PRINCIPLES OF TOXICOLOGY - Biology East Borneo

160 DERMAL AND OCULAR TOXICOLOGYP450-mediated) and phase II enzymes (e.g., epoxide hydrolase, UDP glucuronosyl transferase,glutathione transferase). Some chemicals that cross the skin are simply degraded and eliminated asinnocuous metabolites. For others such as benzo(a)pyrene or crude coal tar (the latter is often used indermatological therapy), metabolism of the parent compound can produce a metabolite that is a skinsensitizer or carcinogen. In addition to metabolizing foreign agents, the skin also has anabolic andcatabolic metabolic activity important to its maintenance.8.3 CONTACT DERMATITISIrritantsIrritant contact dermatitis is one of the most common occupational diseases. The highest incidence ofchronic irritant dermatitis of the hands occurs in food handlers, janitorial workers, constructionworkers, mechanics, metal workers, horticulturists, and those exposed to wet working environments,such as hairdressers, nurses, and domestic workers. Contact irritant dermatitis is confined to the areaof irritant exposure, and since it is not immunity-related, it can occur in anyone given a sufficientexposure to a chemical. Previous exposure to the chemical is not required to elicit a response as isneeded for allergic contact dermatitis, since contact irritant dermatitis is not a hypersensitivity reaction(discussed below). A range of responses can occur after exposure to an irritant, including, but notlimited to, hives (wheals), reddening of the skin (erythema), blistering, eczemas or rashes that weepand ooze, hyperkeratosis (thickening of the skin), pustules, and dryness and roughness of the skin.Unlike corrosive chemicals (e.g., strong acids and bases), the ultimate skin damage from irritant contactdermatitis is not due to the primary actions of the chemicals but to the secondary inflammatory responseelicited by the chemical. It is important to note that even though the ultimate inflammatory responseelicited by different chemicals may appear the same, they often occur through different mechanisms.A wide array of factors influence the ability of an irritant to elicit an inflammatory response. Asdiscussed in Section 8.2, factors affecting skin permeability and chemical composition of the irritantdetermine the rate of percutaneous penetration and how much chemical reaches the viable layers ofthe skin. A variety of other factors determine whether irritant dermatitis occurs and to what magnitude.Higher concentrations and greater amounts of a given agent contacting the skin surface are more likelyto elicit a response than lower concentrations and smaller quantities. The surface area of skin exposedto an irritant can also be important. For some irritants, a certain area of skin exposure is required totrigger a response, and below that threshold dermatitis does not occur. The genetic makeup and age ofthe individual plays a critical role in the sensitivity to a particular agent since the same chemical cancause no response in one individual and a dramatic response in another. The genetic factors influencingsensitivity are unknown, however. In general, children appear to be more, and the elderly less,susceptible to irritants. Concomitant disease may increase or decrease sensitivity to an irritant, andcertain medications such as corticosteroids can suppress the irritant response to some agents. Extremesin temperature, humidity, sweating, and occlusion can lower the threshold of irritation for a givencompound.The range of agents that can cause irritant dermatitis is extensive and diverse, and all cannot betouched on in this section. Table 8.2 lists some of the most commonly encountered classes of irritants.All of these agents have the potential of causing irritation on primary exposure; however, in theworkplace, exposure to a potential irritant often occurs repeatedly and to relatively low quantities.Since the response is dependent on the amount of irritant to which the individual is exposed, repeatedexposure may be required before clinical signs of dermatitis appear. Management of contact irritantdermatitis is based on reducing or avoiding the amount of exposure to the irritant. Wearing gloves toprovide protection against wetness or chemicals and minimizing wet working conditions and handwashing can be very helpful. Complete healing of lesions may take several weeks, and the likelihoodof a flare-up is often increased for months.