Document zQGVNMLmam680G3RnNaDwK1GB

F,: ',, -( X-Z :., fifeI X : FEBRUARY 1976, VOLUME IS. ff* *7 30 0) 03 C* O) to N> INFORMATION BULLETIN Current Developments in Food Additive Legislation and Toxicology :j f 7. : s'..1'-', v ` ;* * ,. ^ V . r ' .^ - .i T- r ' -. i i /' * * ; ; ; * i J-l . * British industrial Biological Rluaach Association i R&S 134623 - 6- V. CoMlttM* Mid In tteix torn. on behalf of *11 tte bon of 1IMI for boot tenfit tte fork ho* boon ccrrite oat. I ten gnat jIumm Is inirirrl r oar deep the*** to *11 then OT1A rUff Ao hm tean lanlnd latte Safety Iral nation Stadia* Aioh ten oateteatte la tte wwrt 1mm of nporta. Steoanly. ^ **, Oi*lT--i> l*eanb Bollcy Co-ordiaailag CowltUo 27 Jeooary 1976 ARTICLES OF GENERAL INTEREST tibzl c&Loxrs--Pi i <f 7// Wortoera inrolrte la tte prodaotloa of polj-rinyl ohlorlAe (BTC) expand to differing lenle of einyl chloride wit (TO), tte rxpoaure telng In tte cleaning of polyaerlaatloa aatocla^aa. oca lead to ecro-oeteolyaie (BQB1 Ball. 1973* 12* 313), mmU*m oolite TO dlcMM' i Mid to angioearoam (ibid 1974, 13. 333)* ten *ann - poeure to TO oca ocoar daring eobeequeet prooeealag of BTC cad altlmgi ollnlool oteogae aey not te naifeat, pathological toot* detect offoot* charactariatio of clinically advanced oan* (Lange tt ol. im. I.T. Bel. 1975. 18). im-wEtriinai la mi ill-defined eervey of vortexe expand to TO la Japan (tefcate. Ibid 1975. 78). 49 oat of 1597 onplalned of finger truAle. aootly pom*tte*l* (mtun md tingling) Mid poln. X-ray exaniaetlon of tte flBAn of 1*99 mker* mealed ateoxaal finding* te 104 .ae.a, SO of Aioh oeold te attributed to oenaa unrelated to TO c i[ni e*i a end only too of Aioh koto door owe* of aaxo-ot*alyni*. Non thnrwiA *nteatten ten boon carried oat oa 70 potlMit* Ao ted boa c^layte te WO* production plant for 0-5-21-7 year* (mngi 7.7 yeon) la nrlan yinrmr 1 no!tiding autoclave cleaning (TelteMi t *1. Ibid 1975. 24ft. 4). or tte Initial eynptoe* xvportod, upper ehdmlnal ooaplalate mm tte Mat mmh (In 42 oat of 70), followed by tirtenaee, dlsalana, liniMit pemplaatln nd iiiMliini, tingling cod enaction of oold 1a flagcn Md/* ten. A neny by acllod queetiocnalzw ocrrlte oat on mfeere la a BTQ fiatectlw Ptent (Spirt** te. lad. Bjg. An. J. 1975. JJft. 779) nnalte Am- nr-iaoM pattern* for ell tteo* cj^itua* except ihdnMlMl aeenlalate. A1A mr. not lnvaatlgated. Teltaea tt 1. (loo.olt.) tcbolotte ttelr pattelogloal fladlagi. tte net fraquent affeota telng thmbooytopm* (late of platelota la tte blood) la 01#, laonwd broanulphthalela (MB) rataertlaa (Indicating tepatio dyeftmetim) la 67#, anlcrga--nt of tte oplaaa la 57# ate ntlaalte aytnte (ttelnM ti--of alA IittI"* ftete* % a^te Mt) fUte to pn*4 loot flatted Atet la allalnny Ai MUdndil Ala, itteA * ru \ I -7- cytoolo (lndloatlwo of aotiTO Mood ropoaorotloo) la 41jf* bxtamal n**P oooalotod of oIob-Ii.V owolliag Mid obortoolap oxoaid om or ooto of tho toralaal fiapor bonoo. ooooopaaiod by wotob-glooo-llio sails and ohortoalnf of tho sail platoo. aad of oolorodoToo .Ilho ehonpoo of tbo akin of tho tanokloo Mid fozwoxn. With oomo of thooo nhonpto. oonploto w|m1m ooald bo oxpootod pxoridod that a oortain doproo of onoxlty mi sot lanudid. Xlatoloploal flndlngo ahowod hyyoihojstoolo, mi lnoxoooo la oobopidomot oopniarloo Mid a lynphooytio lafiltrato. Tho oollopMi bwdloo woro owolloa Mid tho olaatio fibxoo woxo thia. flsoorod ond fripahl. ffclo loot finding diotiagslahod tbo dlogtnoln fron that of ayotoalo ooloxooia. la oliaioally ohMipod akin, tho hiotologlool flndlnpo woxo alwoyo pwiMt. bat la six ant of 29 ooooo thoy wn f^nd om la oliaioally vnohongM Ala. althoogh this ofaowod so dlxoot oorrolotlon with tho oovoxlty of la> tm hm] findln^io OhongM la tho bonoo woxo notod ao a bood-llho oaro-ootoolyola. particularly at tbo booo of tho fiapor sail. In aoot ooooo. oo^libo xootltatlon oommrd aftor xoaowal of tbo patlost f*un TO iqini. Toooular oboapM woxo doooly oonooetod with tbo bona otiao^o, and rwnpod fron allaht saxxoodag of tho ooonlor lualaa la tbo digital artorloo to oo^loto ahooaoo of filling of tho nrtorloa along tho idwlo loogth of flagon affootod by aaro-oatoolyolo, tbo doproo of oooorlty bolag oolaOod to tho oararity of tho bona ohongoo. km Moatloaod aborw, thooo ontboxo aotod a high laiidonoo of tJooohoajrtoponla, prooontlng Aot woo oppazwntly tbo firot royort of this oooPTTvaoo la oomxloa with TO oipomo. HlAt to 0000*0 00000 vooo fbmd la Qlff of all paxoano oronlaod and walaoo rongi i fxwn 17 tOOO to 143*000 ilotoloto/|il (lowor non, 150,000/d)- Tboro woo, howoror, a* door-out oorrolotlon botwooo tho platolot Mot oad oltbor tho yorlod of oxpuomo or onloxgoooat of tho oploon. Tho authors ooggoat that a ylotolot <mnt ahonld bo as obligatory toot la WO woAoxo. Zagrovonont of platolot oovito ooonrrod la only six of 29 potionto Ao hod boon aonowod fron TO oipoouro for 1-1*$ yooxo. Two opoolfio oaaoo of ooro-ootoolysl* hoot booo. xwpartod la woitaoro orpoood to TO for 2 yooxo only tho oorwnd yoar bolag at a high loaol of oxyooor* (Valkor, Proo. I. 8oe. Mod. 1973. 343)* both aoa dorolopod onto attacks of Boynond'o phonononnn (opaM of digital Mrtorloo. blonohlag Mid twudwnoo of flagoxo), to^thor with lytlo bans loolono aad thiokoalag of tho okla. iftor xonorol of thooo woxfeox* fXoa oryooao. tho Ala looloao oppoaxi to xogEooo md tho lytlo looloao to hoal, hot tho waooola* dlo- oxdoro oooMod asro po-aonoat. Is 0 ooboonnont <11 o00001 no It woo iUH4 that tboxo woo bo ovldoaoo that any ontalyata or oddltlwoo oood la tbo W polyMoriaatloo pro0000 woxo oapohlo of pxodoolag thla m/uttmm. Znoootlgatlano hart aloo boon oarrlo* oat la TTI1 pumoolog ladootrloo (haopo ot ml. loo.olt.). Mid oltboogb ollatoo.1 omiI foot at loop oooh oO oolomdorao 11 Vo akin -thnc or Kaysond'o aynixoao woro oat ohooswod. pathological flndlngo In lahoratoxy tooto woro olallor to tbooo la wqihoio Is WG-prodaotlon ladnotxloo. ldwro ozpoooxo to TO la pMoaally oooldiod to bo fxootor. Solatlanohl-n batwon TP .-mctm. 1 in ooooolatlon of PTC ooanfaotsxo with tho lnoldoaoo of hooaootploMroooa woo firat onopootod oo o xwoolt of oorwrol doatho la tho iadootxy fxoa thlo othorwioo voxy roro typo of Uwor tonoor. hot orltlolaoo haoo . R&S 134624 1 *1 . R&S 134625 i -8- been levelled at a *ub**qo*trt analysis of 161 death* la two TO-fVQ pleat* abating that th* icrtxr of death* due to oil o*no*x* km 5qpt hl^eer than that la o ooapaxahl* tat uaaxpomd popul*tioq (coup (XZtai Ball. 1974. JJ, 9$4). taoana* 19 to threefold regional variation* la oanoer lnoideoo* or* } known to oocar,. It * #ugg**t*d that th* data from TC plant woxtexe taowld haw* boan ooetpcred dth local and aot national Mortality data (Fexetan* A ' VilUmeao, lanoat 19741 fi. 591)* Zt waa alao polatad ont (Falk at *1. ibid 1974. H> 784 ) that 155 ont of tba 161 death* tamed fro* a plant la loulevAll*, Kentucky, oonoazaad additionally with synthetic ratbar pro duction, and that i\ large proportion of th# wnfcara wax* not directly exposed to YC, thus ruieing problem of lntarpratation of th* i*#ult*. Forthor support for thaaa orltiolaaa ha* taan offs*4 by a ntady af g-*tnd*rdi*d nortallty raise for a population of 2100 aala wextax* la Twaarth, 01Morgan, axpoaad to TO for period* of up to 27 yaar* (task at al. ibid 1975. fl. 1197)- Zn th* 13$ daatha in nan under 73 year* of a#*, a* oaaa* of andoaaroana wax* Identified within th* study parted althmta an* haa ooonrrad #lno* than. Observed nd *xp*oted fneytencli* of death from various oenoaa la th* tael* population of worker* corresponded *l*ely, and th* fheepenoy of naoplaatio dlaoaoa waa aiallar la all eatgraepc of th* population. 1 subsequent report dl*cloa*d that eight of the 27 --f<-aaroonaa diagnosed In Holland also* 1950 wax* of tho liver, tat mm* of the 27 patlanta had had any txaoaabla oontaet with TC (fialdexep at al. Ibid 1976* i 24$), Conclusive epldeniologloal *tudl*o are aot possible at psaooat awing to dlfflaultlaa In tracing all individual* axpoaad to TO, to the long latent period* of ooonpatlonally lndaoed oanoax* ombined with th* selstlvely rwoent ua* of TC, ad to a look of infoanotiott on lew*la of apa*xa. However, th* urgency of th* situation ha* pxoapted several other oohort studies of TC-PTC worker*, and their zaoulta indloat* npart for th* result* of th* IoularlU* study (BXBK1 tall. 1974. H. 334) A study of relatively loug-teni *ff*ot* (Xiatoleoa at al. inn. IT* load. Sol. 1975, &, 225) Involved 237 individual*, each of taan had taon xpoood to TC for at laaat 3 year* tatween 1946 and 19$8. Of th* 23) in dividuala traced, 24 had lied (ompared with 19 expected) and of th* nine death* da* to cancer (3*9 expected) three were da* to tagimirema af th* liver. The angioaarooaa* all ooeurxed in Individual* tao had weatad etwee before 1951 in FTC production, suggesting that a* the tine from axpoeuee tacrea*** la oohort neebere with aiallar exposure*, attltioaal eenee nap oocizr. 9w author* of another etady (Ott et al. ixuh* anvlr. XIth 1973, 30 533) were able to relat* tmour lnoldeno* to level* of TC expem**. Of 394 cohort want era, 72 were expoeed to axeonla (taloh la kn*m to jredes* an - Increased oan**r risk) a* wall a* to TO, and seven of th* ton doatho In thl* } group war* da* to nallgnant aeoplam* (l*9 expected). Of th* 322 in- dividual* expoeed to TC alon*, 79 had died (99-1 expected). 13 a* a remit of aallgnant neoplasm (16 axpeoted). ta d*ath* da* to T1 -- **m obeerved. Although th* umber of death* from nalignent eeoplamn we* anall ; nine out of 13 wore obeerved in individual expoeed to hl^t level* af TC (4-6 expected) while only five (9*4 expected) war* obeerved la all attar group*. thaaa author* reoognlaed that mx increase in th* tin* ftan initial expocor* and In th* umber of individual* involved would ij^ewe the ** liability of th* pid*nlologloal data, tat in th* latarln ttaix eaowltn an* supported by four rpeoifio oaeee of mglossrooen. Zn Sweden, %atai h mu-- m live* ftantd* tad. m. m t* V* mwiMni pavtal oE&xe* ftteeile to 1 plant ngstai Petal pretaU naiwevUc it Iteen-^ataA eta.mr.IMg 1 eamelattaa t ealecd to Ita ta ottt null to to ( ad pneetetato to), to tta ftbnari?. * ohnlft 6-pta tta lcr_' 1 * ton ertodt (tato t Bel lotto, to R&S 134626 / *' -9- Bolster* (dm. I.T. load. Sol. 1975. 24$. 249) dlagwaid mdoeazoonM la tea TO-PTC plant worker* erpoeed to TO for IS and 25-27 yeara w^Mtlwly. Blaoa both tteoo ooaoa wara Initially planeHlad aa prlaai7 Hoar lanw. tte zeal of tecloeaxooaM aeeooiated with TO-WO prodnatlaa nap te lax^r tea hitherto teas obaarwd. Two farther oaaaa ware w|rt4 moag mtoolavw olaaaara In Gexnany by Lan#e at al. (loc.olt.) teo aotad that tte oaaa hlatorlaa ooatained no lnfomatlon on 'TO dlaaaaa*. Althea^ arltenoa atewa that tte Incldenoee of both aaxoo*taolyala aad Mdaaareana ana zalatad to TO arpoawra, there la no oorxalatloo between tte te dlaaaaaa. Of aaran oaaaa of aoxo-onteolywla tented, nooa ahowad ateofal lira* fonctione attributable to TO expoenre ( Creech A teklc, inn. I.T. Aaad. d. 1979. 4> ) Mamala of TC-latooed llwr dlaaaaa tjataaatla taata carried oat in an attinpt to relate 11war ahnaanallty to TO aipuanra lamia zamaled two oaaaa of an*1 mamma and alna aaaaa of portal flbroala In 274 WO production wmharn and two aaaaa of portal fltooel* la 909 workarw not aaaoolatad with PTC predaetlon la tte Laalaallla plant mmit,1 rami ahora (Craaah k tekk, loo.alt.). Hood oaa^lee wm etelactad to tte atandard aaipwntlal naltlpla aaaiyala known aa MA-11, iamlrlnc <Wtamlnatlon of oaloloa. total bUixwbla. altanUn, atelaataanl. total protaln. alkaline phoaphataaa. laotla dafcpdxo#maae, flntmleoalaoatlo tranamlnaea, dlnooee, bn nltro^n. wrle aald mi lai i^ml phoephnrua. ihnaznalltlaa In 3KA-12 taata war* followad te *7 a battaay af limr-function taata. fhoaa oaaaa In which tte battery ahowad aana najaa abnomallty ware aobjaotad to apaolal prooedaree and txaatnant. Ba paaltlaa correlation waa fomd batwaan ahnomal Ml-12 Tlaatlona md nten lnmlmd In PTC prodnetlon. bat tte lnoldanoa of ahnosal battarlaa maatat no production worker* (lO#) waa al^lfloantly hl^tar than that la wten In otter azaaa of promotion (4*l). Tte afflolanoy of tte nomal *1-12 In looatlnf llmr atenmellty tea atlll to ba dataxalaodi particularly In tte ll^tt of art lanna fran a patient teo wi Intentl*atad 2-5 yeara after bain* renewed fzon TC ii|>iui ten*, of porelatent liter dyaftatoilon (lash at al. inn. I.T. toad. Sal. ttT5. 2M' 70). At tte follow-op irrreatljatione, noatlne taata #em nanal mlwee, bat hlatolo<y ahowad tte pazalatanoa and poaalbla prudi'aaalun af tepatla flbroala. Clearance atndlaa oainc bilirubin, MP, lndaymlna fween md otelyl dyool ahowad only tte ilaapyiaimua of ohalyl flyeel ta ba wteaanal. Tte look of raaponaa In umy taata of tepatooallalar fteatldn waa nttrlbntad to tte xelaiim epezinc of hapatooytaa In TC aaaoolatad flbroala. [*. Pittor] [Part n of thla review, to ba pnbllated In tte nart laana af tte Bulletin, will ba ooooemed principally with tte allnlaal md hlaWiafleal otezaotarlrtloa of vinyl ohlorlda-lndaoad ancloaeroma, with atwdlaa In mlnula arpooad to Tlnyl chloride ad with arldaaoa xolatla* ta tte neehm of action ml tte aetaholJm of tte ou^i :naal. J mm hob m nx K'j <.rj Tte iacieeaed oooorraeoa of teaaohlorobwaoai (BBS) la tl a clTan rlaa to aona ooooazn. It la uead aa a fteflalda ta af idiaat and cn alao oooor aa a want# by-prohaet af ohlarlaatad H-fH-iU .1