Abstract

Irritant and allergic contact dermatitis are undesired side effects in the development of drugs and cosmetics as well as after contact with environmental or industrial chemicals. Over the last decades, a great deal of progress has been made in the development of alternative In vitro test to assess these issues. Driven by the 7th Amendment to the European Cosmetic Directive, the EU policy on chemicals (the registration, evaluation, authorization and restriction of chemicals (REACH) system), the update of the European legislation on the protection of animals used in research, and emerging visions and strategies for predicting toxicity, in vitro methods are likely to play a major role in the near future. On 12 December 2013, the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM, part of the European Commission Joint Research Centre) published its Recommendation on the Direct Peptide Reactivity Assay (DPRA) for skin sensitization, capable of distinguishing sensitizers from non-sensitizers. Other assays (i.e., KeratinoSens™ assay) will follow shortly. While a number of methods are at various stages of development and use, currently it is not possible to rank chemicals for their sensitizing potency, an issue that is important for a full safety assessment. It is expected that a predictive method to totally replace animal testing will be in the form of a test battery comprising molecular, cell-based, and/or computational methods, the so-called “Integrated Approaches to Testing and Assessment”. This review aims to discuss the state-of-the-art in the field of in vitro assessment of contact sensitizers.

Highlights

  • The immune system has evolved to protect the host against invasive microorganisms such as bacteria and viruses, and against malignant cells

  • This review aims to discuss the state-of-the-art in the field of in vitro assessment of contact sensitizers

  • Immunotoxicology represents an important aspect in the safety evaluation of chemicals, as they can lead to:

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Summary

Introduction

The immune system has evolved to protect the host against invasive microorganisms such as bacteria and viruses, and against malignant cells. It can be targeted by many chemicals, including environmental contaminants and drugs, with potentially adverse effects on the hosts health. Immunotoxicology represents an important aspect in the safety evaluation of chemicals, as they can lead to: Inappropriate immunostimulation, which may result in immune-mediated diseases, including hypersensitivity reactions and autoimmune diseases. Hypersensitivity reactions represent the most frequently reported immunotoxic effects of chemicals, with prevalence in the general population of 15%–20% [2]. This, especially during in utero or early life exposure, has been related later in life to autoimmunity and abnormal hypersensitivity [8]

Current in Vivo Models to Assess Hypersensitivity
In Vitro Assessment of Immunotoxicity
Antigen processing: dendritic cells maturation and migration
Conclusions
Findings
Conflicts of Interest
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