Manganese Health Research Program: Phase 2, Core 19

Research Core Project Number:	W81XWH-05-1-0239
Research Core Project:	In Vivo Micronucleus Assay of Manganese According to OECD 474 Guideline and Critical Review of the Genetic Toxicology of Manganese
Core Principal Investigator (CPI):	Leslie Recio, PhD DABT ILS, Inc PO Box 13501 RTP, NC 27709


Key Collaborators:	None

Project Objectives:

Conduct in vivo micronucleus assay in mice compliant with regulatory guidelines to assess the genotoxic potential of manganese chloride
Conduct literature review of genotoxic effects of manganese

Project Description:

The purpose of this project is to assess the in vivo genotoxic potential of manganese chloride in an assay that meets international guidelines for genotoxicity assessments. The micronucleus assay in mice is the only in vivo genotoxicity test that is part of the genotoxicity test battery required by regulatory agencies worldwide. The in vivo micronucleus assay detects chromosomal damage in the peripheral blood of test species. This project will assess the in vivo genotoxicity of manganese in a study that meets the experiential design of regulatory guidelines for the conduct of the in vivo micronucleus. The second objective of this project is to conduct a review of the literature on the genotoxic potential of manganese.

Project Status:

Project started: April 15, 2008
Scheduled completion date: January 31, 2010
Anticipated completion date: September 30, 2009

Publications:

Stankowski J., Leitch D., Aschner M., McLaughlin B. and Stanwood G. D. (2008) Selective vulnerability of dopaminergic systems to Manganese: Relevance to occupational exposure. Neurotoxicology And Teratology 30, 259.

Key research accomplishments:

Female mice are more sensitive than male mice to the acute effects of MnCl2
A top dose of 200 mg/kg will be used to conduct a micronucleus assay in female mice in compliance with OECD 474