Document rpkMXyDvgMokLDQrKrjNM5qrV

r V 35 l v f e y REPORT W -m S Inhalation Experiments Q-V55tV'v\ Animals. S h its rata haTe been employed throughout. They permit the use of a la rg e ntaber of animal* la a r e la t ir e ly .small Inhalation I n s t a lla t io n . They th riT * upon a diet wary sim ila r to man, and la the case o f these ch lo rin a te d compounds i t is possible th a t d iet say. be very s ig n if ic a n t . F in a lly , th e ir normal c h a ra c te ristic s have been described so w ell as to make the detection of abnorm alities both easy and c e r t a in . - Hathod o f Exposure. Tha Inhalation experiments were carried out in four large a ir - t ig h t wooden boxes, each capable of holding ten ra t cages, sin e 22" x 22" x 14", in two tie r s of flY e cages each. Then the experiment as not in progress the doors vers opened elds and the cages kept in p lace (aee Figure 1 ) . At the center of one end of each box -- the inflow end -- a ir was Introduced through a pipe 7 inches in diameter (see Figure 2 ). Each box was equipped with an ln d irid u al e le c tr ic blower which blew the air through seTeral fe e t o f 7-lnch pipe before entering the end of the box. An o r ific e was placed in the pipe lin e , and the flow o f a ir in cubic fe e t per minute could be read o ff d ire c tly fraa calib rated flew meters. A damper placed at the entrance o f the pipe into the box was adjusted to assure a uniform d istrib u tio n of the stream of a ir to the two tie r s of cages. At th e opposite end o f the box -- the outflow end -- the a ir fre n each box was exhausted through a 7-inch pipe f it t e d with a damper and connected to a larg e contral exhaust fan (sea Figure 3 ). About 4 inches from the entrance of tha 7-lnch pipe Into the box, the fumes o f the substance were Introduced into the inflowing a i r . I 36 r V 1 - : i _ : t - - ,-r * Specially' d e s i g n pyre* glass fla s k s (Figure 4 ), 7 3/4" leas a- i a d isaster o f 1 1/2", vara uaad to bold tba beatad waxes. These fla sk s wart made with a aid ora and tub which extended to tba bottaa. Tba top of the fla s k was ground, and into th is fit t e d a abort tuba l 1/2" 1- le n g th . This abort tuba was lnaartad into a large rubber stopper which f it t e d t ig h t ly into a bole cut cut o f tba 7-iach pip an the under sid (s Figure 2 ) . The fla s k In turn a t placed in an e le c tric beater node to cover i t completely below tb aida a m and ground glass top. Rubber tubing connctd tba aids a m with a compressed a ir reservoir and a gentle stream of a ir blown through tba h alted wax kept i t in motion and assured uniform heating. Into each fla s k was inserted & long stem centigrade thermometer which was kept in place and could bo read at any tin e above the 7-inch pipe through ^ llc h i t passed (see ?lgure 2 ) . Approximately 23 gm. of pulverized snssasmama^zsgdznbabasrsnss: acempomeff chlorinated diphenyl were placed in the 'vapbrizidgtr.;n fla s k and melted in the e le c tr ie beater. Fresh samples were used every other d a y . to-^h^gcrmirtgtTTdnxid:nBnaa mr.a iVv.ndi.ljlQ, a-eca'i 1vn-m -r a-L-i-i-; ns ifJaS .h-r-3 nhWn-r*,. ^>1 r""nr"T The co llected sublimate was always removed from tha upper part of the fla s k and a clean top used eaeh day. No sample was ever used for mors than two runs. The fla s k plus the contents was c a re fu lly weighed at the beginning o f the run and at the end, and the lo s s in weight used to oaloulate the average amount In a cubic meter of a ir per minute as determined by a series of flow meter readings. The figu res obtained were not ebaolute because o f a lig h t variatio n s in the a ir flowing through the boxes and because of deposition of m aterial on the thermome te rs and co the Inside surfaces of the box, but they checked a ll with d ire c t determinations through a ir s e t t le s . CC 2 1 r f ^ c Approximately cue hour a allowed for the wax in the flask s to malt and come to a ocnstant tanperature. At that t ie s tha box sera wars t ig h t ly cloaad, a ir bubbled through tha fla a k s , acd tha blowers turned c a . Thia was tha beginning o f tha expoeurs period. By noana of the theoatata cd tha faaa and the dampers ia tha outflow pipes, tha amount of &ir flowing through tha boxea was adjusted and. an a t t e s t wna made to keep the four boxea aa uniform aa poaaible -- usually between 165 end 175 cubic feat par minute*. Experimenta Expoaura to chlorinated diphenyl was begun ca Tuly 1, 1335 and ceased on November 18 o f tha same year. The average length of exposure was 16 hours d a ily fo r 6 days a week. Each morning at about 9:00 exposure ceased, acd between th is time acd 4:00 p .a * the rata were cleaned, fe d , weighed, e t c . In order to secure uniform ity of exposure the cages were sh ifte d on a regular schedule, since wax concentrations were somewhat higher at the inflow end of the boxes. Prelim inary runs showed that once properly adjusted, wax concentrations la the a ir remained Tory uniform from day to day, but to insure absolute safety readings of temperature, a ir-flo w , e t c . were made every night between 10:00 and 12:00 p .a . aa wwll as on sta rtin g and atopping. I t d iffe ren t time a during the course o f the experiment te s ts fo r free chlorido were made but ware uniform ly negative and ahowed that under the temperaturea used no decomposition ooeurred. Table 1 C* Conditions liaintained in Inhalation Experiment fr e e Ju ly 1 to Nov. 13 % CC3s Juaterlal Chlorinated lpbenyl Temperature Average ecncentratlcn of a ir in box Total length of exposure C 153-173 M g./cu Jd . Han a9 G-."Z7, Hi ~^ 1.19 Low 0.23 hours 1235 Average a erpesure a 16 42 Results of Tnhlatlca ^marimanta No abnorm alities ver sean a t any tin la tb s liT in g r a t a . Elc^.4 and urina examinations wers sad; there vers no losaoa in nolght, and one would hare considered that the a n sale were p e rfe c tly sound. However, r a ts s a c r ific e d a fte r 6 weeks exposure showed s lig h t liv e r dasage, which advanced during the next two months. The changes consisted in slig h t to moderate sw elling o f the liv e r c e l l s , increased g ran u la rity , and many m ito tic fig u r e s . Hyaline inclusions were present and were invariably p le n tifu l in animals receiving chlorinated diphenyl by Inhalation or by mouth. One la foreed to conclude from tbs experiments that an average concentration o f 0.37 s ^ . per cubic mater Inhaled 16 hours d a lly produces d e fin ite s lig h t changes in the liv e r and in th is organ alon a. These changes are re siste d e f f ic ie n t ly by the animals and causa no depreciation o f h e a lth . The situ a tio n i s not unlike that seen in fa c to rie s where acute yellow atrophy of the liv e r has occurred. In the case of such instances the p atien ts have been singled out in some way or other from large groups of fello w workmen who have been p e r fe c tly h ealth y. In considering the en tire matter i t seemed to us that the KSEXXXXZ chlorinated hydro-carbons,/if inhaled in s u ffic ie n t concentration, might cause a s lig h t degree o f damage to the l i v e r . This damage is resisted e f f i c i e n t l y and causes no depreciation o f h ealth , but i f the Individual in question happens to su ffe r some ordinary disease of the liv e r the condition is superimposed upon a substratum of in ju r y . In accordance with th is hypothesis we determined th at a dose of 0.75 c c . of carbon te tra ch lo rid e plus 0.75 co . o f ethyl alcohol per kilogram o f rat was e n tir e ly non-toxic to normal animals, ben, however, th is dese ras given to s a la a ls which had inhaled chlorinated diphenyl as has been described in th is experiment, the result ras scute yellow atrophy 43 CC5^ i "J-- y, . v of the l i v e r . I t would seam therefore that inhalation of & concentration o f chlorin ated diphenyl in the manner I haTe described is capable of producing a condition which may be dangerous to the IndiTidual inhaling i t , though o f I t s e l f no T is lb le harm w ill be dene. Animals m o v e d from exposure to chlorinated diphenyl a fte r two months in h alatio n and given two months fo r recorery s t i l l shored lir e r changes when k ille d and examined, so that i t is evident the alteratio n s produced by th is hydro-carbon ars persisten t and ind ivid u als who have been caused trouble by i t should be removed completely and fo r a long t i a s . The Inhalation of a sarewhat hither concentret1on of chlorlneted dlnhenvl over en 8 hour dev The circuostences attending th is experiment are given in Table 2 . M aterial Chlorinated diphenyl Table 2 Temperature 0 C Average concentration of e ir in box Mr./cu.m. Pamre Total length Average of exposure d a lly ex; Kcura Hour: 153-174 0.93 High 3.23 Low 0.C3 920 a Again 60 rata were used in th is experiment, I.'cne at any time showed the s lig h t e s t evidence o f i l l n e s s . Idicroscopio examinations, however, shored a degree o f change very comparable to that found in the 15 hour experiments which have been described end the carbon totrachlcrid o te s t raa uniformly f a t a l . Ceneral cHrnmrr From these experiments we are forced to conclude that cem oertratim s of chlorin ated'dip hen yl in workrooms should not be aliened to rise above C.5 mg. per cubic meter o f a i r . This ccmcectratica is roadiiy obtained by care fu l U' CC 2* - s hooding I t ifl in our opinion M ia for worknan t t o would not ba exposed trt.tii t ie absolute steadiness ch a ra c te ristic of our experiments cs rats end such a concentration H a l t would probably do away with the troublesome skin lesio n s which hare been ths p a rticu la r cause fc r worry in regard to these corapcruada in the p a s t. In addition to the inhalation experiments naay feeding experiments were done with/chlorinated diphenyl. The general changes in the lir e r were the same as those already described. Ho diarrhea or g a stro -in te stin a l aspects seemed to be p resent. c I (K m i 6 - y* 45