Document ga4EL6yrzyYa3mOGe1X51Z9MG

(" 31 JULY 1987 VOLUtlE 237 NUMBER 481 EXHIBIT Amerlcan Association lor Ihe Advancornen1Of Sclmce Screnre serves 1:s renders as .I 'orurn fw Ihe preswrralion anc JISCUSSIO~o! mpocar: .SLY?S rela!ed lo ;he aavancemepi 01 sc:ence. irrt.ujiry :;e oresemaiion of m:norily or CWllc:inq poms 01 wew. ra:he: :aan by puOlishingonly malerial on wnich B consensus has Wen reamed. Accordinql?..all articks published hi S,-e:c-r?ctuaing wdiloriak. news and iommcni. 3:d bnok r,wwsJie signed and rellecl VIB molvdual W ~ W E01 ilie aul-.c:s a,-o no! olltial pain:, 01 VW adaplea by :ne W S cr !ne ins::Iu!io"s wilh which tne 3u- inors arz anirinttw. I Publisher: Nvon W TriveipeC+ Editor: O m z l C k?sh!dnd JI h p u t y Edilorr: Jni.tp ti Abelsin IErymerrrgacd #lpp/& Screrrcesr. .kmn I O-wlr'a~{f~?\scaS/crences) EDITORIAL STAFF Managing Editor: ?a!ric:a A Vcroan Asrialant Managing Editors: %arc{ J. Hacnagel. John E. Rmqle Senior Editors: Eleam:e 8ulr. Ru:3 Yulslad AssOCIaIO Edllon: KJ::?a CGl rs. earbara Jasny. Kalrina L. ue,ner.Eai!t. Meye's. i'twti3 0 Szurorni. Cavia F VJSS Letters Editor: Cnris:ize cJ:!3eri Book Aevlows: A.l:hcr.l!e Lwrgston. earfor, Deborah F. wasnourn This W n k In Scienrx Rclh Levy Gcyer Contributing Editor: Laurepse I.olossmar, Chiel Production Edilor: Ellen C Murollv Editing Doprlment: Le: s Sxrri!!. r+aa Marq MsDaniel. Bartl~raE. Palterwn Copy Desk: iyia L. Gwen. Sharon Ryan. 2everly Scields. h r Jvicoreen Production Manager: <arm Sinoors Assislant ProduclionManager: Jaaes Candry Graphics and Production: h?lki?iskoo. James J. Olivam. Eli-arw 'N.lrner Covers Editor: Gra;ce F i n w ManuscriplSystems Arulyst \Y.!iarn Car:er Cancer Phobia \ or more t h m 10 years, the public has been subjected to a niedia barrage leading to widespread, misinformed fear of chemicals. Through the use of qucstionablc evidence, many major substances havc been labeled carcinogcns. If data arcddjustcd to eliminate effects of cigarette smoking, thcre has been no overall increase in cancer due to orher factors. The higlily publicized cancer epideniic that was predicted earlier has not niaterializcd. With increasing use of synthetic chemicals, it was desirable to screen them for possible carcinogenicity by tests on shorter li\*cd aiiimils such as mice and rats. The gcncral ' procedure is to subject the mice or rats to massive doses ofthe chemical to be tested, usually by feeding, gavage, or inlialation. I'reliminq cspcrinients determine a maximum tolcrated dose. This m o u n t , rcpeatcd over a 2-week period, L I S U ~ lYeads to a noticeable but tolerated reduction in weight. A chronic dose regimen is then employed in experiments that last for the animal's lifetime. T h e levels used vastly exceed thosc to which humans are likcly to be espsed. M a n y of the cxpcrinictws that have been cited as proving a potential carcinogcnicity ufa chemical for hunians havc been pcrfomied on inbred strains of mice that havc 3 natural incidence of liver tumors. In humans. thcre arc taboos against inbreeding, which oficn lcads to genetic impairments. Thus the use of inbred mice, though convenient experimentally, is suspect. More important is the fact of high natural incidence of liver m o r s in the test mice. The usual rcspoiise of thesc animals to massive doscs of a chemical is to develop an men liigher incidence of liver tumors. When this happens, the chemical is labeled a potential carcinogen in humans. It so happcns that in humans primary liver cancer is rare with the exception of alcoholics and those who have sutfcrcd from hepatitis. With thesc esceptions. incidence of liver canccr in thc United States decreased substantially during the tinics \\hen use of industrial clicniicals cxpandcd greatly. Thus extra liver tumors in a naturally tuniorigenic mouse is of dubious rclcvmcc to humans. Results from the massive doscs are extrapolated linearly to low doses, and the assumption is made diat hunians arc as sensitive as the most c;t?cer prone of the specics of animals tested. Use-of a l i n m exuaplation to low doses implies that humans do not have rcp'6ii'mechanisms aginsrinjury; Counllcss milIions of animals have been sxrificed in testing chemicals. Comparati\dy little eEom !us bcen devoted to studying th? niechaiiisnis of chemical carcinogenesis. An important exception is work conducted at the Chemical Industry Institute of Tosicology (CIIT). The CIIT, which has .ichicved an escellcnt reputation among toxicologists for its careful work,has cxaniincd the detailed mechanism of the interaction of formaldehyde wid1 nasal p u s a ~ c osf rats .iiid 11% sliowi tliat tlie linear niodcl is iiot correct iii predicting nas.11 cancer in die rats. R.iclicr, J more relr\.ant measure is the cstent of intcraction of formaldchycic with the nasal DNA. l l i e m o u n t of binding of formaldehyde to DNA decreases much faster than the concentration offormaldehyde in the nasal pissages and is a lxttcr predictor of c.;irr.inogaiesis. Another impoiisnr study of C I IT has k e n an investigation of the iiiechaiiisiii 01' the carcinogencsis of hranclicd-chiin Iiydrocsrbons in male rats. These 1iydroc;irhons are key components of unleaded gasolinc. The studies sho\vcci t h x the Iiytrocarhoiis iiitcrfcrc with the nicchmism for cscretiiig a lo\~~-niolcciilar-\vei~prhottein by the mile rat. licsc.ircIi JC CIIT indicates that this may be tlic cause of kidney c.uiccr in niilc rats cxposcd g.lsoIiiic. A siniil.ir iiicclianisin with related cancer docs not tsist in fcmalc rats. in inale or fcm.ilc mice, or in Iiumiiis. This r y e o f result calls into cpcstioii the pr.ictiic d r l i e rcgtil.itoy .igciicics in sclrsring tor csrrapoI,rrioii t o hrinim r l ~ tarom tllc iiiosc snisirivc aiiiin,il. .- Aiiiiii.iIs ditiiir by IIIOTC iIi.tii a factor of 1000 ill ~ l i cIcvcls required tiir IctIi.11 rcspiisc t o diosiii. RoAmts and hum.ins arc know1 iiot to b ~id.entical in their hicxhciiiistn. To att.iin J rcalistic csrimite ot'ttic tiaz.ird-ifau~--presciitc.d by a chmiicd, spccitic iiih>rm.itioii.iIrotrt its iiictdx)lisin and physiolo~ic~cflfccts is iiecilcd. 'The nvo esaiiplcs involving tonnaldc- hyde . i d hycirtx-.irhons illurtrnc thc power of .in Jpproich in which dct.iilcd nieclianisnis of chcniicil circinogcnicin are cxmincd.--Pi 111.11' H. AIWLSON -