Superfund Basic Research Center
Neurotoxic Superfund Chemicals and Biomarkers
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Superfund Basic Research Program

The SBRC is funded by a grant (5 P42 ES010338) from the National Institute of Environmental Health Sciences (NIEHS) through its Superfund Basic Research Program.

May 21, 2004: SBRC Co-Sponsors Regional Symposium On Trichloroethylene (TCE)

SBRC research featured in NIEHS Research Briefs series
Research Highlights for 2003

Research may have implications for current EPA exposure standards. Dr. Karla Thrall (Project A1) has been using a novel breath analysis system to accurately measure the amount of volatile organic chemicals that are absorbed into the body by any route of exposure, and has developed mathematical models to describe the absorption, distribution, metabolism and excretion of these chemicals. This allows a more accurate estimation of the amount of chemical contaminant that has entered particular tissues.

In 2003, the Thrall laboratory performed a series of controlled dermal and inhalation studies to assess the bioavailability of toluene in human volunteers under exposure conditions designed to mimic bathing scenarios. Their data indicate that human skin is more than 80 times less permeable to toluene than previous U.S. EPA estimates suggest. This finding may have important implications for the re-assessment of current EPA exposure standards and for improving overall risk assessments for toluene, as well as other compounds.

Data may help develop better predictive models for human dermal absorption of volatile organic compounds. Dr.Thrall’s lab has compared species differences between rats and human volunteers in the dermal bioavailability of aqueous xylene. These comparative studies suggest that, while aqueous xylene is rapidly absorbed through the skin of both rats and humans, rat skin is approximately 12 times more permeable to aqueous xylene than human skin. These experiments provide an opportunity to better understand species differences in dermal bioavailability and may ultimately aid in developing more predictive models for human dermal absorption from rodent data.

The development of reliable human-specific data describing the dermal bioavailability of two commonly encountered solvents (xylene and toluene) has important implications for scientists’ ability to accurately assess the toxicological risks presented by exposure to volatile organic compounds. These methods will ultimately reduce uncertainty in the risk assessment process involving volatile organic substances.


Research on the microbial degradation of trichloroethene (TCE) may lead to improved remediation technologies at Superfund sites.
Dr. Jennifer Field (Project B1) is developing methods to enhance the microbial degradation of TCE to nontoxic products (e.g., ethene or carbon dioxide) by manipulating the microbial growth conditions that exist underground. Such technology has the potential to substantially reduce the impact that TCE and other chlorinated solvents have on human health and the environment. This project addresses a critical need, because TCE is present at many Superfund sites and is the organic contaminant most frequently detected in groundwater.

In 2003, approximately 70 field experiments were conducted at TCE-contaminated sites in Oregon, California, Washington, South Carolina, and Tennessee. An important result of this work was the demonstration that fluorinated analogs of TCE can be used as chemical tracers to indirectly monitor the microbial degradation of TCE in heavily contaminated environments, where direct monitoring of TCE degradation is not possible.

Based on this important result, Dr. Field’s group has developed a suite of chemical tracers to probe each step in the TCE biodegradation pathway and to assess the ability of microbes to completely degrade TCE to non-toxic products. At many sites, biotransformation of TCE was shown to produce the toxic intermediate, vinyl chloride, which suggests that the microbial community at those sites is not able to completely metabolize TCE to ethane, a relatively non-toxic compound. Dr. Field has developed an assay for monitoring this transformation, and has shown that the biotransformation of vinyl chloride to ethane can be enhanced and is feasible under field conditions. The chemical tracers have allowed comparisons to be made between the effectiveness of non-microbial (e.g. chemical reduction using iron) and microbial TCE degradation processes, and has allowed investigations into the use of lactate and hydrogen to stimulate the growth and activity of biodegradation organisms. At one field site, it was shown that subsurface addition of iron produced a more complete chemical transformation of TCE to non-toxic products than did lactate and hydrogen additions.

Collectively, this work represents a major advance in our ability to understand and manipulate microbial processes to degrade TCE and similar contaminants. The tracers that Dr. Field is developing provide us the ability to probe relevant microbial processes under actual field conditions and have a variety of applications to industry (e.g., to perform rapid feasibility assessments and pilot testing of remediation technologies).


SBRC research presented at international forum. Dr. Field’s work has generated substantial international interest. In 2003, she was invited to participate and speak about her work on TCE bioremediation at the U.S.-Vietnam Scientific Workshop on Dioxin Screening, Remediation Methodologies and Site Characterization, held Nov 2-5, 2003, in Hanoi, Vietnam.


Findings suggest that some commercial industrial solvents have the potential to cause nerve degeneration. In 2003, Drs. Mohammad Sabri and Peter Spencer (Project A2) determined that the solvent 2,5-hexanedione (2,5-HD, a structural cousin of 1,2-DAB [1,2-diacetylbenzene] and the active metabolite of the industrial solvent n-hexane) produces a chromophore (a protein-chemical combination that stains tissues and urine a bluish-purple color) that is closely related to the solvent’s neurotoxic effects. The Sabri/Spencer laboratory is the first to demonstrate that:

  • an aromatic hydrocarbon solvent metabolite (1,2-DAB) is able to cause nerve degeneration in the central and peripheral nervous system
  • the neurotoxicity and chromogenicity of aromatic solvents are related phenomena, and
  • a common pattern of axonal degeneration is associated with repeated exposure to neurotoxic aliphatic (2,5-HD) and aromatic (1,2-DAB) solvent derivatives.

These results raise the possibility that a number of other reportedly chromogenic organic solvents, including substances that are in very widespread commercial use, have the potential to cause nerve degeneration. Moreover, chromophores may be able to be used as biological markers of exposure to aromatic hydrocarbon solvents, because the chromophore appears in tissues and urine before neurodegenerative changes appear. Since 2,5-HD is the ultimate metabolite of the neuropathy-producing aliphatic solvent n-hexane, and 1,2-DAB is the equivalent of the more potent neuropathy-producing aromatic solvent 1,2-diethylbenzene (1,2-DEB), permissible limits for human workplace exposure for 1,2-DEB need to be re-assessed.


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