CINCINNATI, Ohio, June 17, 2009
/
Toxicology Excellence for Risk Assessment (TERA) has been engaged as an
independent third party to convene a Science Advisory Board (SAB) that
will provide guidance on the design and conduct of a series of studies
investigating the mode of action by which hexavalent chromium is
carcinogenic in rats and mice following drinking water exposure.
The research project is being organized by ToxStrategies and the
studies are being conducted by The Hamner Institute. More information
about TERA may be found at
www.tera.org; ToxStrategies, at
http://www.toxstrategies.com/index.htm; and The Hamner Institute, at
http://www.thehamner.org/. Funding for the research and the Science
Advisory Board is from industry. Background
The authors expect that these secondary responses will lead to
dose-dependent transitions where Cr(III) and Cr(VI) DNA reactivity
finally leads to DNA damage, mutation, and transformation. The
contributions of these various pathways over the range of doses and
concentrations will be determined by a combination of genome-wide
microarray analyses in intact animals, high data content imaging of
activation of key DNA-damage pathways, and consideration of dose
dependences in dosimetry. It is anticipated that the data generated
through this research program will be useful to regulatory agencies as
they make decisions regarding oral risk assessment for hexavalent
chromium. Contact:
TERA is inviting interested parties to observe the SAB meeting and
provide input about the types of data that would facilitate a regulatory
decision regarding mode of action and dose-response approach for an oral
carcinogenicity assessment of hexavalent chromium. The SAB meeting will
be held in the Raleigh-Durham area of North Carolina on
July 28 and 29, 2009. The meeting is open to the public, and TERA
encourages individuals or organizations with expertise in hexavalent
chromium toxicity and risk assessment to attend the meeting as observers
and to submit comments on the proposed research plan. Observers may
submit written comments and make oral comments during the meeting.
The National Toxicology Program recently completed a two-year cancer
bioassay for sodium dichromate dehydrate in drinking water (NTP, 2007)
that reported intestinal tumors in mice and oral mucosal tumors in rats
following lifetime exposure to hexavalent chromium. Therefore, a
research program is being initiated to investigate the mode(s) of action
underlying these tumorigenic responses in rodents in order to determine
the shape of the dose response curve and the human relevance of these
responses prior to the development of an oral quantitative assessment
for hexavalent chromium. The overall goal of these studies is to
understand the contribution of different modes of action for hexavalent
chromium across a broad range of doses in order to provide both
statistical and biological understanding of thresholds for chromium
carcinogenicity. While high concentration tumors in laboratory animals
indicate some level of genotoxicity, these tumors may also arise in the
presence of other cellular responses, including cytotoxicity,
inflammation, and high levels of oxidative stress.
Logistics
Please see the meeting web page at
http://www.tera.org/Peer/Chromium/Chromium.htm for more specific
information. Observers will be able to attend in person or remotely
(either webcast or teleconference, still to be determined). Interested
parties should register on the meeting web page. Note that due to the
size of the conference room there will be a limit of 30 in-person
observers.
Joan E. Strawson, TERA
Peer Review Coordinator
910-528-9768
strawson@tera.org