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

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results of a query run
in the ICE PBPK tool.

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

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

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characteristics:
how the chemical is absorbed, distributed,

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

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We will be viewing 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 Results view is a heading
labeled "Download PBPK Files".

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

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one with query results
and the other with query inputs.

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The results page in the file provides all

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results described below
in numerical format.

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Further explanation of the content of this

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file can be found within the Information
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

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to download the contents
in text or Excel format.

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Also above the table,
we can see the number of rows in the table

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and the number of chemicals
with returned results.

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Each row of the table represents

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a chemical-compartment
combination. To the right,

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the dropdown labeled "Chemical Identifiers
Not Returned By Query"

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has a list of any identifiers in your
query that have no relevant data in ICE

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for PBPK modeling.
The first three columns of the table

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contain identifier 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 in Biological Systems database.
This resource provides data from NTP

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studies that were
conducted on the chemical.

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Clicking on the Chemical's DTXSID
directs you to the U.S.

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Environmental

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Protection Agency's CompTox Chemicals
Dashboard entry for that chemical.

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This resource provides the chemical's

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structure and other physicochemical 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 Css,

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the concentration of the chemical
in that compartment at steady state.

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The sixth column provides Cmax, the maximum

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concentration of the chemical
in that 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.
The "Number of rows" listed above

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the table will be updated
to reflect 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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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 outputs of these

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tools, please refer to their
respective user guides.

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You can also copy a list of chemical

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identifiers to the clipboard.
Below the table,

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click on the "Curves" dropdown to display
interactive graphs showing

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the concentration profile
of the chemical over time

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in the model compartments,
also referred to as the time series.

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There is a separate graph
for each chemical.

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These graphs let you inspect a chemical's

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pharmacokinetic profile,
which can help identify accumulation or

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clearance issues in a tissue
compartment of interest.

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You can zoom in on an area of interest

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in a graph by clicking and dragging
around the desired focal region;

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double-click on the graph area
to restore the original display.

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You can also click on the right-hand side

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legend to remove and add
compartments from the graph.

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Hover the mouse over a curve to display
the concentration for each compartment

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at the time corresponding
to the position of the mouse.

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

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

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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 Compartment(s)" dropdown
list. Limit the display to specific

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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

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to browse through
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 as in ascending or descending order.

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Below the time series graphs,
click on the "Box Plots" dropdown

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to display box plots showing
the distribution of Cmax values for each

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model compartment across
all chemicals in the query.

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This allows you to quickly scan to see if

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a chemical in the list clears
the system rapidly relative to others.

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The points in the box plot correspond
to the compartment Cmax for each

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chemical, and the boxes show the median
and interquartile range of Cmax values

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for each compartment across
the list of tested chemicals.

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Hovering over each point displays the Cmax

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value and chemical name,
as well as the summary values

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for the distribution of all chemicals
in the query for that compartment.

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As with the graphs above,
hover over the plot area to display

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a tool bar in the top right corner
that will let you zoom in and out,

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click on the legends to remove

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a compartment, and save
the plot as a PNG file.

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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"

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and select "User Guides."