Mechanism involved in trichloroethylene-induced liver cancer: Importance to environmental cleanup. 1998 annual progress report

PDF Version Also Available for Download.

Description

'The objective of this project is to develop critical data for changing risk-based clean-up standards for trichloroethylene (TCE). The project is organized around two interrelated tasks: Task 1 addresses the tumorigenic and dosimetry issues for the metabolites of TCE that produce liver cancer in mice, dichloroacetate (DCA) and trichloroacetate (TCA). Early work had suggested that TCA was primarily responsible for TCE-induced liver tumors, but several, more mechanistic observations suggest that DCA may play a prominent role. This task is aimed at determining the basis for the selection hypothesis and seeks to prove that this mode of action is responsible for ... continued below

Physical Description

3 pages

Creation Information

Bull, R.J.; Thrall, B.D.; Sasser, L.B.; Miller, J.H. & Schultz, I.R. June 1, 1998.

Context

This report is part of the collection entitled: Office of Scientific & Technical Information Technical Reports and was provided by UNT Libraries Government Documents Department to Digital Library, a digital repository hosted by the UNT Libraries. It has been viewed 84 times , with 6 in the last month . More information about this report can be viewed below.

Who

People and organizations associated with either the creation of this report or its content.

Sponsor

Publisher

Provided By

UNT Libraries Government Documents Department

Serving as both a federal and a state depository library, the UNT Libraries Government Documents Department maintains millions of items in a variety of formats. The department is a member of the FDLP Content Partnerships Program and an Affiliated Archive of the National Archives.

Contact Us

What

Descriptive information to help identify this report. Follow the links below to find similar items on the Digital Library.

Description

'The objective of this project is to develop critical data for changing risk-based clean-up standards for trichloroethylene (TCE). The project is organized around two interrelated tasks: Task 1 addresses the tumorigenic and dosimetry issues for the metabolites of TCE that produce liver cancer in mice, dichloroacetate (DCA) and trichloroacetate (TCA). Early work had suggested that TCA was primarily responsible for TCE-induced liver tumors, but several, more mechanistic observations suggest that DCA may play a prominent role. This task is aimed at determining the basis for the selection hypothesis and seeks to prove that this mode of action is responsible for TCE-induced tumors. This project will supply the basic dose-response data from which low-dose extrapolations would be made. Task 2 seeks specific evidence that TCA and DCA are capable of promoting the growth of spontaneously initiated cells from mouse liver, in vitro. The data provide the clearest evidence that both metabolites act by a mechanism of selection rather than mutation. These data are necessary to select between a linear (i.e. no threshold) and non-linear low-dose extrapolation model. As of May of 1998, this research has identified two plausible modes of action by which TCE produces liver tumors in mice. These modes of action do not require the compounds to be mutagenic. The bulk of the experimental evidence suggests that neither TCE nor the two hepatocarcinogenic metabolites of TCE are mutagenic. The results from the colony formation assay clearly establish that both of these metabolites cause colony growth from initiated cells that occur spontaneously in the liver of B 6 C 3 F 1 mice, although the phenotypes of the colonies differ in the same manner as tumors differ, in vivo. In the case of DCA, a second mechanism may occur at a lower dose involving the release of insulin. This observation is timely as it was recently reported that occupational exposures to trichloroethylene results in 2 to 4-fold elevations in serum insulin concentrations, as well. The increases in insulin have not been shown responsible for the induction of liver tumors. Therefore, this problem is a subject of a proposal to the Office of Biological and Environmental Research Low-Dose Initiative. However, even if this is demonstrated to be the most sensitive mechanism for liver tumor induction, it is unlikely to contribute to induction of cancer at lower doses, since this involves modification of normal endocrine function. As doses are decreased to levels that do not induce increase in serum insulin level, there should be no risk from this metabolite either. Therefore, there is clearly a rational basis for considering a margin of exposure for low dose extrapolation of liver cancer risks for TCE.'

Physical Description

3 pages

Language

Item Type

Identifier

Unique identifying numbers for this report in the Digital Library or other systems.

  • Other: DE00013582
  • Report No.: EMSP-54684--98
  • Grant Number: NONE
  • DOI: 10.2172/13582 | External Link
  • Office of Scientific & Technical Information Report Number: 13582
  • Archival Resource Key: ark:/67531/metadc624865

Collections

This report is part of the following collection of related materials.

Office of Scientific & Technical Information Technical Reports

Reports, articles and other documents harvested from the Office of Scientific and Technical Information.

Office of Scientific and Technical Information (OSTI) is the Department of Energy (DOE) office that collects, preserves, and disseminates DOE-sponsored research and development (R&D) results that are the outcomes of R&D projects or other funded activities at DOE labs and facilities nationwide and grantees at universities and other institutions.

What responsibilities do I have when using this report?

When

Dates and time periods associated with this report.

Creation Date

  • June 1, 1998

Added to The UNT Digital Library

  • June 16, 2015, 7:43 a.m.

Description Last Updated

  • June 13, 2016, 6:06 p.m.

Usage Statistics

When was this report last used?

Yesterday: 0
Past 30 days: 6
Total Uses: 84

Interact With This Report

Here are some suggestions for what to do next.

Start Reading

PDF Version Also Available for Download.

International Image Interoperability Framework

IIF Logo

We support the IIIF Presentation API

Bull, R.J.; Thrall, B.D.; Sasser, L.B.; Miller, J.H. & Schultz, I.R. Mechanism involved in trichloroethylene-induced liver cancer: Importance to environmental cleanup. 1998 annual progress report, report, June 1, 1998; Richland, Washington. (digital.library.unt.edu/ark:/67531/metadc624865/: accessed July 18, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.