NORA Manufacturing Sector Strategic Goals
921ZJWK - CDC Foundation-APIStart Date: 2/18/2000
End Date: 9/30/2011
Principal Investigator (PI)Name: James O'callaghan
Funded By: NIOSH
Primary Goals Addressed9.09.0
Secondary Goal Addressed
Attributed to Manufacturing
The purpose of the project is to determine whether fuel and fuel additive cause neurotoxicity in a rat model of human exposure.
Neurotoxicity risk assessment
All data have been collected and reports (nine) have been submitted to Huntingdon Life Sciences (HLS) and subsequently to the American Petroleum Institute (API) (the sponsor). These reports are currently under review with the U.S. Environmental Protection Agency for final approval. Several of the nine reports remain under review. Pending the outcome of these reviews, more sample analysis may need to be performed or the data may be accepted, as is, in final form. In aggregate, the accepted reports will be utilized by the US EPA to evaluate and determine the neurotoxic potential of specific fuel additives and gasoline based on the 90-day inhalation exposure to rats. These data will serve to further validate the use of the GFAP assay by CDCNIOSH as a preclinical index of neurotoxicity.
The purpose of the project is to determine whether fuel and fuel additive cause neurotoxicity in a rat model of human exposures Conduct 90-day subchronic inhalation exposures of rats to gasoline and gasoline plus 5 fuel oxygenates (methyl tertiary butyl ether, ethyl tertiary butyl ether, tertiary amyl methyl ether, disopropyl ether and ethanol). A contract laboratory funded by API will perform this work. Perform GFAP assays on no less than 7 brain regions prepared from the exposed rats (90-day study) or the second-generation offspring (developmental exposure). The GFAP assay will be performed at CDC-NIOSH. Brain tissue will be prepared by CDC-NIOSH personnel at the respective contract laboratory site. Publish the results of these studies in a peerreviewed scientific journal. This will be a joint publication of CDC-NIOSH, API, and the contract laboratories.
CDC/NIOSH personnel were instrumental in development and validation of the GFAP assay for neurotoxicity assessment to acute exposures. This project will use a subchronic inhalation exposure regimen to validate the use of GFAP as a biomarker of the neurotoxic effects of gasoline and gasoline plus each of 5 oxygenate fuel additives. A 90-day subchronic inhalation exposure of rats to gasoline and gasoline plus 5 fuel oxygenates (methyl tertiary butyl ether, ethyl tertiary butyl ether, tertiary amyl methyl ether, disopropyl ether and ethanol) will be conducted and CDC-NIOSH personnel will use its validated GFAP assay to examine rat brains for evidence of neurotoxicity. The time and expense alone of conducting the exposures to these agents would preclude CDC/NIOSH personnel from undertaking this project. Thus, at no cost to the Government, CDC/NIOSH will receive information on the use of the GFAP assay as a biomarker of neurotoxicity using subchronic exposure to potential occupational neurotoxic agents GFAP assay for neurotoxicity will be used to determine the adverse health effects of gasoline additives on the nervous system.
Workplace-related adverse effects on the nervous system continue to be of concern for most work sectors. A large number of workplace-related exposures, and the physiological and environmental factors with which they interact, are associated with subtle neurological effects. Establishing the potential adverse nature of these effects is hampered by the lack of biomarkers of neurotoxicity. Traditional morphological and/or behavioral indices of neurotoxicity have proven to lack sufficient sensitivity or specificity to define the neurotoxic condition. Thus, the success of this project, which is concerned with the development of specific and sensitive biomarkers of neurotoxicity, will have important implications for many of the NORA sector programs.
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