though PFOS levels in blood serum of workers tested are about 100 times that in the general population. "We have done extensive research and we never observed health effects from working with fluorochemicals," he says. "I don't anticipate there will be any health issues related to these chemicals." Zobel adds that, during the two years the company has been talking with EPA about PFOS, 3M never felt pressured to pull products from the market. However, an EPA official says that if 3M wasn't pulling PFOS from the market, EPA would have begun a regulatory investigation based on the preliminary findings that the chemical persists in the environment and could be toxic to mammals. Alex Tullo
Leaked Dioxin Report Stokes Controversy The Environmental Protection Agency's long-awaited draft reassessment of the toxicity of dioxins—leaked to the press this month—quickly became controversial because of the high cancer risks the agency estimates for current exposure to dioxins. EPA will officially release the draft reassessment in early June. In late July, the document will be peer reviewed, and before fall the EPA Science Advisory Board will meet to critique the document. These actions could result in substantial changes, one way or the other, in the report's conclusions. EPA says the premature release of the report has been problematic, but has refused to comment on the contents of the report. The document, under preparation for nine years, concludes that 2,3,7,8tetrachlorodibenzo-/>-dioxin (TCDD) is a known human carcinogen and that other dioxins and some dioxin-like compounds are likely human carcinogens. Cancer risks for people exposed to these compounds range from 1 in 100 to 1 in 1,000, the report says. In the report, dioxins are defined as coplanar polychlorinated biphenyls and polychlorinated and polybrominated dibenzodioxins and dibenzofurans. The only dibenzodioxins and furans that are considered toxic are those with at least four chlorine or bromine substitutions in the 2-, 3-, 7-, and 8-positions. Although the risk of cancer from dioxins is high, the situation has improved, the report says. Dioxin emis-
sions from large industrial sources declined 75% from 1987 to 1995, and environmental levels have fallen. However, uncharacterized sources, such as backyard trash burning, remain unaddressed, the document says. In addition to cancer, the report says dioxins adversely affect the immune and endocrine systems and the develop-
2,3,7,8-Tetrachlorodibenzo-p-dioxin
ment of fetuses. Some effects have been observed in people exposed at only 10 times the background level. Each person in the U.S. ingests on average 1 picogram of dioxins per kilogram of body weight per day from animal fats in the food supply, the report
continues. The most heavily contaminated foods are freshwater fish, marine fish, pork, beef, poultry, and dairy products, in that order. Air deposition onto plants and bodies of water is the principal source of dioxin contamination. Greenpeace is calling on EPA to mandate the use of chlorine-free substances in the manufacture of products to prevent the formation of dioxins or dioxin-like byproducts. 'This is the best moment in history to tell the giant chlorine producers that judgment day isfinallyhere and stalling will no longer be tolerated," says Rick Hind, legislative director of the toxics campaign at Greenpeace. Marcie Francis, senior director of science policy at the Chlorine Chemistry Council, believes that the cancer risk from dioxins is much lower than EPA's figure. If dioxins are a large cause of cancer, "we would expect to see a blip in cancer mortality," she says, noting that, overall, cancer death rates are going down. Bette Hileman
Protease Inhibitors Styn ie Glucose Transport Scientists appear to have solved part of I as Glut4, from bringing glucose across the mystery of how HIV protease inhibi- cell membranes into the cells for energy tor drugs cause a panoply of side effects, storage. including insulin resistance and even The biochemical chain reaction inType II (adult onset) diabetes. volved begins with insulin, which is reCell biology and physiology professor leased in response to glucose and binds Mike M. Mueckler, researcher Paul W. to muscle and fat cells, stimulating a casHruz, and graduate student Haruhiko cade of events in which the cells release Murata at Washington University, St. Glut4, among other things. The transport Louis, find compelling evidence that the protein then makes its way to the cell drugs interfere with the ability of fat cells to membrane surface and waits there to store glucose \J. Biol Chem., http:// transport glucose across the membrane. www.jbc.org/cgi/reprint/C000228200vl]. Mueckler says he noticed that the The research also strengthens the syndrome in HIV patients was similar to link between drug-induced insulin resis- | that observed in genetically engineered tance and another, more noticeable pro- mice that lack the gene to produce tease inhibitor side effect: a redistribu- Glut4. These mice are insulin resistant, tion of fat in the body that results in the have an increased incidence of diabetes, wasting of arms and legs and increased and have no body fat. fat around the midsection, a condition To test their hypothesis that protease popularly known as "protease paunch." inhibitors affect the action of Glut4, the Protease inhibitors, as their name sug- group exposed fat cells to insulin and to gests, interfere with an HIV protease es- the protease inhibitor indinavir, and then sential for viral replication. The drugs, measured glucose uptake as a function of which were hastened through the Food & drug dose. They found that, as the dose Drug Administration's approval process, of indinavir increased, glucose uptake dehave greatly increased the quality and span creased, ultimately by up to 63%. of life for HIV-positive people and for peoThey also expressed Glut4 directly in ple with AIDS. But the peculiar side effects frog eggs, effectively bypassing the inof the drugs were largely unanticipated. sulin-stimulated biochemical steps and The Washington University group's creating a system ready to transport gluexperiments demonstrate that the drugs cose. Again, they found that protease inprevent a key glucose transport protein hibitors diminished glucose uptake, this produced in fat and muscle cells, known time by up to 45%. MAY29,2000C&EN
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