WEBVTT

1
00:00:01.800 --> 00:00:05.690
Welcome to the Integrated Chemical
Environment, also known as ICE.

2
00:00:05.720 --> 00:00:08.090
This video will provide an overview

3
00:00:08.120 --> 00:00:14.060
of the ICE In Vitro
to In Vivo Extrapolation or IVIVE tool.

4
00:00:14.090 --> 00:00:16.860
We have other videos that review in detail

5
00:00:16.880 --> 00:00:21.740
how to build a query and how
to interpret results in the IVIVE tool.

6
00:00:21.760 --> 00:00:24.900
Here's the IVIVE tool Input view.

7
00:00:24.920 --> 00:00:26.780
But before we build a query,

8
00:00:26.810 --> 00:00:30.380
let's take a quick look at the
results produced by the tool.

9
00:00:30.400 --> 00:00:32.900
This will help you understand
the inputs better.

10
00:00:32.930 --> 00:00:39.220
We'll take more detailed look
at IVIVE results in a second video.

11
00:00:39.250 --> 00:00:45.020
The IVIVE tool uses pharmacokinetic models
and reverse dosimetry to relate

12
00:00:45.050 --> 00:00:50.620
an in vitro bioactivity concentration
to an equivalent in vivo exposure.

13
00:00:50.650 --> 00:00:53.180
Each chemical has unique absorption,

14
00:00:53.210 --> 00:00:58.700
distribution, metabolism, and excretion
or ADME properties in the body.

15
00:00:58.730 --> 00:01:03.900
Pharmacokinetic models can simulate
these processes to put in vitro

16
00:01:03.930 --> 00:01:10.440
bioactivity concentrations
into a more in vivo relevant context.

17
00:01:10.480 --> 00:01:16.410
The ICE IVIVE tool uses open source
pharmacokinetic and physiologically based

18
00:01:16.440 --> 00:01:18.920
pharmacokinetic, or PBPK
models

19
00:01:18.950 --> 00:01:25.280
from the U.S. Environmental Protection
Agency's httk R package to predict plasma

20
00:01:25.310 --> 00:01:30.210
concentrations from specified
doses, species and routes.

21
00:01:30.240 --> 00:01:32.660
These are used to calculate the equivalent

22
00:01:32.690 --> 00:01:38.540
administered dose or EAD needed to obtain
a plasma concentration

23
00:01:38.570 --> 00:01:43.290
equal to the in vitro bioactivity
concentrations for the same chemical.

24
00:01:43.320 --> 00:01:46.380
For more details on the PBPK models used

25
00:01:46.410 --> 00:01:52.560
in the IVIVE tool
go to "Help" and select "User Guides".

26
00:01:52.920 --> 00:01:56.260
The IVIVE tool shows EAD predictions

27
00:01:56.290 --> 00:02:00.210
and other results in a summary
table in two graphs.

28
00:02:00.240 --> 00:02:04.930
In addition to the EAD predictions,
the graphs can display relevant in vivo

29
00:02:04.960 --> 00:02:10.340
data to provide context
to the in vitro estimates.

30
00:02:10.370 --> 00:02:14.400
Now let's go back to Input view.

31
00:02:16.960 --> 00:02:19.340
Located throughout the tool are green

32
00:02:19.370 --> 00:02:24.170
information buttons to help you better
understand key features and results.

33
00:02:24.200 --> 00:02:28.820
When you hover over a button,
brief explanatory text will appear.

34
00:02:28.850 --> 00:02:30.260
When you click a button,

35
00:02:30.290 --> 00:02:32.610
more details will appear in a text box

36
00:02:32.640 --> 00:02:36.780
that can be moved on the screen
for a clearer view.

37
00:02:36.810 --> 00:02:42.170
If you encounter a problem using the IVIVE
tool, click "Report an Issue" button

38
00:02:42.200 --> 00:02:47.640
on the left side of the display
to send an email to ICE support.

39
00:02:49.760 --> 00:02:54.340
Thank you watching our overview
of the ICE IVIVE tool.

40
00:02:54.370 --> 00:02:56.260
For more detailed information about

41
00:02:56.290 --> 00:02:59.600
the IVIVE tool, go to "Help"
and select "User Guides".