Document MDn6E9EOV9mnwjZZnrKO3RVk

FILE NAME: Metropolitan Life (ML) DATE: 1955-1960 DOC#: ML321 DOCUMENT DESCRIPTION: Dr. Lanza Disinformation Campaign; Stokinger 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 exoected to appear."1'" In the puolished discussion of one of Smith's papers, Dr. A.J. Lanza offered this incredible critique of M erewether's data:1* I think it is im portant to distinguish betw een 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 w ith 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 control 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 asbesto- tics. 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 Sm iths report on European research on occupational cancer was Dr. Paul Cartier, of the Thetford Industrial Clinic in Q uebec.1* 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 CMICAOO 10, It MO U **( *11. il.. ', i a. 5. !;,,>> m cm vcs ot Industrial Hygiene and Occupational Medicine C-iM Iti', CaiiuAMII Ul|, ClMItff, CAD. P*ia?i, C't<a*'i . 0'**. IlkM. li.at.Ml M. ftNtfe etM:VM 9 !* fv. li- c Jfl M. lu*o(* i'i.r i NlMIlt . c. 1014 N. Broadway, Cincinnati 2, Ohio, January 20, 1958 Dp Oanifl C. Braun ifa 4 |iilv 3 |iy rp P to r Zlriuptrigl HJygiena Foundation of America, Inc. Hallo Institute, AAOO Fiftb Avenue ' Pittsburgh 13, Psnnsylvani* Dear Dr. Braun* fifth Dr* Princi and I , having reviewed your paper, "An Epidoad.logical Study of Lung Cancer in Asbestos Miners" are pleased tP accept i t fo r publication in the AMA. Archives of In d u etrial Health. Wa find the report not only of exceptional i n j e c t ^ b u t a model of the epidemiologic method in diseases of only criticism was th a t in pursuing the epidemiologic d e i ll popr became a t r i f l e long and one got the impression toward tb f s o d th a t one had read th is before. 1* lyPilJf was p artic u larly pleased to learn the main con elusion of the paper was against the association of lung cancer with asbeetosis, fo r I had come to a sim ilar conclusion on oi>* viously ia r le ss information but was afraid to say so fo r th is reason. I am enclosing a review which contains a few aantencee th a t I have marked in th is connection th a t appears in the Annual Review of Medicine, Volume 7, 1956. You w ill recall a t thia time evidence greatly favored the poaitlve co rrelatio n of lung cancer on exposure to asbestos. Sincerely yours, Enclosure iilykr. H e r b e r t E . S t o k l n g a r , ...P h .D . -- Acting' Editor, AMA Archives of In d u strial Health 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 E1TTOMICAL STATEMENT ninth 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 clianpe 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 suflicient 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. Stolinger is chief toxicologist, Occupational Health Program of the Public Health Service, Cin cinnati, Ohio. Hr is a member pf the Subcom mittee on Toxicology, Rational 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 was chief of the Industrial Hygiene Section, Atomic F.nergy Project, Rochester, A'. )'. V n l. 70 , N. 1 , J n n t tit ry 195S injurious agent 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 hygiene-standards 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, which is composed of persons work- 1 iitp iii State and local industrial hyggiene depart - nu'iits nml in Fedora] industrial hygiene units, and members of the armed services in ihe United Slates and C'nnndn. Only tlie Foiled Slates and Knssia nppear to lie currently developing; sneli lists as the tliresliold limits list, oilier countries preferring; to use tlmse already develojied. Tartly because of Ibis, but more especially because tbc ab- brevialed preface to (lie Ifel'oiilv briefly refers to its application, tlie following; pnrnggraphs discuss in some detail the nature of tlie list and its purpose, met bods by wbicb tlie values are deAeloped, and interpretation and proper nsn^e of tlie values. " Noture and Purpose of he List Tlie tliresliold 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, vnpor or g;as. wbicb are in siiflicientlv wide use industrially to warrant control of their concentration in the breathing; zone of the in dustrial worker. (lYrmissihlc levels of expo sure to radioactive materials are indepeudcntU set bv various radiation protection commit tees throug;honl the world. Values for many radioactive substances may lie found in the Na tional Hureau of Standards Handbook No. r,2.) Hecnuse of the rapid development and applica tion of certain cheyjicnl substances, often a timelngr occurs between the industrial use of a substance and the appearance of the thresh old limit value. This interval, however, is becoming; shorter as a result of increasing; at tention of the 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 repi'esent the maximal atmospheric concentration to A\hich workers may be exposed repeatedly day after day without, injury to health. > ^ Imrpose of the list is to provide a limit ing; Millie of air concentration for injurious substances for use by plant engineers. industrial-hyg;iciiists. and others concerned with the health and comfort, of the workers. The list, is intended to be a aide for the control of work ing; atmospheres and to provide nianagrement, labor unions, and the worker alike an assur ance of healthful conditions on the job. Development of Threshold limits A vaine for a toxic substnncc is assiemai on th laisis of data accumulated frolli animai inlmlatimi toxicilv studies and on Ilio basis of industriai experiencc. Toggcthcr, Illese reprcscnt, of conrsc. ideal tripli mnents noi. nlways fullilled for eacli solista lice in th* lisi lini ap proximated as far as possihle. Of th two. industriai experiencc is (he test ou wliicli (In validitv of a vaine must ultimately test. He-1 cause ndiable informai imi frolli industriai cx~l>erience is fiwpicnlly dillicult to obli in. th Committee on Thresludd Limits is often forced *> pinion or industrial hygnenists. rather 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 hyg;ieiiisls throngdiout the country. The t-mrent lo x ico lp ^ id jitc r a lnrc is also scanned continually for usable informaFioh7~\Vheii the ne(*d for the assignment of a value seems urg;ent. a tentative value is assigrned on the basis of the l>est information available at the time. Originally, preventing; impairment of health was virtually the only consideration in the selec tion of the proper limiting; air concentration of an injurious substance. Now. however, with the increasing; emphasis in occupational health" m the "total man,"' more subtle "effects on health, such as the effects of annoying; or irri tating; ag;cnts. are also considered. Thus, whereas a threshold limit value of or J p.p.m. for chlorine would insure no impairment of workers' health, this value is reduced to 1 p.p.m. in the interest of g;renter freedom from irritant effects. Ihe levels of other g;ases and vapors with irritant or other discomforting; effects on the workers have been similarly adjusted. The rapid g;rowth in the number and diver sity of industrial substances to which workers are exposed and the increasing; attention lieing; griven to occupational health in this country have griven rise to a very real problem of main taining; the threshold limits list current. To meet, this problem, the Committee oii Threshold Limits reviews the lists annually, considering; 2 I'nhlir 1tentili Iti-porl. ttr- 4gnod on in animal /ic basis of hese reprenot always lis1 but. a|>'f flip two. which tin rest. Bcdnstrial exobtain, tbp fton forced hygienists. i. or sonic1) opinions, cnee with cupnlinnal The ctir<> scanned When tin* m s urgent, basis of tlie* ><*. it. of lieallli in tlipsclec"centration -ever, with "iial bcaltli effects on ii" or irrid. Tims, nr 4 p.]i.m. lirnient of to 1 p.p.m. m ir r ita n t iml vapors effects on >isted. and diverli workers 'lion being is country m of main* trout. To Threshold misidc.ring til 1t*p o rl` cnrefttllv encli value and any new information pertaining to a change in level. When a value is clinnped. it is designated. In tbe tbrcsliold limits list for 1 . a fur ther accommodation lias been made in an ntt,.n,i,t to keep pace will, tbe ever-inerensinp use ,,f new industrial cbemicals. This is tbe addi tion of a tentative list separated-imm the list of establishedValues. Henceforth tbe tenta tive iist will include all substances not pre viously listed. Because, of tbe lesser certainty ` Konietimes associated with these tentative valm.s>tbev should provide only peneral puidam-e in tbe control of exposure and should carry no leiral weipht. The tentative list is looked upon n.."'providing levels under trial and test, to lie revised when new information justifies. Subifnnees in tbe tentative list will not. be incorpo rated in tbe main list until tbe values luive been proved bv experience to be acceptable. H is hoped that the tentative list will stimulate a ffre.,ter nnml>cr of yearly additions Ilian in Hie past, as well as tbe critical evaluation of these values by preater numbers of industrial hypicnists. Overall Maximal Upper Limits It is now considered desirable by a majority of tbe persons concerned with occnpatic.mil health to assign a maximal upper limit of 1.000 p.p.m. for most, nlthouph not all. of the puses and vapors that are apparently nontoxic or nonbazardons. Such a limit lias lieen set for certain Freons and other apparently innocuous substances, althouph it is known that neither health nor safety are endangered by expo.-nre to far higher levels under ordinary conditions. In favor of this practice is the argument that it will prevent excessive or wanton exposure to air contaminants. I t is recognized that all the facts needed to assure safety are seldom at hand. Physiologically inert substances, such as certain Freons and sulfur hexafluoride, in unlimited concentration may suddenly become* hazardous, in the presence of welding or plumb ing operations, through decomposition hv heat to highly toxic products. A similar concept is developing with inspect to dusts that in the past, have been considered essentially nonhnznrdous or not incapacitating. Numerous reports from various countries make it all too apparent that many dusts formerly considered inert, are rnpablc of producing pul monary changes tlint are oftentimes disabling (/-? ). It would therefore seem that all in soluble dusts of whatever n atu re`should be held suspect until proved otherwise (.$) Un fortunately. the assignment of a specific level for each mineral dust is impossible at. present. Mineral dusts are commonly of complex nnd inconstant composition, often varying accord ing to locality, and tlms are potentially capable of causing a variety of physiological response's. As a ease, in point, pulmonar}' carcinoma is commonly associated with the long-term in halation of aslieslos in England, but. not in America (.V). Assignment of specific levels is also difficult because pulmonary changes de rived from tin*, inhalation of mineral dusts commonly require years to assess, beenuse sound information ^relating exposure to response is not. for the most jm rt. available, because ex posures are not uniform owing to changes in the industrial process and job changes, and be cause dusts from operations involving the same materials often differ in size and surface area. Therefore, it is believed that flit? validity of the present standards for dltst should bo re viewed nnd consideration given to the follow ing suggestions. In the absence of informa tion and in view of tin* poor prosper o ob taining any in tin* near future, the conclusion seems'inescapable that if protection from dusts is to be guided by hygienic standards, an overall limit value should be selected. Actually, two values appear desirable, one for dusts contain ing free silica, and anot her for nonsilireoiis dosis. For silica-bearing dusts, a limit of from - toT. million particle per cubic foot (m.p.p.c.f.) is suggested. It would be applicable to tlios** substances containing free silica of any ap preciable percentage ('HI percent or morel. Such a level appears justifiable on tbe basis of usage and experience, ns shown in table ], and tacitly assumes no other mineral is more hazardous tiian silica and/or any combination of II mineral with silica. Actually, this value represents a rather low level of exposure when V o l. 70. N o . 1, Jn n im ry 1955 expressed in terms of milligrams of subst-niico per cubic meier of air. Depending upon pnrtide size, ft m.p.p.c.f. silicon dioxide (Sif)..) witli n density of 2.2 might range from 0.(11 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, concentration, of course, would occur. The question then arises of how host, to express the dustiness of an atmosphere. Although tins concerns matters too involved to he entered into here, it would seem that, with an absolute method now avnilnhle for the measurement of industrial dusts, the limiting concentrations should be expressed in terms of either millions of particles per cubic foot or milligrams per cubic meter, or both, but within a definite size range, this range to be 0-3 ? diameter. Other wise, dust counts, ns well ns expressions based on weight per volume of air, become meaning less. Particles of the size 3 / 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 subinicroscopic particles arc included is n very important proj ect for future investigation. Table 1. Recommended permissible limits of some silica-bearing dusts1 industry or sourer Ifcported percem free SiO. 1 Iteeom! mended j coneoi i t rut ion in .p .p . c. f. Sydney sandstone...................... Gold mining (Union of South Africa!............................... Granite........... ....................... Pottorv.................................... Gold mining (Ontario, Canada) Pyropli.vllite.................................. Anthracite (haul r o c k ) ............ Nonfcrrotis mines........................ Anthracite (haulugewa vs)......... C em en t............................... <10 SO so so ao-w :to 20--10 i:t 0 * G 2 A 0-204 4s. r, 10 5-10 5-10 10-15 20 1 1'roin a table prepared by professor of industrial hygiene, burgh. ` * Values are approximate. * Owens Counter. ' * Konlmeter. Theodore ]'. lintel., University of Pitts ' 4 A practical threshold limit value for nonsilieootis dusks would appear to be 5 mg./m.* This val ue lias been in satisfactory use for some years for controlling hematite this! 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 With increasing industrial hygiene knowl edge and experience, refinements in designating " specific substances to which values are assigned will assuredly follow. As yet. however, only n lieginning has been made in this respect. For chromium, the designation specifically refers to chromic acid or to chromates. The highly poi sonous ursine gas has a threshold limit- value of 0.05 p.p.m., whereas the value for nrsenic and its compounds is 0.5 mg./ni.3 Differences in toxic action of- uranium compounds have been recognized by individualizing the soluble and insoluble compounds. It would appear that manganese 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 organic 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 to selenium compounds which re 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 the lead industries in this country over the past ]0 years. Data show that, whereas there is no reason to alter the value, of 0.15 mg./m.s for load fu me or for lead dust of subinicroscopic size, (his value is unrealistically severe when applied to the more, insoluble lead salts, and probably too lenient if applied to certain or- Public Heulilt lieporl- in know]* signnting o assigned or, only iv mot. For v refers to iglilv poimit value >r arsenic rt*ronces in linvp. been Hiblo, nnil dioxide >r mangathe most element, o mercury iid should ic organic lie newer in toxicity bided, and uld apply are highly which is 1 mg./m.* lly to the t for most Is imposes t levels for peeifically 'uinulated y over the `reas there IT. mg./m.* licroscopic vm* when salts, and certain or ilth llrport- ganic lead compounds. These and other tie ' Arable refinements in the list will undoubtedly be made, in the near future. Table 2. Biologicol fhroihold limit* ' Sulisltince I blond I (mg./ | 100 m l.)1 Urine (mg./IA Biologicol Threshold Limits One new feature, of occupational health standards that appears destined to play a use- f,,l role in evaluating personnel exposure in i, dustrv is what might be called biological threshold values, for want of a better term. These values refer at the present time to the neatest permissible content of an a.r conL iin n n t or its metabolic derivatives in the l*.dv fluids, usually in blood or urine, allllol> h changes in other bodily constituents innvIn time serve also ns measures of exposure. a list of biological threshold values, winch eor'ivspond to the threshold limits for concentra tions of the substances in air, is gi\cn in lable 0 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, h or 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 liniitg of only a few selected substances will ultimately find an accepted place in occupational hygiene standards, since all sub stances are not amenable to accurate analysis in Itodv fluids (complex organic molecules) by reason of wide individual variation in metabo lism. interferences from dietary sources tarsenic), 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. "\\ ben bio logical threshold limits are used, they should supplement determinations of air concentra tions. not replace them. In etloct, these biolog ical limits substitute diagnosis for the control or prevention of injury provided by air analysis. Currently, in the lead industry, considerable enthusiasm is being expressed over the ap- Inorgauir emisi Incut Arsenic____. . . . b ery lliu m ......... 1 (0.5 for arsine or lewisite). 0.002. . Copper............ - - __ 0. ) Chromium........... Lead.................... .. ; . os Mercuri-............. l ........... Manganese Thorium............... 0A.2n.v delectable umouiil 0.25. 0.001. Noi eliminated in chem ically ineasurnble ninnimi . V a n a d iu m ......... Cranium . . . Chloride. . . . . S ele n iu m .......... Tellurium . . . . . ......... 0.05. . ............... . . i............. ; 0*1..01. ................. n.07. 0.01. Orinine constituent* benzene. ------- b rom id e.------ - ...100 I'arhoti disulfide.----------Dinit ro-n-eresol........ Medivi alcohol......... - - Medivi in n a te ................. Toluene, (ns hippurie j----- neid). I T r ic h lo r o e th y le n e ------ (us trichloracetic neid). 15 percent below nomini sulfate ratio of inor ganic to total sulfate. 0.15. 5. _ 5-7. Analyzed as methyl al cohol. 3,000. 1 Many of the values given here are found in or have been revised from Chemistry of Industrial Toxicology by II. 11. Elkins, New York City, Wiley, 1950, and In \iiftlvscs ol biological Materials a Indices of Exposure Jo Organic Solvcnls by Elkins, A. M. A. Arch. Indnst. llv g . and Oecttp. M. 0: 212-222, March 1954. -' 1!. II. Scliretik, in New Information on Arsenic Trioxidc, Ind. Eng. Chein. 45: 11A (1953), atatea that urinnrv arsenic values of 4-5 m g./l. arc common y not associated with signs of arsenic poisoning. Use of urinurv values is considered of doubtful worth because of great variation in normal values. Dietary arsenic, Mich a* that obtained from seafoods, would greatly alter the urinary arsenic picture; moreover, arsenic is excreted chidly in the feces. j ITinary values mav not always be reliable in long term exposures owing to possibility development of lower nephron nephrosis and for other reasons. t Inasmuch us manganese is eliminated clnelly via the intestine, urinary determination is not a particularly valuable indicator of cxjx.surc-. Tentative value. Voi. 70, No. 1, Jan u ary 1955 :tu::gm--nr>----j MMM patently successful use of urinary lead values witli or without, prior screening by urinary coproporphyrin determinations. The argunuMitin favor of tin* use of urinary values is that in prurt ice most, industrial exposures are neither uniform nor simple, hut are mixed, and, there fore, that. the. laxly serves as a lietter sampling device 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 anion" 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 list'd. Because there is some lack of agreisnent among industrial hygienists as to the use of the"values, it might be worthwhile to consider what is .meant by 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 ami abstract concept which may be explained philosophically and operationally. Philosophically, the threshold limit repre sents a level to which a normal healthy worker may be exposed for 8 hours each workday with out harm to his physical or mental well-lx'ing. 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 be 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 the workroom air that have heen obtained in a complete cycle of operations during the day. Proper averaging of eoncent rut ions should take into consideration the duration of exposure at each concentration: this is referred to as a "weighted average." Concentrations far above tlu* limit for periods of Bo minutes or more and prevailing sporadically throughout the day, although possibly ei|iialing the threshold 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 bused 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 lie regarded us line lines between safe and dangerous concentrations, that is, a point above which injury is limind to occur and below which complete safety may be e x is te d for all exposed persons. ( 'om|H*tent judgment, is re quired here as in the interpretation of any standard. Misuse of Limits The threshold limit .vulues should be used only for control of exposure atmospheres for repealed 8-hour working days. They should not lx* used in the. following ways*. 1. For brief acute exposures. (The thresh old limit, values have been 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 sum mated effects of each component.) As levels for community air pollution or for levels to be derived therefrom by simple extrapolation. (The threshold limits have been set on the basis of an 8-lionr exposure day with the assumption that a subsequent Hi-hour jx'iiod of nonexposurc 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 H ealth Itf-porl*. `.v y * _ , . .B| U,,f ,,crmissiWc concent visions in . 4. Ab 'P'>:i,|0V s,,,)|,|i,.s or for in ..... ' , V |ir ,, |ir i,,l,' Irv rlf linvr lw n I'*TM1 lowered content occurs in the absence of any ob jective or subjective signs or symptoms in tbo workers, and it has been experimentally demon strated in the hair of animals ingesting vana- ; S H v or -vrr.11"' l"'1"1''" .1.,,... m m.mimts tlm, , " * ` "" 'T b tl.r tasis for srliKl'niir il.mnrr,ms , fm. )abcii,,p. (Hazards involved m pounds frequently arise, from rontes demonstrable signs of toxu-iU (Jo). used in combination with urinary vanadium determinations, the test appears to he highly suggestive of early metabolic changt-s result S i 'S . 'iS l.io o .'r r llic l. in * ' T t ' l S i i for flight prrsonnrl in via , (Higher standards of safety and peiV ^ c n c e an- required. and degree and duration ing from exposure to vanadium. The well-known urinary coproporphyrin m screening test for lead poisoning might well be classed as a pn-toxieosis lest. Used in com- ~ bination with urinary lead values, it is now ,,,1,0m- and duration at sea level.) considered a reliable guide to uicipienf damage |>v h-d (/}). A* potentially harmful body levels, lead is believed (If,) to convert more of Pretoxicosis tests Closelv related to the biological threshold value are tests of pretoxicosis, the detection of Mihtle metabolic changes in the body jurv of serious proportions has doveliwd. T o (,P;, is not new, the first reported test of tins l.uviim been applied to the hematologic reS t r . ? `p re -tu rii-n i by Heim de Ihdsac in Hats ( 11). Although the determination of pie the normal)v occurring colorless precursor to the chromogen while increasing the total copro porphyrin of the urine. The relative paucity of such procedures a - u.sts to the extreme difficulty of their develop ment. Investigators should he encouraged to develop this aspect of preventive medicine, however. la-canse its value obviously transcends that of diagnostic tests of established disease. toxic reaction is unquestionably one of the hbddv desfVnble goals of the industrial toxieol- Prophylactic and Antidotal Agents o<dst few such tests have been developed mainly 1h,~.uU the mechanism of action of most toxic agents on which such tests are based is not gen As the realization of the importance of toxi cology in the development and safe use^of in dustrial chemicals lias widened, more diversi- eral lv known. , A pretoxicosis test for carbon disulfide has 1.CCUreported by Hotirguignoii (12). This test, is bed on the change in chronaxie, which, m turn, depends upon the knowledge of the vas cular and neurologic changes caused bv carbon disulfide during the early stages of injury, rhronnxie. by definition, is the minimal time that an electric current of standard strength is ,,mured for the excitation of the tissue. Itonrguignoivs report indicates that after men had been exposed to carbon disulfide for only - mouths and before any clinical signs of disease were manifest, their chronaxie clianget . - ' cordingly, this test permitted early detection of intoxication bv carbon disulfide. Another test of pretoxicosis that, is promis ing although it is still in the developmental stage is the lowered cystine content of finger nails of individuals exposed to vnnndium. 1 he lh-d -roups of scientists have become attracted ln i,: problems. Such attraction has resulted in the development of a metal coniph-xtng the. calcium salt- of ethylene diamine tetraace.tie acid (CnEDTA), for the treatment of lead poisoning (10). This chelating agen has been given good evidence of effectiveness in numerous clinical trials (J7, W ,.and d gves promise of considerable versatility. It has been found, for example, to la- a satisfactoiy antidote in experimental vanadium poisoning ( iff) and to give promise m the treatment of essential hypertension ( ^ ) . Furtlu-r use o Cil-'DT \ for the more rapid elimination (1 other toxic metals having the capacity to con.- ,,lox firmly with this chelating agent at body ,,11 condit ions will undoubtedly he made. Since !hc advent of HAT. (`J. a-Dimercaptopro- ) for combating arsenic poisoning. no Yol. 70. Mo. 1, Jan u ary 1955 other organic rnmplexing agent Inis proved of Kiieli value, ii]t.]ioti<r]i others, such ns uuriii tri carboxylic. acid for the eliminat ion of beryllium (/), have been suresteil from time to time. Ati ingenious and novel use of a complexing apent for combat iiijr cyanide poisoning has been recently reported (22). (.'yanidelrss vitamin Ih? (vitamin H,s", hydroxo-eobalamin) is capable of tight ly coordinating wit h 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 etlcctivcprophylnet rally against a variety of toxic agents. For example, vitamin 0 was shown to function as eliectively as CaEDTA against vanadium poisoning in animals and this vitamin is reported (23) to reduce substantially fatal pulmonary edema and hem orrhage in animals inhaling ozone or nitrogen dioxide. Essentially complete protection against fatal ozone exposures in animals was afforded by a mixture of such reducing sub stances as glycuronatc, cystine, and other sim ilar substances that include vitamin ( \ Two-carbon- fragments administered as ethanol, acetate, and propanol have been re ported \o be capable of combating the highly toxic fluoracetate (1080) in animals (24), and they give promise of successful therapy for this poison. Cystine, methionine, and other sulfurcontaining 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-dichloroethane (23) 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 limit values goes hand in hand with the development oi accurate procedures for sampling and analysis of the industrial atmospheric con taminants. 8 The MMitore Filler Inqueslionably, the greatest bixm in recent years to such a development has been the in troduction into the field of industrial hygiene of the Millipore filter (27, 2$). known also as the membrane Jilter or molecular filter. This filter has an eflirienry of sampling airborne particulates approaching 100 percent for all particle sizes of hygienic significance. The ];`>0 fi thick paper of cellulose acetates and ni trates with SO to 8a percent voids possesses a high dielectric constant and effectively attracts ven noncliarged )articles of infinitely small size to its surface despite a mean pore size of 0.8 /i. Thus, the pnper possesses a collection efficiency independent of the particle size of the aerosol. A limitation of the paper is that oils and tars clog the filter in a very short period of time, making if. useless as a sampling medium for these materials. Valuable use may he made of the properly 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, mav he quantitatively 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 particulates. Jn outline, the procedure consists of (a) col lecting a sample, of airborne particulates on the Millipore filter, (h) effecting transfer of the articles to a prepared electron microscope spec imen screen after solution of the. paper, (e) photographing the particles, and {</) deter mining the size distribution of the articles by visual measurement, from their projection on a screen. * ]( is strong*ly urg*ed that industrial hv*g"ienists take, advantage of this powerful technique to exJlore the hero!ofoiv unsampled and fmscen particles of industrial atmospheres and use. such information to aid in the determination of their I'nlilir Heullli |{r|uirl< cut 3 ingicne ,-llsO lis /. Tliis airborne ! t. for all re. TIM 'S ami niissesses a v attracts <-1y small >-e size of oHcction ize of the flint oils rt period .r medium opertv of upon tin* out (acensparcncy e directly :>e over u ' Iter, tlms it may be n of tbe * pore filter iii^li samsol ability !o develop d of samrticulates. ; f (<i) e d ites on tbe fcr of the 'ope spec>n)er, (c) '/) deterirl iele.s by t ion on a hygienists hniqne to nd nnseen d use such Mi of their Ob Itrporl industrial health significance. Hie results of such study could well revise some of our con cepts of the effective number of particles reoiiired to produce pneumoconiosis. ],, ibe light of Ibis and other recent develop ments the Engineering Section of (lie Occupa tional Health Field IIead<|narters, Public Health Service, has 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 has led t<>a promising use of the transparent prop erties of the Millipore filter, referred to above, as a dry. permanently fixed, dust- sample for dii-tlie-site use in plant or factory. An automatic instrument which continuously records the mass concentration of dust in the atmosphere has recently been introduced {30). This instrument is based on the photoelectric measurement of forward-seatiered light from solid or liquid aerosols and has a range, from ]0-3to 10,= Mg./l. in terms of dioctyl phthnlntc as 0.;i fi diameter droplets. A further modifica tion of this device is being undertaken by Da vid Sinclair of the ,Tolms-Manville liesoarch renter iu the development of an instrument which will indicate the size of the particulates a* well as their concentration by electronically computing the ratio of backward and forward Mattered 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 and its physiolog ical effects. At the Occupational Health Field Headquarters, such work is being done on the various forms of diatomaceous earths,.and in Scotland, on various types of silica {31). E f forts along this line arc expected to go far in helping elucidate the etiology of various types of pneumoconiosis. Vatorn aml (tun .v 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 ratlier they have found application for many of the methods long used in other Helds. The study of air pollution hagiven a sudden impetus in this direction. Among the recent innovations used in the. air pollution Held an* the portable Venturi scrub ber (33), which lias proved satisfactory for sampling ammonia, nitrogen oxides, aldehydes and sulfur dioxide, five/.e-out trains, large* ~ capacity plastic bags, silica gel, and other solid absorbents (33). For tbe analysis of organic pollutants, tbe in frared analyzer and tbe mass spectrometer are being explored rather widely. Chromatographic procedures have also aided in the confirmation of many often closely related organic sub stances present in the air. Automat ioiTappcars to be tbe only really new basic development in this Held in recent years. This principle lias been most successfully ap plied to tbe measurement of sulfur dioxide in the form of the Thomas Autometer (31/). This instrument is especially useful in situ ations where round-1 lie-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 (35), and for other substances. It should be emphasized that such automatic recorders in their present state of development require careful standardization and repotted attention and maintenance to assure, faithful recording of actual concentra tions. Commercially available recorders vary widely in this respect. I f original design lias heen 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 air concentrations of contaminants. 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, No. 1, Jnmiury 1055 J (xpcuMvc ami imupurl nlilp. Jmnmhilil y, Inn not expense. is fust lieitijr overcome when tin* nm 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 fnet or necessarily nssorinleil with increased complexity mid sensitivity, will ho slower to ho overcome. Copies o f the American Conference of dovernmental /m l listn o / 11/t/ielists' Jixt o f threshold lim it value? 111111/ he obtained from A llan L. (,'airman, chairman o f the Com mittee on Threshold Lim ils, Connecticut State Depart ment o f H ealth, H a rtfo rd <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 . 1J1 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: 400 411, 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>i1Io lead). Sled. lavoro 44: 113-123. Slareli 195:!. 1 /i-'i ltnliin. SI., (igiim-, S., llessniaii, S. P., and lielk- nnp. 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 magne sium 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. Piumini eoi. 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 12}) 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. 125 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 H ealth lte|Miri<  pr,,. - jxlnnor, 1!. 1. Hcdut-- i<- riti lmlr. M>. >1. h: 4(Hi- l'Ion, 1. A. ; A iixiin1 o f lcud of relnllvely >Imitisi. Ilyp. (Il 1111 l'iiilrlno nelle con piombo 'ireeursor ni 'seti to lenii). i l*,, iind llelk- 'exeretlon in 'ylenedinniiiie >;r>0, .lui),. !:>, polsOllllip liy '-POS 110,74). . II. r*. \V,, miti 'ini jlisuUliim ' lenii poisoiiA pril 3. llir.-l. Ascorbio ueiil iik im i idotes ninp. Prue, brunry 10.74. >1 n u b ili, Al. ; >n liy nin pile .i-town Vniv. Xnvenilier. bori. .1. : Pril li iuni pO SOII- .1. Plinriun- Mimi ). >. l. K,, nini v of vittimili xporimciitnl MM>r. Bini. A Hi n f nanne. -Hitip nf tlie `( iillinn. Chi- >1 nf niellili >i(l in llnornKx|M>r. 1lini. "(I Slm rjiless. illune (etlivll>y l.-eysllne. nltli Keportk ni.-nietlilniiliie nnil eertnln other Millin' ennlnlii- inp rniniMMimlH. .1. Pliiirnuienl. A Mxi>et. " Them]). 01: 385-394, December 1IM7. , g g m ith , W. W.: B ellitiulislilp betw een i.rniein mill * ,,uiriiM -nntiilnlnp itmlnn elds in iirnleellnn opiilnut inetliylelilnrlde l*d*onlop (n lisln iell. F eilerntlnii Prne. 0 : 20(1 (BM7 ). (271 (ineiz. A .: A]iplientinii of ninleenlnr tiller mem- briineM 1(1 tlie nnnlynis n f iiernsnls. Am. .1. Pnl>. <2M <2*1 I.Vi I H enltli 4 3 : 1.70- 1.77 <19731. Kir, M. W., unit Sllvoriniin. K.: Air sampling ivllli uiemlirune filters. A. M. A. Areli. liulust. Hep. ond Oecup. M. 7:1-11. .liniunry Bl.i.1. Frniicr, 1. A.: Alisolnte method of snmplinp mid measurement of solid nlr-linrne particulates: Combined use of Hie ninleenlnr llller niemlirnne mid electron microscopy. A. Al. A. Areli. lniliit. Hyp. mid Ocenp. M. 8: 412-119, October lOA'l. Sinclair, I'.: Light seiillerinp inslniineiils ns mi uid in air pollution measurements. Air Be|inir 3: nl-nd. Aupust HIM. 3 /i (III., J. G., Bitclde, P. D-. and Sluirp. .1. W.: Pbysioeliemicul studies on dusts. VI. Kleetronopticnl examination of finely pround silica. J. Appl. Chem. 3: -13-218, May 1973. Militili, P. 1,., mal ntliers: Sampling eertuln utinosplierle eniitnnilnmits li.v siimll-senle Venturi serubber. Annlyt. ('beni. 22:1174-1177. Septeinlier 1930. (flS) Stmifnrd Beseareli Instltule, Stanford Univer sity : The smop prnlilcin In l.os Anpeles t 'nunty, 10.10. Tlilrd Interim report. Kos Anpeles. West ern Oli and Gas Assnelntloii, 10.71, Apiiemllx A. (fl/,1 Wiisldiiirn, II. IV., and Austin, B. B. : O ntlnuniis nieiisurement nf sulfnr dloxlde (imi liydropen siiltlde enneeiitrntiinis l>.v nutoiuatle turatimi. hi Prue. 1'. S. Teelmleal Oonferenee on Air Pnllutlnn. New York, Metrnw-11111, 10.70, in. .ISO ; .3.70, .307. (.1.7) Blindali, lt. A., and llutislad. N. A.: Bolialilllly of euniliustible pus alarms. Be|iort dellvered ut the mimmi .......tlug of th American Industria) llypiene Associatimi, t'hieiipo. Aprii 27.10.74. (.0) Cliu)iiunii, B. K.. mal 'J'nrley, B. K. : Mobile infra red speri romei or for rapili on-tlie-simt mialysis. Annlyt. ('beili. 22 : Pio-090, Aupust 10,30. (.17 Miller, 1'.. and otliors : Alvoolnr vcntilathm stuilles iislnp th mass siicctromeier. l 'roe. Soo. Kxiier. Bini. 74 :13 (10.70). Com m unity Health W eek, M arch 21--27 Community Health 'Week programs ale recommended fur March jl-o;, 105,7, ly tlie United Stales Junior ('handier of Commerce in cooperation with tin* National Health Council. Chapters of the Junior Chamber of Commerce have been asked by their national ollicers to name program chairmen for Community Health Week and to seek the aid of local health leaders. The prorram theme is "Know Your Community Health Kesonrecs." Voluntary organizations arc recommending that their afliliates pro vide the programs with cooperation and guidance. Basic 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 ofliec. Suggested activities include health fairs and forums, special news paper coverage, television a n d j'adio programs, exhibits, and school health projects. Program leaders may wish toeonsull Guide to Health Organizations; in the United Slates. 11151, by Joseph AY. Mountin and Evelyn Flunk. Public Health Service Publication No. 1i(i. Available from the Su perintendent of 1ineumenls, AYashinglon 25,1). C. 10 cents. Voi. 70. No. 1, Junuury 1955 11 TOXICOLOGIC ASPECTS OF OCCUPATIONAL HAZARDS1 By Herbert E. Stokinger Department oj Health, Education, and Wel/are, Public Health Service, Cincinnati, Ohio * - ' Vit.hiV ' e,Y recnt yTM control of industrial hazards in the United frill' .!* bef 0me " P*" oi Plant operation. If the common Indus- 2 2 ^ ,uch " heav>` metai# in * *olvents still prove troublesome ! ere'lCert1a,nly 11" the ^ oi application rather than the mean, ia iSa I! t,nn' i0f theM * ? n0W wel1 dcfined *n mo#t Rtances. The accent ia th i!i. n nrtr" '-enU0A: th.?,ghtf ,r f bein directed to tests ol pretozicosis TMther than oi injury. Considerations oi comfort. rather than merely health. S l i ! i . ng ? ''t,,nt0 th! threih0,d o{ indurial exposure. The concept firid. of*. H *h U,d ** con,idered hM broiht into the fold many oU vL nnUdyiih . hf ve.ne)'er ga,aed consideration before. Toxicology has f>lyed no small role in the broadening of these concepts. Serious attention tv sf *'T< t0.whf t we5c iormer,y iringe endeavors: psychology, psychia f fad,*Uon,-j heat' bght. vibration, noise, fatigue, color, and the J S S i ' * machuiet` fitted t0 the comfort of man. These enlarged and fore* S S r iff t* * * been reCOgm'" d in the PBCent ch " ic of name from industrial health to occupational health, and have served to expand the ^ i t0T j T " ,ivity- For the " me reMon- tht nooiber of fields that lriT f t!ii * P ' * rCV,fWf Pro,wnen! amon8 thU the is 80 largc " topics omitted are o* to permit the indiscussion, on occu- pjftonal dermatoses, toxicology relating to pesticides, plastics, water quality, food, drugs and cosmetics, and methods of sampling and analyzing air-borne co&tutuenu* 'A few volumes (la) have been added to the toxicologic literature in the S S I* 0 .I*?: rWptogy of Industrial Organic Solvents, by E. Browning; dffOjMK Toxtcology, by the Aero Medical Association; The Halogenated Hydrocarbons, Tketr Taxtctiy and Potential Dangers, by VV. von Oettingen. K **? W l W` 0n t. 'icoio*>' have appeared within the year; the one b y poldblatt on Research in industrial Health in the Chemical Industry" fW e x p r e s e e s * decidedly English point of view. Also in England there ap- pew ed a^ critical review of experimental methods in determining chronic IS P flty by Jkcne & Denz (2). An incisive addreu by Seevers titled "Per* fPfCSive vs. Caprice in Evaluating Toxicity of Chemicals in Man" (3) de* ittention. The Manufacturing Chemists' Assn., long a leader in the held of labding dangerous chemicals, has published a third revision of its WOUal L -l, "Warning Labels." New Jersey has recently developed a state 04* for labeling based on these recommendations. The Subcommittee on The survey of literature pertaining to this review was completed in July, 1933. 177 Toxicology of the National Research Council is planning to establish a toxi cologic center where information may be obtained; presently, limited toxi cologic information is obtainable front 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 new chemicals yearly to the original list, A series of Hygienic ('iiide# on Hazardous Industrial Chemicals, useful for plant supervisor*, is k in g prejtarcd 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 chat 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 asltcstos, and, to a leaser degree, on beryllium and vanadium. In the United States in 1052, 52 deaths were recorded (4) from pulmonary tuberculosis associated with occupational diseases of the lung; pneumoconioses, including silicosis, amounted to 1425; similar figures for England rc|*orted by Mcrewethcr (5) showed 1500 died of pneumoconioses m 1951. Tulterculosis was not the sole disease associated with pneumoco niosis lor 16 per cent of 500 workers dead of asbestosis over the years had primary lung cancer also. It is of more than passing interest that the higher 11 can,'er *n asbestos workers in England is not paralleled in the United i j States or in Canada, according to Lanza (6), The cause for this difference *'j may ,n the type of asbestos; asbestos is a fibrous form of several differ jrnt species of minerals, a point often disregarded. ' A symposium held in Boston in October 1955 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 front other pneumoronioscs (10) and the functional abnormalities of indus trial pulmonary fihntsis (II). Current study of the fibrotic diseases of the lung related to occupation may be d i\idcd 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, Dautrcbande (12) discusses, as important, particle size, amounts of free crystalline silica, the presence of associated dusts and fumes, and breathing patterns. Particles of 5 p and below in diameter, with special attention to those of 1 p size, are now generally considered the most injurious from evi- T k rcW lio n " ' K r , ( ktiuh, ...u n u c v i.,u li iio n of p a n ir lo M o o 1 a r iin l i T " ! i( "" M te r of partidr. the .miw-i and nature of the ensuing silicmi,. and especially the c fiS iS e d nST " S M- " *< '> *W P0.,d J l I , -J ' y ,,,,m c ,| raU 10 in,lic3tc " ***. the various hv erT^' L ? y",,te Wa` n''" ra|>id in P a c i n g " `u e reaction. W f. ^ -d silica. in that order. The m o S i n a C|im ? t i ? C7 * ' a,l,nc ha* > * he explained. In this con- E , T T ' n ilS) n po#` ib,e Pneumoconiosis from silica S* ( ^* * *theI m-nd, Z nnoTdu,,ar` llrllcomwW, !r,ohme fuinndtrienagt<' Koji diatomPa^fc'ioouutseaaurfthhor, (iKu " ` S ,a,c* diatomitc industry by the Public Health Service r '0 ,x r a ,,''n w,th ,ta t* health departments of California. Nevada ^PW jton. involving live plant, and 869 workers, showed, in a'sreement five cxriu ^ f 11 nl^ nc ot 25 cm Pl> e<s who had worked more than U - ` ^ 1 " >amorphous silica in the quarry had diato. n u j e j ^ m o r o n i,,,,.. 22 per cent of 286 employed more thaVfivc t a r , d S a m h t j h ` high ,em PeTM'ure calcined, or fluxcalcined. n t e w h h" WC<, ``ir1'* cons,i,*cnf ttith Pneumoconiosis. Calcining diatovariLn- f '" `"r " -U* (#od`U'" carbona`e) converts the far less active vartets to cn.tol.alitc. a crystalline form, which is believed responsible for niit 1 `- T '* rc%ponbC t0 {n th and I t water forms of diato- r,dfnr t,,nt,,ic {#i,iro#* by n,ct hasund ocfctL ^ h iubf tanccs a,on8 with *<l`ca. The alkalinity as- 60 ^ with sand in a scouring preparation was reported (17) to have S lT J r v Z 2t t0u26 n'nth* ("nping-silicoM,) in a small individuals; the silica dust concentration was tremendously s t ^ t . LCan T* ,he riKinal r'* n - RaP" l'y Progressive ,,rCVM'U1S'>' rT r,cd in thi` `"unir>- (18) from the same J r u 4 t i o \ T f j nU*Ua V fap'd development (16 to 24 months) was re- n Unridi ? n t ? l tu 2 0 V t C; rr n" ,anCM uf vely high talc concentrations. "( rtuorspar. in mixture with quarts has also been re- V i h l ^ i 2 u ,l>P al,>' 10 ,nduce ,norc fibrosis than quarts alone ? h fm i u ' C " "`ay ** Pre8en` !n 0,,,>' miaUt* aroount# <* Mn|) ^ Mslfjou particles per cubic feet of air. < Isolated report* 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. Mtckaniim.--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 develop ment 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). It 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 a* 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 Wood and urine values was found, so that silica values could not be condemd of either diagnostic or prognostic value. These facts have led to modi fied solubility theories. Experiments with silicic acid and proteins by Holt & Bowcott (43) showed, indeed, adsorption at the isoelectric points through amino groups chiefly. It had already been shown by German workers (44) tb it quartz particles become coated with serum constituents with no sign of dissolution, and Scheel it al. (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 as shown by immunologic reac tions. This important conclusion would appear to render less significant the opinions o f Holt ei al. (47) that the action of silicic ad d in silicosis is a process Whatever the final answers to the mechanism may be th* M r iZ ! t'nC\ n0W iaVOr* ,peci,ic chemical combination of crystalline lie* T a ,n ! " *Ue consequent . S t u S alteTM ,0Ca! i ,lUfb*nC* and * * *-lico" c?e.pL:TM; nrci ^Trr. ^ existent. Publications an the control *tud,e* ,n man are almost non. i S t h c ? n the Mbie* TMay be obtained from the McIntyre j^ iM rch Foundation, Toronto. Canada. Dautrebande has proposed a trial- S a in r".*1 t i v ^ and keoT S (32)**"*ss* ; a " leium-sodium salt solution charged nega- S t r C l a m . l T n8,0n " 40 e,eCtr,C fidd M o n halation by the g f f n t a . Claims tor effective treatment also have been made for an electro- f f n S ? n | d ' T M Water (S3,` Interm`" ent. positive-pressure breath% n C l t? :bV k* m ` t prom" in* mclhod affording relief and control i ^ S t o M o T ? 2 |0 f emphy8enw * nd fibrosis with dysp. Stl ud,e` 10 >MeM *he benefiu of the method. H m K 2 2 2 <45) * b e ~ mpl,ca,ed bV ^ e use of bronchodilator J w S o ' a n d .L b u V " i S f * " WM cooduded tha` administration of 2 R ^ 2 ? ? ^ * " ? W,lh impr Ved brealhin* *chnics .1:t j;. dust b> Child & Clancy (57); during grinding and |xmilcring of ihc synthetic resin, dryness of the mouth and nasal mucosa, coughing and sneezing, and other signs o i respiratory irritation were in evidence. Experiments in ani mal* produced wheezing, rales, blocking of major bronchi with distended renin granules, and salivation and atelectasis; the must prominent effects were caused from the loosely cruss-linkcd resins. Dust and jiowdcr of Tvilon (tctralhinroethylvnc polymer) have been known for sewrnl year* to produce respiratory condition akin to inetal-fume fever (58); more recent investi gation of the inhalation hazards of heaterI Teflon (Vi) showed the evolu tion of highly toxic fluorine-containing decomposition products. 'Printers' asthma" has Iwen re|iortcd front England (60) to arise from inhaling a sprayed fluid containing gum araria. Although considerable study has been given to m u o n 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 rcs|ionihlc for the "early" and "late" reactions. In bagassosis the endotoxin 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 bronchitis, 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 disease* from inhaled (tartirulaics makes it difficult to escape the conclusion that all dusts, irrespective of rheir 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 oi cue of both acute and chronic beryllium poisoning continue to ap|tcar, despite the fact that one of the major sources of exposure. Uryllium phosphor in fluorescent lights, h;u been eliminated. In addition, an extremely low air standard of 2 ug.D e/m 1 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 ligure for chronic ex- posurc is a reliable one. The rases that arise are partly from exposures long past, but also partly from beryllium put to new uses such as glass, glazes. and alloys, 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 continues 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 identi fied. one doubtful, have appeared in their factory since their earlier rc|M>rt ^ ' . ` ' ;i! 5 none conclusively demonstrated Pcted. but beryllium extraction. r P d u t t * 2 1 , " " "A (66) in * W i 10 J'fW i ber) Ilium fom ent ration ... he f b" Ca`wr,1 cov*r'S a period o n g e d from a ,-tt- mirroKr,,,w r,, 6W 7 " f0UKh ,he >- " ha* climcaJ types i |,eryllioi* ,,W n . ... / f ? ` ' *",n1niar>' *,,rv` V <>( all PeNardi ft ,,/. , 67). a tlJfill of I2,>`*ar Pr'0<l ha. been give,. |,v iHfjllitlni ,,....,,.i,,, Curlf.' ,i! l T 'TM 1 ' " I ("r to Iw the ***nM,ng allereen Tli i "! *he hcnlliun. ion believed alim iud n ,.n ,b ^ wi,h " kmi* IW tiw tm ^ a l l t r .C ?! bile n egatiu repul were ul.taincd i n ' n , w ' '* ryiaum. RranMlnma 1 he l.H!ry,l,um 'nvohcine.it, ljm worker*. ,\ registry tu a .ller. i * "arco,d *nd norm*1 beryl- N a o n in g * being accumulated In ' f j r 7 l ' a t c da,a on c a sc * "ith kryllium C W I Hospital H -to n UWk . 1 ` " *?>' ,hc ^ " chusetu 1(9) on the nierhaniM*. o protection o o ^ 'u h e r t and co-workcr* Praaoningj ACT! I treatment hat ,,rmi iJt'" tl'u`ilr,'*'Vv,icarid in beryllium Hardy (70) believe* that either ailr ' ^ l'Cntficial cff*. but 'W > i t controlling*ym" * itof lW d .am .~T h e * 3 ? tnry di*ewe ha* Ih',, L^ T ' "" " i ,he di* a* - 7 *T * rC,a,ion t0 ' * " W the mining and nilli"^, 1 3 1 3 I T " 1* 1952 ior ,w o rca#OM: I ^ M W y ,, , IliU) in thh l " ' T ^ Cn,Cd `.,uant,`ic* o r a o tite ore for atom ic em rgv p n i l ,, * 7 7 7 7 " T * W,,h and second, the m vanadium compound* fur high-grade *tcel an.l*rfrh"8 WfkCr* producin* (7|) and by IWhin ,7 ) -J * hcr pur,,`cl< bV Sjoherg with vanadiu,..bearing oik hv VVillL,"'?"?) fircd tine & Frost (75). and iron?*,!. , i 3)' hjobcr f741` and by Fallen- a monograph ,77) in Kneii*h on .h."!* . l"!."6 ^ `d* rR hat written vaf#W priMoxidc. The rpMuinaes to aTrl-w ****** *? lhc Prduction o M lltioii o thcconjunetivac^^ diekor c o ^ T ' ' "" ^ ."'" dMt are: *,ih* b y W W tic v h a n g e * in th e .J .* a l^ n ,u n * .d " nm '"Trrimt *" ? ' 0"'6 With chronic atrophic and ^ ne** .r ,rntat,on oi he throat. m i l i t e change* iu the mucous m c m b L T ^ ' 5 h*nB` : hoar*n * : only the mu*t outtandinu avmnt , brane o the larynx, and a cough as examination ahowa'only'niildl>h ma"y . rl'_nchl- a,lhogl. Imm- diagnosed in several m u . . d bronchitis. Pneumonia has been ewporarily inca,m atine but not *r*i 4 w U ,n , b"' thu* acute*not chronic. " ' * .m o , feature States Public l i c a ^ w T wic ** l ha 9 CCUpa onal lit a llh Program. United m enu 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 ng 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 efTccu of vanadium, whereas borderline d ieu failed to do so, suggesting the value of nutritious and well-balanced d ieu 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. C eruinly vitamins exert a beneficial effect, for it has been shown (80) that ascorbic ad d can counteract the effect of lethal doses of vanadium compounds in animals, if administered in small repeated doses within a short period after the fa u l vanadium dose. Vanadium has also been shown capable, at nontoxic vana dium levels, of reducing elevated plasma cholesterol in rabbiu fed high cholesterol d ie u (81). Reduction in arterial plaque formation was 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 am ounu of materials may cause deepseated metabolic alterations in the body. Eoatbamil in Mstal Poisoning Poisonings from a variety of m euls are still 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 metals, 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; (e) case of lead in toxication are still being seen in some smelting operations, brass foundries, auto-body shops, lead storage-battery plants, and printing csublishments. Reported cases of infant m orality from lend are as high as 30 per cent, in aeaam f to 63 per cent when complicated by encephalopathy (82). Stim ulated by fa c u like these, the American Sundards Association has drawn Up specifications to minimise hazards to children from residual surface- CMbng'materials; this activity was sponsored by the American Academy of r e flis tn c s .lt s m a ll wonder, therefore, that early reports of the effectiveBi of ED TA in children (83. 84. 85) were recieved enthusiastically. The 7 "? " f ,ts Ui* in adu,u b* Si* bvry <> would seem ip leave little doubt of the value of EDTA in lead poisoning. This report prepenta a renew of the action of EDTA with reference to papers showing it distribution and excretion in man and in animals, dosage-schedules, and cse reports with Icad-cxcrction curves following therapy. The value of a chelating agent such as EDTA is its capacity to combine with metals so as to render them tin-ionized. The combination often has reduced toxicity and allow* an increased rate of excretion via the kidneys. EDTA is used as the calcium salt because this form eliminates the development of low-serumcalqjim tetany. As with most drugs, there may be obvious dangers from prolonged, wanton or excessive use. Dudley tta l. (87) have already described toxicologic changes associated with the use of EDTA in treating hypercaiccmta: "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** 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 not reverse the serious effects of manganese on the nervous system. Edathamil has been reported (91) to accelerate the excretion of plutonium in man, especially directly after plutonium intake and "offers promise in a situation formerly considered hopeless." CaEDTA was reported (92) to decrease-the excretion of mercury in a single case of combined mercury- and Iratl fxpm ure in which the patient was successively treated with dimerraprol and KDTA. Ratal doses of vanadium administered to experimental animals were successfully counteracted by later treatment with CaEDTA (93). h duham il has also lieen shown experimentally to increase excretion of ytMiitm aad americium (94) and zinc (95). CaEDTA. combined in an ointm qit. has been reported by Maloof (06) to be of value in the treatment of chfume ulcers; E D TA loosens and permits easier removal of the ulcer base io | | must two or three applications. EDTA has also been recommended in the treatment of lime burns of the eye (97). Solvent - . The lt few years have witnessed a gratifying trend generally in the apprueeh tp the development, marketing, and use of the safer solvent. The contact of industrial workers with solvents is probably the greatest of any single group of substances; their injurious effects range from extreme hazards awarenessof the hazardsof in v ^ T h U knoTV" ini rmati0n and d a tio n on the risk, involved. 1 h i, U M kc ha* *crved * curtail `he use of many oi the more hazardous aolvent: the highly flammable solvent is now |c,, commonlv umcI without admixture with a nonflammable component: the seriously r.,\ic to lu ln ? * re,tnc,ed t0 l,n,``cd and controlled use,, and the less hazardous toluene or xylene substituted for it; several safer chlorinated hydrocarbon o vents lire 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 mail quantities. Unauthorized or flagrant use still persists, however, as two recent excellent revews testify (98, 99). Supportive treatment of severe U h intoxication now emphasizes, in addition to attention to the liver in jury, the management of renal tubular damage with its possibilities of pul- T TM yt dema and r>otas,iuim " cation. Death frequently result, from in i !* I |h " ,"ow.clear that " y oi the *vcre and fatal cases of poisonng involve chronic alcoholics or individual, who have ingested alcohol prior to. during, or after C t l, exposure. Despite the known potentiation of toxicity of halogetiated hydrocarbons by alcohol, the chief approach to safer sol vents is the use of chlorinated hydrocarbons of lesser toxicity than CCL namely, trichloroethylene (TCE) (100), pcrchlorocthylene (101) and. more recently, methyl chloroform (102): the threshold limit value, for these agents are. respectively. 200 200 and 500 p.p.m. in comparison with 25 p.p.m for CCI. 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 ! thc `` h o ld limit, presumably several thousand p.p.m. Study s being given thc excretion products of TCE. especially trichloroacetic acid (TCA) (104) as a measure of exposure, but thc results and interpretation, are com -plicated by the variability of the liver's capacity to metabolize thc TCE ? r r , ,nn that TCA Cann ` bc Ufcwl as a of exposure to TCE (10a). Another solvent, methylal (dimethoxymethane). of relatively low toxicity with a threshold limit approximating 1000 p.p.in. (106), ap- p e a 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 u*> of the azeotropic mixture (107) wherebv a cona u n t b.p. for all components is achieved. This has thc practical advantage that the vapor from the mixture has the same composition as thc original mixture, thus permitting a more exact knowledge of the composition of thc exposure vaimrs and preventing the disproportionate build-up of vapor con centrations of the more volatile substances. The use of solvent mixture, as a substitute for the single solvent is now common with all producers, thc com ponents of the mixture being selected for their nonflammability and lowered H'r, toxicity. A typical solvent mixture now on the market is methylene chloride 25 per cent, pcrchlorocthylene 5 percent, and Stoddard Solvent 70 per cent, having a threshold limit approximating 500 p.p.m. Associated with the use Oi advent mixtures is the i|uotion 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 haiogenated hydrocarbons, and there are other. LaBelle (108) has hown that particulate substances may enhance, decrease, or have no effect on the toxicity of a vapor, depending on its nature. The same worker (109) khpwcd also that the toxicity of a solvent mixture of eight components was c?aettaliy 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 n a tu r e could be mathematically predicted from the composition, i.e. no synergistic effect. Thus, whereas one should always be mindful of the possi bility eff synergistic effects of mixtures, synergism is by no means a necessary consequence of 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 un saturated aldehydes and alcohols that will have large application as paint W>4 varnish solvents, components in safety glass, vitamin intermediates, and nw ny other uses. Price margins 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 vaporising liquids for fire extinguishers. CCI is by far the must common and important; however, other haiogenated hydrocarbons arc being introduced as replacement for, or in combination with, CCI (111). Of the newer agents chlorobromomethane has received the widest usage; the hazards of this liquid arc somewhat less than that of (112). the main advantage in firefighting being that CHjClUr can be used a t lower temperatures and is not as corrosive on metal extinguishers. Ata Pollution f b e increasing importance of this subject to occupational health would appear to justify greater space than has been heretofore allotted it (115). d t t r six years of research and study and an overabundance of discus* *`ufl! *9d symposia, three major areas of accomplishment appear to have ***fcflffd* Much is now known of the nature and amounts of solid particulates coqlxibujtiog to the air pollution of many cities, both in the United States ( j l i ' U S ) and abroad (119). The total particulate load in the air over many I njtcd States cities ranged from 200 pg/m* in residential areas to 500 Mg/m* in the our over industrial areas, of which identifiable metallic constituents accpuntcd for from 5 to 10 jntr cent; the bulk of the remainder was carbo naceous material. Considerable uniformity of the particulate matter in the Mi-.; I w.*.# uvy w i i louna, ana tne more toxic elem ents, such as Jb Mn t r . t o , fie. etc. were invariably less than I p g /n i` on the a v e r s e , and ab ` H r `"abIy COntr`butine t0 over-a" b<xJV burden, these levels were ueli below those usually considered hazardous. Recently, however new importance has been attached to the water-soluble fraction of these par-' irritation ^f'n T*60" (,2 0 >* t0 which he ascribes the capacity of respiratory irntatton. in this connect.on. ,t should be noted that the particulate, over a u e s 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, a . 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 search for evidence, that still proves elusive, of the ung term effect, of air pollutants on human health, a second possibly i.,,. 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 base been identified in the atmosphere and in gasoline engine exhausts. Whether the amounts found in the general atmosphere (less than 1 pg/m*) are sufficient to induce lung cancer in man is still to be demonstrated. Thev have been shown, however, capable of causing skin cancer in mice (124). u ih er types of air-borne carcinogens such as printing inks (125) 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 gates 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 ^-workers fr 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 n o photochemically catalyzed reactions involving oxygen, nitrogen oxides. *nd hydrocarbons. Among the products detected, and they are numerous, ozone and oxygenated hydrocarbons (peroxides) are considered to be the enous offenders. More recently Haagen-Smit has demonstrated that ozone w ay lie photochemically generated from auto exhaust gases (129). It has long been known (130) that combuation engines .are capable of forming ni trogen oxidea by fixing the nitrogen in the air and. like unburned hydrq- ozone' tbe Quantities formed depend upon operating variables ** . ` *n.^ r*kted information (132), has provided speculation on the poaaibility of either better engine design for more complete burning of fuel. I ' IIif I J z& s r .x T z : i: r ^ r r " ' ' " 'V -- ' * * p""uon -- -TM , w s s r js r * ^ --~ TM -rnri " , t7i^"aouLncftaio!n ??* `*7" "h"1"''" ,UI1***,',i"'""'op- test* specific enough to differentiate between the Ming*etc. Eoidem'^ nt* and th0lC 0t t0bacco ,m oke' infectious p r o c e s s . S a i i n Ef d, ?r . glC *"rVey* are , ui uW i n d i c a t i n g the areas for in- W r ^ r w S oh -i * ? P ,,"U n tt " to organ system , fa ta l^ a TM * e en" ir m *e ,U 01 iuncti0dni oi the af. Ozonb asd Oxides of Niteogeh iitia lly "dean" odor, osonisersare periodically 2 C W !T * " ? a,ri ea" in8 val"* in hospitals, homes. Offices, and S w S d i n i d l c t ^ u i " a^ c" t*d with "" y industrial activities, such W W eldiog. electrostatic precipitators. or other electricgenerating devices. ttecauae ol oxone powerful oxidising action it is now being used in the fine w H i b V u n la A ttn `r " nUmbcr oi P*ndniiy ecriou. exposures A * , U ce I** kn wn ior * to*aty. Moreover, the role of ozone in Los n S eT fh ? a" Umed m*j r pr0portio"*- Recently, however. S j y . i l h. ,Ci ty p,cture oi 0,0ne w u injected by Thorp (134) who <*JM*ttiiat the oxides o i nitrogen associated with osouc production were S S w i L I S r i n ^ i T Cd t0XicUy' M u tia * evidence w u recorded by .a iT w k . " a t a c i rev,ew on *0ne toxicity. Because of the dancer * jjjtu s z 2 iound thc,r way ioto recent toxicology texu t W w b u ^ . f l ^ r f * Ui f Undm k * revicw **d 4t"dy o i the problem oi H "Wr08Cfl XOne toxici`y- The review (137) show! 10 ` Up,,0rt <h* Coutention that the oxides oi nitro.K^ , r >! d - CCOUnt h r .,0 ,,e C0XJcity- ^ ie fly because. under usual circum- E 3 ^ 1 ' " f "" 0"1 onl] ` ,maJI amounts (usually 1 or 2 per cent or t 2 t ^ d h i n ? ! f *!i a" . ,,roduccd Animal studies (138) further showed tta ilS r o / d" u ? T Sta l *ne "P w 30 per cent (ailed to alter i "*' the LDm oi wWch ior "ice approximated 4 p.p.m. ior T Z l l * T TM 01 "* * C*** a "Tie* J u d i e s ## ,b# * `dea * nitrogen (chiefly NO J produced (torn rod fuming I:|,!; i V * * the u f . level t o , u i y J L V " '" '" " " 1* ' ?P-n,.. and value ha, | iecn incorporatefl fn(o^hcUtrh/K T m - ' ^ 5 P p m '; ,his la,t" ference of <;over,,, neP,, t a , , ' ^ A '" 'rica" C- Pears till unsettled, for report, from i*!*' P matter- however, ap. r "*> far y *i'C4 C l" > importance ol StO i 1 rhar -r . i. , (treater than that of ozone: the -t;: of a m . o ,o n ,. The e lp e r im e L oI d 'u u ! T C a " N ' " 7 Pr" ' resolve this c o n tro v ert! and didicuU o r o h lT ^ P ' ^ r * ` a t*empt ,0 undoubtedly lain tj,c inademiai,. P r em` Pa,t 0 the A c u i t y has overcome these diilicultics Byera et a T ^ a v n l ^ ^ n"*1**" procedure*- To . Jed the method of Smith and Diamond f y eva,uated and nodi- h*s developed a highiv sensitive and 2 0r 0,0ne and Saltsman f141) lyring nitrogen dioxide. Other difl.cLltTe ^Iv'T***0*1 * " wpling 3nd where in this review, from varvimr eandtJ*** *!*? ai ,u 8i'Mted else * yet undemontrated free radicals of nf . humidily' or he presence ay prove responsible for the d i f f e r e d in d f ? t0*,C " tUre` and the4e t elusions. Cea ,n tae Proent experimental con- LITERATURE CITED la. Drowning, E., ToxUol,>t y ,,/ industrial 0rtam- . . . . S * , 1* * ! JIlpp TOJ) <H" S" ' T*a* D <Tta c.. ** " a s {tegs*-*- - *- m" - wd^ '" ' * " . i S i E m ' c " 4J0 pp" 6 Lanza* A l ' A s ^ r ^ ' *o*" ' / /,r *ada'*4*365'*2 (1953) ' F~ " h* * - -- r w nynCb.* ^ o ? n,,`.d ' *TJ - Arck- #u4A. 11, 115-9 {|9*t) Htalih, n , H9-96 (1955) Ss r f ^ . h JJ W riA? C p " i" i' * I I . 201-12 (1955) u j. 3 ` `JLi Areh. Indust. Htalih, u , 196-204 (19551 * * .. a. u U d S r ' King, E . j., h S a i y "" : pd w .- * / :C" .if a ; " i ` "* "" , fafcfa. N. V.. 1955) i/sd., 10, 9-17 (1953) C` V- and ^ehehnudt. C.. tirU. J. in i. W. Lecocq, J.. Cuyot-Jeanniii. C , and leU v f w ., . , ,, *<*(* inw /i, l j , J6J-5 (1952) V* ` ^ PhlWd Prcliminar>- Report, -Study of Pnsumoconio. Hazard in the a. ,7' _ mfd. Ir1a*ta' tIl 'eat t,i,cSu"nDticlloprl4iacl<r*. v14<,**2n7d9--C8.a1v(igI9nJe.aJ)u*. A.. Anh. maladies peafet*s' ,o ] Krt. Tubert.,43, 117-31 (1041) S T ' PntikAki`-A' E- " T er. B.. *,*. / . M . Med., 12, 43-49, ^ P1 n > `"i9jj0)llet'A'Anh' m k d iu M m ' mt4`" a '7* 21. Panda. A., Med. Segur. Ttab., 2, 11-14 (I0J4) * ***' *"* ,brl GmUfgrbifU, S, 31 -34, (19501 ' Gartner 14 23 J t l r X ^ % H^ P 0 ,n fM * * * <* ,L Z n t'- rbtttt^ - ArbeiuckuU, 4. 35-40 (1954) 25 i 'T V S 1* ': PatknL " . -S 2 (953) m f T T ' ** *w,f` SsUhost^Farsth., 25. 1-29 (1953) n 3 3 T (W W ,0d C,WBing*R- R- ^ 27. Mandoli, C., fe u . aud. ind., 23, 7-16 (1954) 0upatU*al Med. 8 " * Ram* " * . D'Onofno. V., Abu. med. ind., 21,344-6 (1952) m Mclvtr, F. A., Am. J. Pathol., 30. 1117-27 (19541 . . * t s S `v - *" *Co,h*' A - " * * L22217, w " T ,v i ^ i ' ( S 3 | w ', , " d C im " . " " l u * . u u . Q S,,,, JJ. Martin. J. E.. Jr.. Am. J. Publie Health, 44. 581-91 (1954) H*67,^-35(' \ 1954f * " * * * - *> * 3 - <` 3 ); J. PathcL Baetenel. 31 n p * M cHealthMBMu. (U'.'5.;), 2S70T. H:8-pHj,,p(-19J4o1n)e* J<L- *T*. R- w..JO. Hannon, J. \ \. G.. ArrA. 7nJiu/. Health, 12, (1955) L l " '- " H '* " ` * * + * - UK a E<j'* J1*" ' ' 2WrA., 00, 2I2-.10 (1950) , B S M ,r ui di W- A' l i - Hyt' "* * < * .. 136, 1-4 (1952) * '* S kk*' .T*: *i"tw ra' T,t ,Matluda' Cm Ntthioka, Y., and Olcumun Y u. ISPhhatlasti, 29,404-22 (1954) " 2 ^ ? ,^ ? 'ii"nd5 'n i* n' C,` Z- a *" ' . 135-64 (1951) 4 H ,andB o" n,Uer- C . i f , d . iheeCrenagehiete, 7 ,435-9. U* K , r \ v ' ` S T ' J` E L * " 1-3 (1954) J r i g ^ .^ a ^ & h l i p k o te r . H. IV.. Anh. Hyg. a. Bahtennl.. 137.53-60 (1953) F' W *" ^ - Ouupal * " ** * * " E ' ^ '*' * ' 47. Holt, p. F., and Oubcrae, &C., Brit. J. Ind. Ue., 10, 152-5 (1953) V " tiSJk&M !052)SU*h*rUnd' Schlamowi" ' M**J' Am` Cktm- 74. 50. Hcffeman. R, Tuberete, 34, 246-9 (1953) 5!. Dautrcbande. L , VanKerkom, J,, and Ccreghetti, A.. Essai i t Pretention i t U Selvoso (Untai Miniera du Haut-Katanga. Belgium, 177 pp., 1954) 52. Rosenthal. E., Colliery Guarita, |$S, 561-4 (1952) 53. Ceuer, H., and Neymann. X., Stoub. 33, 293-307 (1953) 54. and J- F., Areh. Ini. Hyg. end Occupational Mei., 3|(Ira) 55. %1l93' ^ `ller` w*F'*C" ,fR" ,nd R`chbm. P-. Rn. Tubere., 71,693-701 56. ' V" *"d Crel,'n' A- J - Arck. Intern. Mti.. 91, 408-13 (1953) 57. Child, C. R, and Clancy, C . Federation Pttt.. 12, 311 (1953) SS. Stokinger, H. E.. Occupational Health Hetes. 13, 88 (1953) "SP1 Rroiytit Products of "Teflon" (Presented at ind. Health Coni., Buffetto, N. Y., Aprii 23, 1955) 60. Fowler, R B. S.. Lancet, II, 755-7 (1952) 61. Cayton. H. R., Fum*, C.. Jackson, D. S.. and Maitland, H. B., Brit. J. ini. Mei., 9, 138-45; 146-53; 303-8 (1952). 62. JW 5 ()1!;9,4.Fo)tnhart< H'*,nd Carainiu' B- H.. J. ni. Hyt- Toxicol., 30, .63. CAcn, V. L., and Osgood, H., J. Alier, 24, 193-211 (1953) 64. Van OrdstRind. II. S-, Anh. Indusi. Health, 10, 232-4 (1954) 65. ueben. J., and Jackson, A. W., Ini. Mei. and Sur/., 22, 507-9 (1953) 66 Sbifcn, J., Koppcnhaver. F. B.. Cldand. J. G.. Luta, L. R., and Vougbt, V. M.. Ini. ilei, ani Suri., 23, 291-9 (1954) 67. OeNardi, J. M., Van Ordstrand, H. S., Curt, G. H.. and Zielinski, ]., Arch. Ind. Hyg. ani Occupational Med., 8, 1-24 (1953) 68. Curtis, G. H., Arch. Dermatol, and Sypkilol., 64, 470-82 (1951) 69. Schubert, J., and White, M. R., Arch. Biotkern, ani Biophys., 52, 143-7 (1954) 70. Hardy, H. L , Arch. Indus!. Health, 11, 273-9 (1955) 71. Sjobcrg, S. G , Arch. Ini. Hyt. and Occupational Mei., 3, 631-6 (1951) 72. ' Ruechin, 1. V., Gifiena i SoniL, 11, 49-53 (1953) 73. William, X., Brit. J. Ind. Med., 9,50-55 (1952) 74. Sjoberg, S. G,, Arch. Indust. Health, 11, 505-12 (1955) 71. Fnllendne, B., and Frost, J., Hard. Hyt. Tiishr., 3,58-64 (1954) 76. Browne. R. C , Brit. J. Ini. Mei.. 12,57-59 (1955) 77. Sjobeig, S. C., Vanadium Penioxide Dust, Stockholm, Sweden, 188 pp.. (1950) 78. Mountain, J. T., Stockeil, F. R., Jr., and Stokinger, H. E., Arch. Ini. Hyt. and Occupational Mei. (In press) 79. Talvitie, N. A., and Wagner, W. D.. Arch. Ini. Hyg. and Occupational Med.. 9, 414-22 (1954) 80. Mitchell. W, G.. and Floyd, E- R , Proc. Sot. Exptl. Biol. Med. 85,206-8 (1954) 81. Mountain, J, T., Stockeil, F. R., Stokinger, H. E. (Unpublished results) 82. Ennis, J. M.. and Uarrison, H. E., Pediatrics, 5, 853-67 (1950) 83. Rubin, M., Gignac. S.. Bvstman, S. R. and Beikuap, E. L., Science, 117,659-60 ` (1953) (IMS) 'V` Uhl' S M" Drem' J r J/A. 252. 138-tO J?" M*looi<C. C, Am. /. Diseases Children, 7, 359-42 (1934) 6. Sidbury, J. B.. A m. / . .!((., 13, 2 - 7 (1933) U 4) V ' 1 5 S fS v j j m ^ C *Schil,i,,f*A" and B#klr* W- , N ~ Engl. J. M. Kehoe. R. A., J. Am. AM. As m ., 157, 311-2 (1955) rU, ^ er`/ C., and Peters, J. H., Clin. Rtstatck Proe., 3,80-32 (19531 . Rodirr, ].. M >ta. r ,, Rodi. L.. A,,k. M ta ^ , . . J ^ ,, iituftU soaaie, 13, 210-23 (1954) " " 9 ,` F<M M i 0954F)UqUa' Pl A- Md NurW00d` W- D- /** m l . 10, W' B*U9iS)F ' Calil"nd, J` C ' " d I>ttnl,, >V` * * ll, 2J1-3 * H S ' T * W J; t P`f * * * BiU- U ed> 206- (1934) 95* H|' Hr-' I" * w rf; and * " * * " d . 7, 137-47 (1953) 8 0934)' F *M> M*W" n*C A - a" J Elonata, P. V.. Nature. 174. 96. Maloof, C. C.,Arck. Indust. Health, 11, 123-5 (1955) a* u ^ i* * n'' Aimaisl>i- Augenkeith., 123,99-102 (1934) IT Hardin, B. L., Jr., Ind. AM. and Surg., 23, 93-105 (1954) Si`lra0nJ, J` A- Auh- lHi- I I n ' Md Occupational Med., 6, ! Ir r i;i,S i ,itiMi)D`,*nd,rUh*D- ^ ^ C T i g i i S a v-* D- - w*. D. n . 102. Adams, E. M., Spencer. H C.. Rowe, V. K., McCbOisttr. D. D., and Irish, D D 103 f t w i i i f V Occupational AM.. 1, 225-36 (1950) " 103. " j J ^ ' ^ T a b e n h a w , I. R., Arch. Ind. Hygieneand Occupational Med.. m . Ahlmaric. A., w d Forununn, S.. Arch. Ind. Hyg. and Occupational Med., 3, JJf* ^ U" k' *1andf ra^elko''3- E-. Pratonx Ltharstn 5, 62-68 (1933) 106. A- R-. Highman. B., and Fairhall, L. T., Brit. J. Ind. ,07* 1M . 01 i H_A_ T ? h 10i* * ? ***lA4dmt deU" " * &>'* Eng. f 0? " ,nd.u" ,y' Sew York. N. Y., April, 1954) {19555^"^' J' E" 40<1 Chri*t0<*n0' * A*. / .a. ff | , n , I in at ,<Mi- Health Coni., Buftaio, N. Y., April, 1955) 110. N ^ o U n J ^ O . f t . d l i n m t h . R. L.Oyeu, F ...n d R ow ^ v! K., Compaq Ill' ^ H; ' * rti .ind-11** anJ Occupational AleeL, 6, 435-W (1952) 112. Tke H a u rb oj 1apartung Liquid Extiuguiskimg Agents (Nad. Fin Protection A ^ , Boston, Mass., 4 pp., May. 1955) II.. Smyth. H. F., Jr.. Ann. Kn-. Med., 3, .149-62 (1934) 114. Stokingrr. H. E.. Am. J. ruhlit Health, 4J, 742-31 (193.) 115. Keenan, R. <., anil Byers. I). H.t Aeek. lad. Uyg. and Occupational Med., 6, 22h-.il) (1952) 116. L*J ` Vo""kfr. W. J.. and Yeager, D.,Arrh. Udust. Health, 117. Chotak, JmSchafter, L. J.. and Hoffer, R. F., Ank. Ind. Hyg. and Occupational 118. Air Pollution Study Project, (Calif. State Dept. Health, 1953) 119. Beaver, II. and Associates, Ank. Ind. Health, 11, 313 (1953) 120. Hcmeon, W. C. L.. (Presented at 126th Natl. Meeting oi Am. Chem. Soc. New York. N. Y.. Sept. 14. 1954) 121. Bloomlield, B. I).. .4. Ind. Hyg. Assoc. Quart. 16, 141-31 (1953) 122. Waller, It. E,, lirit. J. Cancer, 6, 8-21 (1932) 123. Cooper, R. L.. Chen. Week. Dec.. 1364-3 (1953) 174, Kotin, 1'., Falk, H. L., and rhottue, M., Arch. Ind, Hyg. and Occupational Med., 9, 164-77 (1954): Ank. Indust. Health, 11, 113-20 (1933) ' 125. Ask-Uptnark, E.. Diseases of ikt Chest, 27, 337-63 (1954) 120. Hutchison, I). H,, and 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, 1935) 128. Haagen-Smit. A. J., Ind. Eng. Cheat., 4 4 ,1J42-6, (1932) 129. Haagen-Smit, A. J.,and Fox, M. M., Air Pollution (Presented at S. A. E. Golden _ Anniv. Ann. Meeting, Detroit, Michigan. January 14. 1953) If*' f K.Mlon*A-c - Hanon, T. K.. Ptot. Roy. Soe.. London. (A|163,90-95 (19J7) 131. Spindt, R. S.. Wolle, C. 1.., and Stevens, D. R,, Science, 121,836 (1955) 132. Haagen-Smit. A. J., Eng. ami Sri. Dee. (1954) IJ3. ilenchbcrger. \\. 1).. Munnvate Method as a Tool in Studying the Composition of A ir (Air Pollution Synipmiuin, Pasadena, Calif., April, 1955) 134. Thorp, C. E., Ind. Med. and Surg., 19,49-54 (1950) 135. Ucaver, E. R., V. S. Dept, of Commerce, Soft. Bureau of Standards, Rapt. So. - 1*28 (1951) 116. Aero Medical A*n., Ann/io Toxicology (The Blakiston Co.. New York, N. Y., 120 pp.. 1953) 137. Stoklnger. H. E.. Arch. Ind. Hyt. and Occupational Med., 9, 366-83 (1954) 138. Stukinger, H. E.. Byers. D II.. Suiuman, B. E.. Hyslop, F. L . and Wagner, W. D., Toxicity ofOtone 11'resented at Ind. Health Coni., Chicago, 111., April. 139. Gray, E. LeB., Goldberg, S. B., and Patton, F. M., Ank. h d . H y g . and Occupa tional Mai., 10, 409-25 (1954) 140. Diggle, W. M.. and Gage. J. C.. Brit. J. Ind. Med., 11, 140*4. (1954): Br. J. in i. Med., 12,60-61 (1955) 141. Saluman. B. E.. Anal. Chem., 26, 1949-55 (1954) 142. Smith, R. G., and Diamond. P.. Am. Ind. Hyg. Au h . Quart., 13,233-8 (1952) TO 13014521039 P;01 it- V f y? 4 Industrial JMedicine . .. / R u th e r fo r d T .J o h n s to n e , M . O . j CONSULTANT IN INDUSTRIAL MEDICINE. T-. . CUN,CAL OFISSOR OF FIEVENTIVE MEDICINE,AND PU8UC HEALTH AND CLINICAL PROFESSOR OF MEDICINE, UNIVERSITYOFCAUFORNLVATlos AKOELES ' \ . V* Seward E. Miller,Jd, D, - DIRECTOR, INSTITUTE OF INDUSTRIAL HEALTH PROFESSOR,OP U ltriliM w , w u raem ' ' ./'I PROFESSOR OF TNni.tS l kIAL HSajlTM, m i O A i n n m iiu ti* i u a l t h U N IV D S It Y OP M lClUOAN, ANN ARBOR . r 1v .j>i '.* 'M' . ' v* ' *w. /4;; :v*r '17-1992 1'0i.:.28 FROM Chapter 13 Occupational Cancer lb e r r a n many diverse forms of neoplastic growths constituting agroup of disorders rather than a specific disease entity. Ewing, years ago. defined a neo plasm as an altonomous 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. Within 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 PageW 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 History Air) among t Percival cancer. I phasued assemble dates, re] Eck much la< skin can as adequ carcinog She the wint  APR-17-1992 10:29 FROM TO 13014521039 ning a group cfmed a neodcfinition of of the body ponsc co the cer has been utt> o f stu d y se agents as w chemicals the develop- and arc not vorkcr suffer lio il o f Mill* icing agents v called Car tory system, oils, waxes, cel dust and re dusts and :ion and abneers of the est intensity nor among intensity of OCCUPATIONAL CANCER * 323 the exjosure 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 dues not prevail ilic dcvclupmcm of cancel. Wutkci who have been exposed a few or a number of years to a carcinogen and then dunged jobs, hs.ve been known to develop cancer many years later. In the intervening years, no sigr s or symptoms appeared. Perhaps a microscopic cancer in situ existed for some u n t prior to the development of overt cancer, but such lesions never have been dcinonsnaicd in connection with an occupational exposure to a carcinogen. As with all occupational diseases, occupational cancer is poorly reported. Or dinarily, the establishment o f a specific case o f cancer as occupational in origin it impmiihlr nnril a rarrinogenk substance has been identified in the work en vironment. Mnrrnvrr, rht occupational cancer has no specific identifying charac teristic!!. 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 ha;, been exposed to a carcinogen, readily are recorded as Occupadonal because of the low incidence of diese cancel in ilic general popula tion. In view of the inherent difficulties in establishing a diagnosis of an occupa tional cancer and the paucity of materials established as carcinogenic to men, it is not iistonishing that the total iccoidcd cases of occupational cancers is small. In 1954. Huepcr collected all such cases. He has recorded 730 cases of occupa tional cancer in the United States. About halif of these arc bladder cancels from AjfVhut tw tiivttivii*. Mt. r titl t.t mmI aiVA.tAN*fl I1rt stein cancers, chromates for 73 lung cancers and a few heavier petroleum oils for 70 skin caicers. H istoiy Although in 1531 Paracelsus noted the prevalence of a deadly lung disease Iw i t M itlttirlp tit* 1 ^ mi i^tii M tl * # Ci* Ptrcivtl Pott, in 1773, identified and described the first recorded occupational cancer. His description cf scrotal cancer from soot among chimney sweeps em phasized both Severe prolonged exposure and llie latent period. Eckardt (1959) has assembled the historical dara on a world-wide basis in an interesting table including dates, reported ugent, site and number of cases reported (Table 13.1). 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. We have not accepted arsenic, saltpeter, and asbestos U g4s.vsbljr ^auvwxi Cki'C tn^cni Ar4 I w liw eKnt *liy pmKnkty only os CO carcinogens. Sluxplicidcis in the Balkan* and outdocr workers in Kashmir, who during the winter catty beneath llicii clothing, next to the sktn, pots of coals to keep PlPR-17-1992 10:30 FROM TO 13014521039 P.04 34 T H E O C C U P A T IU N A I. fJlftEA & ES T a lk ii-1 H istorical O ut* 0 Occupitiivmd Cstmtr* PROBABLE' TOTAL FIRST REPORTED YEAR reported BY AGENT OR PROCESS SITE NUMBER OF CASES REPORTEDto date 1775 Pott 1822 Paris Soot Arsenic Scrotum 190 stun 1875 Volkmann Crude Wax from Coal Skin 254 1876 Voikmann Coal Tar 1876 Bell Shale Oil 1879 Harting 8c Hesse Ionizing Radiation 1894 Unna Ultraviolet Radiation Skin Skin Lung Skin >3000 >200 >300 Unknown 1895 Rebn 1898 Mackenzie 1906 Fricbcn Aromatic Amines Creosote X-rays Bladder Skin Skin >1200 20 >125 1910 Wilson Shale Oil and Skin 2C00 Mineral Oil Lubricants ' P 11991117 PLfeeyiml ann CChrurdome AatnethPrraocdeunceing LSkuinng 12400 (coal tar?) V 1926 Prunes Saltpeter Skin 17 1929 Martland Radium Rnnr 9 1932 Grenfell Nickel Refining Lung 6c .35 .!" Sinuses 1935 Lynch AcSmith Axbet.tor Production Lung 59 with Asbestosis 1952 Weilctal. Isopropyl Alcohol Sinuses 10 Manufacture Vy permission. From Incuwrial Ctrctnngens. .Modem Stimuliuj.ln tn InJujcml Mctjfcinc. Grunt & Stratton, New York. 19)9. warm. iff chronic bumi. and squamous cell carcinomas have developed in the skin of the abdomen and thighs. Whether the radiant hen and chronic bums atone ate the ciiologic factor, or wlmlm mu',rial*. perhap* tars, from the smolder ing caolt, charcoal, or leave* may he rhe spevihe 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. Experimental Work Despite knowledge of the carcinogenic action of certain agents, the precise natuic uf uccupatiohol cancer remain >* rluciv* that of other cancers. Experi mental work ro determine the carcinogenic ability or potency of a material uti* nnn 17 100a 10 : 31. rnoM TO 1301-4^01030 r . o s (PROBABLE TOTAL tUMDEft OF CASES EFORTEP TO P ATH 190 <25 2>4 >3000 >200 >300 U nknow n >1200 20 >125 2000 140 20 17 9 135 59 10 Industrial Medicine. tL-.vlvpn.vJ ill lilt nd chronic bums Tram rhe smolderi* nut known. In - name given rhe cocarcinogen. jems, the precise r cancers. Expert a material uti- OCCUPATIONAL CANCER liFes animals that as* known ro h 4u . P;bU lo The ^ ^ taacy of a material ordinarily is greater with increased concentration. Certain sol vents and other muteriuls have been shown to hasten the action or increase the potency of carcinogens; chcsc arc called cocaiduugcus. It is not clearly understood just how carcinogens act upon crib to alter their type of growth to a malignant pattern. Attempts have btrn made to explain this c ngc in terms ot cellular metabolism. Moreover, it was hoped that a relationship between chemical structure and carcinogenic activiry could be found. Neither o f these rhenrie,ihn been proved. Gicciiiugced* muy be described as the process of conversion of a norm*) cell to a malignant one and its subsequent growth to a detectable t"/ 11" - However, whether tumors develop from a single M l , fl numOff of relk rbat have undergone malignant trUnform,ri,>n due to a common cause is unknown. Of the thousands of chemicals tested in viiriou qnimnls, hundreds have proved o e carcinogenic. However, only L* of these sic used ill industry CilUSServing as possible occupational carcinogens. The experimental work has emphasised the necessity of repealed exposures and the relatively long latent period. Moreover ex- penmen have rub.cantiuicd the belief ,h*t the tirrue p. i.....iir .fltcitd U Uic'uiw WU Merit;!! J ?MMf fttvlonaed contact with the mrriiw, Materials absorbed into the body may be metabolised and a few metabolites ZZ demu,'slliUcU * ** cafcinon`c- Thus, /J-naphthylamme is metabo lized to 2-ammo-1-naphthol that is eliminated rapidly by the kidneys. After ad- mmisrcring ^naphchylamine. the ratio of 2-amino-l-naphthol found in the urine to that found in the blood serum is about 200; 1. Dogs who readily develop blad " iwmuni rem ^f nttphthylnmt.lv uivicliuiicc 70 pci cent of such material ro 2anmo-l-naphthol. wl,,|e ms who ordi,,.,,ily .1 d*v*lp bl.ddcr w > : f,,,,,, th,s chemical only metabolize 15 per cent o f the material to the carcinogenic metabolite. From this and other work ,h,- m,,,,boU * h*a bei-n established as rhe carcinogenic agen t. I, produces cancer in the urinary uau llOorTgReastt period ot time. TThhehse research finding,sh*hahviehaed#dtedcosnigcenniftircaatnicoenbfeocrauthsee o .he possibility ot the body forming this metabolite from related rhemird* Epidemiology Cancer is more difficult tu establish as occupational in origin than any other occupational disease. Silicosis, for example, docs not occur in the adult popula tion from non-work connected causes. All forms of cancer resulting from the oc cupational environmtnt appear in the general adult population. In addition, as the average age of the working population increases, the incidence of "naturally occirrmg" cancer rises. A second factor which make, recognition of occupational can.crs difficult is the long latent period or interval between exposure and the TO 13014521039 P.06 32.6 THE OCCUPATIONAL DISEASES development o f overt cancer In the intervening period o f years, the worker may have chtnged jobs or the Industrial processes may have been altered changing the completely. The latent period in mule-spinner's cancer o f the scrotum is exceptionally long. A Study o f 300 cases in Great Britain indicated that the in terval between a mule-tpinnor't lint day in a textile factory and the devclojiment o f trrnttl ranrer varied between 16 and 6$ years. O f these patients, 67 per cent were b<tween 55 and 54 years o f age. Because o f low incidence in the general p o p u la tio n , tw o typ e o f c a n c e r-- iC K 'f t l a n d b la d d e r a n d p o s s ib ly t h ir d , n a sa l sinus cancer--should be considered occupational in an industrial employee until proved otherwise. Because o f the difficulties in establishing the diagnosis o f occupation^ can* cct in a single cast, group studies seeking an increased incidence of cancer in the work group constitute a fruitful approach. Unless it is excessive, an increased uumbci o f cancers in a papulation group ordinarily is not self-evident. Pu,,ittak ing statistical Studies o f mottality by occupation usually are required to establish a specific type o f cancer as occupational in origin. Hueper has expressed this well. "The d tmonstration o f an occupaiiiinal m igin o f cancers depends mainly on sta tistical evidence which often shows an excessive incidcnrr n f a certain type or types o f cancer in a restricted group o f worker* . . At present only the most potent and obvious cancers and carcinogens have been discovered while tliose o f low incidence fate caused by carcinugi-nN nf low potency have nor yc-t been m u g niaed." In the epidemiological method o f study, the 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 taii>ui.al studies is obtained chiefly from public health or insurance company records. Such studies may indicate an inci dence o f cancer higher than expected in a population. Physicians may discover that an unusual amount o f cancer prevails among a certain work group. Once this suspicion artv s , immediate study o f the medical records o f that work group it imperative. Here it where good indmrrul medical records are most helpful while poor records, lacking in follow-up or final diagnoses, arc practically useless. For details o f the structure o f epidemiological studies, the reader is referred to Eckardi's monograph, "industrial Carcinogens, or a publication hy rhe CUruncil on Ind'istrial Health o f the American Medical Association entitled "Occupational C m iil u m J .A .M .A ., 66.'2171, l { U i . S lo th |,u h litn ,m n i piW fttfnff e x c e lle n t m a te ria l on h o t' 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 generic. 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 af occupational cancer occurring at a particular she, ihctc should be Jess cancer of other sites and this does not appear co be the case. I APR-17-1992 10:33 FROM TO 13014521039 P.07 SEASES the worker may jd changing the o f the scrotum ted that the in- ie development its, 6? per cent in the general y a third, nasal employee until cupauonal can)f cancer in the e, an increased dent Pilniokred to establish essed this well, mainly on s u rertain type or ftrtljr thr most while those of ter been tecog- r in (he popuprevalence, or d chiefly from dicate an incimay discover group. Once >t wvnk group most helpfiil tically useless, is referred to Ir the Council Occupational llent material ulation. C ttt 1 by intrinsic gents might er, the mate- with an inrould be less OCCUPATIONAL CANCER 527 Od 'up*tion#i Carcincgctu There are three categories of carcinogenic materials to Consider. First, the established occupational carcinogens that fiave been proved beyond doubt as caus ing occupational cancer. Second, materials that ate suspected of causing occupatiurai cancer bur not proved. Third, materials in use in industry that have been estahljchfd at rsrcinopenc for come types of animal it, the laboratory but Which hav: not been implicated as producing occupational cancer in man. Agents id l ing into the first two categories ate presented in Tables 15.2 and 15.5. Table 15.2 presents the generally accepted and established carcinogens and the sites character istically affected. a b U 1 5 .2 . Estab lish ed O ccu p a tio n a l Cancer Pro d u c in g A g e n ts , w ith Sites* ...... ........... AGENT TISSUE 4-Arrinodiphenyl (xenylaminc) Anthracene, crude Asphalt Bemidinc and derivatives Chic mates Creosote Diaddcr Skin Skin Bladder, nrr*rer, IriHrw-y Hespiratory system Skin Lip Ionising radiation (all types) Skin Lungs Blood forming organs Bone isoprspyl oil Mineral oil, crude Napk rhylamine-beta Nickel and nickel carbonyi Paraflin, crude Pitch Shale oil Soot ' Spindle oils, aromatic Tar, coal Ultraviolet rays Eye Larynx and sinuses Skin Bladder, uictct, kidney Respiratory tract Skin Skin Skin Skin Skin Up Skin Skin Eye Wax. crude from coal Skin * Modified from Occupational Can, a Challenge to the Physician, New York Start Occuparional Cancer Committee. . APR-17-1992 10=33 FROM TO 13014521039 P.08 THE OCCUPATIONAL DISEASES TabU l}.). Smpwttd Oceupumnat Cancer Producing Agents, with Sites* AGENT TISSUE Aromatic organic chemicals Arsenic Liver Skin ~ Liver Asbestos benzol Beryllium Carbon black Chlorinated hydrocarbons Estrogens Isopropyl oil Mineral oil, crude Naphthylaminc-abha Pitch Respiratory system Lung Bicod forming organs Lung Skin Liver Breast (male) Lung Respiratory system Lip Rladder, ureter, kidnev Up Radiant heat Sodium nitrate, crude Tar, coal Bladder Skin Skin Respiratory system Bladder tp orMAna * Modified from Ckcupitional Cancer, * Challenge to rite Physician. New York State Occupauaml Canrer Committee. Tabic 153 presents those materials that have been suspected o f producing occun atio n al cancer b u r are in d isp u te ... l n - n n r iwvn p>v%ve.J u .pveitie r< n tu ^ u i. Several points should be noted concerning Tables 15 .1 and 15,3. |n Table 15.2, the potency of the established carcinogens is nor indicated. Particularly-amune the oils is this impc runt. For example, shaic oil is a much more potent curcmogm than crude mineral ail. Also, despite the high incidence of mule-spinner's cancer o f the scrotum in the trxcile industry in Great Diituin, none has txYurrcd in the United .W d;AV-*n.-. in .k . r .1. ..11 1,1 ue t me Dcst ex planation. In the United S u m , particularly since the stud es ofbraun and Truan, * there is considerable conviction that asbestosis docs not predispose to the develop ment o f lung canetr. Until further evidence is forthcoming, we have arbitrarily p aced asbestos in (he unproved or doubtful giuup and arsenic in the suspected group. Finally, some substances appear on both list*. This comes about because a substance may be a proved carcinogen for one site, skin fur example, but nor hr established as a cardnngrn for another site, such as the Jung. Analine ilir> not appear on either list since it now has brm established that it is non-carcinogenic despite rep arc Probab apoThe U terials test. P.H.S. Pub referred to C h iefS ite A s in d tissue it rea words, it is that, o f the tory tract--: tract, panic carcinogen TH* Asneth leukemia w. the skin, wii cancer lesior cancer of oc cases occurii ac treated b ait picdomii isties from n tions of the 1 results from vapors direct Pigroen cinogenic oil are^< iif skin assoc re con Iskin < lie m: . APR-17-1992 10:34 FROM TO 13014521039 ES } Silts9 ______ Saw Occupi- ucingoccucarcinogcn. J. in Tabic .vijr ausMMsg uuiiuugdi :*s cancer o f th e U n ite d he best exand Truan, he develop : arbitrarily e suspected it because a but not be te does not uii-iijvgctih. OCCUPATIONAL CANCER 329 despite reports to the contrary in the older literature. Some cuuies 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 Cu- vironmtnts have not been incriminated as causing occupational cancer in man; 4-ben tpyrenc is one cxi.tnple. It is known to be present in the exhaust vapors o f motor vehicle. yet no increased incidence o f 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 tasted for carcinogenic activity. The second edition appeared in 1951, P.H.S Publication 149. The student desiring to look up any specific material is referred to this voluminous publication. C JjU f i'itu As indicated earlier, rhe site o f action o f on occupational carcinogen is the tissue it reaches in greatest concentration for the longest period o f time. In other words, it is the tissue suffering the greatest exposure. Thus tt '* not asronishing that, o f the four major sites o f occupational cancer, tw o--the skin and respira tory tract--are tissues o f primary contact by carcinogens. The third site, the urinary tract, particularly the urinary bladdci, is ilic body wssut. must t.Apusvd when a carcinogenic material rapidly is removed from the blood by action o f the kidneys. The fourth and last chief site, the hematopoietic system, is the site o f origin o f leukem ia w hich is v-auavd by various form s o f io n isin g radiations and benxol. Skin. Eck&rdt states that over 75 per cenr o f occupational cancers are o f the skin, with coal tar an.' shale oil bring the 1hit-f carcinogens. Fortunately, skin turner lesions ulc tcudily uppurvlU and therefore cures are more easily effected Skin cancer o f occupational prigin is particularly poorly reported. It is believed that cave nernring among formers ant? outdoor workers due to uliiaviulct laciatiori first i r e f t t ! b u s y p r ic t in iv n v m b in bclili.* O ct kL iii t'an cer* A' |kr4limin*nf^ (I K>rtA^ nst hratr lstics frem non-occupational skin cancels. A s might be expected, die exposed por tions of the body--the head, neck, hands and arms--incur mo%r mrh cancers. This icsulis from direct contact with the carcinogenic materials or deposition of such vapors directly upon exposed skin surfaces. Pigmentary changes in the skin have been reported from exposure to car cinogenic oils but are not believed to be a prccanccrous skin response. However, areas o f skin hypertrophy and atrophy occurirg on skin exposed ro carcinogenic oil* are awvian-d with kin cancers kin cancer developing under such condi tion ar- considered occupational. Unexposed portions o f the body also ate sub ject ro '.Win cancer, particularly if the clothing becomes saturated with the car c in o g e n ic m a te ria l. T K u , 1 so a k e d tro u s e ts < n n v# j' ih t a il to th e it r a t u m APR-17-1992 10:35 FROM TO 13014521039 P.10 330 THE OCCUPATIONAL DISEASES provoking mule-spinner's type scrotal cancer. Generally the latcnr period in skin rr cancer is long. 20-40 years or longer, thus years o f exposure ordinarily arc requi a: site for the development o f such cancers. In this connection, regular clearin g o f the skjn certainly must play a part in delaying or preventing the occurrence o f li skin cancer. a Several materials produce skin cancer and there are probably others that have ai not bom identified. The presently accepted skin tauter agents include ulcaviolet la lieht; ioniaine radiations.. alpha, beta and uul iat m, pih. nv-rvenn-, 11 crude anthracene, and crude waxes) shale oils and crude shale paraffin oils, petro* h loutn |>ruJu<n, lwL<<a<iis^ util), 2 p*r*ftVd fwvl ullt, it n , aapltalt, pttkli, sc and carbon black. The chief groups exposed to these agents are; Sc U ltraviolet Lig h t . Farmers, ranchers, construction workers and espe cially outdoor workers are exposed, with greater risk in the south and at high b elevations where the intensity o f light is greater. b. lO N tie iN C ; R a is iA T irtM.. T h at* agnt< *e t radiologists, d e n tittt, v e te ri St narians, chiropractors, x*ray technicians, and .scientists and technicians in various p nuclear energy industries. p. Coal PRODUCTS. Work groups exposed to coal tar. pitch, soot, creosote ft or crude anthracene include workers engaged in handling these materials i v * XI St Giik works Briquette works ti Cnhoikser fouvrennasces CRooaald-tabru-iplidtcinhgpaipnde mreapkaiinrigng ta Tar distilleries D xtirry m u k tttg (3 Patent fuel manufactories Cord making Lens industry during polishing Paint making or Building and allied trades Electrical equipment works, making w RoItialinndglinlij.llt preparation and ccraobclke,s!, acnadrboinnsublrauisiuhues, carbon elec* al: Flooring materials Work ot seamen and fishermen W< Weatherproofing materials (jH M n r r o r r:ir p iv x t- rv jfiiin n f w rw vl Sw-eping roads Working with impermeable paper Making o f felt and cardboard Caulking o f ships It ac Shale Products. Work groups engaged in the production of shale oils and slut c paraffin oils, European niulc-spiiiuci*. iiiacliiiiists and otiiers who worked or continuously with shale oils. Little or no shale oil presently is being produced lil in this uuuuy and it appears rhar llrrlr U hong need in American Industry. ra. P etroleum P r o d u c ts. Those exposed to these agents are workers en th gaged h the primary production and refining o f petroleum products, as well as * Tabic modified trom Goal Tar anc Cutaneous Carcinogenesis in Industry, F. C. (Combes, ini Charles C Thomas, l$04. W / APR-17-1992 10:36 FROM TO 13014921039 P.ll EASES period in skin arily are regul ar cleansing o f occurrence o f 'hers that have ude ultraviolet itch, creosote, fin oils; petroasphalt, pitch, kers and espeh and at high ienrists, vetcrian in various soot, creosote terials in;* i making boneiec- nen of wood c paper i o f shale oils who worked ng produced industry. ' workers en ts, as well as F. C. Combes, OCCUPATIONAL CANCER 551 mul :-spinners, gunsmiths, paraffin pressmen, and a large number o f varied metal and tool industrial workers. Carcinogenic Factors. The precise mode of action o f ultraviolet lighi in the production o f cutaneous cancer is unknown. The same U true of ionizinjt radiation. However, in both nstame**, intensify and duracin o f exposure arc important. Alsu, absorption o f these forms o f energy by the basal proliferating lay o f the skin cells appears to be necessai?. In coal products, carcinogenic propwtiet arc found chiefly in the heavy oils and anthracene oil. Pure anthracene itself S net carcinogenic but 1 , 2-bcnzanthraccne and 3. 4-bcnzpyrene are among several identified carcinogens in coal-tar and coal heavy oils. Coal products are the richest sources o f carcinogenic agents yet discovered. The carcinogens in petroleum products arc closely related carcinogens to the benzanthracene and bcnzp>ir..c found In coal products, the bvneenoid uydtocarbons. Petroleum oils VS.ry greatly in their carcinogenic ability depending upon the source, with shale oils being the more potent. Arranged in wider o f carcinogenic porer cy, depending upon their source arc oils tiuin: Venezuela, Borneo. Rumania, Persti, California, Mexico, Mid-continent, Texas, Pennsylvania and Russia. Re-' fined oils are the least carcinogenic and the sulfonated oils used a detergents are hirmless. Pure mineral oil and vegetable oils are innocuous. In the United Scat, carcinogens are not found in the mineral oil fraction o f lubricating or cut ting oils. The chlorinated hvdriv-nrhon present in lubricating and cutting oils can cause a folliculitis but never produces cancer. Suspected Skin Carcinooens. 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 .,f -..nd working with arsenic alloys. Nursery and agriculture workers using arsenical insecticides also i-c exposed. Arsenical skin cancers arc exceedingly rare, if they exist. Such a diagnosis would depend upon: ** 1 . History o f proloriged exposure 2. Characteristic arsenical skin manifestations. i. Demonstration of arsenic in die skin, hair and urine. It is the firm belief of those who have studied the evidence carefully that arsenic acts essentially as a cocarcinogen but is not in itself carcinogenic. A r excessive rate of skin canec has been reported among the sodium nitrate or salqseter workers in Chile. However, it is believed by many that this h;gh 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 mtist they act only at cocarcinogen. . R '"#Pi w o r y ^*kct Cancers. Soluble gases and particulate matter from inhalec air are deposited in the thin film o f fluid covering the respiratory cract. W ith continuous respiration, these rnaccrials accumulate on the walls o f the re- APR-17-1992 10:37 FROM TO 13014521039 P.12 M2 THE OCCUPATIONAL DISEASES spiratuiy uaci liwui die nose to th< ei-minal alwoli. Should caronngrmc ma terial be present in the air, i: is easy to sec bow the respiratory tract tissues would suffer the greatest exposure bulb in duration and intensity. Ionizing Radiation. The first occupational respiratory tract cancers occurred i.mong miners in ihe now famous Schneeberg and Joacbimsthal mines, hirst arsenic, then cobalt, were blamed iVt the excessive iuv.iUwi... v f Un$ ** but now it is agreed that ionizing radiation from both radioactive dust and gases (radon) were the carcinogenic agents. It is o f interest that these mines provided the ore from which the Curies isolated radium. It is believed that between 40 and 70 per cent o f the miners died o f lung cancer. Neither the daily nor the total dosage o f ionizing radiation received by these miners can be calculated at this time because o f the great change in working conditions and ventilation o f the mmes. Radon gas is short lived but its daughters are radioactive. The amounts o f radio active gai.es and dusts present in these mines over the centuries arc unknown. Mines producing radioactive ores in (hr 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 o f increased incidence o f lung cancer. Nevertheless, a lung term study o f the uranium miners in western United States and die levels o f ionizing radiation in the mine* i* being conducted by the Pub lic Health Service. In the production o f lung cancer from lonhdng tadiadoiis, gieat hazard from inhalation o f radioactive dust ;s possible because of the accumulation, dcpxjsicion, storage and long retention of dust particles in the lung. Chromates. Machlc and Gregorius, by an epidemiological study in 1.948, first established the increased incidence o f lung cancel among work- e ngaged in the mjnufacture o f chromates, The Public Health Service study o f seven chro mate plants iivIicareH rh'ir'.jlvint ">? jx-i trill uf the deaths among chromate viutli- ers were ;au$ed by cancer o f die lung. The muuulin from other types o f omcer was about the expected amount. It is estimated that the number o f lung cancer deaths among the chromate workers was about .SO times that expected in rhr gen eral population. Derailed study o f the work environment in the chromarr plants has not identified a specific form o f chromium a* the agent. Dr. Anna Baetter 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 calcium cluuiiiuic. I'olluwlug analysis o f he environ V n uJiw in he ehreina* pi, he rcinog^ni.- fnrm nf rhmmiiitn rant 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 original ore so the mining of chromium and its handling until the refining process j., started bears nb known risk o f lung cancer. Also, machining and work ing with the finished elemental chromium arc riot attended by a risk o f lung can cer, fur puic metallic chromium is nun-carcinogenic. ! 7 come cino sinus lung has s calcii upon supp in th CarCii smal proc< fined o f ni atoic centt forrr one W it canc and ble < cons poly 4CCO uu-u ploy and sutfc hori with tic t mus only lon{ post lied re pc APR-17-1992 10:38 FROM TO 13014521039 P.13 BASES C(lIU^ClUL 111* : tissues w ould y ua.i cancels imsthai mines, of lung cancer dust and gases .tines provided at between 40 y nor the cotaJ ed ar this time of the mines. junts of radio arc unknown, vc some radon ores also have untry, Uinada >f lung cancer. . United States ;d by the Pub- at hazard tram on, deposition, study in 1948, >rkcrs engaged of seven chrohtomate worktypes uf cancer of lung ranrrr ted in the gen* hronurc plants . Anna fiaetjer ing chromates, aicumas in rats at*the environ iitviuiuiu cauacompound and appear to exist til the refining *** und w ork- >k of lung can- OCCUPATIONAL CANCER m NlCKEL. First from C i m t Britain. and more rev-cmly from Mrn-way, haV<- come reports and convincing studies implicating nickel as a respiratory tract car cinogen. The evideA.ee for its being che igvnt rcapuiiaihh. fo, v<f ihc imsaI sinuses is overwhelming. Also, the eviiirntr utclic ai?v wnh certainty that >r is a lur.g cancer carcinogen. Study ol the woik population in a Mond process planr har 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 In yenrs 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 .lmnngcnic Anr. iv* .uhefe u f lu n ^ i.iWKr bcn reposed from A snuil Norwegian nickel refinery utilizing an electrolytic process, not the Mond precess. and so not producing nickel carbonyl. Thus the risk of cancrr is not con fined to nickel carbonyl but is probably inherent in both solid and gaseous forms of nickel. Prolonged inhalation experiments with animals have pmdurvrl adenom atoid changes in the lungs of rats and guinea pigs but no carcinomas. "IsopitorvL Oil-" In the manufacture of isopropyl eicuhul using son* cen(rated sulfuric acid, small amounts of impurities called "isopropyl oil" are formed. As this process was used originally, four cases of cancer of the sinuses, onv Vanin of iiic iatyiiA ami one tancct of the lung occurred in tnc work group. With a change in process, "isopropyl oil" is not formed sn d no further eases of cancer h*> ovcuitcd. H\piiiiucii`.,ill), "isupiopyl oil*' lias produced skin cancers and there is no doubt that it produces sinus and larynx cancer. Perhaps ic is capa ble of producing lung cancer but chis rctmin.1 to be established. Among the chief constituents of isopropyl oil" are isopropyl sulfates, isopropyl ethers, and some polypropylenes. Precise chemical idcntificatUm ol the cuiLiuogen has not been accomplished. Coal Tar. Lung cancer arising from industrial contact with coal tar has occurred wirh certainty only amorvy cnul gin! wrlc*r< Clt-nt-rrtlly. Artly wArlr^f wn. ployed in the retort house, having extensive prolonged exposure to che vapors and fume, have developed lung cancer. These cases have occurred when workers sufTned diicn exposure to me fume while working over or about the old style horizontal retorts. Operation ot 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 Respiratory Tract Carcinogens. As with sk n, nrscnic mtnr he listed ns > pr,ikl/- carcinogen. However, from th. evidence, this is true only when the individual has been grossly overexposed to inorganic arsenic 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- or no effort to canrrol the Oi'Benieal <lu?c in the work atmosphere. Three cases of lung cancer associated with pulmonary berylliosis have been reported. Also, Vortoald has produced carcinomas in rats following the inhalation . APR-17-1992 10:39 FROM TO 13014921039 P.14 $$4 THE OCCUPATIONAL DISEASES of beryllium. Although beryllium may be a carcinogen, evidence that it is the agciu producing lung cancer in man t* lacking. A a precaution!y mustu-c bciyl iium dust should be carefully removed from the v/ork atmosphere. Urinary Bladder Canc-er. A>previously pointed out, beta-naphthylamine and benzicine produce cancer of the bladder. Al pha-naphthylamine is suspected of this, but it has not been proved. Anisine 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-napliihol and has been indicted as the car. cinogcn. Leas dear is the carcinogenicity o f the metabolite of benzidine, but per 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 protsably produced in much smaller quantity. One other compounc, xenvlamlnc, or `i-ammodipncuyi, has proved v 1*.- po, in producing bladder cancer. Studies of its metabolite excreted in the urine indi cates the presence of 4-aminodiphenyl and 4-amino.3-diphenyl hydrogen sulphate, which later increases in quantity and hydrolyze* to 3-hydroxy*4.aminoHiphrnyl. Thus the orthohydroxy amine conjugates have been isolated in high concentra* tions as urinary metabolites from bladder cancel agents beta-naphthylamine and 4-am inodi phenyl. A much weaker bladder cancer agent, the orthohydroxy me tabolite of benzidine, is present in the urine in a lower concentration. W o rk G roups Exposed. in places where the primary aromatic amines bera-naphihyiaminc, benzidine, xenylam inc, and perhaps alpha-naphthylam inc arc used, w in k e d iu n Uve r k o f developing Isleddor tum or T h e m en arrually en gaged in handling these m aterial are m o st e v p m rd w h en scraping o r cleaning fillers, or nrhen m aterials being w orked produce rlu<rt. n r vapors. In modem plants with built-in protection, perhaps the niaintcnance men constitute the most ex posed group. Wor cers employed in the manufacture of basic dyes, the manufacture of some rubber arti-oxidanrs where alpha-nsiphnhyiamir.c or xenylaminc are used in the process, a id wliac beiuidinz 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 alpna-nupluli) lam ine and LuuUiinc a 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 revention. Good engineering control of dusts and vapors, the use of closed sy items, and observance of meticulous personal hygiene arc required.. Es tim ations o f th jm n n n r nl" f r ir in hie in the urine have been reported as useful in checking the adequacy of protective measures. T h e H em atopoietic System. Ionizing radiations, particularly gamma or x-rays and benzol, are th e agents m ost incrim inated in th e production of occupa tional leukem ias. W l i q l i u these ag e n t) are tru e carcinogens o r merely se t rrv. carcinogens is unknown. I ic rite/ to ga clinic 1$ use terial' not b tbc o not b *i there ducec Coba place forgi arc indui thori with been discu tern tion kocy into) refer m art apbu and obse or sl that of lc sure vdo $Uh and j ". *' ' ] ' , J ' ! ! - 1- 1 V'1 ; HPR-17-1992 10:40 FROM * TO 13014521039 3 it it is the sure beryl* ithylamine suspected ce bladder ne is mcis the carbut per* ncertainty t, and th e O ne other r agent in irinC in d i sulphate, diphenyl. :oncentraimine and lroxy me* :ie amines amine are lually cn` cleaning cm plants most ex* c of some ed in the o bladder tleers and ridinc arc ts in coal itely pro- hc use o f aired. Es* i t uM rful amnia or ( occupa* act as co- OCCUPATIONAL CANCER - 3^3 Ionizing Radiation. The action of various forms of ionizing radiation is discussed inChaprcr 20. It is sufficient to state here that occupational exposure to gamma and x-rays occurs in the nuclear energy industry, hospitals, meiiical climes, physicians' offices, research laboratories, and in some industries where ,:*ray is used to detect flaws in metal casting, or to examine a variety of other nu* tcrials. A,1 workers with these agent, should observe'adequate precautions and not be ca reless or indifferent concerning personal exposure. In many industries, the equipment is installed in such a manner that when in operation a worker can* not be ex posed. The incidence of leukemia among radiologists has been reported as high and there is experimental evidence to aupporc such reports. Leukemia has been ?ro- eexxpo^surrelsTov*er^a Kshu"orytSe'rWplertf`toTd.4" Kpcaicd doiC` morc effective than larger r . T^! """P" "'* gimm lira in iiKtarv (Mmculul, Cnbal." , tadium - C cdum -. T , , ,, W - , h,, b ,, P , gamma radiography is replacing x*rays as a means of examining castings orgings, Itc, and no doubt will find increased uses in industry. Such materials are well guarded and shielded and so far no cases of leukemia associated with the ndustnal jscs of radioactive isotopes have been reported. Although radium and thonum have com,doable use in Induatry, a m of leukemia in those working the, substances have nor been reported, /is yet, these materials have not Been mdioed as the causative agents of occupational leukemia. Bcnbol (t,eMi:Bwe), Tiic many industrial uses of benzol as a solvent are tionoftChZ ' nV iscussed in Chapter 1 1 . There its depressant effects upon the hematopoietic sys* ' ` !S pr1 dU ttion o f The gradual n,form a* tion of the bone marrow from aplasia to hyperplasia has been reported. Also, leu* kocytosis t as been reported as a transitory finding in the ,,riy ,,a g o f ben*,i ntoxuattoii. 'n.c varied peripheral blood finding in benzene workers have been to is leukemoid condition." This reaction i, only one o f many bone marrow reactions to benzol, intoxication. Among such reactions are complete aplasia aplasia with leukemoid reaction, acute leukosis without pwriphcial leukocytosis and finally acute leukemia. AH forms o f an,re and chronh- leukemia observed a n o n g workers suffering from benzol ir toxication. However, the acute or subacute myeloid types o f cukemu appeal to daminatc. Vigliani has suggested that perhaps many cases of aplastic anonii actually were aleukemic leukemias. of ion !u idJn ChaP^ r " * n0t inCiinCcl t0 givc credcncc to *hc reports g t * ayCf .f*5" of h.60*01 intOxication developing even years after the expo sure ro ben ml S ee*>cd. However, it seem, possible that leukemia might cle- v<* at *,m* "*Mr * prolonged xpiMiui. to benzol had erased. SUMMARY Thousands of chemicals have been examined as ro their carcinogenic powers and this mlormation ts contained in the previously mentioned Public HcaliJi . HPR-l?-ly92 10:41 FROM TO 13014521039 F'.lb JJ6 T H E O C C U P A T I O N A L 1 K a K Service publication. Numerous materials established as, or suspected o f 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 o f strict controls, chiefly engineering, through, dosed systems, ventilation, personal protec tive devices, and others, which serve to prevent exposure. As more workers in the o ld age groups continue to work ir. industry, more cuses o f so-culled "naturally'' occurring cancel will be found among these older employees. At (his time it is believed that we have established as carcinogens only the more potent of rtese agents. Moreover, it is known that marked variation exists between individuals as to cancer susceptibility. Theoretically, the weaker carcino gens should be able ru produce cancer only in the more susceptible individuals. Awareness o f all. these facts makes it dear that detecting the weak carcinogens is next to impossible solely upon a cl.nical basis. Studies to establish a weak car cinogen o f necessity must be o f the epidemiological-statistical type embracing large groups of people who have been exposed for long periods o f time. Although these studies arc arduous, they are needed ro clarity the status o f doubtful or dis puted cancer-causing agents, and to uncover presently unknown environmental carcinogens. W e should recugnizc the woefully weak and inadequate status o f our present knowledge o f cancer etiology and the means by which carcinogens produce can cer. It appears certain that some or inanv materials we now accept as carcinogens are in reality only eocarcinogens. However, this makes lirtlr difference. If, as a result o f irs presence in the work environment, workers develop cancer, such a material must be entirely eliminated from the work environment. If it is con tinued in use, it must be so completely controlled that no wurkci may be expected to develop cancer. The possibility o f a nort-carcinogenic material being metabolized in the body and a carcinogenic metabolite being produced always must be recognized. Alsu, the long latent period i* characteristic o f weak carcinogens. Particularly in cancer o f the internal organs are these faciois uf impuiiancc. Every physician should be alert to the possibility o f occupational cancer arising from 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 o f 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, thus making complete medical ictuids available for all employees. Such rec o rd s ore in d isp e n sa b le w h e n w o rk g ro u p s a re u n d e r stu d y for a n o c c u p a tio n a l d is ease. particularly cancer. BIBLIOGRAPHY 1 . Ddcijct. A- M-. Pulrmcru/r GimnoTM In Chrofiww Workers. I. A Rc'fe* of the Utcniure and Report vfCtic*. AJMA Aceh. IndtiM. H , 2. Battjrr, A. M Pulmonary laKAtMiu in Chromitr Worker*, li. Incidence on Basil of Hoipiul Rec4/ i AM, A. Alula. l..Je.t. 11..-SOS, lOSO. 1 v> , APR-17-1932 10:42 FROM TO 13014521039 P. 17 . DISEASES xctcd o f being, car* trig h o w liln n i W f institution of stria on, personal protecnore workers in the x u le d "naturally" Only |K& ked variation exists the weaker carcinoeptible individuals, weak carcinogens is >tabli$h a weak car* cal type embracing s o f time. Although : o f doubtiul or dis own environmental tatus o f our present togens produce can* cccpt as carcinogen : difference. If, as a -elop cancer, such a nment. If it is con* net nitty b v m i n i m i tbolizcd in the body * 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* -mployees. Such rccan occupational dis- jrv Cifiinomu in Chromate an Buis of Hospital Rec use. H . 2.503, 1930. OCCUPATIONAL CANCER 337 h. Bdstrup, P. L.: Occupational Causes uf Lung Can cer. Tnr.suc.tifl,. <f the Ann. >tt tn>ju..jl Mi-.li.i] O ft<en. 9.2.1959 4. Bidstrup. P. L.. ard Cise, R. A M Cattinorraol the Lung m Workmen in the Sichiomates-PttxJut- ing Industry m Gic-at Britain Brit J Indus'. Mid. 7J-26Q,1956. 5. Bottser, G. M , F.iulds, J. C . and Stewart, M. J Occupational Carter of the Urinary BladJn in Cryciiun ,perjure ami or t.n. Lung ,,, Ab)i,,> Textile Worker and Iron-Ore Miners. Am. J. ClJirt Path., *'5.126, rot;.. 6 . Braun, D. C .and Truan, T. D : Ar Epidcmiologi- cal Stud of Lung Cancer in Asbesto Mirer A.M.A. Arch. Indutr, H . r . t H IV5H 1 C'aiuvri.frhr I ,m,;- A-. Kvahiatjon | ihv Problrm. Proceeding ol the Scientific Sttaitm Annual Mrrt- in*t NavmnWw I 4 IOU Amfiemrm.<hrW iitc Inc.. 1 W . ennier,.,^ DrvrKtV/^cntV ..*/ ciAOnta from Radioactive Barium Sulfate. A.M.A, Arch. InduM. H 19 m 9. Combes. P. C : Cc-al Tar and Cutaneous Carcinogene m Industry. Charle C Thom, PubliiJlcr. Springfield. Illinois, 1954. 10 . Council on Industrial Health. A M A ; Occupa tional Cancer. Method of Epidcmiiiltigital Study. J.A M A . /66.-2P, I5S. H Ciimdfv, E. V.; Epidermal Catuitogvncsis. In Ad vance ill Cancer Research. V..I I Edited by GItr*c..etr4ntetveiin.l IPk,,, aid.HadJo. A. A.jdettilc Pnn. I. Cramer. W.- The Importance o| Sta:itieal Ime.ti- Xation in the Camparn again! Caiuir Am .1 Cancer,-va. t. t9 J? ` 1 Fin her, H G. M,, Priestley. W .,Jr., Eby, t. T . Wnlr, fi r. . ,n.l 0 , 1.,.?.. J., J,.. P.i>|run ui High.boiJing Petroleum Products. A.M.A. Arch. Indust. H , 1. 515, 1951. 22. Hendricks. N V . Berry. C M., Lione, J. G.. and Thotpe.J J Cancer oi the S;rotum in Wax Press- ->.ient. A.M.A. Arth Indutt. H , /9.`3?4, 1959. 2 ). Huepet, W. C.; Expetimenta Carcinogenic Studio on Hydrogenated Coal Oil*. I. Berguiui Oil. In dust. Med. hurg., 23:31, 19 5 (,. 24. James, W. II. L.; Primary Lung Cancer in South wales t-nai Workers with Pneumoconiosis. Brit J. Indutt. Mad.. 12.S7. 19 J. 25. Kaplan, I : Relatiomhip of Noxious Gases to Car cinoma of tin: Lung in Railroad Workets.J.A M.A., r i : 2o>9 , ro:>9. 2**. Kotin, P., Falk, H. L-, and MuCtmiTHfl, C J.; Can ''** **...... *w*') of wain uuca **< to Aif Pollution m J rhgcnc>ti. CA thillo tin, Manh'Apr.. 1958. page d-L 27. Uone. J G.. and Denholm, J. Cancer of the Saotutn in Wax Pressmen. II. UintcaJ Observaflon A M A Arch Indi.t, | | , fO-StO, 1059. 2 . Msettle, W.. and Gregorius, F.: Cancer of the Re spiratory System in the L'.S. Chromate-producing Industry. Pub. Hcslth Rcp,, iJ.1114,19 4 8 . 29, Mancuso, T. F.: Occupational Cancer and Other Health Haratds in a Chromite Plant; A Medical Appraisal. (I. Clinical and Toxicologic Aspects. Indust. Med. Surg.. 20 )9), 1951. W MiMHimtrrm P birring ol Vy.vviM..e. Cell Carcinoma. Pan I: Incicence in a Plant with a Report of Six Cases. Brit. J. Indust. Med. !} 240. 1955 'S Chill. R.: Muralo, iron. Lung Can.,-, in M. Nau, C. A.. Neal. J,, snd Stetnbridge, V.: A Stud Worker. Brit. J. |rdut. Med.. IJ.KI. |y3 5 . 11. Doll. R.i Cancer .i ll Lung and Non m Niehel Workers. Brit. J. Irduo Med. M .iP . i m O. Doll, R.; Occupational Lung C utter A Reviett. Pm .J. Indut. Met., ici. ini, tviv. to. EekarUi. h . .; cateinogenieity ot Petroleum Pnd- o f the Physiological Effects of Carbon Black. L l.inj..u... A.M.A. A.I, M ax> h .. i l . t i . i n 32. Pelltr, S.. and Pick. P.: Leuk :mii and Other Ma> lignincies in Phyticuna. An-. J, M. Sc., ia. l l 4, ip ` ff Rxvvn. a. W., Al.. C*nm ftancnMri). A Cti., ucts with Partcula* Rtlerethe to the Automotive Ltd., London, Volume 1 , 1917, Volume 3 , I9 i a Industry, induct. Mad Surg., Jo-yyti. 195". 34. Sampcy, J. R. Inorganic Carcinogenic Agents. I . Eckardt, R. E.: Industrial Carcinogens. Mtidcni Indust. Med. Surg., 22.163. I'}. Sluntfnphi in In.ltir-triil Mcsli.ins. (Irene . rtitl* ton. N'w York. ww. 33. Seltscr, R,, slid Sarrwell, P. E.: The Applicarinn of Cobalt Analysis to the St sdy of Ionising Ra Id- Editorial; Silicosis, Ashcstosit, and Cancer of the diation and Longevity in Physicians. Am. J. Pub. Lung. Ant. J. Clut. Path., .'l l tta, l5 5 . Health, 49.-1610,19 3 9 . 19. Ewing, J.: Neoplastic l'ii*xe. Fourth Ed.. W. IS. 36 Smith, W. E., Sunderland, D. A., and Sugiura, Saunders Company, Philadelphia. 1941. K.. Cxpatiiixnital Analyto uf the Carcinogenic iu. Federal Security Agimcy, P.H.S.: Health of Work, Activity of Ccttain Petroleum Products. A.M.A. ers in Chromate Picdicing Industry: a Study. Fed Arch, indust. H.. 4.'299. 1 9 3 1 . eral Security Agency, Division of Occupational 37 Unsolved Cluneal Problems; in biological perspec- Health of the Bureau of State Service, P.H.S.P. No. 192. 1951. t tive. Votunie 11 o f Mediegl F^seercht A Midccnturv Survey l ittle. Brown arJ Co., Boston. 19 3 3 . it..-*.- TO 13014521039 P .1 8 338 T H E O C C U PA T IO N A L DISEASES in. V ilijui. E. C . und Siitu. O Li-tkvmiAs: Irum ttenecne, Med d lavuM, j!Ml, li8. J;*- Von H aam, E , and M alm e, f. *>; studies on the Totitit,- i t i Skin I'.tifcis ol Compound* IV d ,r fhc RuShe; and Plistie Industrie 111 Csrcinogenicii) of Cirbon Black Excracu A M.A Arch. indem. H , aril-'. 1912. 40 Vorwjld. A J : Adcnocsrcimpna in the Lung of Albino Rats Exporfd to Compounds of Beryllium. Proceedings of th : Scientific Session, Am. Cancer Annuftl Mfitmg, Nov, M , t?51.