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Do curso por Johns Hopkins University

Toxicology 21: Scientific Applications

6 ratings

Johns Hopkins University

Toxicology 21: Scientific Applications

6 ratings

This course familiarizes students with the novel concepts being used to revamp regulatory toxicology in response to a breakthrough National Research Council Report “Toxicity Testing in the 21st Century: A Vision and a Strategy.” We present the latest developments in the field of toxicology—the shift from animal testing toward human relevant, high content, high-throughput integrative testing strategies. Active programs from EPA, NIH, and the global scientific community illustrate the dynamics of safety sciences.

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Module 4

The first lesson in this module will explain the concept of read-across, why it is important for regulatory risk assessment, and how it can be implemented by industry in response to REACH legislation. The organotypic cultures lesson will teach you about existing in vitro cell-based models starting from simple monolayer cultures of cell lines and ending with complex combined organ-on-a-chip and human-on-a-chip approaches.

Welcome to Module 42:36

Introduction to Read-Across18:59

Good Read-Across Practice21:18

Supporting Read-Across with Biological Data12:49

Creating a Database of Toxicity12:24

Creating an Automated Tool for Read-Across9:55

Conheça os instrutores

Lena Smirnova
Research Associate
Center for Alternatives to Animal Testing
Thomas Hartung
Professor
Environmental Health and Engineering

In this module, you will learn about read-across.

What is read-across?

Imagine the following scenario: you're a group leader at Dow,

the major chemical company,

and you produced a new chemical you want to bring to the market.

There is zero information on its toxicity,

so all toxicity tests should be run to get this chemical accepted by the EPA.

It will take a lot of time and cost

a lot of money to run all these tests regulators require.

In addition, you are under time pressure by TSCA,

newly-passed update of Toxic Substances Control Act.

So what can you do at first?

Yes, you can run read-aross.

Read-across will allow you to place your new chemical in a chemical universe,

and predict its toxicity based on its nearest neighbors.

Basically, based on chemical structure and properties,

you can see where the chemical is located in the chemical universe.

Chemical universe is filled with toxicity information for thousands of chemicals,

and you can see whether your new chemical smells like a problem.

For example, if your chemical's nearest neighbors are

skin synthesizers producing allergic reactions,

there is a high chance your chemical will be skin synthesizer, too.

This first computational screen will allow you to probe

prototypes and see what tests to conduct first.

This will drastically reduce Dow's time and dollars spent.

Dr. Harton will explain in the lesson newly-developed

tools which allow you to perform read-across basically with one click.

The lesson on organotypic cultures given by Dr. Holbeck will guide you through

the existing cell culture-based models for in-vitro toxicity testing,

highlighting the advantages and disadvantages.

You might know this children's book series,

Flat Stanley by Jeff Brown.

Flat Stanley's two-dimensional guy walking around.

So Flat Stanley is unique,

and we humans are rather three-dimensional.

The traditional cell culture models, however,

are like Flat Stanley, two-dimensional.

The cells seated on culture dishes in monolayers is a pan fried eggs.

They are quite bored with limited cell-to-cell interactions,

and they cannot recapitulate the physiology of two-dimensional organism.

So, current trends in toxicology and modern biology is

the development of

3-D human-relevant organotypic cultures and macrophysiological systems,

so-called organ on a chip,

to better recapitulate human physiology on a dish.

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