08:33pm Saturday 18 January 2020

Prenatal exposure to dioxin-like PCBs interferes with brain development

“We have identified a subset of PCBs that seem to have the strongest effect on babies’ developing brains in terms of mental function,” said study senior author Irva Hertz-Picciotto, a professor of public health sciences. 

The study is published online in the journal NeuroToxicology. It the first to examine more than the most common types of the 200-plus PCBs, or polychlorinated biphenyls, in order to determine which might be associated with deficits in neurodevelopment, Hertz-Picciotto said.

PCBs are made up of several different structures of compounds that have different effects on the body. Use of the chemicals, manufactured for many purposes, including in industrial transformers and capacitors, was banned worldwide some 30 years ago. But the chemicals are known to persist in the environment and have significant impacts on human health and the environment.

Scientists also categorize PCBs by their resemblance to dioxins, a class of highly toxic petroleum-derived chemicals that are byproducts of the manufacture of herbicides, the bleaching of paper products and the burning of plastics and are known to cause cancer and birth defects.

“Most previous studies looked at PCBs in one block,” said Hertz-Picciotto, who is a researcher with the UC Davis M.I.N.D. Institute. “Instead, we categorized PCBs by their chemical structures and hormonal activities.”

The study was conducted in Slovakia, where researchers recruited mother-and-baby pairs at delivery from a district called Michalovce that was known to have high PCB contamination from a plant operated from 1959 to 1984. The plant dumped chemical waste into a local river and on nearby land.

Mother-and-baby pairs from Svidnik, a town that did not have such a plant and had lower levels of PCB contamination, were also enrolled. The participants were recruited between 2002 and 2004.

The researchers measured major types of PCBs: non-dioxin-like PCBs, dioxin-like PCBs and anti-estrogenic PCBs. They also measured babies’ mental development and motor skills at 16 months and interviewed mothers to obtain information on other factors that might affect brain development, including the mothers’ education levels, health status, and cigarette and alcohol use. Because of an overlap in the PCB levels between the two areas, the study focused on measuring the chemical loads in mother and child.

The researchers found that only the two dioxin-like PCBs, #118 and #156, were associated with deficits in neurodevelopment.

 “We found that the prenatal dioxin-like PCBs were associated with reduced mental and motor-development scores,” said study lead author Hye-Youn Park, a UC Davis graduate student when the study was conducted who now works for the California Department of Public Health.

Park said that, surprisingly, non-dioxin-like PCBs as a group did not seem to have an impact on mental functioning.

“Many studies done in the lab have shown that non-dioxin-like PCBs impact neurodevelopment, but we did not see that here,” she said.  However, non-dioxin-like PCBs did show an adverse effect on motor development.

Hertz-Picciotto said some Americans have been exposed to levels of PCBs comparable to those measured in Slovakia. For example, people living near a chemical plant in Anniston, Ala., had similar exposures to PCBs. The plant produced about 10 times more PCBs over the years than the one in Slovakia.

“It was a similar situation in which the chemicals were literally dumped into the community,” Hertz-Picciotto said.

The specific mechanism by which PCBs affect neurodevelopment is not known. The study authors theorize that hormonal activity and interactions with certain receptors may be important.

Earlier this year, other UC Davis researchers published three separate studies providing evidence that they had identified the mechanism responsible for the harmful effects of PCBs on the developing brain. Based on a combination of lab and animal experiments, the researchers showed that low levels of PCBs alter the way brain cells develop and that they do this by binding to ryanodine receptors, calcium channels found on the surface of brain cells.

“We’ve never really understood the mechanism by which PCBs produce neurodevelopmental problems in children and eventually adults,” said Isaac Pessah, a professor of molecular biosciences and director of the UC Davis Center for Children’s Environmental Health.

“We have now shown — from the whole animal level to the molecular level — how PCBs alter the development of brain cells and that could explain why they are associated with higher rates of diseases like autism,” said Pessah, who is also a M.I.N.D. Institute researcher.

While Pessah and his colleagues try to determine how PCBs impair brain development, Hertz-Picciotto and other epidemiologists are trying to determine the continued public-health impacts of PCBs and similar compounds that were released into the environment before they were banned.

“Though these chemicals persist for years and even decades, it takes a while for the epidemiology and the toxicology research to catch up and find out what these chemicals are capable of doing to humans,” Hertz-Picciotto said.

Other study authors include Eva Sovcikova, Anton Kocan and Tomas Trnovec of the Slovak Medical University, Bratislava, Slovakia.

The research was supported by grants from the National Institutes of Health, the Environmental Protection Agency, the Slovak Ministry of Health and the European Commission.

The UC Davis M.I.N.D. Institute, in Sacramento, Calif., was founded in 1998 as a unique interdisciplinary research center where parents, community leaders, researchers, clinicians and volunteers collaborate to study and treat autism and other neurodevelopmental disorders. More information about the institute is available on the Web at http://www.ucdmc.ucdavis.edu/mindinstitute/.

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