E.U. Shifts Endocrine Disrupter Research Into Overdrive
by Sonja Lorenz

CAMBRIDGE, U.K.--The European Union is embarking on a massive new effort to pinpoint the harmful effects of hormone- mimicking chemicals. Last month, the European Commission launched a collaboration involving 60 labs across the continent to investigate the threat that these substances, primarily pollutants, pose to humans and wildlife. The intent is both to give the E.U. the information it needs to ensure that chemicals are tested adequately for endocrine effects before reaching the market and to flag effects in compounds already out there.

Concern over so-called endocrine disrupters arose in the early 1990s, when studies tentatively linked rising levels of pollutants to declining sperm counts and cancer of the testicles, prostate, and breast in people and to genital malformations in wildlife. However, many of the studies have been controversial. Establishing a cause-and-effect relationship has been a "hot potato, politically and scientifically," says toxicologist Andreas Kortenkamp of the University of London School of Pharmacy, who coordinates the E.U.'s new Cluster of Research on Endocrine Disruption in Europe (CREDO).

The 4-year-long, $23 million program is meant to complement a substantial amount of research already under way around the world. For instance, many labs are probing the effects of chemicals that mimic or block estrogens, female sex hormones. One thrust of CREDO will be to look hard at compounds that block or behave like androgens such as testosterone, the main male sex hormone. Thus CREDO will "act as a counterbalance" to the stack of findings on estrogen disrupters, says Ulrike Schulte-Oehlmann, an ecotoxicologist at the University of Frankfurt, Germany. Her 13-lab consortium hopes to zero in on invertebrates, perhaps sea urchins or snails, that might serve as "sentries" in polluted environments and as standard test systems for detecting potential effects in higher species.

Another gap in understanding that CREDO will try to fill is the risk posed by bromine-containing flame retardants, used widely in polymers and textiles. These high-production chemicals, some of which bear striking toxicological similarities to known endocrine disrupters such as polychlorinated biphenyls, have been accumulating in aquatic food chains for decades. "This is a warning: We should be concerned about them," says toxicologist Joseph Vos of the National Institute of Public Health and the Environment in Bilthoven, the Netherlands, who is coordinating this part of CREDO.

The E.U. initiative will enter one controversial area: how hormone-mimicking chemicals interact with each other. Gauging the risks of individual chemicals in the milieu encountered in nature is "a nightmare scenario" for risk assessors, says Kortenkamp. Much work needs to be done to develop proper test methods and assessment strategies that can untangle these risks, he says, particularly at low doses.

Once an endocrine disrupter enters the body, in principle it can target any organ having hormone receptors with which it can interact. "We have to check from top to toe," says Wolfgang Wuttke, a biomedical researcher at the University of Göttingen, Germany. His lab consortium will focus on known estrogenlike rogues, including pesticides, ultraviolet absorbers in sunscreens, and phytoestrogens used in hormone replacement therapy. The researchers' goal is to reveal to what extent these compounds influence gene expression in nonreproductive organs.

Observers predict that the initiative's megacollaboration credo will bear fruit. "They have the critical mass to advance the field and see what is really important," says Tuomo Karjalainen, a scientific officer at the European Commission in Brussels.