The metabolite of the PCBs bind to this protein, so it does not deliver the natural hormone to the fetus but instead delivers this mimicking compound. So now the fetus lacks the hormone it needs, and instead it gets a compound that is not intended to be there. So what does that do for fetal development? And does this exposure early on in life have effects later in life? Those were the debates on this issue. The placenta, which should be a barrier for these compounds, does not behave as a barrier for them. So the issue of PCBs becomes important not just for the environmental effects, but for human development.

We’ve done more work on comparative effects. It started with PCBs. We found that although PCBs are persistent compounds, they produce these metabolites which by themselves are also persistent and interfere in these endocrine pathways. So we did lot of in vivo early-exposure, long-term-effect studies to find out whether there are these long-term effects from early exposure to the PCBs. We observed effects in both brain development and reproductive cycling performance. Now we have proof that this compound doesn't just cross the placenta, but evidence that this particular metabolite has long-term effects. We don’t have proof of the latter, but the evidence pointing in that direction is pretty compelling.

The experimental studies, of course, are in lab animals. We can follow the transfer of the compound and really zoom in on these various stages of development. We’re not just looking at the biochemistry of it, but also the behavioral functions. But we also have multidisciplinary studies, funded by the European Union, involving clinical and epidemiological studies. We are doing behavioral studies in humans, in children. We have all kinds of tests—on visual recognition, memory, etc.—and we can correlate how children score on these tests to the PCB concentration in the mother’s breast milk and in the blood of both mother and child. We have also found some correlations between higher concentrations of PCBs in the mother and poorer performance in the child on some of these tests. Now that we have both experimental animal studies and human epidemiologic studies, we are building quite a strong case.

Well it’s easy to do the early-exposure studies—the experimental animal work. We can label the compounds, follow them through the system—that’s easy. But then we have to try to understand which aspects of development may be affected, which requires that we make guesses. These guesses, of course, have a bearing on the type of tests we can do and when we do these tests. We had to estimate or predict effects, based on what we knew about which neurotransmitters might be affected, which parts of the brain may be more affected; which behaviors might be affected, the timing, the onset of the affects, and the natural variation. How well can we pick it up at low concentrations? All that’s the real challenge. The other challenge, of course, is how to do these studies in humans. Then there are the technical challenges: how do we synthesize these metabolites? What are the standards? How do we measure concentrations quantitatively and reliably, etc.?

One thing we’ve been doing is making methods—tools, if you wish—to measure the effects. We have bioassays that are easy tools to predict the effects of certain compounds. We will be using those more and more. That’s one aspect. The second is that we’ve been doing all these studies related to PCBs, but PCBs have been banned. They’re not really being used any more, at least not in the Western world, although they are still in the environment. So what do we do with this research for the future? Now we’re comparing the structures of these old chemicals with the ones society has been using as replacements. And we are now finding that compounds like the chlorinated and brominated flame retardants, for instance, which are used widely in the U.S. and the U.K. and throughout the world, resemble the structure of the PCBs. So we’re working on comparisons between old and new structures, old and new uses, and we’re finding that we are repeating the same problems with these new chemicals we encountered with the old chemicals. In the next five years, I expect to see more and more of this information emerging—which chemicals are and are not in same ballpark, so to speak, as these PCBs. The other thing we really want to do is further study the links between these compounds and the late-onset effects that are observed in lab animals, and also now in humans. The association is still weak. But I believe this will be strengthened in the next five years. We have to figure out how to measure the effects of these compounds in people at older ages, how to measure whether intellectual capacities are affected. Can we visualize this somehow? What about reproductive problems? There may be other effects we haven’t looked at. These will be areas where this work will continue?

To the public, we always want to make clear that we are not talking about acute lethal effects here. We are looking at the possibility that compounds at fairly low doses, as they occur in the environment, might cause subtle effects. Individuals might never even notice that they were affected by these compounds. It may be only on a population basis that slight changes in capacities may be seen and, in that sense, this research is most important for the regulators who have to take responsibility, who have to make decisions about allowing new chemicals on the market. It’s these regulators who have to know the profile of activities of these compounds based on what we know now and what we’re learning, and they have to avoid, if at all possible, introducing new chemicals that repeat the same mistakes. In medicine, any new drug has to be tested extensively to prove that it’s both safe and effective. And even in medicine we still see mistakes or unforeseen actions. For industrial chemicals used for polymers, paints, and other things, this whole testing strategy is much less stringent. But the exposure and the health effects can still be there. And, in fact, in both the U.S. and Europe, a strategy is being developed to nail down this early stage of development and testing of these chemicals and to establish what their risk profiles may be so that we can avoid them.

Prof. Dr. A. Brouwer
Department of Chemistry and Biology
Institute of Environmental Studies
Amsterdam, Netherlands