Researchers Urge Greater Protection of Developing Brain from Environmental Chemicals

The dangers of lead poisoning at high doses have been known for centuries. But research throughout the 1970s and ’80s showed that low-level lead exposure from paint, exhaust, and other environmental sources has unexpectedly sinister effects: it can dampen the behavior and intelligence of children, affecting them at a level well below the radar of clinical disease. A similar story emerged with mercury exposure, which has been linked to lower intelligence scores and neurobehavioral problems in children of mothers exposed to contaminated seafood. Parallel lessons also emerged in children of mothers who had consumed too much alcohol during pregnancy.

These cases have helped to open up people’s eyes to the possibilities that low-level contaminants can affect brain development in subtle but insidious ways. But what if these are not isolated cases—what if many other chemicals in the environment have similar effects on the brain?

Photo courtesy of Philippe Grandjean Philippe Grandjean believes that industrial chemicals should be screened for their potential to harm developing brains, something that few are tested for today.

Philippe Grandjean, adjunct professor of environmental health at HSPH, and Philip Landrigan, professor of community and preventive medicine at Mt. Sinai School of Medicine, suggest that a large roster of chemicals may be causing a “silent pandemic” of brain disorders during fetal and childhood development. In a provocative review published online Nov. 8 in The Lancet, they argue for more rigorous testing and stricter regulation of chemicals that could potentially harm developing brains.

Drilling Down to Danger
The review grew out of the parallel experiences of Grandjean and Landrigan, each of whom spent decades studying the health effects of mercury and lead, respectively. Research on these substances, as well as PCBs and later arsenic, had followed a similar trajectory. First, extreme events of poisoning and toxicity revealed that the substances at high doses have neurological effects in adults. Later, reports of epidemiological studies brought to light developmental problems in children. Further research began to show more subtle but widespread effects on behavior or intelligence. “We realized that the experiences had been similar in how the knowledge was generated over decades and even centuries,” Grandjean said. At each stage, researchers found that the substance affected a larger population at increasingly smaller doses than
previously believed.

Looking at these toxicants as part of a larger pattern, rather than a few isolated cases, Landrigan and Grandjean wondered whether the story would emerge from studying other substances in the environment: what if some of the hundreds of substances known to cause neurotoxicity in adults could subtly damage the developing brain?

In their review, the researchers summarize what is known about the most studied neurotoxic chemicals: lead, methylmercury, arsenic, PCBs, solvents, and pesticides. In addition, the researchers searched through the medical literature to compile a list of 200 chemicals that have been reported to cause neurotoxicity in humans, often through industrial accidents, occupational exposure, suicide attempts, and accidental poisonings. The researchers believe these are very likely candidates for causing effects on neurodevelopment. The list includes pesticides, carbon monoxide, fluoride, manganese, and common chemicals like acetone, benzyl alcohol, and perchloroethylene, a chemical used in dry cleaning.

The Exceptional Brain
Disorders that affect the brain and behavior of children such as autism, attention deficit disorder, and mental retardation are a growing concern, though researchers disagree about whether they are becoming more frequent. Exposure to environmental chemicals in utero or during early childhood has been linked in varying degrees to these disorders, and Grandjean and Landrigan believe that it is plausible that chemicals have a significant role in their incidence.

About 80,000 chemicals are registered in the United States; of those, about 1,000 are known to cause neurotoxicity in animals, and 200 are known to be toxic to human brains. Only five chemicals have been documented to affect human brain development. Grandjean admits that he and Landrigan lack evidence to prove their argument for a larger pandemic, but that’s the point: they believe that it’s better to prevent the proof from ever appearing and that more testing should be done to determine whether or not common industrial chemicals harm children.

The researchers also argue that the brain is different from other organs, and the standards set for toxicity should be different. “You don’t care about losing one percent of kidney function,” Grandjean said. “But with the brain, it is incredibly important that we maintain optimal function and have access to all the talents we can develop. It’s the key to our education, economic activity, and quality of life.” Furthermore, they say, the developing brains of fetuses, infants, and children are uniquely sensitive to damage. In fetal life, the placenta offers only limited protection against chemicals, and the blood–brain barrier that protects adult brains from many substances is not fully formed until several months after birth.

David Bellinger, an HMS professor of neurology at Children’s Hospital Boston, who studies how chemical exposures affect the developing nervous system, said that pediatric environmental health has become an increasingly prominent concern over the past decade as researchers become aware of the way environmental insults during development can shape later health. But Bellinger said that science still does not have a consistent model for understanding how the brain responds to these insults. Is the emerging brain so plastic that it can adapt to toxins or nutritional deficiencies, or is it so fragile that any small insult will permanently change its function? Furthermore, the mechanisms through which most toxic substances act are largely unknown.

Bellinger does not think it is necessary to answer all of these scientific questions before taking action, however. The problem, he said, is that “we wait for something bad to happen, from poisoning episodes or kids showing up in emergency rooms with brain swelling and bleeding, and only then do we do the studies to screen these chemicals for neurotoxicity.” The cases of lead and mercury, he said, have already laid the groundwork for studying the effects of chemical exposure; it is now a matter of policy.

The Lancet paper was timed to fall at the tail end of a fierce debate in the European Union on legislation, called REACH, to regulate and test chemicals. Grandjean said that REACH does not include neurodevelopment in its testing guidelines, focusing instead on general toxicity and cancer. The United States currently requires minimal testing of chemicals on the market. “For us, the purpose of this study is to put the developing brain on the prevention agenda,” Grandjean said, “because there’s so much at stake and because we cannot afford to wait.”

—Courtney Humphries

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