o ite 4 fro m A sm ill Norwegian nickel refinery utilizing an electrolytic process, not the Mond precess. and so not producing nickel carbonyl. Thus the risk of can cer U not con fined to nickel carbonyl but is probably inherent in both solid and gaseous forms of lickcl. Prolonged inhalation e xp e rim e n ts with animals have pmdurvrl adenom atoid changes in the lungs of rats and guinea pigs but no carcinomas. "Isopropyl O il-" In th e m anufacture o f iso p ro p y l a icu h u l u sin g mjii- centrated sulfuric acid, small amounts of impumies called "isopropyl oil" are formed. As this process was used originally, four cases of cancer of the sinuses, win yf ihc larynx and one cancer of me lung occurred in tne worK group. W ith a change in process, "isopropyl oil" is not formed snd no further cases of cancer have owcuittd. H\piiiiiicii`.<ill), "isopropyl oil" ha* produced skin cancers and there is no doubt that it produces sinus and larynx cancer. Perhaps it is capa ble of producing lung cancer but chis renuins to be established. Among the chief constituents of "isopropyl oil" are isopropyl sulfates, isopropyl ethers, and some polypropylenes. Precise chemical identification of the carcinogen has nut been accomplished. C o a l T a r . Lung cancer rising from industrial contact with coal tar has occurred wirh ce rta in ty only am ong coal /true world* G enerally. on ly w irlre n ton. ployed in the retort house, having extensive prolonged exposure to the vapors and fume, have developed lung cancer. These cases have occurred when workers sudacU Uhcci exposure to me fume while working over or about the old style horizontal retorts. Operation of the modern type retorts may or may not be attended with some risk of lung cancer. It will take time and detailed investigations to set tle Ihis problem Suspected R espiratory T ract Carcinog ens. A s w ith * k n . arsenic B lllir h e listed 4 >prMiiihl/- carcinogen. H o w ev er, from the evidence, th is is true only when the individual has been grossly overexposed to inorganic arten<c for a long period of time and exhibits .gross chronic arsenicism. Probably such an ex posure could occur only when working with inorganic arsenical materials with lirrli* Of n o effort to cgnrrol (he oriienieal <lui in (ho w ork atm osphere. Three eases of lung cancer associated with pulmonary berylliosis have been reperted. Also, Vortoald has produced carcinomas in rats following the inhalation flPR-17-1992 10:39 FROM TO 13014921039 P.14 I* 1j*. . If ! i' >t i 1' ; i ! 'I r 1 :S-!A, <tV f;ti 1 34 T H E O C C U P A T IO N A L DISEASES o f beryllium. Although beryllium may be a carcinogen, evidence that it is the agciu producing lung cancer in man w lacking. A a precauiiuiutiy u i m u c b u y l iium dust should be carefully removed from the v/ork atmosphere. Urinary Bladder Cant er. A;> previously pointed out, bcca-naphthylamine and benzicine produce cancer of the bladder. Abha-naphthylaminc is suspected of this, but it has not been proved. Aniline definitely does not pioducc bladder tumors and should be cleared of this implication. Beta-naphthylamine is me* tabolizcd in the body to 2-s.mino*l->iapliihol and has been indicted as the car cinogen. Lius clear is the carcinogenicity of the ncnhnlite of benzidine, but fr* haps 4, 4-<liamino*3*diphenyl hydrogen sulphate is the culprit. The uncertainty arises because benzidine is si much less potent cancer producing agent, and the carcinogenic metabolite proiiably produced in much smaller quantity. One other compounc, xenvlamlnc, or `i-aminodipncuyi, Iras proved to Lk.- | m u producing bladder cancer. Studies of its metabolite excreted in the urine tricu- cares the presence of 4*aminodiphenyl and 4-amino-3-diphenyl hydrogen sulphate, which later increases in quantity and hydrolyzes, to 3-hydroxy-4-aminoHiphpnyl. Thus the orthohydroxy amine conjugates have been isolated in high concentra tions as urinary metabolites from bladder cancel agents beta-naphthylamine and 4-uninodi phenyl. A much weaker bladder cancer agent, the orthohydroxy me tabolite of benzidine, is present in the urine in a lower concentration. W o n* G ro ups Expo sed . in p la c e s w h e re th e p rim a ry a ro m a tic a m in e s b e ra -n a p h ih y ia m in c , benzidine, xenyUminc, and perhaps alpha-naphthylaminr arc used, winkcm iu u die rial* o f developing bladder tumor T h e men arrually e n gaged in handling these materials are m ost evpmed when scraping or cleaning fillers, or nrhen materials being worked produce rltntrc. nr vapors. In m o d e m p la n ts w ith b u ih -in p ro te c tio n , p e rh a p s th e m a in te n a n c e m en c o n s titu te th e m o st e x posed gro u p . W or iters employed in the manu facture of basic dyes, the manufacture of some rubber arti-oxidants where alpha-nsiphi:hylamir,c or xenylaminc are used in the process, a id w hoe benzidine is used to harden rubber, may be exposed to bladder cancer agents. Adequate protection should be provided for textile workers and employee! in the printing industry where alpha-naplubylainiuc and buuidinc are used. Beta-naphthylamine also has been demonstrated in small amounts in coal tar from gas works, and so workers in this industry should be adequately pro tected. P r e v e n t io n . Good engineering control of dusts and vapors, the use of closed sy items, and observance of meticulous personal hygiene arc required.. Es tim ation! o f the smrtimr nl" frrr inhie in the urine have been reported as useful in checking the adequacy of protective measures. The Hematopoietic System. Ionizing radiations, particularly gamma or x-rays and benzol, are the agents most incriminated in the production of occupa tional leukemias. W inches these agent) are true carcinogens or merely acr < m - carcinogrns is unknown. I ic rite/ to ga clinic 1$ use te ria l' not b tbc c< not b *i there ducec Coba place forgi arc indui th o ri w ith been discu tern tion kocy into> refer mart apbu and obse: or s l chat of lc sure vclo $Uh and HPR-17-1992 10:40 FRUI1 TO 13014521039 P. 15 it it is the sure beryl- ithybroine suspected ce bladder ne is meis the car- but per nceroinry t, and the One other r agent in irinc indi- sulphate, diphenyl. ;oncmtraimine and Iroicy me- :ic amines amine are tually cnr cleaning emplanes most ex- c of some ed in the o bladder ikrrs and zidinc arc ts in coal nely pro- hc use of aired. Esia atefu! amma or f oceupaact as co- OCCUPATIONAL c a n c e r S3S IONi king R a d ia t io n . The action of various forms of ionizing radii.tiun is discusd in Chaprcr 20. It is sufficient to state here that occupational exposure to gamma and x-rays occurs in the nuclear energy industry, hospitals, medical clinics, physicians' offices, research laboratories, and in some industries where x-ray is used to detect flaws in metal castings or to examine a v a rie ty o f o th e r ma terials. A.l workers with these agents sh o u ld o b se rv e 'a d e q u a te precautions a n d not be ca reless or indifferent concerning personal exposure. In many industries, the equipment is installed iri such a manner that when in operation a worker can not be ex posed. The incidence of leukemia among radiologists has been repotted as high and there is experimental evidence to support such reports. Leukemia has been pro duced in mice by x-rays, with small repeated dose being more effective than larger exposures over a shorter period. The vac of radioactive isotopes emitting gamma rays in industry (particularly Cobalt4, Iridium1*2, Cerium137, and Thulium170) has been increasing. In some places, gamma radiography is replacing x-rays as a means of examining castings, forgings, etc., and no doubt will And increased uses in in d u stry . Such matetials arc well guarded and shielded and so far no cases of leukemia associated with the industrial jscs of radioactive isotopes have been repotted. Although radium and thorium have cnnaidt-iahle u se in industry, case) o f le u k e m ia in those working with these substances have not been reported. As yet, these materials have not been indicted as the causative agents of occupational leukemia. B c m s s o l ( s tim w t), The many industrial uses oi benzol as a solvent are discussed i:s Chapter 11. There its depressant effects upon the hematopoietic sys tem are presented, bur not ks production o f leukemia. The gradual tran sfo rm a tion of the bone marrow from aplasia to hyperplasia has been reported. Also, leu kocytosis las been reported as a transitory flnding in rh r e a rly stages of b en zo l intoxication. The varied peripheral blood findings in benzene workers have been referred to is the "ieukemoitl condition." This raction is only one of many bone marrow reactions to benzol-intoxication. Among such reactions are complete aplasia, aplasia with leukrmoid reaction, acute leukosis without pwriphcixl leukocytosis, and finally acute leukemia. All forms of ariire arid chronic leukemia have been observed anong workers suffering from benzol irtoxicarion. However, the acute or subacute myeloid types of le u ke m ia appeal to dominate. Vigliani has suggested that perhzp many cases of aplastic anemia actually were aleukemic leukemias. As stat'd in Chapter 11, we are not inclined to give credence to the reports of long delayed cases of benzol intoxication developing even years after the expo sure to hen ml has ccacJ. H ow ever, it seems possible that leukemia might devi*li-ip at sorae tim e after a p rolonged xp n u m . to b en zol had ceased. SUMMARY Thousands of chemicals have been examined :ts to their carcinogenic powers and th is information is contained in the p re v io u sly mentioned Public Hcalch h PR-17-1992 10:41 FRQM TO 13014521039 F'. lb T H E O C C U P A T IO M A L 1Ka K Service publication. Numerous maccrials established as, or suspected of being, car cinogenic agents are used in industry, yet today it is astonishing how seldom we see a true occupational cancer, t his can be attributed to the institution of strict controls, chiefly engineering, through, dosed systems, ventilation, personal protec tive devices, and others, which serve to prevent exposure. As more workers in the old age group continue to work ir. industry, more eases of so-called "naturally" occurring cancel will be found amorg these older employees. At (his time it is believed that we have established as carcinogens only the more potent o f rtese agents. M oreover, it is known ihat marked variation exists betw een individuals as to cancer susceptibility. Theoretically, the weaker carcino gens should be able ru produce cancer only in the more susceptible individuals. Awareness of all. these facts makes it dear that detecting the weak carcinogens is next to impossible solely upon a cl.meal basis. Studies to establish a weak car cinogen of necessity must be of the epidemiological-statistical type embracing large groups o f people who have been exp osed for long periods o f time. Although these studies arc aiduuus, they are needed to clarify the status of doubtful or dis puted cancer-causing agents, and lu uncover presently unknown environmental carcinogens. the We should recognize etiology means by knowledge of cancer woefully weak and inadequate status of our present and the which carcinogens produce can cer. are It in only difference. If, as appears certain that some or inanv materials we now accept as carcinogens reality eocarrinogens. However, this makes lirrlr a material eliminated the result of Irs presence in the work environment, workers develop cancer, such a must be entirely from work environmrnt. If it is con tinued in use, it must be so completely controlled that no workci may be expected to develop cancer. The possibility of a nori-carcinogenic material being metabolized in the body and a carcinogenic metabolite being produced always must be recognized. Alsu, th e long latent period is characteristic o f weak carcinogens. Particularly in cancer o f the internal organs are ( h o c fa n n u f im p oiian cc. Every physician should be alert to the possibility o f occupational cancer arising trom new materials nor now suspected o f being carcinogenic. Finally, we would be remiss in closing this chapter without making a plea for the keeping of full medical records on all employees, not only as to diseases diagnosed within the industrial clinic, but on all cases diagnosed and treated out side, rhus making complete medical iccoids available for all employees. Such rec ord s are indispensible w h en w o rk g ro u p s are un der study fo r an occupation al dis ease. particularly cancer. BIBLIOGRAPHY Ddvijvii A. M - Pulmt.-n*r)r Civwtm In Chromate Workers. I. A Rc'fe* of the Literature ind Report vfCtic*. A JM A Aceh. IndtiH. H , /A?. I9t0 3. Battjrr, A. M i Pulmonar}* tlaKAonu in G v o m itr Worker*. I*, Incidence on Hoipittl Rcc- 4/14 . A M . A , A iu l* - t - . J -- c. I I . . 15*0 1 t* i ftPR-17-1932 10:42 FROM TO 13014521039 P. 17 . D IS E A S E S jectcd of being, car> irtg h o w wlHntn wo institution of strict on, personal protec tion workers in the xwlcd "naturally" <i 4 i k ,g n a o n l j r i U ked variation exists the weaker carcinoeptibJe individuals, weak carcinogens is itablish a weak cat' cal type embracing s o f time. Although i of doubtful or dis own environmental .tatus o f our present togens produce can* cccpt as carcinogens : difference. If, as a -eiop cancer, such a nment. If it is con* kn uia/ bv m in im i tbolued in the body >e recognised. Also, articular]y in cancer v physician should be v materials not now hour making a plea : only as to diseases sed and treated out* -tnployees. Such rccan occupational dis- iiv Cm.inoro in Chromate an Bats of Hospital Reeuse. H . SOS, 19S0. OCCUPATIONAL CANCER 337 3 Bdstruf, R L.: 0.cu|>honaI Gu>:i of Lung O n ce,. Transaccin i.f (kc Aln. >>t Iniuirrt Officers. 9.3.1959 4. Bidstrup. P. L, ir ti Case, R. A. M O rdnorra oi the Lung m Workmen in the iichiomius-PltnW mg Injusta in Gicat Britain Brit. J InJusi. Med. 1956. 5. Bonsef. G. M . F.iuld, J. C . ind Stewart, M. J Occupational Car ser of the Urinary BladJrt' in P m m A t OpCMimi anil or i. iv Li.ug in n iteiini Textile Worker ai j Iron-Ore Miners. Am. J. Clin Path., ISO, 194:-. 6. Braun. D. C.,anJ Tcutn, T. D : Ar Epidcmiological Study of Lung Cancer in Asbestos Miners. A M.A. Arch InJusr, H . 'X-M. IV18 1 Caiuvristrhr I iw,;- A-. Hvahiition 1she Problrm. Proceeding of the Sciuntilic Sessism Annua! Mretinte NsIVMnW I 4 10^1 A w ir a*ftrvwr W Inc.. 19 H . Ccmlicr, H., jnil Vlsugil, j n-i orwncn>/gi.iiic s.*r- cInoma from RaJioaciive Barium Sulfate. AM .A, Arch, tnduat. H . "'7 SO ipva 9. Combes. P. C : Cs al Tar and Cutaneous Carcino genesis in Industry. Charles 0 Thomas. Publisher. Springfield. Illinois. >954. 10. Council on Industrial Health. A M A ; Occuparional Cancer. M ailivusofEpidciiiinltigital Study. J A M A . /66.-2P;. K5d. 11 Cow-dry, E. V hpiJu m si CsmiiogcncsiN. in Ad vances in Oncer Rt.u-urh. V t.l I Edited by Grcvnstein.J P , aid Haddow. A. Audemic Pnrui. iMUiitdhW <l`wsh| I <.* It. Cramer. W.- The l-npnrfancs'i'l Sts:int-jl Invr'.tiXution in the Ornps'i-'n us.utn.st Cuutr. Am .1 Cancer,-vr. t. (95?. IS R ill. R.: Murialiit twin Lung Cin.vi in A Jav.., Workers. Brit.J. Irducl. Med.. IJ.-Hl, Iy54. i I. Doll. R.! Cancer.i" tin Luiigand Nih mi Nickel Wiwkers. Brit. J. Irdu.i Med. M.-2P. I95H 1 ). Doll, R.t Occupational Lung Canter; A Review. Dot. J. Indust. Men, in.'ini, ivjv. ns. Eckardi. A. v-atiinngenum or Petroleum Pntl- ucts with Partcula- Rtlercthc In the Automomc Industry. Induct. Mai :iurg, _'o jyti. iyy. I*. Eclcatdt. R. E.'. Industrial Carcinogens. Modem Huni^|Ri|*hi ir In.lcir-irill Mcsli. ine. (in n s Sa 6tr,tl- tun. New- York. WML UL Editorial; Silicosis, Asbcstosia, and Cancer of fhc Lung. Aro. J. Clin. Path.. .'V ista, l55. 19. Ewing, J,: Neoplastic Disease*. Fourih Ed.. VP. 1 Saunders Company, Philadelphia, 1941. 3u. Federal security Agency, P.H.S.: Health of Work, ets in Chromate Producing Industry', a Study. Fed eral Security Agency. Division of Occupational Health of the Bureau of Scare Services. P.H.S.P. No. 192,1951. 21 Fischer, H G. M.. Priestley. W , J r., Eby, t. T . Winlf f a . anl PaImiti. J., J*.. Pi of High-boding Petroleum Produco. A.M.A. Arch. Indiai. H , I M5. 1951. 22. Hendricks. N V . Berry. C. M., Lione, J. G., and Thorpe. J .J Cancer oi the 5;rotum in Wax Press aien t. A.M.A. Arch Induit. H , J9.324. 1959. 21. Hueper. W. C.: Esperimenti Carcinogenic S tud on Hydrogenated Coal Oils. I. Berguius Oils. In dust. Med. burg, 25.51, 1936. 24. James, W. ft. L: Primary Lung Cancet in South wales (-rial Workers with Pneumoconiosis. Brit J. Induit Med., li.S 7. 19. 25. Ksplin, I : Relationship of Noxious Gases ro Can rinoma of six; Lung in Railroad Workers.J.A M.A., 1*1.-1059, 1979 2 6 . Koimi, P., Falk, M. L.. and M cC am m on, C J .t Can- ..o. P lllsiU . Wa l m u n w y W |* n ^ C l l IMRCS' cnee to A lt Pollution and Pathogenesis. CA D ylk - tin, March-Apt., 195a. page 6 t 27. Uone. J G . and Denholm, J. Cancer of che Scrotum in Wax Pressmen. 11. Umica! Obsem - tlont AM A An-h Indust I I . 14-5)6, 1059. 20. Machie. W , and Gregorius, F.: Cancer of the Re spiratory System in the U.S. Chromate-producing Industry. Puli. Health Rep., 51.1114,1948. 39. Maneuso, T. F.: Occupational Cancer and Other Health Hasards in a Chromite Plant; A Medical Appraisal, (|. Clinical and Toxicologic Aspects. Indust. Med. Surg., 20-393,1951. hV M lk in im ir m i F f'iirHRfl i^tf* 4*il Vpivrawsira. Cell Carcinoma. Part 1; Incicence in a Plant with a Report of Six Cases. Brit. J. Indust. Med. 12 2-aO, 1955 11. Nau. C. A.. Neal. J., and Steinbridge, V.: A Study of the Physiological Effects of Carbon Black. L Imsoiwii. A.M.A. Aivli- ImlwM. I t , t t . i i , ivaa. 32. Ptlltf, 5.. and Pick, P.: Leuk :mia and Other Ma> lignincies in Physicians. Arr- J. M. Sc., 321.-1) S, 1o '7 SS Ra'M, R. W., adlsot. Can feoficrwott). O Co. Ltd., London, Volume 1, 1917, Volume 3, 1958. 34. Sampey, J. ft. Inorganic Carcinogenic Agents. Indust. Med. Surg, 22,-165. r.75). 55. Seltacr, R,, and Sartwell. P. ft: The Application of Cobalt Analysis to the St ady of Ionising Ra diation and Longevity in Physicians. Am. J. Pub. Health. 49.1610,1959. 36 Smith, W. E , Sunderland, D. A., and Sugiura, K , Expasiiiimital Analysis of the Carcinogenic Activity of Cestaio Petroleum Products. A.M.A. Arch. Induit. H.. 4.299.1951. 37 Unsolved Clinical Problems; in biological perspec tive. Volunie 11 of Mvdieal F-cacarcht A Mideen- tury Survey l ittle. Brown arsi Co., Boston, 1955. TO 13014521039 P.18 338 THE OCCUPATIONAL DISEASES 3. E . C , and 5 i< to . O ' L c .ik iT n u > : Iru m ttenicne, Med. d. lavuM, 39.41, 1 * 18 . ). V o n H u m , E , a n d M a J irta e , f . S : s tu d ie s o n th e Toftitifr it6 Skin r.titct* ol CoftifHmnd* l '>ed m rhc Rubber and Plastic Industries. |J] Circin gfnicii) of Cuboft BUck Encracu A M.A Arch. Im Ium H , 0 .} 2 ?, 1912. 40. Vor*ald. A J ^.dcnocarcimpna in the Lung erf Albino RjtsExporfd to Compounds of Beryllium. Proceedings of th: Scientific Session, Am. Cincet jKKWf Annuftl Mailing, No*. M , 19)1.