Tobacco Documents Online

18/0a '93 17:55 $'d2 2 2878069 P.Y.C.S BRUSSBLSIa005/012 1 1 Is the concept of linear relationship between dose and effect sti71 a valid model for assessing risk related to low doses of carcinogens? A zestrict;+ed iaternational ataentiac seminar May 10, 1898 - Paz'1A (P9'tsnce) L1At,.'KCIi(MI Vf) Assessing the risks to a population due to exposure to high doses of carcinogens has become routine t+ractice for to.-icologir.ts, canrerologists and epidemiologi9t.. Although neither simple nor completely devoid of uncertainty, thie practSce is based on te9ted methodologies which lead to rellable predictions. Although axper+mel3tF on animals provide valuable data (whatever doubts may remain on the diEtlaulty of exrsapolating from animals to man), epideauology, practised with the necessary rigour, takes us beyond hypotheses into the field of incontestable facts. Uccupational safety regulations usesuch facts as a reference. Questions arise when deeiaion eentres, trade unions, assodation+ and "environmentalista", in short, lobbies as a whole, se'.•ainq on the observation that a substance is -carc+noqenic in high concentrationa", put increasingly heavy pressure on the scientific community (and on epidemioloQists in partiiculaii to obtain data assessing the risk tn populationa who, at work or irn their everyday life, are subjected to loa - even vary low - concentrations of substances proven carcinogenic tn high doaea. The classic epidemlological use of clinical observation of effects on a representativo population becamea inapplicable because of the size af the samples needed to validate the findings. While a few hundred individuals :uSice for a fairl,y accurate asseeementof the risk related to high doss, hundreds of thousands and even millions are needed to assess the potential risk when the dose is a hundred timas sraaller. 8uch numbers, once the cohorts have beon rid of possible bias [presence of co-eareino(ens,, age, sex, l'tfe style, manner and source of exposure. latency tima, direct and indirect exposure, etc.) are quite beyond our reaoh, tochnically, materiaIIy and financ:ally. "The need to know" - and among decision makerst,hmneed too know what to base their dacisionew on - remains. ln 1959, during debates on the "Food, Drug aad Cosmetics .1ct", US Senator Delaney'iatroduced an amendment which postulated thauL any molecule of a carcinop,enic substance can cause caacer.. - in 2969, duringg debates on the "Food. DruC and Cosmetics aet-,. L'$3enator Dnsaney introduced an amendment wbicii bara bis aame andd which postulaced the norlon that t7•ara is no doSe without en e3e<t. This aoncept raMdly went beyrond the ti+nita of produets intendad for human eonsutnptioa rad was eacand.dm assessmenc in geners] -wichouL refereneaW tba dose - os all carcutoyens. No dose 1s safe:" Delaney mafntained. 'One fiber can kill,' irxio Selikotrrctyrted a f«w years mWr.

18/03 '93 17:56 Q32 2 2878089 P.M.C.S BRUSSELS ®008/012 2 This naw notion had reverberations well beyond the 4h'nted States. upsetting ideas held by the in6ernationa1' community of toxiculogist9 which had been based cn a saying atttibuted to Paracelsus: Euerything is a poison. nothing is a poispn, the dose alore makes the poisoa." At the same tinae., incredihla advances ware being made in physical and chemical measuring techniques. which meant that indinitesitu.l tracei of snbatances could be measured - trx~,~as of anything in everything. Lpidemiotogy, originally an expcrimencal scdence, had tu renpond to this urgeAt demand and took the approach of the Delaney amendmant: "No dase is safe." Numbers of mathematical models were devised, perfectecl and used to assess substances with proven carcinogeraie elCects in high doses, by eEtt'0.jlolabng fi'om the affects observed in high exposure towards low exposure. The principle chosen was linear: the effEct was proportional tu the dose, starting from the principle Lhat any dose - no matter how low i£ was - would have some effeet. This concept, which often yields very different results from one etudy to another, is currently used as the basis for evaluating low exposure effects and, conseauently, for drafting national and international regulations- Many apidemiologistm themseh:es doubl the validity of these extrapolatio.ns but they use them, for lack of anything better. For many substances omnipresent in mmati s environment, the application of the concept of linearity also poses an insurmountable problem eoneerning the elimination of natural'sources of exposure. The combination of new developments in methods of analysis and measurement and the very human desire to enjoy total protection (zero risk) seems to lead more and more often to dead-end or incoherent regulr.tians. liow l3ar can we legiliucamely push the principle of precaution r Tt was felt that this is aa opportune time to pose the question in its very principle now that we are in a position - for some substances at least - to compare predietions resulting from the linaar mathematiual approacki with observable facts. This seminar. reserved for internationalspecialistsl will Address the following question: must we persist with a principle of a<sessment, even if ita predictions are not confirmed by real events. if the answer is "Yes", the limits of credibility of such a principle ought to be defined. ifthe answer is "Iti'o", a new apprcach ought to he proposed.

18/03 '93 17:57 $]2 2 2878089 P.Y.C.S BRUSSELS ®007/012 3 l'nrviluratsl Agettda 5unday May 9, 19.93 7J7 p.m. • Welcome and registrstimn far p.nYli*du HJtel Hilton - Paris 1$, avenue de SuQien - 75016 Paris 7/8p.m. - WelenmP cnektail 8110 p.m. . • Diuttor. Monday May 10, 19J.Y 8/7f.1ti a.m. • Registration - l:ottbe 8-15/8.30 a.m. • We2oome address by PierrB.koly, Chau+••n of the Intesnal3anal Center for Sciantift Ecology 8.3" e.m • UpeninQ epaacb by ,Biologiet, Dir., Nat. I Alealrh Scfences Center, Berhele-v, U.S-AJ 9PY.YU a.ai. • MetbwluluLty af prevision etudies throueb latta5 _?~ mathematical extr& ftglist2d BjMaiSg•e~ r1Yfi..ntiian (.pidemiul4gist, Dir., 3eeMion oj8pid., Inst- or Caruer RcseareA. E:ondnes. U.K.) 9.za&su a.m. • Ctitieal appro" af mathematical CxLUaNulaL'un~ Hnt Edmtne Fmunier /7bsicoLOgfstJCanaErologist. Hbpital Fernnnd Wfdal. Naris, Frana) 9.40/10.00 a.m. • 7Pha Delsney atneudlaent and its consequences PrnL P'red S. Singer f~vaielst_ forrner_IS r.; E7S Wecther Sataltite Propram; Prealdent. Science & Enutranmental t'alicy ProJeet.. fJ.S.d.l .. 10/10.16 u_m. ... • f.'u(Yu brcmk

18/05 '93 17:57 302 2 28780~69 P.M.C.S BRUSSELS 1@008/012 4 SO.1iS/11.8A +.m.• Cases ctudies:: Yreviriunr at realitv.- Tne Asbeawfs case. ~. J. CarhettMaci)otald (Epidentlolog64t.. Rsseareh Unit in Epid., Heart and Lung Inst., Londrza, LIK.) • The Amenic cane. .. PeeL (i.r#wd 9luees- f~ rmer ehiej. De~pt of chemical risk, Researoh lnst. 31oen-ACattertng, U.B.A.i - The case of eblor[ne and derivated products (:V(:M). Suggested spaakes : Pro£ Jean-Marie 1<.hn-- (No6e1 Prize Winner CAemistry, 19tr7, Prof.. Cdtl@ge de France. Lab. ds Cli#n.ie 8upramoltculaire, Uniuersitt Lorsts Pesteur, Strasbourg, b'raacc) - The llll'1 case.. (not y et decided) - The$accharine casa-(aot yet decided)- e`ease-_' aesive smo)iing.. .llr7rf ~' uieeraf@-eoniputing, Sutton, U.Ka (1'he paaeliets will be sent we11 in advance a 6/La fold te:t frem each eoattibndon, the oral presental3ou not exceding 10 mtnutes). 11.90/12.15 a.m. • Questions / A neWerfi . 12.16/14.00 p.a. • Lunch 1A/l/;_R/l ~~..e. . • (•ie17e1'el d~BcWlion 1&3/17.00 P.1L. • ('.uffeefl'ea break )7/1)! p.yu. - Carrying of a canunsua text. Eud nf Seminar 18119 P.ni. . Speeaal meeting with internationai adentific press for WA and interviews. 19.30/9.00 p•m. • Dinncr

18/03 '9J 17:57 $32 2 2878089 P.a.C.S BRUSSELS A009/012 6 Pl9rtll:ll]Hnhl Invitations have been sent to tlhe people listed in the appendix. We e*pect fram twenty to thirty 3cientl,n..y Lu utlund. Audience A number ot personalLttes ftom Industry. the administration and thc. press will be pcrmitted to attend the seminar proceedings withnut mtervening, except for personal cantacts which may be made during meals, breaks and when ses.dons are not in progress. They wlfl be asked to lnaka a tlnancal wntributiun. Orgamirietian The seminar is orKanised by the Iaternatiesual Centre lbr a Scienti&e Ecology (see Introdnction to the Centre in the appendix}. The seientiftc work fs organised by Dr Michel 3alomon, the courdinator of the Heidelberg Appeal. Tranalation The papern and' comments made during debates may he d.livered in either English or French. Simultaneous translation will be 9uppHed ln both Languages thrnuYhont the san.nar. Pcess (:onference Itepresentatives of the international scienfiCic press are asked tc regiRter if they wish to attend the sesstona. A press conference will be held by the members of the acientific panel at 6 p.m. an .'Vl.,v 10. 199:i, to answer qneetious frotn journalisu.

18/03 '93 17:58 '032 2 2878089 P.Y.C.S BRUSSELS ®010/012 6 1'he lntertlational (:enter for a 3eienfiHc Pn>Iktgy The Center has been ereatsd at the beginning of 1993 under the french law for rwn-profit organizations. The purpose is to answer a request from a number of the Eiaidalherg Appeal signatories in view to eYtend its impact in examinitig actual issues u21e scientific connnunity is confronted with. The purposeof the t;enter 2s ezpressed inn the eyia.vs : "Tyte parpose of this sLssociaeton is ro promote o.nd jacilitate the exchange of seienfific knowledge, bassd on scientific data, regarding the protection of mankind, other living ipeefes, natural sites, and the resources of the planet. The AssoctaUon thus proposes to steppty the most reteuant eeientiftc facts to the authorities responeible for denelopir,g enuironmental protection pollctes, to soetety as a whole, mhteh, eo that decistons may be made vpenly, is called upon tu espress lts point oj aiew, as well as to all socio• eeonomic actors desirous oP contributinp both to the conseruation of thc} Earth and the ton4•term deveiopment of the human groups which yupulale it. The Assaciation is a non-profit organization." The Board of the Center includes in partieu1ar : - Mr Pierre Joly, President ot the Association !!'aan;aise pour la Reeherche Therapectique; former President of the Lnternationat Federation of Pharmaceutical ]Rsnufacturer9 Association; of French ustlonality; • Mr Constant Burg. honorary member of the State Council; honorary r.+•m9ei*+~ diraetor of )XSERM; President of the InsCitat Curis: of French nat9oaality; - Mr (iilb.rt RnfSnaa- chief lninitiY cngineer. President of the Conseil National des Ins€nieurs et des Sciontit"iques de France: of French uationality', - prot- S. Fred Singer, Doctor of PhysiCal Science: Presldent of the Science & Environmental Policy Project: former : Director, US Weather Satellite ProCi'am: Dean of tho school of Eaviranmental Sciences, University of Diiaeoic deputy assistant Adae4aistrator of US Environmental Protrction Agency (EPA): of American nationaliT,y: - Mr Gaxy Nash, mining E Secretary GenersJ of the International Council on Metals and the nvironment (IC34R): fortner Director of the Mineral Resources of Uanada;; of Canadian nationality. - Dr. Michel Salomon. coordinator of the Heidelberg Appeal; former science journalist: tnagazine editor; of bYench nationality. The Seniutar dswvd to the linear dosetresponse relationship is the first event erestea by thelateraaaonat Center tbr a®ciendfBo Fso4+gy.