[ascct] Member webinar: Using new technologies for risk assessment
- From: Kristie Sullivan <KSullivan@xxxxxxxx>
- To: "ascct@xxxxxxxxxxxxx" <ascct@xxxxxxxxxxxxx>
- Date: Tue, 7 Aug 2012 13:55:33 -0400
You are invited to an ASCCT member webinar:
Incorporating New Technologies into Toxicity Testing and Risk Assessment:
Moving from 21st Century Vision to a Data-Driven Framework
Russell S. Thomas, The Hamner Institutes for Health Sciences
See below for a description of the presentation.
-----------------------------------------
Meeting Subject: Member webinar: Using new technologies for risk assessment
Meeting Date: Thu Aug 16 2012
Meeting Time: 02:00:00 PM (GMT-05:00) US/Eastern
-----------------------------------------
To join the meeting from your computer or mobile device, click or copy and
paste this URL into your browser:
https://www.fuzemeeting.com/fuze/e7071e9b/17106082
To join the audio portion of this meeting, choose your dial in method:
Toll and international dial in: +1 (775) 996-3560
Toll free: +1 (800) 741-4032
Skype in by dialing contact: fuzemeeting
When prompted enter the room number:
Room #: 607845
___________________________________________________________________________________________________________
Incorporating New Technologies into Toxicity Testing and Risk Assessment:
Moving from 21st Century Vision to a Data-Driven Framework
Russell S. Thomas, The Hamner Institutes for Health Sciences
The release of the National Research Council’s Report “Toxicity Testing in the
21st Century: A Vision and a Strategy” in 2007 initiated a broad-based movement
in the toxicology community to re-think how toxicity testing and risk
assessment are performed. Since the release of the report, efforts such as the
Human Toxicology Project, Risk21, and others have added to the momentum, but
the majority of these efforts have focused more on a vision of how things
should be done rather than the development of a data-driven paradigm. The
focus on vision has been due to a lack of adequate datasets that would be
required to develop a data-driven paradigm. This lack of data is gradually
changing with the release of the ToxCast Phase I data, the development of
high-throughput dosimetry approaches, and the collection of short-term in vivo
transcriptomic studies.
This webinar will briefly cover a series of studies that together inform what
could be seen as a basis for a new data-driven paradigm to toxicity testing and
risk assessment. The first study is a comprehensive cross-validation model
comparison to evaluate the predictive performance of the more than 600 in vitro
assays from the ToxCast Phase I screening effort across 60 in vivo endpoints
using 84 different statistical classification methods. The predictive
performance of the in vitro assays was compared to that of chemical structure
descriptors. The results showed that the current suite of ToxCast
high-throughput toxicity assays have limited applicability for predicting in
vivo chemical hazards using standard statistical classification methods.
However, if viewed as a survey of potential molecular initiating events and
interpreted as risk factors for toxicity, the assays may still be useful for
chemical prioritization. The second study involves the development of
high-throughput methods for estimating pharmacokinetics for in vitro studies.
Hepatic metabolic clearance and plasma protein binding were experimentally
measured for a subset of the ToxCast Phase I chemicals using rat hepatocytes
and plasma. Computational pharmacokinetic models used these results to estimate
the rat daily oral dose necessary to produce steady-state in vivo blood
concentrations equivalent to the AC50 values obtained in the 600 in vitro
ToxCast assays. The estimated rat daily oral doses associated with the in vitro
assays were compared to the low effect levels (LEL) for apical responses
obtained from in vivo rodent studies. The results showed that the daily oral
dose equivalent for the most sensitive in vitro assay provided a conservative
estimate of the in vivo LEL value. The third study involves short-term in vivo
transcriptomic measurements that were performed in dose-response and a multiple
time points. When transcriptomic changes were grouped by pathway, the
transcriptional dose-response changes were strongly correlated with both
noncancer- and cancer-related apical endpoints and the correlations appeared
stable over time and target tissue. In addition, transcriptional
points-of-departure for the most sensitive pathway differed by less than an
order of magnitude from the points-of-departure based on traditional apical
endpoints.
Together the three studies argue for a new tiered toxicity testing framework
that is not based on the traditional model of hazard identification in animals.
Rather, the new paradigm identifies a region of the dose-response curve where
no significant biological perturbations are expected. A comparison of the
region of safety with human exposure estimates provides a means to eliminate
chemicals from further testing or transition chemicals to higher tiers while at
the same time providing points-of-departure for risk assessment.
___________________________________________________________________________________________________________
Having trouble joining this meeting?
Click or copy and paste this URL into your browser to visit the FUZE Support
page:
http://www.fuzemeeting.com/fuzemeeting/support
Thanks for using Fuze Meeting.
Kristie Sullivan, MPH
Secretary
American Society for Cellular and Computational Toxicology
www.ascctox.org
Other related posts:
