WEBVTT

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

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This video will provide an overview
of the ICE in vitro to in vivo

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extrapolation (or IVIVE) Tool.

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We have other videos that review in detail
how to build a query and how

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to interpret results in the IVIVE Tool.

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The ICE IVIVE tool uses pharmacokinetic
models and reverse dosimetry to relate

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an in vitro bioactivity concentration
to an equivalent in vivo exposure level.

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Each chemical has unique absorption,
distribution, metabolism, and excretion,

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or ADME, properties in the body.

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Pharmacokinetic models can simulate these
processes to put in vitro bioactivity

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concentrations into an
in vivo-relevant context.

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The IVIVE tool uses open-source
pharmacokinetic or physiologically based

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pharmacokinetic, or PBPK, models
from the US Environmental Protection

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Agency's httk R package
to predict the maximum plasma

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concentrations from specified doses
(such as one milligram per kilogram),

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species, and routes.

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By assuming a linear extrapolation,
these Cmax values are used to calculate

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the equivalent administered dose, or EAD,

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needed to obtain a plasma Cmax equivalent

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to the in vitro bioactivity
concentrations for the same chemical.

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The IVIVE tool shows EAD predictions
and in vitro bioactivity

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in a summary table and two graphs.

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In addition to the EAD predictions,
the graphs can overlay relevant in vitro

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or in vivo
modulations, custom uploaded in vivo data,

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or predicted human exposure to provide
context to the in vitro estimates.

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Located throughout the tool are green
information buttons to help you better

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understand key features and results.

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When you hover over a button,
brief explanatory text will appear.

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When you click a button,
more details will appear in a text box

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that can be moved on the
screen for a clearer view.

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If you encounter a problem using the IVIVE
tool, click the "Report an Issue" button

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on the left side of the display
to send an email to ICE Support.

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Thank you for watching our
overview of the ICE IVIVE tool.

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For more information about the IVIVE tool,
go to "Help" and select "User Guides".