When one considers the huge spectrum of chemicals that are available in the world today (sometimes estimated at greater than 100,000) the opportunities for adverse health effects following exposure to these chemicals can appear to be very great. However, the reality is that most of the substances do not cause any significant impact on human health. Perhaps the most common effect, and certainly the most common in the field demeanour toxicology, appear to be the allergic responses that arise in susceptible individuals following exposure to chemicals that possess skin sensitising properties. It is not appropriate in this chapter to delve into great detail concerning the mechanistic immunobiology of skin sensitisation nor to provide a detailed account of the substances that are sensitising and the clinical effects known as allergic contact dermatitis (ACD) that they can produce. The mechanisms of skin sensitisation have been extensively reviewed elsewhere (1 - 3). In brief, to behave as a skin sensitiser a chemical must penetrate into the viable layers of the epidermis and once there form a stable association with skin proteins, typically via covalent binding. If this event occurs in the presence of danger signals (4, 5), the dendritic cells of the skin will be triggered to migrate to the draining lymph nodes where, in their mature form, they will interact with T lymphocytes. Those T lymphocytes bearing surface receptors which recognise the chemically modified protein being presented by the dendritic cell will be stimulated into clonal expansion and the daughter cells released back to the systemic circulation. When this process happens to a sufficient extent, the sensitised state has said to be to have been induced. Subsequent exposure to the same chemical by the dermal route can then elicit the characteristic delayed inflammatory response which we recognise as allergic contact dermatitis (ACD). The panoply of substances which can give rise to ACD and are most commonly diagnosed, include transition metals (nickel, chromium and cobalt), fragrance chemicals, preservatives, various topical medicaments, rubber chemicals, epoxy resins, acrylates, plant defence substances (e.g. pentadecylcatechol in poison ivy), and many others. They are fully detailed in current textbooks of contact dermatitis (6, 7) and in guidance concerning diagnosis of this disease (8).
From the perspective of the practicing toxicologist what is therefore most important is to have the capacity to identify potential causes of allergic contact dermatitis, i.e. skin sensitizing chemicals, so that such hazards can be characterised and the risks they present to human health the assessed and appropriately managed (9). In the material which follows, a very brief account of in vivo predictive methods will be given so that an appreciation of the information these tests produce and how it is used can be gained. Subsequently, the details of in vitro methods that seem close to successful validation will be offered, together with the discussion concerning the strengths and limitations of the information that the yield. Finally, the focus will be on how we may in the reasonably foreseeable future try to close the remaining gaps so that using only non-animal methods, at least for this endpoint in toxicology, human health can people be protected as, or even more, successfully them in recent years
BASKETTER David;
CASATI Silvia;
2014-06-18
Springer Science + Business Media
JRC89309
978-1-4939-0520-1,
1557-2153,
https://publications.jrc.ec.europa.eu/repository/handle/JRC89309,
10.1007/978-1-4939-0521-8,
