By the mid-1970s researchers around the world had documented cases of lowered IQ in children exposed to lead from air pollution, mercury-based preservatives in grain, and polychlorinated biphenyls (PCBs) in fish, as well as in those exposed to alcohol in utero. The effects were much greater in children than in exposed adults. These were, as the neurotoxicologist Pam Lein of the University of California, Davis, puts it, “the blunt ones”—exposures whose effects became apparent after some concerted research. But no one really understood how the toxins worked, and they didn’t know if other, more subtle, discoveries awaited. In 1972 a Danish medical student named Philippe Grandjean saw a young woman on television who was suffering from so-called Minamata disease. Exposed to mercury in the womb, she could hardly talk and was afflicted by a severe spastic limb condition. Grandjean wondered why he wasn’t being taught about environmental exposures if they could cause so much damage. He decided to spend his life researching neurotoxicants, which he terms “brain drainers.” Since then he has written more than 100 papers on mercury, taught a couple of generations of scientists, and as both a physician and a researcher has an understanding of the micro and macro scope of the problem. What he told me wasn’t comforting. “Because the human brain is so complex, it’s incredibly vulnerable,” says Grandjean, now an adjunct professor at the Harvard School of Public Health and the author of the 2013 book Only One Chance: How Environmental Pollution Impairs Brain Development and How to Protect the Brains of the Next Generation. “Even if something goes a little bit wrong, you don’t get a second chance,” he says. “You’re stuck with it, and even small deficiencies can be quite significant.” As Grandjean explains it, shortly after conception, the brain begins to form from a tiny strip of cells. At its fetal growth peak, 12,000 cells are generated every minute, or 200 per second. These cells start sending and receiving messages and migrating to specific locations. By the time the brain is fully baked, it has close to 100 billion nerve cells and roughly as many caretaking glia cells, which provide nutrients, sweep out dead cells, and insulate nerve fibers. “If cells are in the wrong place or they don’t form the right connections,” Grandjean says, “that’s what you’ve got for your whole life.” In a groundbreaking review published in the Lancet in 2006, Grandjean and his co-author, Philip Landrigan, of Mount Sinai Hospital in New York City, identified 201 heavy metals, solvents, pesticides, and endocrine disruptors known to have toxic effects in the human brain (at least 1,000 other substances are neurotoxic in animals but haven’t been tested in humans). Of those 201, about half are “high production volume” chemicals, made in or imported to the United States in excess of one million pounds per year. At the time, the authors could point to only half a dozen as showing evidence of developmental toxicity in the fetal brain, but the count is now up to 10 and growing. All of these neurotoxicants are relatively common, routinely found in the blood of pregnant women. They include the usual suspects—lead, methylmercury, and PCBs—but also organochlorine pesticides like DDT (which was banned in the 1970s but still persists in soil and water), organophosphate chemicals like the roach-killer chlorpyrifos, PAH, PBDEs (this pervasive class of flame retardants is now being phased out), arsenic, ethanol, and the solvent toluene. We are beginning to learn more about how these substances may alter brain development. Their strategies are complex and varied. Under the
influence of methylmercury, for example, the brain’s nerve cells “are lying helter-skelter, not in their usual logical locations,” says Grandjean. Pesticides are designed to be neurotoxicants—that’s the whole point—and some, like chlorpyrifos, work by inhibiting cholinesterase, an enzyme critical to brain-cell communication. Different neurotoxicants affect children differently. At high levels, methylmercury appears to cause memory deficits, while lead primarily decreases attention span and pesticides tend to impair spatial perception. Black carbon apparently affects attention and processing speed. Not all kids are equally vulnerable. Other factors matter, like genes, psychosocial stress, and, interestingly, gender. Boys tend to be more vulnerable than girls to the deficits associated with PAH. Studies of prenatal exposures to phthalates and bisphenyl-A (BPA), both endocrine disruptors, philippe grandjean also show gender differences. Phthalates says, “if cells are are considered antiandrogens, while BPA in the wrong acts like an estrogen, and the developing brain place or they takes important cues don’t form the from both hormones. With chlorpyrifos exporight connecsure, for example, boys have greater difficulty tions, that’s than girls with working what you’ve memory. Many of these subgot for your stances disproportionately affect the poor, but whole life.” not all. Poor kids are exposed to more lead and first- and secondhand tobacco smoke. More affluent populations accumulate more mercury from their diet. Urban kids may be exposed to more PAH and black carbon, farm kids to more pesticides and arsenic from well water. Of all the suspects, brominated flame retardants may be the most democratic. Although levels of PBDEs are now dropping in pregnant women, Americans still have the highest levels tested anywhere in the world. Flammability standards enacted in California in the 1970s resulted in the addition of PBDEs to everything from electronics to home furnishings nationwide. Unfortunately, the molecules easily migrate, accumulating in blood and breast milk and persisting for years. Structurally similar to PCBs in some cases, they appear to interfere with thyroid hormone signaling, either by directly altering the amounts of hormone or by blocking the hormone transporters. As researchers learned from studying cretinism, thyroid hormones are critical to brain development, among other functions. A University of California, Berkeley, study of children in the state’s Salinas Valley reported that those born to mothers with the highest levels of PBDEs during pregnancy averaged six points lower in verbal IQ and had lower scores for fine motor skills and a higher risk of hyperactivity. And PBDEs probably don’t act in isolation. Per Eriksson, a Swedish toxicologist, has found that when lab animals are exposed to both PBDEs and mercury, the neurological effects are significantly stronger than those of mercury alone. winter 2013/2014
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