3R Training Switzerland


	Module 3R Sensitization in-vitro?	Author: Pierre Aeby

	Allergic contact dermatitis (ACD) - Sensitization in vitro?	A A A

Draize test replacement

Sensitization in-vitro?

Predictive in vitro testing

Implementation of the 3Rs

Pyrogen test in vitro

Receptor modeling

3R-Bologna declaration

Continuing Education

Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity reaction. It is induced by small reactive chemicals (haptens). In pharmaceutical and cosmetic industry, it is mandatory to identify chemicals that are potential ACD inducers before they become part of a new product.

Inhaltsverzeichnis

Identification of the sensitizing potential of chemicals
Contact between a chemical and the skin may result in allergic contact dermatitis.

Sensitization
Sensitization is the result of the complex interactions of a chemical with the different compartments of the immune system.

The Elicitation Phase
Repeated skin exposure to a chemical suddenly leads to a cutaneous inflammatory reaction (allergic reaction).

Diagnosing allergic contact dermatitis
Patch testing is a well-established method of diagnosing allergic contact dermatitis in human.

A predicitive test for sensitizationi in guinea pigs
The guinea pig has been widely used to evaluate the potential of compounds to produce contact sensitization.

Local Lymph Node Assay
A refined predictive test in mice: The Local Lymph Node Assay (LLNA):

Cellular mechanisms and signals
Understanding molecular mechanisms and associated cell signals supports the development of in vitro approaches.

A cascade of in vitro assays
Skin penetration - protein binding - metabolism - DC activation: The sequence of events taking place during ACD in vivo may be covered by individual in vitro assays subsequently combined to a new approach.

Like dendritic cells?
Human derived dendritic cells, a way to refine or replace animal testing?

Differential response: Surface markers
Sensitizers and irritants can be distinguished: Differential expression of surface markers on dendritic-like cells.

Differential response by IL-1 beta
Another assay to distinguish sensitizers from irritants: differential secretion of IL-1 beta.

Predictive in-vitro testin is more than measuring gene expression
The combination of different in vitro tests may reflect the complex in vivo interactions.

In vitro Skin permeation
Skin permeation can be tested without animals.

In Vitro Metabolism
The metabolic profile can be determined in vitro with human, rat and mouse hepatocytes.

In vitro prediction
Predicition of the skin sensitizing potential of chemicals in vitro seems to be possible.

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