Document by26rezkYx9NYOaB4eBLy8pxg

JUNE 1974. VOLUME 13. R&S 131317 Current Developments in Food Additive legislation and Toxicology Bio MSH iNi>M`. 'x A. Bn n n,n a: Rf .! a*. A\SU( IA / 'ON 3) flp a) 0-3 0-3k GO KDI'lOUlAl. vur/',, CHLORIWit A iirTORT OF A FXHOI'EAH UZr^X&r `(f J m 'J till Clt* *JJ* 1 X*'l I I 'I . ' .** ' . ?lat:or.iI InctiV.:* ;f Pubti'.- `if. *. irorinc V?7J- iner-- u;ir..' u..i..,v;t - 'i : it ' ' . ;:>w*T.ie and other -1': -.1' vinyl -hlor; : . T`. : r .........!>., the health of indurtrl >: >(.r.r 1 '*; s;iim.piietim* st.`l j r i.-.p!:;"..* { I V-;, 1. !"7r! hoc be..-r. ur.c.p.iv ,* ; r1* . * ` .. ; .irirx pv-.: T'l'l :r. i:.' the atmoapheiv !V)r i'Vfl -a !;' . . ; .;. ; ir.-- , pr'if.Ml ity. . 0!'. <`t riar:h Yili, . K.,rv> a. .................... ibi. *"ri vjiC,i`1 i-. , t, ;rr. - J; ! SjiTi1 1 : i. '. . Tt ;j i L r.t; inutiiutc -.1' KiL'tic II. li a, r` i tt.i i .ft to ipanto were Dr. ivjhn*- (F*-le;\.. Ik; ,t. i f (Potioark), Or. Cramp".!; (IK), Pr>sVri'.r i *J` vy: Lcrten (The Nctheri.'ir.la) , Pr&'Vunor Schi Profesaor Truh.nit (Praiire), with L>r. vw; Kct.ii V : . ' .a V .. 'Jw:1,-- r1 j * i : ("n u r v . T!:< nnBuntiil pr.irjtn of the itrf w ! .: . .jf.NU i;.t known Eo i'.ir cay ours: fi .' i ..a f:>l, .w.:t . ) Lr.hal.ition r'u'iiur with mir. .!. ri.-m r:*tv . - ffectc. In IT.'I, Vioi.i ('l.wj-.-r Ir-a. ! i-; . tumoura of the akin. w.;:-. .u >1 bon -a h. r.*!' . . i . . . chloride concentration (tC,01 H> pt-s) .ti th.- nr 1' : n .i i .. 3 days/week for K' aonth;'. The jkin "us. arn ,i *. ; .? - auricular region. Reports of furth- t ;'.!:ii:.:j . .rr. t ; .* 1 ,* .. Italy (Chemical .aid Epirineeriii*; B.!wo i */4. Fetm ^ the c;ircinoctnie njoponot- .uid Boa- r-cui t ' itr( utw-M. . n T' ;. Table l. C^cinojynK"jnrnjain r it.- . vinyl "hiondo in th. . ; 1 Expoaun* level (ppm) 10.000 oOOO ?500 500 ?50 50 Hatn wi th 1 tv. r *SL* if, .'1 1 u ti-. 1 * ; ip 11 * . i 4 The T'julto oh>wn in T-iM- ! w.r>- ..Mur. ir. ,:(.r mto orpOBci to the ntal.-l n* r ,* i....i . ` v.t.-. t.l. r, i. :m,. - ?47 - inspired air for 4 hours <kUly on 5 dayn/veok uv. r , p-rl't >*' If months. In addition to the angiosarcoma indlc.tr.. i 1:. TaLl I boss rats aira developed zyubal -gland tuaoura ir.*i ricpbroblastmas. In concurrent studios, exposure <-,[ rats to vinyl are tato at levels up to 2*>00 ppa was not followed by the ap^aranco of any tunnur*. (2) Than are strong indications that vinyl ehlcri e rxposuiv * results in liver tumours in aan. A nunbor of cafl'-r it arwi'itsr'.naa of the liver have been reported in the United States in aperitive*' exposed to vinyl chl oride. This tumour is wry rar*- in non. It ta possible that the Initial cases recorded will be fol1 owed by the appearance of others, and cement on this possibility has alreo-iy been Bade by the Cen-er for Disease Control. US Department *1 Health, Education, and Welfare. In addition to the possible carcinogenic response in non. vinyl chloride exposure has been associated with the rlini'&l syndrome, acroosteclysis, ?ull descriptions of the signs and symptoms and clinical findings of this condition have been published (Dlnaan st al. Archr. nvlr. Hlth 1971 2, Cl| lUrris A Adam. Br. Bed. J. 1967. ! 71?t Jtlhe ct al. Dt. aed. Wschr. 1973. 22* 20541 Lange et al. Int. Archs Arbeitsmd. 1974. J, 1). (3) Other effects in aan have also been recorded (Krafter A Mutchler. Aa. ind. Hyg. Ass. J. 1972. 19). In individual* occupationally exposed to concentrations in the air varying free 10 to 300 ppa over periods up to 25 yearn, indications of liver dysfunction have been observed. This particular effect has not been confirmed in animals, in that inhalation of vinyl chloride by doge, rabbits and guinempigo over a period of 4- aenths has not produced any signs of liver disturbance (Torkelson et al. Ibid 1961. jg. 354). The relationship between the chemical structure of vinyl chloride mi Its toxicological offsets was discussed. A large nuafaer of ooapounla contain double bonds which nay lead to free-radical formation. These It-- clude styrene, aarylio acid, acrylonitrile, acrylate, vinylidine chloride, vinyl acetate and safrnle, a substituted allyl bensene known to have car cinogenic properties in experlaentml animala. TIM absence of a earelnogenlo response to vinyl acetate indicates that other factors affect us biological activity. Therefore, the reactivity of vinyl chloride w<th other compounds In the environment and in food and its metabolic route in tlm body ace of considerable importance. Little info, nation on these points is availebl| for instance, no data exist to indicate the degree, if my. to which vinyl chloride may sot am an alkylating agent. The factors that affect the migration of vinyl chloride from PTC wer* discussed. In January 1973 the Vbod and Drug Adalnistration began to receive reports of possible stability problems with PVC bottles weed for distilled spirits. The lewl of vinyl chloride migrating varied, with aoam eaaples in a high range of 10-20 pjm. As there were no prior indications that contact betmen PTC and food would result in aigrettes of Mimr, tlm figure of 10-20 ppa waa astonlahingiy high. Soae data ware available for migration into non-alcoiml tv b*r^i, food and other materials. It ia not possible to include all the beat'* l.t t. but the following will indicate the order of amplitude of migration. Tima JVC in which vinyl chloride was present at a level of JO ppm, migration lul-j water, toft drinks and blood (after 40 davs) produced concentret ions of R&S 131319 ..... i R&S 131320 - ?4fi - 0*02-0*05. 0*0002 and 0*014-0*06 ppm respectively. Tbe xtnt of migration .1**ponds on the initial of vinyl chlurtl*- in FVC* and tfci* cun very greatly. Thus, in PVC bottle*. the content of vinyl ciUorido Bay bo as low an b ppm and ashirdt aa 400 ppe (and up tn mod p*xa in PVC film). Tigr.ition also depends upon time of storage, on llluotr.tei >y % sample of beor which contained 2 ppo vinyl chloride after 6 yearn in iTC bottles containing 70 ppe. Otbar factors that might influence migration or* lh- typ.- *,f ln!.lrl tl prt sees used, the offsets of additives to PVC formal;.r.t w.a onli 11 vir f usage. It is Known that information on ttece ,-eu othei-iupcti h.oi lawi. garerated by Industry, anil the need f.jr round-tab lir.-icd'.i. with industry was agreed by uii participants. On the baoia of available migration d.-itn. tin iintimit.' w ui a..!*- less than 100 ug viI. chloride Is the lively oral tally in; wee by n-tr (it Sunopc). However, further data are needed to quantiv-ite this, und !<- ation should also be given to compounds formed by the lntor;u.l i jii of vinyl chloride with the chemical constituents of food *nd drirwc. on which r.o tat wore available. The following conclusions were reached .oil tgruei u.ai.imnuslyi (1) Industrial exposure to vinyl chmrldo .2 tlw m-imp,.rtv problem. Pull epidemic,o.jical data, inciudliw' (let-,. ;*d rl ir.l--' records of operatives with tuaourn or other alleged nffecte. -I be reviewed. The no-effect level of $0 ppm la inspired ut in dicated by Professor C. Haltoni is too high to adopt as a Threehniii Limit Talus*. Present levels of Industrial exposure should be seduced as far aa possible. Environmental considerations should include tha atmospheric affluent from industrial plants. Of particular importance ie the elimination of hazard to in operative* from expoeure to high levels of vinyl chloride luring the cleaning of t-ilymerisation eeneels. (2) Methods for reducing the residual vinyl chloride in pi ietlr products to very low levela should be explored urgently. This is of particular importance where FTC is used for fuel end lrl<wc cotw tainers and wrappings. (3) It the present time there is no need to reeiuwnd that FTC should be banned aa a food-wrapping material. provided active steps are taken as indicated above. The basis of this conelueuv. ie tht relatively high concentrations of vinyl chioridt (by iah-Ualiuni axe needed to produce a carcinogenic effect, 11 compariet-n. the expoeure of man from food intake is probably micfe lower. Tie further quantitation of this factor will be possible when *r*i studies on vinyl chloride have been completed, Purttv>*> t*-. it was noted that even less toxicological data were av-ll a;.- 1. possible alternative pi act ice for f-vxi wrapping. It *ea thomr.t desirable and poaslble that FTC used for food and drum paek^liur After the eeetlng it was learned throieft personal c<mmunicwtion < hit **, || vinyl chloride In Inspired air is also carcinogenic to rats. This in dicates the need for further evaluation, as soon aa results of the oral studies on vinyl chloride beetle available. iV-JT - 249 - should contain less than 20 ppn vinyl chloride monomer. la effect this represents tbj establishment of a food grade of FTC, to ensure very low levels of contamination. (4) The current situation is that *he problem of vinyl chloride has been broadly defined. Its final solution depends upon the evaluation of further data, such aai (a) Epidemiological studies in man concerning vinyl chloride-linked diseases. (b) bevels of industrial and environmental exposure, (e) Effects of oral dosing of vinyl chloride in animals. (d) Investigations on whether the induction of liver t'loo'.ra by vinyl chloride is preceded by liver dysfunction / . cirrhosis, as can be found with selenium, or whether it behaves like nitrosamines, with which no cirrh>aia of th* liver is observed. (e) Hotabolias of vinyl chloride, including alkylation studieo. (f) Percutaneous migration of vinyl chloride. (g) bevels of vinyl chloride in fnodf estimated daily Intake in children and adults. (h) Interaction of vinyl chloride with food and drink com, pedants. (l) Levels of vinyl chloride in OTC products (Shsets, film). (j) Levels of vinyl chloride in potable water and PVC tubing. The vinyl chloride problem should be capable of solution without recourse to total abolition of PTC manufacture and usage, but it was recog nised that the latter policy might be adopted in eone countriee ae a matter of e.-podiency. Should thla occur, there would be considerable risk to other plastics materials. It is obviously desirable that the co-operation of nil Interested parties be attained to facilitate and expedite the resolution of this problem. D 9(?/)