WEBVTT

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Welcome to the Integrated Chemical
Environment, also known as ICE.

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This video will show you how to interpret
results of a query run

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in the ICE PBPK tool.

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As discussed in the previous video,
this tool lets you build

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a physiologically based pharmacokinetic or
PBPK model to explore a chemical's ADME

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characteristics,
how the chemical is absorbed,

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distributed, metabolized, and excreted
in the body of a human or animal.

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We will be viewing the the results
of a PBPK query built in that video;

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if you have not yet viewed it, you may
want to do so before watching this one.

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Once the query is complete,
the window will switch to Results View.

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At the top of the Results view is
a heading labeled "Download PBPK Files".

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Click on the heading to access a link
to a file in Excel format with two pages,

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one with query results
and the together with query parameters.

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The results page in this file provides all
results described below

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in numerical format.

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Further explanation of the content of this
file can be found within the Information

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box and in the PBPK User Guide.

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The first thing you'll see
in the PBPK Results view is an interactive

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table providing a summary
of model results.

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Icons above the table allow you
to download the contents

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in text or Excel format.

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Above the table, we can see the number
of rows in the table and the number

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of chemicals with returned results.

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Each row of the table represents
a chemical-compartment combination.

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The first three columns of the table
contain identifier

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information for each chemical.

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Clicking on the chemical's CASRN directs
you to the test article page about

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that chemical in CEBS,
the National Toxicology Program's Chemical

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Effects and Biological Systems database.

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This resource provides data from NTP
studies that were

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conducted on the chemical.

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Clicking on the Chemicals DTXSID directs
you to the U.S. Environmental Protection

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Agency's CompTox Chemicals
Dashboard entry for that chemical.

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This resource provides the chemical's
structure and other physico-

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chemical and experimental properties.

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The remaining table columns provide model
predictions for the chemical.

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The fourth column provides a compartment
representing a part of the body such as

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plasma, an organ or organ system,
or "rest of the body".

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The fifth column provides plasma CSS
the concentration of the chemical

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in plasma at steady state.

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The sixth column provides Cmax,
the maximum concentration

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of that chemical in the compartment.

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To filter results on a specific chemical
or tissue compartment,

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click the filter button below the column
heading and select items of interest

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in the dialog box that opens.

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The "Number of rows" listed above the table
will be updated to reflect

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the filtered results.

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Clear filters by clicking the "Clear
Filter" button above the table.

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Any filters applied to the table will
also be applied to any downloads.

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Below the table,
click on the "Interactive Curves" dropdown

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to display interactive graphs
showing the concentration profile

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of the chemical over time in the model
compartments, also referred to as

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the concentration time series.

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There is a separate graph
for each chemical.

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These graphs let you inspect
the chemical's pharmacokinetic profile,

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which can help identify accumulation or
clearance issues in a tissue

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compartment of interest.

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You can click on the right-hand side
legend to remove and add

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compartments from the graph.

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Hover the cursor over a curve to
display the concentration for each

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compartment at the time corresponding
to the position of the cursor.

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Hover over the graph area to display
a tool bar in the top right corner

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that will help you interact
with the graph or export it as a PNG file.

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You can zoom in on an area of interest
in a graph by clicking and dragging around

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the desired focal region
or using the "Zoom in" icon in the tool bar.

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You can click the "Autoscale" icon in the
tool bar to restore the original display.

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Some display options are
provided above the graphs.

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You can filter the display for all plots
to show one or more specific compartments

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using the "Select Compartments"
dropdown list.

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Limit the display to specific chemicals by
using the "Select CASRN(s)" dropdown list.

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Up to five graphs will
be displayed on a page.

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The "Select Page" dropdown list
allows you to browse through

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multiple pages of graphs.

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Use the "Sort Data By" dropdown list to
sort graphs by chemical names or CASRNs;

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use the "Direction" dropdown list to view
them in ascending or descending order.

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Below the concentration-time series
graphs,

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click on the "BoxPlots" dropdown
to display box plots showing

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the distribution of Cmax values for each
modeled compartment across

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all chemicals in the query.

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This allows you to quickly scan to see
the differences between chemicals in

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their ADME under the same dosing scenario.

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The points in the box plot
correspond to the compartment

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Cmax for each chemical,
and the boxes show the median

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and interquartile range of Cmax value
for each compartment across

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the list of tested chemicals.

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Hovering over each point displays
the Cmax value and chemical name

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as well as the summary values
for the distribution of all chemicals

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in the query for that compartment.

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As with the graphs above, you can click
on the legend to and remove a compartment.

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Hover over the plot area to display
a toolbar in the top right corner

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that will let you zoom in and out
and save the plot as a PNG file.

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Using the "Select Compartment(s)"
dropdown list above the graph.

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You can also filter the graph to show
Cmax distribution

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for specific compartments.

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Send PBPK parameters to other ICE tools
to run additional queries by using

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the "Send filtered results to" dropdown
list next to the download button.

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For details on the use and output of these
tools, please refer to their

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respective user guides.

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A new feature on all ICE tool web
pages streamlines the citation device.

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The "Cite ICE" button leads
to an Acknowledgments webpage

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where you will find ICE citation formats,
examples of citations, and references.

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Thank you for watching our video on how to
view query results for the ICE PBPK tool.

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For more detailed information on the tool,
go to "Help" and select "User Guides".