PRINCIPLES OF TOXICOLOGY

160 DERMAL AND OCULAR TOXICOLOGY
P450-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 as
innocuous metabolites. For others such as benzo(a)pyrene or crude coal tar (the latter is often used in
dermatological therapy), metabolism of the parent compound can produce a metabolite that is a skin
sensitizer or carcinogen. In addition to metabolizing foreign agents, the skin also has anabolic and
catabolic metabolic activity important to its maintenance.
8.3 CONTACT DERMATITIS
Irritants
Irritant contact dermatitis is one of the most common occupational diseases. The highest incidence of
chronic irritant dermatitis of the hands occurs in food handlers, janitorial workers, construction
workers, 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 area
of irritant exposure, and since it is not immunity-related, it can occur in anyone given a sufficient
exposure to a chemical. Previous exposure to the chemical is not required to elicit a response as is
needed 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 not
limited to, hives (wheals), reddening of the skin (erythema), blistering, eczemas or rashes that weep
and 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 contact
dermatitis is not due to the primary actions of the chemicals but to the secondary inflammatory response
elicited by the chemical. It is important to note that even though the ultimate inflammatory response
elicited 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. As
discussed in Section 8.2, factors affecting skin permeability and chemical composition of the irritant
determine the rate of percutaneous penetration and how much chemical reaches the viable layers of
the 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 likely
to elicit a response than lower concentrations and smaller quantities. The surface area of skin exposed
to an irritant can also be important. For some irritants, a certain area of skin exposure is required to
trigger a response, and below that threshold dermatitis does not occur. The genetic makeup and age of
the individual plays a critical role in the sensitivity to a particular agent since the same chemical can
cause no response in one individual and a dramatic response in another. The genetic factors influencing
sensitivity 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, and
certain medications such as corticosteroids can suppress the irritant response to some agents. Extremes
in temperature, humidity, sweating, and occlusion can lower the threshold of irritation for a given
compound.
The range of agents that can cause irritant dermatitis is extensive and diverse, and all cannot be
touched 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 the
workplace, 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, repeated
exposure may be required before clinical signs of dermatitis appear. Management of contact irritant
dermatitis is based on reducing or avoiding the amount of exposure to the irritant. Wearing gloves to
provide protection against wetness or chemicals and minimizing wet working conditions and hand
washing can be very helpful. Complete healing of lesions may take several weeks, and the likelihood
of a flare-up is often increased for months.