One of the nation's leading voices on children's environmental health has called for focused and expanded research into the cause-effect relation between industrial chemicals and autism.
"Long and tragic experience that began with studies of lead and methylmercury has documented that toxic chemicals can damage the developing human brain to produce a spectrum of neurodevelopmental disorders," Dr. Philip Landrigan from the Mount Sinai School of Medicine wrote in a Jan. 16, 2010, article in the medical journal Current Opinion in Pediatrics.
Today's children, he noted, "are at risk of exposure to 3,000 synthetic chemicals produced in quantities of more than 1 million pounds per year, termed high-production-volume (HPV) chemicals. HPV chemicals are found in a wide array of consumer goods, cosmetics, medications, motor fuels and building materials."
"The developing human brain is understood today to be exquisitely susceptible to injury caused by toxic chemicals in the environment." - Dr. Philip LandriganEight of those 3,000 have been "implicated" in the development of "neurodevelopmental disabilities," Landrigan wrote. And a recent review of the world's literature identified roughly 200 industrial chemicals that have been documented to be neurotoxic in adult humans.
"These are primarily industrial chemicals -- metals, solvents and pesticides -- and nearly half are HPV materials," Landrigan wrote in the paper titled What causes autism? Exploring the environmental contribution. "This search also produced a second list of approximately 1,000 chemicals that have not been examined in humans but that are neurotoxic in experimental models."
The short list of eight identified as human developmental neurotoxicants -- lead, methylmercury, polychlorinated biphenyls (PCBs), arsenic, manganese, organophosphate insecticides, DDT and ethyl alcohol -- "may be only the currently visible tip of a potentially much larger problem," he wrote.
Landrigan is the long-time head of the Children's Environmental Health Center at Mount Sinai in New York City. The Harvard-educated pediatrician and professor specializes in the study of industrial toxins and their impacts on human health. His work in the field dates to the 1970s.
Journalist Bill Moyers introduced him on a May 10, 2002, edition of PBS's NOW: "Dr. Phil Landrigan is a renowned expert on environmental health and pediatrics who has worked to translate science into public policy and introduce children's environmental health into mainstream medical education," Moyers said.
"This vulnerability is greatest during embryonic and fetal life, and may be especially great in the first trimester of pregnancy."
Landrigan has long characterized the release of industrial chemicals into the environment as a "massive, toxicological experiment, with our children and our children's children as the experimental subjects."
In his latest article, Landrigan narrows his focus to one possible outcome from that experiment -- the worldwide epidemic of autism spectrum disorders (ASDs). Diagnostically, ASDs include Autistic Disorder, Asperger's Disorder and Pervasive Development Disability-Not Otherwise Specified (PDD-NOS).
"Given current understanding of the great vulnerability of the developing brain to toxic chemicals, likelihood is high that many of the materials ... have potential to cause injury to the developing brain and to produce neurodevelopmental disorders, possibly autism among them," he wrote.
One hypothesis Landrigan suggests would explore genetic predisposition for autism induced from exposure to individual or combinations of toxic chemicals. "Variation in the interplay between different environmental exposures and inherited vulnerabilities may account for the observed heterogeneity in the autism phenotype," he wrote.
A genetic component to autism has long been accepted among autism researchers. But for the moment, at least, genetic factors are thought to account for only 7 to 8 percent of autism cases, Landrigan wrote. "This fraction will likely increase as genetic research advances and additional genetic causes are discovered."
A purely genetic explanation, however, doesn't explain "certain clinical and epidemiological aspects of autism," he continued. "... This situation therefore raises the possibility that environmental exposures could also play a role in causation of autism."
The article lends support to the argument that developing children are not little adults when it comes to toxic exposures, that, in fact, children and fetuses are uniquely vulnerable.
"There is substantial imbalance between the extensive and highly sophisticated information on the genetics of autism and the scarcity of investigation into potential environmental causes."
"The developing human brain is understood today to be exquisitely susceptible to injury caused by toxic chemicals in the environment," Landrigan wrote. "This vulnerability is greatest during embryonic and fetal life, and may be especially great in the first trimester of pregnancy. There exist windows of susceptibility in early development that have no counterpart in the mature brain."
And pregnant women and developing children are under constant assault from HPVs and other toxins, he warned: "They are routinely detected in air, food and drinking water. Measurable quantities of several hundred HPV chemicals are found in the blood and urine of nearly all Americans, as well as in human breast milk and the cord blood of newborn infants."
And little is known about their potential effects. "Fewer than 20 percent of HPV chemicals have been tested for potential to cause neurodevelopmental toxicity," Landrigan said.
Some clinical and epidemiological studies have already linked autism with specific environmental exposures, producing what Landrigan called "strongly positive, 'proof-of-concept' evidence." He discussed five: Thalidomide, Misoprostol, valproic acid, prenatal rubella infection and chlorpyrifos.
"Measurable quantities of several hundred HPV chemicals are found in the blood and urine of nearly all Americans, as well as in human breast milk and the cord blood of newborn infants."
Chlorpyrifos, for example, is an insecticide that was widely used to control insects in schools and homes in the United States until a few years ago, Landrigan said. It is still used extensively in agriculture.
An organophosphate, chlorpyrifos was recognized as a developmental neurotoxicant in experimental studies published in 2001, Landrigan said. Perinatal exposure of newborn rodents to low doses of it correlated to reduced numbers of neurons, decreases in intelligence and persistent alterations of behavior.
Assessments of infants exposed in utero to chlorpyrifos have shown a variety of reactions. Between 24 and 36 months, they showed significant developmental delays, cognitive deficits and increased risk for attention deficit-hyperactivity disorder, or ADHD.
"Most recently these studies have found, on the basis of maternal report, an increased incidence of PDD-NOS," Landrigan noted.
In chlorpyrifos and each of the other four proof-of-concept examples, environmental exposures relevant to autism appear to have occurred prenatally, early in the first trimester of pregnancy, he continued.
"These findings have substantial implications for understanding the environmental contribution to causation of autism and for the design of research that seeks to discover these causes," he wrote.
Landrigan proposed a shift in autism strategy from genetic to environmental and, presumably, preventable causes of autism. He called the potential for breakthrough high.
"Fewer than 20 percent of HPV chemicals have been tested for potential to cause neurodevelopmental toxicity."
"There is substantial imbalance between the extensive and highly sophisticated information on the genetics of autism and the scarcity of investigation into potential environmental causes," he wrote in his conclusion. "This situation raises the possibility that unsought environmental exposures contribute to causation of autism.
"To discover the undiscovered environmental causes of autism, an interdisciplinary autism discovery strategy is proposed that combines toxicological screening, neurobiological research and prospective epidemiological study. Likelihood is high that this strategy will identify new environmental causes of autism, causes that can in theory be prevented."
Steven Higgs is author of the "Autism and the Indiana Environment Blog" and editor of The Bloomington Alternative. He can be reached at .