Report: Chemical mixes can affect nerve growth: BRICK FAMILIES STILL SEEK ANSWER

When parents William and Bobbie Gallagher pressed government officials to investigate why their children and so many others here are autistic, they suggested it might be worth checking into pollution and environmental factors.
When parents William and Bobbie Gallagher pressed government officials to investigate why their children and so many others here are autistic, they suggested it might be worth checking into pollution and environmental factors.

A 2001 federal report discounted possible connections between autism and pollution. But the stories coming out of Brick got the attention of other scientists, who have published new findings showing how some of the chemicals detected here more than a decade ago — when tested in combination and at higher concentrations — have the potential to affect nervous system development in shellfish embryos.

“That’s exactly what we were trying to say. What no one ever looks at is the cumulative effect of these chemicals,” said Bobbie Gallagher, a mother of two autistic children. “That’s one of the scariest things about when they do these (environmental) studies. They only look at each compound individually.”

The contaminants bromoform, chloroform and tetrachloroethylene triggered increases in a component of an enzyme thought to influence neural development — perhaps offering a clue about how exposure to pollution mixes might affect human neural development and enigmatic conditions, including childhood autism that was reported at a higher than expected rate in Brick, said lead researcher Carol L. Reinisch of the Marine Biological Laboratory at Woods Hole, Mass.

“The issue really came down to looking at the chemicals singly and in combination,” said Reinisch, 59, a scientist known for her work on polychlorinated biphenyls (PCBs) contamination in lobsters and other marine animals. “What this study showed is it’s the mixture of these chemicals that cause the uptick in an enzyme that’s very important to neural development.”

Reinisch said the study was inspired in part by news stories about a 2000-01 survey by the federal Agency for Toxic Studies and Disease Registry (ATSDR) that looked at rates of autism among Brick’s school-age children population.

ATSDR experts then said they could not connect autism cases and local pollution, and found no clear or convincing evidence of environmental pathways that would have consistently exposed pregnant women to contaminants in water.

ATSDR officials wouldn’t comment on the new toxicological study, because the scientists used upper test levels that exposed clam embryos to 100 and 1,000 times the concentrations observed here.

“We have seen the study, but the mixtures in that study are at different concentrations” than reported in 2001, said Rachel Powell, a media officer with the agency.

Even with that caution, several Brick parents, who worked to focus official attention on the township’s autistic population, said the latest findings may lend credibility to the idea that local environmental conditions can play a role in autism.

“Do I think it’s environmental? I’m leaning that way,” said Diana Gerlach, president of a newly formed parents-teachers association for Brick’s special-needs students.

Significant milestone

The study itself is a significant milestone in environmental toxicology, according to Reinisch and her colleagues, Jill A. Kreiling and Raymond E. Stephens.

“This is one of the first reports demonstrating that a mixture of environmental pollutants can act synergestically to alter a critically important biochemical pathway in the developing embryo,” they wrote.

Autism is a neurological disorder that leaves children with limited ability to communicate or interact socially, a condition usually diagnosed by age 3. Experts have been worried by an apparent rise nationally in autism rates; scientists are trying to determine how much of that reflects more accurate diagnoses, or an actual increase in autism frequency.

Studies by the federal Centers for Disease Control and the ATSDR estimated that one in 150 children in Brick was autistic, or three times the average national frequency. Since then, a study of autism frequency in Staffordshire, England, has suggested such higher rates may actually be the norm. Some research suggests genetics, rather than environment, may be key to causing the condition.

In the ATSDR effort, researchers reviewed medical literature and compiled a list of contaminants suspected of contributing to autism or similar conditions, such as pervasive developmental disorder and Asperger’s disorder.

Out of a list of about 60 contaminants, three substances — trichloroethylene (TCE), tetrachloroethylene (PCE), and a family of compounds, including bromoform and chloroform, known as trihalomethanes (THMs) — were found to have been in some of the wells supplying Brick’s municipal water at various times from 1987 to 1995 in very low levels of a few parts per billion, well below public health guidance for drinking water.

TCE and PCE were present in several small wells that supplied a small percentage of drinking water, but in levels too low to cause harm, according to the ATSDR. Levels of trihalomethanes were elevated during certain periods and places, but no clear pattern was found between those elevated levels and the pregnancy period for children in the CDC’s prevalence study.

Ground water under the long-closed French’s Landfill, a Superfund toxic waste site on Sally Ike Road, is contaminated with hazardous chemicals, but the study concluded that residents would not have been exposed to that water. ATSDR scientists looked, too, at potential upstream pollution sources in the Metedeconk River, but concluded the river could not have been contaminated at levels capable of harming people.

Study of clam embryos

In the toxicological study, Reinisch and her fellow scientists treated developing surf clam embryos with different combinations of PCE, bromoform and chloroform and observed the effects.

At the upper levels, they tested the embryos with combinations that were 100 and 1,000 times higher than the traces reported in Brick — multiplying by factors of 10, in what scientists refer to as orders of magnitude. Chloroform was used at a maximum concentration of 240 parts per million, above its maximum reported incidence in Brick at 240 parts per billion.

Bromoform and tetrachloroethylene were tested at 5 ppm and 6 ppm, above their Brick occurrences at 5 ppb and 6 ppb respectively.

Clam neurons are a useful model for studying cell development, said Reinisch, who helped develop the method for use in polychlorinated biphenyls research, along with her student, Cynthia Smith, while they were at the Tufts University veterinary school.

Treating the embryos with a “cocktail” of all three compounds boosted production of a subunit of protein kinase A or PKA, an enzyme that is believed to play a key role in neural development, according to the team’s report. Fluctuations in PKA help activate or inactivate other important proteins, thus influencing nerve growth and how neural networks are constructed during early life stages, they wrote.

Earlier research on polychlorinated biphenyls showed they inhibit enzyme production, while “the Brick chemicals do not, they bump it up,” Reinisch said.

Funded with a grant from the U.S. Environmental Protection Agency, the peer-reviewed study was published in this month’s issue of Environmental Toxicology and Pharmacology, a scientific journal. The question of why some chemicals have such enhanced effects only in combination is a leading edge in toxicological studies, and more are on the way, Reinisch said.

“Most chemicals in the environment do not exist in isolation, they exist in mixtures,” said Chris Saint, a scientist with the EPA’s National Center for Environmental Research, which funded the experiments. “Our particular interest is in developing new methodologies.”

Since the mid-1980s, such risk assessment was “traditionally done on a chemical-by-chemical basis,” Saint said. More recently, newer laws on food quality and safe drinking water have empowered the agency to look for “cumulative estimates of risk” that encompass chemical and environmental factors, genetics, nutrition and other combined stresses on human health, he said.

“The Canadians are really looking into this,” Reinisch said. “This is going to be a big push in the Great Lakes region.” As for the Brick chemicals study, the Environmental Protection Agency is funding a second phase for the Marine Biological Laboratory to test the contaminants on zebrafish, Reinisch said.

Parents feel vindicated

The 2001 ATSDR report fell short of what parents were expecting, when the paper was presented at a public meeting without explanation or additional information from federal workers, Bobbie Gallagher recalled. Now, she says, she’s happy that other scientists picked up on those findings to explore the potential of chemical synergy effects.

“We feel a little vindicated, because ATSDR kind of hung us out to dry with that study. The town was going crazy,” said William Gallagher, Bobbie’s husband, who had pressed local officials and members of Congress to get the investigation started. “We didn’t deserve that. Now, we feel a little vindicated.”