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excitement on the Inst day of' the meeting. Instead of direct measures of receptor bind ing, they used a handy surrogate: the in creased activity of the cytochrome 1*450 enzyme system, widely considered the most sensitive response to dioxin in all species. No toxic ellccts arc known to occur at levels Ik low those required for enzyme induction. After reviewing data on the necessary dose for enzyme induction in all species, Gallo, Ilirnbaiim,Schcuplcin, and others took turns at the blackboard, trying to calculate what the "safe" level in humans might be. Their rough, back-of-the-envelope calculation: I to 3 picograms per kilogram per day--several hundred times higher than current. U.5. standards and in the same ballpark as those set by some European countries, which ar rived there by an entirely dilfcrent method. Not so fast, says Maryland's Silbcrgeld, who cautious against "replacing one stupid model with another." For one, a receptorbased model does nut necessarily predict a "hockey stick" curve, nor does receptor bind ing necessarily imply a "safe" dose, says Silbcrgeld, who thinks her colleagues arc underestimating the intricacies of receptor theory. Nor is she convinced "that the result |o f the new model] will be that dilfcrcnt from EPA's current figure. As a scientist, I object to the EPA model. Hut {its predic tions] may be very, very close, lor totally irrelevant reasons." Working with El*A scientists, Gallo is now setting out to reline the risk number for dioxin. George I.ucierand his colleagues at N1KHS arc doing the same. The idea is to build a conceptual model of cellular re sponses to dioxin and then turn that over to mathematicians to develop a predictive tool to estimate dioxin's risks--not just for cancer but for any toxic endpoint. William Farland, who runs the dioxin risk assessment cUbrt at EPA, expects a "straw man" model to be complete in about a year. The next step would be to see if it passes muster with the Monsanto Studies Under Fire The Environmental Protection Agency has launched a criminal investigation to determine whether Monsanto Corp. o f St. Louis falsified three epidemiologic studies of its workers, which showed no increased health risks from dioxin other than the skin disease chloracnc. The investigation, which ErA is mandated to conduct in response to a petition requesting it from the activist group Greenpeace USA, should resolve, once and for all, the allegations that have been swirling around these studies for almost a year. EPA ollicials would not confirm or deny the existence of the investigation, but Science obtained internal agency memos discussing it. The EPA has not notified Monsanto that it is under investigation, but says Dan llishnp, the company's director o f communications, "We hope there is one, we welcome it. It is the only way to put this matter to rest." In fact, the company wrote to EPA twice over the past few months, begging the agency to perform a scientific audit of the studies, bishop calls the fraud allegations "bald-faced lies." The main charges are that Monsanto epidemiologists misclassified exposed work ers as unexposed in their control group and that they omitted workers who had died o f two cancers that have been#linked to dioxin exposure in other epidemiologic studies. The charges first came to light last February when a plantilFs lawyer in Kemner v. Monsanto, a ease involving a tank-car accident, reviewed the studies, decided they were fraudulent, and alerted the press to the alleged cover-up. That brought in Greenpeace, and also Cate Jenkins, a chemist in EPA's regulatory branch. She has since made the Monsanto studies something of a personal crusade, petitioning EPA's Science Advisory board to audit these and other studies, and meanwhile sending numerous copies o f her memos to various environmental groups, Vietnam veterans organizations, and her friends on Capitol Hill. Jenkins maintains that Monsanto's studies have directly afleeted how EPA regulates dioxin. Other agency ollicials deny tiiat, saying that EPA's current--and very stringent--standard for dioxin exposure is based on animal studies. Everyone Science spoke with who is familiar with the Monsanto studies agrees that they are flawed, but probably not as the result o f criminal intent. The scientific questions about the studies may now be moot, however, as all but six o f the Monsanto workers in the three studies have been carefully reexamined as part or a larger federal study just published, which suggests that high dioxin doses can cause human cancer (see box on page 625). The other questions may be tougher to resolve. When EPA completes its investigation, the agency will report to the Justice De partment and recommend either that they prosecute or close the case. L.R. scientific community--and if*il in litct oilers an advantage over the status quo. "This is an improvement, not a cure-all," warns Lucicr. Once the model is complete, perhaps the biggest question, in terms ofdioxin's danger, is the background exposure of the general populaiiou, wliieli comes cliielly from diet but also from environmental sonices. I('back ground exposure is comfortably belmv the practical "threshold" needed for receptor activation (point 11in the figure), then there may indeed Ik a sale dose, but irbackgrouud exposure is higher, near the "threshold" (point A), "then there is no margin lor ad ditional exposure," says Moore, background exposure is now estimated to be about I picogrntu per kilogram per day--slightly be low the rough "safe" number the Katibiny group came up with--which may nut leave much room lor additional exposure. At this juncture, EPA ollicials arc enthusi astically embracing the new scientific ap proach. Don barites, a dioxin expert and executive director of EPA's Scientific Advi sory board, talks of "a real breakthrough, a sea change in our view ol'dinxin." In fact, the topic is deemed important enough that a special briefing is planned lor KI'A adminis trator William Reilly and top agency ollicials. bur how far is EPA likely to go if the modeling exercise does reveal that dioxin is less risky than the agencies now calculate? Gough o f OTA, for one, thinks that the answer is not very far: " Dioxin is the most potent carcinogen ever tested. If they back off this one, they will open the door to every chemical manufacturer in the world" whose chemical acts in the same way. "Thai is a door they will reluctantly open." Gallo con tends that the door will open just a crack, as there are less than a dozen carcinogens known to work the way dioxin does. And he predicts that the new receptor-based risk model will cut both ways: some carcinogens will turn out to be far riskier than now predicted; others, like dioxin, less risky. Moore agrees that change will not be easy. "For issues this emotional, you have to be purer than Gaesar's wile anytime yon propose to change the status quo. 'There would have to be a lair degree of-support within the scientific community for it to come to pass, especially if the potential change is a `relaxing' of the number." Erie brcllhauer, EPA's assistant adminis trator for research and development, con cedes that "the agency hasn't traditionally relaxed numbers." but, he says, " I think there is a willingness at the policy level to take it on. My view is we have to be open in changes in science, whatever their elleci on regulatory policy." lie adds, him cut, that "the science has to Ik verv clear." 000319 Ll-StJU IlOllURTS 626 t i *i i' t\ SCIKNCK, VOL. 251