Skin Sensitization: Strategies for the Assessment and Management of Risk

D.A. Basketter

Disclosures

The British Journal of Dermatology. 2008;159(2):267-273. 

In This Article

Abstract and Introduction

Abstract

Allergic contact dermatitis (ACD) is to a considerable extent a preventable disease. Limitation can be achieved by correct identification of skin sensitizers, characterization of their potency, understanding human skin exposure and application of good risk assessment/management strategies. Various methods exist which are accurate for the predictive identification of chemicals that possess skin-sensitizing properties. These are enshrined in regulations that aim to provide a harmonized approach to hazard identification. One of the methods, the local lymph node assay, also delivers information on the relative potency of sensitizers. Efforts are continuing in the European Union and at the Organization for Economic Cooperation and Development to use elements of this information for regulatory categorization of skin sensitizers. However, greater use can be made of this potency information in the application of quantitative risk assessments. Such assessments depend also on the availability of accurate data on human skin exposure, one aspect where legislation has little role to play. Management of risks by restriction of skin exposure is, in contrast, a key point where legislation can play an important role, helping to establish a level playing field for industry and setting good standards based on the legislator's ability to access all data. Ultimately, the combination of accurate hazard identification, potency measurement, risk assessment and management, underpinned by enabling legislation, will lead to reduction of ACD. For individuals who do still develop contact allergy, avoidance of ACD should continue to be a goal, based on raising awareness of skin protection, allergen labelling and other skincare strategies.

Introduction

A proportion of chemicals can behave as electrophiles and can therefore react with skin protein, altering it such that the immune system recognizes it as 'foreign'. This leads to an expansion of cells in the body which recognize the chemical and/or the protein alteration it produces. Subsequent contact with the chemical can then lead to a heightened response in skin, seen as redness, oedema, itching etc. Chemicals which can do this are called skin sensitizers, and where humans are sufficiently exposed they may develop the sensitized state called contact allergy; once they have acquired that state, then further sufficient exposure can lead to the disease allergic contact dermatitis (ACD). This is, of course, an overly simplistic explanation of a complex immunobiology, but it serves both as a basic introduction and an explanation of the definitions that will be used throughout this paper. The mechanism of skin sensitization has been thoroughly reviewed recently both from chemical and from (patho)physiological perspectives.[1,2,3,4]

The primary questions/challenges relating to skin sensitizers and human health protection are these: how can skin-sensitizing chemicals be identified (hazard identification)? How can identified skin sensitizers be ranked in terms of potency (hazard characterization)? How can characterized skin sensitizers be assessed in terms of risk to human health (risk assessment)? How can the risks to human health presented by skin sensitizers be managed (risk management)?

It is recognized that the terms above in parentheses may not correlate exactly with the definitions of the terms used by others and/or in other areas of (eco)toxicology, but they do work well for skin sensitization.

In this paper, the approaches to hazard identification will be reviewed, but with focus on the most modern and European Union (EU) preferred method, particularly in the newest legislation, the murine local lymph node assay (LLNA). Emphasis will then be placed on how an identified skin-sensitizing chemical can be characterized and the risk to human health assessed and managed. This will include a critical discussion of the value and limitations of regulation as it exists currently in the EU. The challenges presented by the drive towards elimination of animal testing are also considered.

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