Document b5RbgQZ1kV19x5XRnb0wBdaDg

August 18, 1044 1084 for which were recorded relatively high frequencies of sickness or re spiratory diseases. The mean proportion of short absences for all sickness varied in the 4 quarters from 52 percent in the first quarter to 02 percent in the third, with 58 wfr&sint and GO percent representing the second and fourth qunrtewC respectively. The corresponding upper and lower limits for tli/rcspiramry diseases were 51 and 64 percent, with 58 and 01 peroent for the st'coml and fourth quarters, respectively. Thus the elimination of the nonrespirntory diseases teffected relatively little clyfnge in the pit<oportions for all sickness, However, the range o the proportiuus corresponding to the 40 quarter-years increased from 45-08 pernt nt to 41-74 percent when the nonrespirntory discnsesXvere eliminated, .he frequency range changing from 400-1,700 to 100^-1,300. Thus, w die the range of the proportions widened, the frequency range remafined almost the same but was translated necessarily to n. lower lcvd, the downward movement covering approximn/tely 300 frequency units. The inverse asscadation of frequency and proportion of short-term absences is of pameular interest from tl e standpoint of seasonal varia tion. The efl eet/of the winter month.1 on absence frequency is Veil known; it now i/ppears that the perioi ic increase in frequency is not evenly distribut'd among the disabilit.es of different durations but is less in cvidencyamong the short-term absences. Likewise, the general decrease in frequency during the sumn cr months is accompanied by a relatively simpler decrease in the frequency of the short-term absences. sum maiJy . The present inquiry, the fifth of a si ries on the duration of disabling sickness, js concerned with the fro piracy of short-term absences lasting less than 4 days and its relat on to the total frequency. Based /on the 10-year disability experience of a public utility company, it is shown that high total frequencies regularly occurring in the first quarter of each year are associated with relatively small proportions of short-term absences, the proportion tending to become smaller in epidemic periods; on the other hand, the low total frequen cies g/nerally appearing in the third quarter of each year are associated with relatively large proportions of sich absences. A further investi gation of this relationship by means ol scatter diagrams for all sickness and/the respiratory group of diseases! revealed, in general, an inverse assm/ation between the magnitude f the total frequency, and the proportion of short-term absences. Two cubic equations describing the trend of the relationship are presented for all sickness and the respiratory group of diseases. \ TuLi'c d-24lth 1085 ----------__ I August 18, 1014 REFFUKXCES / (/) Oafiifer, tV. M., and Frasier. R,: Studies on I hu/e ration of disabling sickness. I. Duration of disability from Kickncs/iiii<l nonindiistrial in juries among the male and female memborsliiiis oj/25 industrial sick benefit organizations!, 1035-37, inclusive. Pub. 1 Icaltl/liep., 55: 1892-1903 (Oet. 18,10-10) (Reprint No. 2201.) / (#) Oafafer, W. M., and Frasier, K. S.: Studies on the duration of disabling sickness. II. Duration of disability from sickness and nonindustrial in juries among male workers, disabilii ic.yfasi ing one calendar duv or longer. Pub. Health Rep., 67: 137S-13S4 (iWt. II, 1912), (Reprint No, 2101.) (5) Oafafer, tV. M., Ritgreaves. R.. and Frasier, R, R.: Rtmlie.s oil (lie duration of disabling sickness. Ill, Dura/fon of disability from sickness and mu/ industrial injuries among the ufnlu cin]ilovee.s of an oil refining comjvmv with partieulnr reference to/he older worker, 1033-39, inclusive. /Puli Health Rep., 57: 112-425 Dftn. 23. 1912). (Reprint No. 2350.) / (4) Oafafer, tV. M., and Sitgroovus, R.: Rlmlies on the duration of/disabling sickness. IV. Duration/iif disability from the iionrc.spiratoi'yymndigestivn diseases among maleyPmplovres with pariieulnr refercnco/o the older worker. Pub. llealtft Rep., 58: 909-979 (June 25, 1913)/ (Reprint No. 2-187.) 7 '/ (6) Oafafer, tV, M,: Jniscntceisiu, Olinpler 24 in Mannar of Tmlitslrial Hy giene and Medical Service in War Industries. t7 13. Saunders Co., Philadelphia,7)43. / (6) Oafafer, tv. M.: Frequency and duration of distmilities causing absence from worloamong the emplovccs of a public ulimv, 1938--12. Pul). Health Itep., 58 71554-1500 (Oet. 15, 1913). (Repihft No. 2520.) PATHOLOGIC CHANGES IN ANIMALS EXPOSED TO A COMMERCIAL CHLORINATED DIPIIENYL ' By J. tV. Millkr, Surgeon (R), United States Public Health Service The demands of industry as a result of the war have greatly increased the use of chlorinated naphthalenes and chlorinated diphenyls. In " the past few years the hazards associated with their application have attracted much interest and a number of reports regarding the systemic and dermatologic effects of exposure, including fatal cases, have been made. Only the pathologic changes in animals exposed to a commercial chlorinated diphenyl arc given here.. The chlorinated diphenyl used was viseous, almost water white, and clear at room temperature. It consisted of a mixture of isomers of diphenyl chlorinated in different positions and extent, with an ap ' proximate chlorine content of 42 percent nnd an approximate empirical formula of Ct2lI7013. It was insoluble in water but soluble in mineral and vegetable oils, other chlorinated hydrocarbons, nnd fat solvents. Its specific gravity was 1.374 to 1.393. Guinea pigs, rats, and rabbits were exposed to the above compound by subcutaneous injections, feeding, nnd applications to the skin and cornea. The survival times given here refer only (o animals subjected to pathologic examination in each exposed group. Certain additional* * From the Industrial Hygiene Hesearch Laboratory, National Institute of n,ealth. This material Is _ based on experiments conducted by Burgeon Benjamin F, Jones ami Physiologist J). D. 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A|3ujsuo.iou; oumooq onssj) siio.kjjj jo s.ioAuj .iopio oq^ jioijjii.ioo su.vv ju;jo)uhi oi)o.ioou oq) 01 luooujpu uoj).iod oq) jmu `jjuav isAo oqj jiotuj p piuu dojo.voj) o) pomnpioo uuujoqpdo oqj `juioij.iodns su.vv uojsoj oqi uoq \\ Aup qpj3io-A|Jjqi oqi 0) qpj3jo oq) iuo.ij jiosso.iSo.id uojuqnstluoirq sjuiuj3 oqi ujijp.vv uoipunos jo uoipquuinoou tu 3iupuso.i spup oq) JO Uoisiqooo juojuuqootu o) oup oq ip )i]3noq| o.m .io))Uj oqi q.oiioqi `(a '*/ `g) ouou.iojqo jo osoqi Apnipiosso .mu soduuqo osoijj^ uoiiuzuupuoq Ajjuo jo oouu.moddu oqi 3ni 1 uoso.td siuj) '[oj.mu po.'joiq puu `jjouoipip `jjqdAxo A[3uo.iis ojoav sj.iqoj) ojio.ioou oqi o) pioouf|)U spoo jo s.ioAuj oqj^ sjuuojijdo oq) iuo.ij u.vvoj) 3ui|)uo)xo luiujoqpdo snouiuiibs poijjiu.iis a'ij poiuj Apuji.uid suav ojustluo oqi jo uojjjod .lomu oqi `uui.ioj) oqj jo uoiptod [Ujoij.iodus oqi tu jiooujd uooq jiuq jinjopiui .poioofm oqi `.lOAOvvoq `jt ojosmn pu 11 pq pioouf|)U.oqi opr; nojuioixo qoujAV sisujqojcpj jmu onssi) oAiioomioo jo ojnsduo poiujoj) jjo.vv Aj.uuj u jmu `spioiuSu.ij auojonu jo ouoz u Aq jiopimo.uus pij.iopiui jiiout.iipj puu .tujnun.iS Aj.hiij jo uoji.iod ju.ipioo u su.vv o.ioqj, -ojijiidmusoo ouioooq puq juj.iopjui 01)0.10011 oqi sAup y ip A.ioqdj.iod oqi ui j>o|ou suav souupiduo siKMomuu Aq jiojtiudiuooou s|su|qo.iq;j jo ouoz jioujjoj) -AjjoocI ti sAup p uj 'onssj) siiooim|noqns jmu ojosuut niooufpu oqi opu pojiuojxo qojq.vv s)sujqojqij avoj u `Ajjuujoixo `jhiu `sojAooqdiuAj `soiAooouoj `so|Aoouoiu joouo uoqi `iu.kjij jo'ouov! u js.ip `o.io.vv A.ioqdj.iod oq) UQ 'Ajondj.iod oq) ju iuoso.id suav jinjopiui .luojomi oqj jo qonj\j soiAooqduiAj jmu `s.niojouuoqd.ioiuAjod Amiui 'sj.iqoji juojonu q.miti 3iijii;u)uoo ssuiu oj)0.ioou ojjjqdosuq Ajiujuj `jiupioo u jo po|sjsuoo uojjoofuj siioouupioqns jo ops oqi pi uojsoj tups oip sAiqi z uj--`ui'lh,' '(&) AT uujmg jhiu iiijAxopiiiioij ijpov suopoos ii.izo.ij jmu `(/) oiqq ouojAqioui ouiojqoAjod-ujsoo 'insoo jmu ujjAxopiuioq qp.vv jioiuuis o.ioav puu `itjjjs puu `).moq 'suo.iouud `s|Uiio.ij)u `sAoiqijq `uoojds `s3mq `joAjj oqi jo opuui o.ioav suopoog uojioofuj ,io)ju sAuj) 88 dit sjua.io)u; Auji-j; pi jiomtuuxo pmi popjq o.ioav sjuuuuu osoiji jo ouiog [Auoijdip poiuuj.iojqo oqi jo ( ^iii GO) 90 0 jo osop oj3uis u qp.vv Ajsiioouupioqns jioioofiij su.vv s3[d uoinn3 xg jo sojjos y sow vaxini) (v) SNOi.i.jarNi sno.'ixv.i.n.oiius u upip oj3ojoi[iud tuuiqo 01 Ajojos j)osodxo sjuiujuu jo sduo.in uiojj o.iu (topotloj spuso.i nony U6I'8Usn3nY WATER PCB-00054565 some eosinophilic inclusions. rl'l)e amount of involvement of the si'cin appeared to have no relationship with the dose or length of ex posure. The reaction was not that of an acute inflammation. ' (II) RATS Sixteen rats received 25 daily applications of about 1/40 of a cc. (34.5 mg.) of the undiluted chlorinated diphenyl and were killed at 10-day intervals beginning at 30 and ending at 90 days after initial treatment. Very little fat was found in the liver of 6 of the animals. Three rats showed the hyaline bodies in the liver cells at the GO- and 90-day intervals. Slight to moderate degree of congestion of the cavernous veins of the spleen was noted. Pulp myelosis was present in a moderate degree. In 7 of the 10 animals, a slight to moderate amount of intracellular hemosiderin was noted. No significant changes were found in the kidneys, heart, pancreas, and lungs. In some of the rats the treated skin was much thickened, and the hair follicles were swollen and poorly defined. (C) RABBITS Eleven rabbits received cutaneous applications, at 2-day intervals, of about SO mg. for the first 7 and 172 mg. for the last 8 applications of the undiluted chlorinated diphenyl. The animals were examined as death occurred between 17 and 9S days. The number of applica tions varied from 9 to 15. Seven of the rabbits received the latter number. Fnlty degeneration and central atrophy of the liver cells were more prominent than in the previous series of experiments. The spleen showed less pathology and in two of the animals (90 and 98 days) was normal. The changes noted were slight to marked con gestion of the cavernous veins and slight to moderate follicular lym phoid hyperplasia. Focal caseous necrosis occurred in four instances, but was probably due to intercurrent infections. Changes in the heart, lungs, adrenals, and kidneys were slight and consisted primarily in congestion. The skin showed thinning of the prickle cell layer and relative thickening of the outer eornified layers. III. FEUDING EXPERIMENTS (A) GUINEA niiB A series of 8 guinea pigs received 2 doses of 0.05 cc. (G9 mg.) of the chlorinated diphenyl 1 week apart. Death occurred in 11 to 29 days after initial feeding. Public Health Reports, Vo). 59, No. 35. August 18. 1944 Plate I 1091 August 18, 1914 The changes in the liver were more marked in this scries than in the others. Fatty metamorphosis was extensive in all of the animals and was of mixed fine, medium, and large droplet variety. Central atrophy was noted in only 2 animals dying 18 and 29 days after the initial feeding. The changes in the other organs were of the same negligible char acter and degree as observed in the other experiments. The gastroin testinal tract showed no abnormal histology. No changes were noted in the central nervous system. ' (B) BATS ' Twelve rats receiving 25 daily doses of 0.1 cc. (138 mg.) were killed and examined at 10-day intervals, beginning at 30 and ending at 90 days after initial feeding. The pathologic findings were practical!}' ident ical with those of the series of rats receiving skin applications of 25 daily doses. The intracel lular hyaline bodies mentioned previously were found in the livers of 2 of the animals. No changes were noted in the gastrointestinal tract. IV. APPLICATIONS TO CORNEA BATS A small amount (1 drop from a 25-gage hypodermic needle, approxi mately 1/80 ce. or 17 mg.) of chlorinated diphenyl was instilled into the eyes of 8 rats for 25 consecutive days. Beginning 30 days after the initial dose, 2 of the animals were hilled and examined each 10 days. . Tlfc pathologic changes were very scant in degree. Slight central atrophy of the liver cords occurred in half of the rnts at various irregu lar intervals. Slight to moderate congestion of cavernous veins of the spleen was constant. The presence of blood pigment, both free and intracellular, occurred rather frequently in the spleen. The conjunctival tissue presented no gross changes when examined I under magnification in, the living animal. JIi SUMMARY AND DISCUSSION Guinea pigs, rats, and rabbits were exposed to a commercial chlo rinated diphenyl by subcutaneous injections and applications to the skin. The material was also administered to guinea pigs and rats by ingestion and to rats alone by corneal instillations. The doses varied from 17 to 1,380 mg. and were either single or were repented at regular intervals. Two conspicuous pathologic findings were observed--liver damage in all sei'ies of experiments and skin changes in the animals receiving subcutaneous injections or applications of the material to the skin. Fatty degeneration and atrophy of the centrolobular cells were present in varying amounts and in varying numbers of animals in 609577--14----- S WATER PCB-00054567 "August 1, 1041 1U1J2 the different test groups. In the rat an additional finding, hyaline bodies within the liver cells, wns noted in certain animals. It was possible to detect a difference in response of the three species to the material on the basis of liver damage. Most liver damage wns found in the guinea pig, loss in the rabbit, and least in the rat. This same species Older was followed, regardless of dose, duration of test, or mode of administration. Hepatic fat appeared in the guinea pigs receiving 0.05 ec. subcu taneously in 10 days and remained in significant amounts throughout 38 days. Hals receiving the same amount showed fat in 2 days but only small amounts were noted in some of the animals over a period of 90 days. Fat appeared earlier in both rats and guinea pigs re ceiving larger doses. The involvement was generally centrolobular. Fatty degeneration, when compared with the other routes of ad ministration, was most marked in the guinea pigs fed the chlorinated hydrocarbon but was absent in rats similarly treated. Ccntrnl atrophy was more or less the same throughout the, series of tests. Only slight central atrophy wns present in about half of the rats treated by application of the material to the, cornea. Intracellular hyaline bodies were found in the liver of the rat alone. They were present, usually in large numbers, in all of the rats receiving 10 0.05-ec. doses and in some of the animals receiving 25 doses by skin and corneal applications and ingestion, bub were not observed in any of the animals subjected to single doses. These bodies were noted in the animals sacrificed 50, 00, and 90 days after first exposure. Xono were observed in rats examined prior to 50 dnys on test. They occurred in from 20 to 38 percent of the animals treated m the various ways. They were somewhat less marked in degree and in number of animals when the chlorinated diphenyl was ingested. These find ings agree with Bennett (7) who reported similar hyaline bodies in liver cells of white rats exposed to mixtures of ehlornaphthalcnes and chlorinated diphenyl, chlorinated diphenyl, and less frequently to mixtures of chloruaphtludenes. To dale such bodies have only been observed in mis exposed to such chlorinated compounds. It is interesting to note that while the bodies appeared in all of a series of 4 rats receiving 10 0.05-cc. subcutaneous doses given on alternate days, they were absent in 4 rats treated with the same amount by 27 consecutive daily injections after GO and 90 days following first exposure. The liver cells in the latter series showed very slight deviation from normal, namely, arens of oxyphil granula tion of cytoplasm and occasional loss of nucleus. It is possible that the gradual accumulation of 1,8G3 mg. over a period of 27 days so damaged the liver cells functionally that they were unable to form the. hyaline material. The hyaline bodies are morphologically differ ent from those produced by butter yellow in hepatic tumor cells (8). They probably represent further development of the same general type of hyaline degeneration as has been observed with certain azoh cm/ cues (0). The. skin lesions produced by subcutaneous injection were histo logically similar to those of ehloracne in man. The changes produced by direct application to the skin were not constant and were essentially those of low-grade irritation. The failure of local applications to produce acne lesions may be due to relatively early deaths from systemic, toxic action before pathology could be produced in the skin or the amount tolerated without causing death wns too small to cause such lesions. Attention is called to the fuel, that the chlorinated diphenyl used in the above experiments produces liver /manges in the rut having marked differences from those resulting from other toxic substances and that such changes were not fouin the guinea pig and rabbit. IlEFEUmKCES (7) Lillie, Ti, D.: Pomanowaky stainiffg with buffered .solutions. III. Extension of the method to PoiiinnouVky stains in general. Stain Tech., 16: 1-0 0041). / (2) Ilerxhniiner, G.: Zur Fottfartiong. Ontralbl. 1. Allg. path. u. Anat.. 14: 891 (1003). / (5) Schwartz, L., and Peek, S./!.: Occupational acne. New York State Mcd.J,, 43: 1711-1718 (Sept. \3, 1943). (4) Schwartz, L., and Harlot/ F. A.: Chloraenc from cutting oils. Pub. Health Pep., 57: 1747-1752/Nov. 20, 1942). (6) Schwartz, L.: An oiitbr/il; of halowa.v acne ("cable rash") among electricians. J. Am. Med. Assoe./122: 158-101 (May 15, 1943). . (5) Lillie, It. ]).: Personal communication. (7) Ilcnnclt, G. A., Drin/er, C. K., and Warren, M. F,: Morphological changes in (lie livers of rat/.rcsulting from exposure to certain chlorinated hydro- ^ carbons. liultist. llvg. and Toxicol., 20: 97-123 (February 1938). (&')"-Ed wards, J. K., ai/d White, Julius: Pathologic changes with .special reference to pigmental inland classification of hepatic tumors in rals fed p-diinclhyl- aminoazobenzene (butter yellow). J. Nat. Cancer Inst., 2: 157-183 (October 1941). (0) Smith, M. I., Lillie, It. D., and Slohlman, E. F.: The toxicity and histo- palhology of some azo compounds as influenced by dietary protein. Pub. Health Pop., 58: 304-317 (Feb. 19, 19)3). DEATHS DURING WEEK ENDED AUGUST 5, 1944 IFrom the Weekly Mortality Index, Issued l>y the llurenu of the Census, Definrlincut of Commerce] Week ended Correspond Auk. 5, mi ing week, 11)43 Data for 03 ltirj-'o dlics of the United Stales: Total deaths................................. ,,........ ...................................... ,,................. Average for 3 prior yenrs...................,,.............................................................. Total deaths, first 31 weeks of year-............................................................. Deaths under 1 year of ago.................,,............................................................ Averape for 3 prior years.................................................................................. 1 H'lUhs under 1 year of nfie, first 31 weeks of year......................................... Data from industrial insurance companies: Policies in force.................................................................................................. Number of death claims. ..... .......................................................................... Deal It claims per 1,000 policies in force, annual rutc..................................... Death claims per 1,01.0 policies, first 3t weeks of year, annual rale.,........,, 8. 125 7, SOI 28B, <XIH (*54 000 10,218 on, oil i, wit 11. MB 0. 1 10.3 8,286 204,6:io 030 20.027 65. GOB, 4fi8 10.880 8.6 10,1