THREATS TO OUR HEALTH
It is extremely difficult to obtain direct evidence that endocrine-disrupting chemicals cause reproductive damage in humans, for reasons beyond the ethical one. For instance, determining the effect of any particular chemical on an individual is nearly impossible because it is so difficult to figure out which chemicals the individual's mother was exposed to during pregnancy. However, Shanna Swan, director of the Center for Reproductive Epidemiology at the University of Rochester School of Medicine and a researcher who is at the forefront of this effort, published last May the first study to link prenatal exposure to phthalates to outcomes in offspring.
She had recruited a group of pregnant women and measured nine phthalate metabolites in their urine. This chemical group had already been shown to disrupt the endocrine system in rodents and is ubiquitous in our world -- in plastics, nail polish, perfumes, toothbrushes, pesticides, paint, and the coating on time-release pills. Then Swan asked pediatricians who knew nothing about the maternal exposure levels to measure the distance between the genitals and the anus in the male babies. Then this distance was divided by the infant's weight to establish an anogenital index (AGI), a biomarker animal researchers have long used because it is predictive of the healthy development of the genitals in rodents. Short AGI correlates with smaller penises, smaller, ill-defined scrota, and incomplete testicular descent.
Swan found that a boy born to a mother with a high exposure to dibutyl phthalate (DBP), for example, was 10 times more likely to have a short AGI than a child of a mother with a low exposure to DBP. Swan points out that this was a small study of 85 infants; she has proposed a larger study of 600 families to investigate these effects further. She believes the research is necessary because the mothers of babies with short AGIs had been exposed to levels of phthalates that, according to estimates from the Centers for Disease Control and Prevention, are present in the bodies of one-quarter of all
It is already clear that synthetic chemicals can also powerfully affect the thyroid gland, which is critical to brain development and function, according to Thomas Zoeller, an endocrinologist at the University of Massachusetts Amherst. But work is still in an early stage; much remains to be understood about how the thyroid functions and how that functioning can be disrupted. Zoeller's lab works with PCBs even though they were banned in 1979, largely because the behavior of these chemicals is well understood, which makes it easier both to predict their behavior in the lab and to interpret it. Moreover, although PCB levels dropped at first after the ban, these chemicals have such a long half-life that the rate of decline leveled off in the mid-1990s, which means they will belong to our bodies' burden of toxins for a long time to come.
Zoeller has determined that exposing a fetus to PCBs leads to profound changes in the brain. "The corpus callosum is a big bridge of white matter that connects the two hemispheres, and in our experimental animals, the PCBs cause a reduction in the size of the corpus callosum," he says. This may prove to be a very important finding, he explains, because "a number of neuropsychological diseases in humans have been linked to the development of the corpus callosum -- for example, autism and Tourette's." However, he emphasizes that we don't know yet if the link is causative. Zoeller also suspects that disruption of the thyroid may be contributing to the sharp spike in learning disabilities observed over the past two decades, a spike that cannot, he says, be explained away by improvements in diagnosis.
A careful study published in 1996 by Joseph and Sandra Jacobson suggests Zoeller is right to be concerned. Testing children of mothers who ate Great Lakes fish contaminated by PCBs, they found that children whose mother's blood and breast milk, along with umbilical cord blood, showed the highest concentrations of PCBs had lower IQs -- on average six points lower -- than children of mothers with the lowest concentration. Joe Jacobson points out that what he and his wife documented was a correlation between exposure and a drop in IQs rather than proof that PCBs caused the drop. The children with greatest exposure also exhibited memory and attention deficits and were twice as likely to be at least two years behind kids in the lowest exposure group in reading comprehension. None of these impacts sounds catastrophic, but they could mean more kids who can't sit still in class and are miserable in school. The Jacobsons followed these children only until they were 11 so they do not know how those exposures affected them later in life. But children who have diffficulty in school may well grow up less able to read, write, or think clearly.
Two brooding questions have hung over endocrine-disruption research. One: Are the effects of endocrine-disrupting chemicals additive -- if you are exposed to many of them, will their effects add up to produce greater changes in hormonal activity? And two: Are the effects handed down from one generation to the next? The first attempts to study these questions suggest that the answers are likely to be: yes and yes.
In 2005 Kevin Crofton, a neurotoxicologist who works for the EPA at Research Triangle Park in North Carolina, published a finding that helped to confirm many researchers' worst fears. Crofton gave rats different doses of mixtures of three classes of chemicals -- dioxins, PCBs, and dibenzofurans -- at concentrations ranging from approximately those that would be found in humans to levels 100 times higher. The chemicals in the mixture were chosen because they are found in foods people eat, from fish to breast milk. The highest dose he used for each chemical was still so low that he had seen no endocrine-disrupting effects for that chemical at that level. At the lower doses, Crofton found that the effect of the mixture was additive and that it significantly reduced the animals' level of thyroxine, the most common thyroid hormone. At higher doses, he observed that the mixtures reduced thyroxine synergistically so that the sum of their effect was slightly greater than simple addition. A fetus must have enough thyroxine for the brain to develop properly; adults need thyroxine to regulate metabolism and heart rate.
This and many other recent studies of mixtures up the ante considerably. They cut right through the endless debates about whether the levels of exposure to a chemical in any given experiment accurately reflect the levels at which humans or animals are actually exposed to that compound in the environment. These studies suggest that we can't solve the problem by taking a handful of the most dangerous chemicals off the market; instead, we will have to consider whether all endocrine disruptors need to go. The European Union has already begun to move in this direction.
The second question, whether effects are handed down from one generation to the next, got an answer almost by accident. Michael Skinner, a molecular and cellular biologist who focuses on reproductive biology at Washington State University, wanted to look at how cells communicate during the development of ovaries and testes. He dosed a group of pregnant rats at mid-gestation with vinclozolin, an anti-androgen (a substance that blocks androgenic hormonal activity), and another group with the pesticide methoxychlor, which is estrogenic, to see if either would alter the development of their offspring. A research fellow in his lab bred that first generation of babies, which was not part of the plan. She apologized, but Skinner told her not to worry, to seize it instead as an opportunity to examine the impact on a second generation. Everyone in his lab was stunned when they found that both chemicals wreaked significant damage. According to Skinner, of those exposed to vinclozolin, "greater than 90 percent of the males developed subfertility with a dramatic increase in developing sperm undergoing cell death" for not one but four generations. Further analysis established that the rats in both experiments had suffered germ-cell defects, the result of a chemical modification of their DNA. Both males and females developed various diseases as they aged. For example, female offspring of the first generation developed a condition equivalent to pre-eclampsia in human mothers, which can result in severe complications for the baby and death for the mother. In humans, incidence of pre-eclampsia has risen sharply over the last 20 years, and no one knows why. Skinner points out that he used a level of toxins higher than what people would be exposed to in ordinary circumstances, but he believes that "women in their mid-gestation pregnancies should be very cautious about their environmental exposures."