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~~...vrv P:.,44a wrW.'YNb IZECLIVED US j~P®verr~ment orders new look at di )(M C 4 1991 DR. TERRI DAh9STRA The Environmental Protection Agency is evaluating data from the past decade that suggest dioxin's toxicity may be overestimated. A risk assessment model based on biological mechanism is being drawn up. DtoxtN is widely thought of in the United States as the most toxic chemical known to man. As a component of the infamous Agent Orange that the US used to defoli- ate the jungles of Vietnam, after the war dioxin was blamed for cancer in service- men who szw duty there. Although com- pensation was finally offered, neithersolid epidemiological nor biological proof of cause and effect has been conclusively demonstrated, When a chemical plant exploded at Seveso, Italy in 1976, spewing dioxin- contaminated agents in,,) the air, it was feared (and assumedj that the exposed citizens of the town would experience increased cases of cancer and/or birth defects. In fact, severe chlorachne was reported but, fortunately, more life-threat- ening diseases were not. When, in 1982, the soil in the small town of Times Beach, Missouri was found to be contaminated by dioxin at levels around I part per million, US government officials closed the town down perma- nently and evacuated its 2,000 residents to safer ground across the river. Nearly a decade later, clean-up work is still going on. Someday, when the soil is incinerated and the bui ldings are all torn down, Times Beach may be turned into a park. Over the years, hundreds of millions of dollars have been spent getting rid of dioxin, which has earned its reputation as akillerbecause it is highly carcinogenic in guinea pigs anJ and causes birth detects in mice exposed to small concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin or TCDD. Now, into2his politically charged arena comes William K. Reilly, the head of the US Environmental Protection Agency, saying that dioxin may not be so excep- tionally toxic after all. During the past several years, data in humans has accu- mulated that question the validity of ex- trapolating TCDD data from guinea pigs to man. Reilly has called for a total re- evaluation of dioxin in all of its many chemical forms (there ace 75 or so). It takes a brave man to put scientific evidence ahead of deeply ingrained pub- lic opinion. The last time a federal official suggested that dioxin standards could be relaxed was in 1989 when Vernon Houck of the Centers for Disease Control in At- lanta advised the state of Georgia about waterstandards. Shortly thereafter, he was subjected to a congressional inquiry into his possible bias toward the paper indus- NATURE • VOL 352 • 29 AUGUST 19Ql try which puts dioxin-contaminated wastes into streams after bleaching pulp. Houck stood his ground. testifying that "new information indicates that we should be less concerrted than we once were." In March of this year, Reilly and other top EPA officials received a briefing on dioxin that Reilly credits forhis change of mind. First, his advisers reported an un- usual consensus from a recent dioxin con- ference at the Banbury Center at Cold Spring Harbor, New York. Researchers agreed that the toxicity of TCDD depends upon its binding with the aromatic hydro- carbon receptor, or Ah. Most to the point, they agreed that receptor binding medi- ates TCDD toxicity in virtually every test system studied, and that receptor binding needs to occur in thousands of cel ls, though the dividin- line between safe and toxic concentrations is not known. Nevertheless, this observation leads directly to Reilly's conclusion that "work should begin on a new biologically-based model for assessing the toxicity of di- oxin." Until now, the Environmental Pro- tection Agency has relied on the standard linear multistage model that predicts no threshold of safety. Based on this model, US standards for exposure to 'back- ground' levels of dioxin that is in the environment are stringent:.006 picograms per kg body weight per day for intake from food or water, for instance. Interest- inaly, Canadian and European scientists generally have not accepted the US posi- tion that dioxin is the most toxic chemical around. Conservative estimates put a safe dioxin intake at I picogram per kg per day, while more liberal standards go as high as 10 picograms per kg. Although no changes in US regulations have been put forward, it is likely that the US will move in the direction of its nei;hbours abroad. A second bit of data~that figured in Reilly's request for a new look at dioxin comes from a large epidemiological study reported in the 24 January issue of The New England Journal of Medicine. Re- searchers at the US National Institute for Occupational Safety and Health in Cin- cinnati, Ohio, conducted a retrospective mortality study of 5,172 workers at 12 chemical plants that produce agents in which TCDD is a contaminant. Theircon- clusions: ";vlortality from several cancers previously associated with TCDD (stom- ach, liver, and nasal cancers. Hodgkin's disease and non-Hodgkin's lymphoma) was not significantly elevated in this co- hort. Mortality from soft-tissue sarcoma was increased but not significantly." Government scientists, working with colleagues in universities, have been asked not only to develop a biologically based or receptor model, but also to construct a plan forevaluating the new epidemiologi- cal data so that any new standard-setting regulations encompass the new data as a whole. March of 1992 is the target date for completion of the work. Environmental Protection Agency sci- entists seem to be ful ly aware that they are entering dangerous territory: Even though data may exonerate dioxin somewhat, it remains a toxic contaminant of the envi- ronment that has no compensating ben- efit. Furthermore, a reassessment ofdioxin has obvious implications for related polychlorinated biphenyls. Ultimately, it could lead to a biologically based model for any agent or group of agents for which toxicity is understood at a mechanistic level. That the government must proceed carefully, and openly, is vital. Reilly has promised independent scientific review, which is certain to be subject to harsh scrutiny by groups committed to the view that the only acceptable risk is no risk at all. Over the years, this has become the unstatedgoal of many groups-in the United States, but with science's ability to mea- sure chemicals at ever smaller concentra- tions, it becomes crucial to rank toxic compounds in some sensible orderofhaz- ard. As Reilly has noted, "There simply are more anxieties than we can possibly create laws to alleviate, and far more risks than resources to eliminate them." There is no doubt that a decision to declare dioxin less hazardous will be pain- ful, particularly to the people at Times Beach and elsewhere whose lives have been so totallydisrupted. At the time steps were taken to evacuate the town, the decision was entirely in keeping with scienti fic data avai lable. Human data were scarce. It was thought prudent to rely on animal data and they made a strong case for judging dioxin to be unusually toxic. Although researchers may be comfort- able with the idea that new judgements should correctly follow new data, it remains a difficult concept for the public. Nevertheless, it is time to set priorities, even if it is politically treacherous. Barbara J. Culliton 753