Document pmLj96dbnrpd0g7L4Eq5Vk3Md

,>iw 3*?^^ m JTJSH MEDICAL JOURNAL (31 20 APRIL l^y BaJvr's view, but a subsequent trial in Paki stan* faded to demonstrate a statistically ligmfxani effect. In addition Rao tt d` in a controlled arJ supervised trial with a Cn..<.ly related compound. shown to be highlv effective in the laboratory, were able to show only a minimal prophylactic effect. If the thiosexniarbazones are really as effec tive against variola virus in man, as Dr. Bauer claims, jt is surprising that they have no appreciable effect on the success rate of vaccination with the closely related vaccinia virus,-' did or d ' not occur in rats bearing implants. That the - is a need for a series of simple inexpensive tests which suggest that some substances ' ; more likely to be carcinogens than others is indisputable. N'or would one reject the view that short-term in-vitro studies may be of value in warning that substances may be carcinogens and in the elucidation of mechanisms of arcino- geniciry.: Bur what must be disputed is whether mutation of a micro-organism of transformation of cells in vitro should be patients poisoned with these drugs. I: evident from such communications that i perience in the management of tnoc antidepressant poisoning is limited, as DPrice and Powlethwaite admit. The antidote available for tricyclic ar.: depressant poisoning is physostiemme was first described by Slov-.s f of*1 in 19` followed by Rumack: in 1973. In the tir- futurc this agent will be recommended drug companies marketing tricyclic andepressants for use in the event of ow dosage. It is important that a cri: . Until more conclusive evidence is pre regarded at reliable evidence of caremo- appraisal of rhis form of treatment show sented in favour of hyperimmune gamma gemcitv. Thv reliability of such short-term be made available. globulin and antiviral drugs of the tests for predicting carcinogenicity needs to In this centre we recently treated w thio>emicarbazune series we consider that be assessed and the false-positive and false phvsosticmme salicvla'e 21 conecur-. vaccination with all its limitations must re negative rates ascertained. Unfortunately patients with acute tricvclic *.n*idepressc: main the first line of defence m containing this can onlv be done laboriously by com poisoning. In this <ries unconscicusti' outbreaks of smallpox. In our view this should be combined w-ith hyperimmune gammaglobulin for those a: particular risk. At the present time we do not believe that thiosemiafbazones have a parr to play in the routine prophylaxis of smallpox.--We are, etc., Ronald T. D. Emond Department of Infeeuout Dnea>e', Roval Free Ho*piral. LonJun T.C-1 G. Donald W. McKendrick Detwrtment erf In/ectiow Diteieer, Si. Ann t General Hotptal, LanJan N IS l Di\c>n. C- VC . 5<naf/rujr LonJon. Churchill. 196: t Kemre. C H.. Bcfge. T O.. ftd England. B . Pediatrics. 19S6. I*. 1*7. 1 Kemre. C- H . ri a.'.. Bulletin a) the VTitrlJ Hta'th Orram.-jtr *,. 1961, IS. SI, * Bauer. D. J St Vincent. L.. Kemre. C. H .and Do*`nie, A. T . Lancet. 1965. 11. 494. s Do Valle. L. A R . De Mela. P R- G"-e*. L F fle S,. and Proenea. M L . Lancet. 1966. Z. s>*6. * Herer. G G . / ai . Ameeiecn Journal of Ertdemtolncv. 10*1. 94. Jis ' Rao. A R. M,KcnJnck. GOT. Velvu-<hn. L. and KamaiaS^tu. K.. Lonerr. 1966. 1. 1072. paring the results of short- and long-term tests. Where 'his has been done in the pest the approach has generally been to show that known, usually potent, carcinogens give positive results in short-term tests, and even this-- has not always proved easy. The opposite approach--namely, of seeing whether suh'tances which give rise to weekly positive results in short-term tests or which unexpectedly give rise to positive results predi-pose to neoplasia in rhe long term--has rarely been followed. Clearly much more thought is going to have to be u`cd to protect workers against possible canevr hazard from new chemicals and materials used in industry, but con fusion and little benefit would result from falsely labelling substances as orcinoccns on the basis of short-term tests of unproven vaiidiry. Committees of experts that have reviewed carcinogenicity testing during re cent years have invariably rejected short term tests fo* the purpose of establishing safety.*1 We should be equally careful io reject them fer the purpose of establishing hvperreflcxia. bilateral exrenv>r piantaf :. sponses. and the cl3ss-.cn! pyrrhen! an- cholinercic effcvt* were alt rap d!v revet- --a clear indication rhar phvsovigm.-, salicvlate is an an'idore in rncvdic poison ine. On rhe other hand, rhourh 409 patier wi*h tricyclic an'idi-prcssanr po:on:r.e has- been admitted to ih:s centre durms the pc^ five vear< no fa-a'.i-ies have been e- countered using the conserva'-.ve suppor'.'.- regimen described by Mairhew ar.c Lawson.'1 Phvsostipmme has thus no pi: in rhe routine management of such patier. This s'atement is suppoped bv occurrence of potcnriallv dancerous y effects assoc^'ed with administration of drug. In our series two of the 21 patients had convulsions and two others hvgr? saliv-a'cd and developed a severe bradvarc:- due to cholinercie action. De<p:te the'e dancers phv-.tic7r:rc is of value severeiv pcsonedpatien's where oth- medical complica'ions demand that the period of unconsciousness should be shortened.--I am, etc.. Six,--I could nor help feeling that your otherw-.se well-balanced leading article on this subiecc (30 March, p. 590) tended to oversimplify two problems. Reference is made to the induction of sarcomas at the sire of subcutaneous implantation of plastic films and it is sureesred that tumour in duction is dependent on the "uninterrupted area of the film." This is not universally true and the possible importance in relation ro car.ccr induction of chemiol agents that can be leach-d put of plastics has not been ruled out.1 Plastic sponce is potently pro ductive of sarcoma' on implarvation: and hazard.--I am. etc., London SW19 Francis J. C. Roe l Heuper, X. i . and Conway, T. D.. CAr*nic! Carcinofene'is and Cancers. Springfield. Thomas. 19">4, ! Duke. C- E-- and Mitchley. B. C V.. British journal el F'ainc Surfery, 1962. U. 215. 1 Carter. R. L-. 4nd Roe. F. J. C., Bnrtsfc Journal el Cancer, >969. 23. 40t. * Carter. R. L . Roe. F. I C-. nd Peto. R . Journal of I"? .S'arionol Canter Institute. 19*1. 4*. 1177. s Gf"0. P., an-.' Golherg. L., Feed and Ce*metic Toxicology, 1966. 4. 297. * Ganircrfii. S. D . Grao. P . end Golhcrf. L . Fn.td and C"nietic Toxicolor*. |967. J. 601. * The Tftine ! Chtmieels lor Carnneeemcuv. Aluiarrnmiv and Teratatemcity. Defiarsnent of National Hc'lh and WelUre. Oiiawi. Canada. 1971. * Tor Id Health drcsnisarii^n. pnnop;ei lor 7Vf-*ie an,I Eva'uali-n of D'UC, for Careinofennty Ray Newton RTeh^rinRnoavl aPl oIinfoirnminarvT.reannent Cerive. Edinburgh EG3 9YT l SlovI. T L . Oil. 1 F . Tt-rlhium. D T.. L4S>1Dcaine. VC.. Clinical Ttitieoioey, 1971. 7 Riimak. B H . Prd-atnct. 19-3. S2. 4*9 J Marrhew. H . and Lawon A. A H . T-eaimr-r of Ci-i-ii'i'i Arufe P'l'ftnmfj, 2nd cdtv, Ed.r. t>urgh, Qiurchil! Livingstone. 1970. Sir.--The letter from Drs. K. M. Goel arc R. A. Shanks '73 March, n 57ro reolv TO Dr. R. N. Wilson's crircism (9 March, p unfortunately- indvites that the authon themselves have not quite appreciated the sirn-ficance of 'heir own piper. Dr. Wil fragmented pchethvlene proved just as Ttchrial R 'port Series No. 426. Geneva. son has cleanly pointed out the consequence T H O . 1969 potent as a solid piece of rhe same material * Food and Dr is Admini'Cenon fL'.S.A.t Ton- of not distincuishine between inndverTenc in producing sarcomas.5 Also other factors such as the relative numbers of anions and cnlney and Applied Pharmacology. 1971. -. (accidental) incest-on and deliberate419. pimped 'rheraoeutx) ineestion. In fact ir. cn- may be important.4 In anv case, in their original oaoer f\6 Februar.-. p. 263) *!. of thv work of Orasso and Go1berg' * few- authorities in the field of experimental carcinogenesis would now Amitriptyline and Ii.iipramine Poisoning in Children Drs. Goel and Shanks have themselves fal len into this error for thev stats' that "chil dren who in-ext tricyclics rn ti-iar*fer dos~ accept the induction or non-induction of Sir,--Drs. K. M. Goel and R. A. Shanks arc fmv italic'] should always be admiued sarcomas in the subcutaneous tissues of rats (16 February, r. 261) outline the numerous for nbsen-anon and convnuoux cardiac in response to the subcutaneous injection or dancers of tricvclic antidepressant over- monitoring for 24 hours, because am*th- implantation of fore.cn materials as provid- dosacc and sot'nd a verv timelv worninc on mins in these cases are common snd danb*.*- ine information that is indicative cither of thv folly of preseribinc such drucs for ous." By saving this thev include all who safetv or hazard for man of materials to children. I am concerned, however. that lhcv are heme treated for enuresis too. which he is not exposed by a parenteral should stare that there is "no known anti Dr. Wilson savs that the Dui.'v Afimtr route. On the other hand, an imerprerable dote." Much more alarminc is the letter afield convess the imprc"ion that the and useful observa-ion from this kind of from Drs. D. A. Price and R. J. Postle- therapeutic dose was *0 blame. How couL experiment in the case of poiw.nv! chloride tjiwaire (23 March, p. `"5' advocatinc rhe the Datlv Mtrrrrr be blamed if the authors would have been that acoustic due: rumours use of parenteral ciphe.-.vLhydantom m did not make the distinction berj. een ir.cra- RSV 0012460 RtSlAKCll * o i V Abstracts of pttpera aubt. .ted Tot publication on th Nor .Key ^tudy of Workers exposed to Vinyl Chloride Monomer. (A) THU MORTALITY i3>mlr3ICb* OF WCuKKUa hXWX>4> TO VINYL iHILOHIDE HUKOHUrf IH THU MAHUKiUTUdn OK POLYVINYL ClfLOdluU IN lirtrlAT BRITAIN Bv A.JmVOX and P.F.COLUSB Identification particulars were obtained for over 7,000 men who were at norne time between lyAO mid 1974 expo sed to vinyl chloride monomer in the manufacture of polyvinyl chloride* Approximately 9% of these hove been traced and their mortality experience studied. The overall standardised mortality ratio, 73.4, show* a aignificant reduction compared with the national rates. Tour cases of liver cancer are found. Two of these have been confirmed by a panel of liver pathologists an angiosarcoma and two as not angiosarcoma There is no evidence supporting the hypothesis that cancers other than those of the liver nre associated with exposure to vinyl chloride, monomer. The two cases of angiosarcoma were found in men who has been exposed to high concentrations although the second man died only eight years after exposure. The industry in Great Britain has expanded considerably since the Second World War with over ljO per cent of men having entered within the last decade. Conclusions drawn about 'the influence of vinyl chloride monomer on the mortality experience of men in this industry must consequently be tempered by the reservation that the full impact may not yet be in evidence. (Submitted to the British Journal of Industrial Medicine) (B) LOW MORTALITY BATUS IK INDUSTRIAL COilO:<T STUDIES DiTg TO JELECTION YOU WORK -' ! : AND 5UHV1VAL lfl'THE INDUSTRY By A.J.FOX and P.K.COLLIUH Occupational groups are often described as relatively healthy because their mortality rates are lower than the national average. Although correct this confuses the issue for those interested in assessing the effects of exposure to a particular chemical. By a further analysis of daea collected in a study of all men ever exposed to vinyl chloride monomer in the manufacture of polyvinyl chloride in Great Britain, three factors h-ve been shown to contribute to the low mortality rates that were observed. The three factors, the selection of a healthy population for employment; the-survival in the industry of the healthier men; and the length of time that this population has been pursued, have all been quantified. The mortality experience within five years of entering this industry was shown to be ns low as 37 per cent of that expected; for circulatory disease and respiratory disease ns low as 21 per cent. There was a progressive increase in standardised mortality ratio with the length of time since entry nuch that the effect had almost disappeared 15 years after entry. To avoid confounding the selection effect with the survival effect the latter was measured by separating men who survived 13 yearn after entering the industry according to whether or not they were still in the industry after this period. Those who had left experienced an overall standardised mortality ratio some 30 per cent higher than those atill in the industry. This effect ulthough consistent in the age groups between 23 end ?h and nil cause groups studied was greatest in those aged between 23 and 44 and for lung cancer und respiratory dinenne. (Submitted to llit? British Journal of Preventive and Sociul Modi cine) COPIED BY MCA FOR DISTRIBUTION TO THE VINYL CHLORIDE TECHNICAL PANEL, AUGUST 27, 1976, MR. M. FREIFELD RSV 0012461