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The Arsenic case Prof. Gerhard Stohrer

International Center for a Scientific Ecoloyy Seminar on lineai ri~;,k ati,essrment May 10, 1993 Toxic Policy at Dead End; The Case of Arserif c Gerhard St8hrer Science and Environtmental Policy Project 2201 wilson Boulevard~, Suite 1003 Arlington, Virginia 22201 1kY#* !'t*ft7R*kttktf:l:t.fr*lc!!c.lr*1xfr/c.k.1Y'R*4*t#xlt* t* 7lJksY4xr~~c.ir~*s#~ Abstract: E;PA`S challenge of its own arsenic drinking water standard with a *linear" cancer risk assessment has thrown the drinking water program into a regulatory crisis. The assessment wouSdhave banne6 arsenic and many other trace elements and xould have essentially ended the use of piped drinking water. EPA's Office oL Drinking water has ignored the cancer risk assessment, E...pA's Science Advisory Board has rejected it and the U.S. Department of Eealth has rejected the linear cancer risk concept in the related case of fluoride. An unacknowledged stalemate over this issue has lasted for more than four years now. This crisis provides an opening to~ rejects categorically the use of extrapolation beyond the observable evidence as a misuse of science. The crisis also shows that risk assessment authority is in the wrong hands. Scientific and regulatory responsibilities need to be clearly separated and ultimate authority for risk assessment transferred to an independent and respected entity like the t7.5. Department of Health. This article discusses the evidence that shows that arsenic causes cancer above a daily dose of 0.5 mg but is safe at the currently used arser,ic drir.king, water standard_ t

,7ust twv atontt,s ago, the new Ad, ir~:~tra~nr of the D.S. Encironmental Protection Agency, Carol Brosrner revealed a serioss defect irs toxic policy. Administrator B.ewner acknowledged that the Delaney Amendment (1) .:~akes it impossible to regulate most pesticides and'that she will seek a change in that law (2;. 3ut the problem in toxic policy far transce:ids pesticides and the Delaney Amendment. All the regulatory programs thctt existed before the EPA, drinking water, waste and garbage, are all in a crisis_ In a stiictly legal sense, the Delaney Amendment has nothing to do with drinking water, waste and ga_bage but its extreme vieK of cancer risk that no dose is safe has since b2en incorporated into official cancer risk as5essmeri.'t in the foriz of the linEar risk e::trapolatio;) (311. The Superfund (4) and 4,t. er ~_ogr,ms ; ave i!: tuxn been based on this risk assessm:ent. AJ Vogether, an estireatcd 40 biIlion in annual spending is just;fied by r.othinq else but the no-dosP-is-safe concept implied in the Dela ne_; n,.,ezdrnent. EPA's admission that DelaneY: is failing in the pesticide program is o;;i1- ani lntroal]ction to a uior~ awful ad?iission, yet to come: tilat cancer risk based toxic policy at a cost of 40 aildion a year is wrecking the sanitary foundatio-i on whdicn al' Envirc: r,ent~l' pol icY rests. In this p{esentatzon I will describe how linear cance:c risk assessment has thrown the drinking water program and its system of standards into chaos. I will explain why EPA has rejected~ its own linear cancer risk assessmerit over arsenic, why this real human carcinogen to --his day is regulated 'ny a moderate standard and wh: EPA's Science Advisory Board, on the basis of current science considers that moderate standard safe. The arsenic standard is no frivolous standazd. Real outbreaks of arsenical poisoning in mountainous and geolcgi:.ally active regions have demanded regulatiori already hundred years ago. It was known already then that arsenic is ubiquitous in food and water and that the leeway for regulatory action between the background concentration and the toxic lievel was small. Arsenic levels onlv ten-fiold higher than background cause 3isease. Under this severe constraint the Royal Com.nission on Arsenic in 1900 (S) estimated the toaic threshold: for arsenic at about 450 micrograms and recommended a drinkin9 water ;tandard of 10f3 ug/L. (Tmeyy expressed it in grains per iiaperial gallon, of coufse,. Later lowered to 50 ug;/L, it now szrves as ti:e arsenic standarc practically all countries of the world' (16). 8ut in 198; , the E, H challenged its own arsenic standard with a formal cancer risk assessment base4f. on the linear extrapolation of risk (7)_ 1 wili

exNlaini briefly how this is done and why it produces results that are so spectacularly at odds with the evidence. In tbis case, the data are from an outbreak of arsenicisc, and arscnical cancer in Taiwan (8). The relevant cancer dose response curve consists of just four points, three of them positive and one a clean zero or 0/7500 cancers in the low dose group. For its linear cancer risk assessment, EPA ignores the clean zero low dose group and picks the lowest positive response instead. This is then extrapolated linearly to zero dose. EPA argues that this procedure is consistent with the data because statistical confidence limits of the linear extrapolation include zero as the lower limit. Z will come back to the science and briefl: consider the consequences if EpA had accepted the ldne,r arsenic risk assessment as policy_ With linear risk, there could' no longer be a standard, no matter how low, to conform wit:R EPA's current use oi cancer risk in the Superfund programl. Ever, the 1074 risk levEl, the most lenient considered in Superfund, falls below the 50 s^ dose that we take up with our food (9). Arsenic, and by the same logic also fluoride, selenium and even water chlorination would all have to be banned_ There could be no drinking water from the tap anymore. Everyone who has thought that nightmare scenario to its logical conclusion realizes just how absurdd and reckless the linear cancer risk concept is as public poiic y_ EPA's Office of Drinking Water has cor.sidered~the consequences and' has rejected', or more correctly, ignored, EPA's own official cancer risk assessment. The EPA Science Advisory Board has rejected it (10). The II_S. Department of Health has rejected linear risk in the very siinailar case of fluoride (11). This stalemate has been iasting for over four years now. EPA has been unable to resolve it and unable to candidly admit it. The American public and the U.S. Congress remain completely in the dark about the cbaos. I will conclude with the scientific evidence which you may judge yourself. Arsenical cancer is unlike any ot-her cancer. It is so unusual that a dermatologist will immeciately suspect arsenic when he comes across the typical picturr of skin cancer on~nor.-exposed parts of the body accompanied by the typical hyperpigrzentation, hyperkeratoses and punctate iceratosea. Figure 1 shows arsenical skin cancEr, , bladder and lung cancer an& ar., enical gan grene from the Taiwan epidemic of arsenicism that involved 40 000 people. nl= of these manifestations aisappear at intakes of less than 500 snicrograuts per day, a fact not.ed by physicians for Y:undre.: ytsrs. 3'

In Taiwan, 7 500 low dose controls showed none of the typical. manifestations and~ no ski~n cancer. The negative result at 19 u5/L provides powerful evidence against the linear risk model and for a classical thrEshold~for arsenic cancer. Two cancers would have been expected according to the linear ;odel plus 30 of the linked ptecursor lesions. If the linear model were correct, the 1000-fold greater Taiwan cohort, compared with the one studied by the Royal Commission would have moved the apparent threshold substantially lower. But the estimated threshold in Taiwan is still 400-500 ug, the same as estimated' in England, ninetz~• years ago. This, more than anything else convinces u;e that the observcd thresholc is a real and'fit'm threshold. I am only one of many, the EPA Science Advisory Be,a,d among the:rt, who has looked at the evidence and conciudE& that arsenic presents no risk at the regulated level. The ev:idEnce could be much stronger yet if the complete pos.itive d'ose response ;aere plotted rather than three compounded data poir:ts _ But the EFA is determined to keep those data in the shoe bo~,es in ^aipei whcre they now are_ The picLute of the Taiwan epidemic agrees well with current understanding of indirect carcinogens such as arsenic. At effective concentrations maintained over many years, they produce chronic cellular stress which chronically activates protea*:s involved in mutagenesis and proliferation. This gives rise to benign and acute lesions that can become malignant over the course of many years. Ineffective doses will not cause either, no matter how long the time and regardless of the presence of synergistic stimuli. But as satisfying as that agreement may be, it should not distract attention from the much simpler fact: The cancer evidence simply does not support the Iinear model. Beyond that evidence begins the responsibility of the regulator. He has specific authority to consider questions of safEty_ Scient=sts Were never given that authority and' sY:ould' stay away from "erring on the side of sarety" particularly when 'erring on the side of safety" rteans legitimizing an extremist policy. The problem with cancer risk assassme-:t is not the evidence but who interprets that eridence. As long as a governmcnt agency 1_'<.e the EPA has the power to ignore scientific evidence and igno_e science advice so long will there be a risk assessment crisis- It is time to recognize that it was a mistake to give such inappropriate power over science and~over risk ass.es:mer.t to a reguSatory agencv. These responsibilities hac in the Yast 'uays 4

been cleanly separated with regulatory responsib-ility in the hands of civil servants and scientific responsibility irn the hands of ad hoc committEes of respected and independent scientists and physicians. The `Fluoride Yanel" of the U,S. Departr„ent of Realth is the modern equivalent of the Royal Comr.lission. Scientists who aze concerned about the misuse of science in regulatory policy have a legitinate demand that risk assessment responsibility again be separated from regulatory responsibility and be placed in independenz and respected hands_ In~the United States, the O.S_ Department of Health has that respect. Specifically, its wFluoride ranel" has demonstrated independence in the face of heavy special zr.terest pressure as it rejected t*-,t linear model for.fluoride _ There would bc no risk assessment controversy today ar.G no regulatoty chaos and we s:ould not be here today deFloring t::-e:-• _, the U.S. Congress had~ Irtaintained the clear division between science and regulation that had existed since the dawrn of satnit-a<<• and occupational regulation in the last century. Instead it started with the De3.aney Amendment a process that first mergF•~r scientific and regulatory responsibility, then ended all independent scientific control and now leaves CongrEss, the public and even the EPA itself with ao control over toxic policy. This is why there must be fundamental reForm and why that reform rrust involve the re-establishment of independent scientific controi over risk assessment. C 0.02 ~ C O a a> LZoryF.taadard f + O O a.e. ~rSazinq I ~ o. e.oi ><atar itiveraqa ; .a s a.~ ma a f / I1 b 1_C 'o o 10 1,06 uq•/L arseaic r iguze 1 rep,oduded from (8)'_ FS$. 1. Ms:nN_-<' diseti+Z c5 a~it:::~crI ef.a:5cr.i.c in dri^.izin; - +.act p•di.uile: prcvalcn-e of s3J0 c r.cu ~Iitd tlr.tes; arui !5l.ckfoa: (opGli rircfcSY3S .l fUfeo.On of 3^ic.'•.iC in ~dfi9ianF vratcr~ i:^. T1.i,•3rr. Adio. agc sraadu~'iz-d' np. _firy forrepr::er.t:!i,c ir.::r;a! :::ncers b:~a• dt" elAeer in rn::1k~(sg.r.tt,) ar•')ar,e ck;-.cer in CC+Crc~i.'tUS for b.lcloYOur7~ TOrujil., bie:::lcr ;:.n,rr: m:aas end 1?.-1i0000G fo; lunp c^a.^ccr. r.,:ks!: Co:.cer.ltetoa ranF-. 0-30tYN:bft wciclt:ed and rep'~cs_~ud as R;gti o*dr~~'c li. Fcrpigrrcntaaon !(1j.af 7r7orp;ch,: 3< a f•:.n•ctMnior t$fr,, ir, ~^. _ 4_tcr in Bcr.ga3. 'I'he brt:l;en dcx n•s1o,x z:rb;irsri1 pD:m C-cn5cttivt. r1s.-ih3'.d of 100 s-•_:? ••_roy.,:cr:1 co^J:;m; c.,..1 5

REFERENCES AND NOTES 1. Schneider K. 1993. EPA Plans to Seek Loosening of a Law on Food Pesticides_ NYTimes 2-2-1993 Al 2_ United States 1959. DDelaney amendlMent to the Food, Drug and Cosmetics Act. 21 USC 348 c3A 3. U.S EPA (1976) Interim procedures and guidelines for health risk and economic impact analysis of suspected carcinogens. Federal Register 31:21462-21405. U.S. EPA (1986) Risk Assessment Guidelines. EPA 600/8'-87-645. U.S. EPA (1988) Intent to Review Guidelines for Carcindeen Risk Assessment FRi,-3435-3, 53 (168) :32656. U.S. EPA (1989) Workshop on Guidelines for Risk Assessment. EPA/625/3-89'-315. U.S. EPA (1990) Use of Human Evidence in F.isk Assess7,ent. EPA: 625/3- 90-01_ 4. United States 1980. Superfund lav or Cor.,rret:e.n.sive Environmental Response Compensation and Liability Act 1980. PL 96-510 5. Great Britain (19$3). Royal Commission on Arsenic Poisoning. Part 2, Report. Wyman and sons, London. A summary is published: The fi:nal report of the Royak Commission on Arsenic Poisoning_ The Lancet, Dec 1903, pp 1674-1676 and 1746-1748. 6. 1942 Drinking water standards. Referenced in: Drinking Water Standards Title 42, chapter 1, Part 72-Interstate Quarantine Federal Register 2152 (Mar.6, 1962)~. SevEral States had drinking water standards of their ok•n before that time. World Health organization (1984) Guidelines for Drinking Water Quality. vol_ 1. Geneva, Switzerland 7. U.S. EPA 1986 Cancer risk assessment for arsenic. U.S. EPA (1987) Special report on ingested inorganic arsenic 8. St8hrer, G (1991) Azch Tox 65:525-532 9_ Cartrell, MJ, Craun, JC, Podrebarac, DS and Gunderson, EL (1986); J. Assoc. Off. Anal. Chem. 69, 146-161 10. U.S. EPA (1989) Scicnce Advisory Board. Review of the arsenic issues relating to phase II proposed regulations fr= the Office of Dxinking Water. A1so: DrafL af that review. 11. U.S. Departmer,t of Health and Rurman Services (199i,' Reviea of fluoride, benefits and risks. Report of the ad hoc subcommittee on fluoride and the committee to coordindte environmental health and're?ated programs_ 12'. Morimoto RZ, Serge KD and Abravaya K_ Transcriptional regulation of Heatshock genes_ indir. induction by heavy . metals. J Bio1 Chem 267:2198'-21990 (1992) O ~~ ' 2