BY JIM HOWE

Among the industrial wastes that have polluted Syracuse‘s Onondaga Lake for decades are two “mystery compounds” related to – and apparently more toxic than – the banned pesticide DDT.

Scientists from Upstate Medical University, Syracuse University and the SUNY College of Environmental Science and Forestry have collaborated to study the chemicals, termed diphenylethanes, and whether they might cause seizures, developmental defects, brain damage or early death.

John Hassett, PhD, a professor of chemistry at ESF, has studied the lake for years and discovered these chemicals in a mud sample he took near the southern end of the lake.

He recognized the DDT-like structure of the two chemical compounds, which have no common names because they were never used commercially.

"It was a eureka moment for me when I realized how these two compounds came to be," Hassett said. He had researched chemical processes going back to the 1880s and theorized that the lake's chief industrial polluter, the defunct Allied Corp., produced the two chemicals as chance byproducts of refining oil produced from coking coal. The oily, thick compounds, officially designated as PTE (1-Phenyl-1-(p-Tolyl)-Ethane) and PXE (1-Phenyl-1-(2,4-Xylyl)-Ethane), had not been identified by industrial chemists, had no commercial use and were dumped in tar pits near the lake and possibly into the lake itself, he said.

Hassett and his team analyzed the newly found lake chemicals, which matched the material in the tar pits.

"When we looked at the structure, it has the same chemical backbone as DDT, so we wondered if this stuff might have biological consequences," Hassett said.

Hassett has found the chemicals in the water all through the lake, apparently coming from very contaminated sediments near shore. "If it's buried in the mud and not disturbed, it should stay there. If you go down about a meter into the mud in the middle of the lake, I think there is a layer through the whole sediment of the lake. It comes up to the surface in that shallow part in the southern end; in deeper parts, it is buried. We're going to see what's still out there," Hassett said.

Dredging and capping of the lake bottom, completed this spring as part of a decades-long lake cleanup, probably stirred up some of the sediment, although any tar should remain buried in deeper sections, Hassett said. Since the tar is not very soluble in water, it probably is not much of a groundwater threat, he said. It is likely accumulated by lake fish, which health officials warn people not to eat. Some refugees and possibly other people, however, have been known to ignore warnings and eat fish from the lake.

To study the compounds‘ possible toxic effects, Hassett partnered with James Hewett, PhD, and Katharine Lewis, PhD, associate professors of biology at SU. Lewis conducted studies on young zebrafish, while Hewett studied mice, both of which are often used as test models for humans.

"Because it looked like DDT, which has effects in development and is neurotoxic -- DDT is linked to tremors and other neurological problems -- we thought we'd test the neurotoxic potential of these compounds at the earliest stages of life," Hewett said. "DDT is linked to tremors and other neurological problems."

"My field of research is epilepsy. There is considerable interest now in how early life environment influences disease susceptibility later in life.”

Hewett exposed pregnant female mice to PTE and found their offspring seemed normal until adulthood, when testing showed they were more susceptible to seizures, such as happens with epilepsy. While it is difficult to mimic precisely how human exposure to these chemicals might take place, the mouse study provides a model for future testing, Hewett said.

Lewis found the chemicals to be extremely toxic at very low levels, hundreds of times lower than DDT. The lowest levels that they tested were similar to the levels Hassett found in Onondaga Lake in 1994. These levels cause heart defects and increased death rates in young zebrafish, and slightly higher levels caused increased susceptibility to convulsion behaviors that are similar to human seizures.

“I would be very surprised if the effects these chemicals have on zebrafish are fundamentally different than those on humans, but there may be subtle differences,” Lewis said. “It‘s highly likely that the same effects would also occur in humans, but you can never say for sure.”

Also participating in the research, now in its third year and paid for by a grant from the Hill Collaboration on Environmental Medicine, is Frank Middleton, PhD, an associate professor of neuroscience and physiology and director of the SUNY Molecular Analysis Core at Upstate. Middleton assessed changes in gene expression – the process by which genetic information is made into a product, such as a protein -- in the brains of the exposed mice offspring and zebrafish embryos. He was seeking clues that might help explain the altered seizure susceptibility and birth defects using a high-powered approach referred to as next generation sequencing (NGS).

“The NGS data are very compelling and indicate disruption of very specific genes and cellular signaling pathways is occurring as a result of the PTE and PXE exposures,” said Middleton.

The researchers all hope to continue studies based on this work.

“I would like to test other chemicals and see which genes might be turned on or off because of these chemicals. That could teach more about what can cause seizure or early development toxicity and might give more potential targets for therapy,” Lewis noted.

What is DDT?

DDT was a commonly used pesticide until it was banned in the U.S. in 1972 because it persists in the environment, accumulates in fatty tissues and can cause adverse health effects on wildlife, becoming more toxic as it moves up the food chain.

The two chemical compounds found in the Onondaga Lake mud -- PTE and PXE -- are related to DDT and appear to be more toxic. They have no known commercial value and have never been studied extensively before.

This article appears in the summer 2017 issue of Upstate Health magazine.