PRINCIPLES OF TOXICOLOGY - Biology East Borneo

8.3 CONTACT DERMATITIS 161TABLE 8.2 Potential Inducers of Irritant Contact DermatitisAgentExamplesWater —CleansersSoaps and detergentsBasesEpoxy resin hardeners, lime, cement, and ammoniumAcidsHydrochloric acid and citric acidOrganic solvents Many petroleum-based productsOxidantsPeroxides, benzoyl peroxide, and cyclohexanoneReducing agents ThioglycolatesPlantsOrange peel, asparagus, and cucumbersSource: Adapted from Rietschel (1985).Extremely corrosive and reactive chemicals can cause immediate coagulative necrosis at the siteof contact resulting in substantial tissue damage. These chemicals, called primary irritants, differ fromthose that cause irritant contact dermatitis in that they cause nonselective damage at the site of contact,which is not a result of the secondary inflammatory response. Primary irritants cause damage resultingfrom their reactivity, such as acids precipitating proteins and solvents dissolving cell membranes, bothresulting in cell damage, death, or disruption of the keratin ultrastructure. The resulting damage is indirect proportion to the concentration of chemical in contact with the tissue. It is important to realizethat primary irritants are not always in a liquid form. Many primary irritants are solid chemicals thatbecome hydrated on contact with the skin, and gaseous agents are often converted to acids on contactwith water available on the skin and mucous membranes. Ammonia, hydrogen chloride, hydrogenperoxide, phenol, chlorine, sodium hydroxide, and a variety of antiseptic or germicidal agents (e.g.,cresol, iodine, boric acid, hexachlorophene, thimerosal) are some of the many commonly encounteredprimary irritants that can cause skin burns.Allergic Contact DermatitisAllergic contact dermatitis is a delayed type IV hypersensitivity reaction that is mediated by a triggeredimmune response. Typical of a true immune reaction, minute quantities of the allergenic agent cantrigger a response. This differentiates it from irritant dermatitis, which is proportional to the doseapplied. Allergic contact dermatitis can be very similar to irritant contact dermatitis clinically, butallergic contact dermatitis tends to be more severe and is not always restricted to the part of the bodyexposed to the chemical.On first exposure to the allergenic chemical, little or no response occurs. After this first exposure,the individual becomes sensitized to the chemical, and subsequent exposures elicit the typical delayedtype IV hypersensitivity reaction. The allergenic agents (haptens) are typically low-molecular-weightchemicals that are electrophilic or hydrophilic. These agents are seldom allergenic alone and must belinked with a carrier protein to form a complete allergen. Some chemicals must be metabolicallyactivated in order to form an allergen, which can occur within the skin as a result of the skin’s phaseI and phase II metabolic activities.Sensitization occurs when the hapten/carrier protein (antigen) is engulfed by an antigen-presentingcell (e.g., macrophages and Langerhans cells) and the processed antigen is presented to a helper T cell(CD4 + ). The T cell produces cytokines that activate and cause the proliferation of additional T cellsthat specifically recognize the antigen. The secretion of cytokines also causes inflammation of thecontact area and activation of monocytes into macrophages. The active macrophages are the ultimateeffector cells of the reaction. They act to eliminate the foreign antigen and, through secretion ofadditional chemical mediators, enhance the inflammation of the contact site. Keratinocytes also playa role in the hypersensitivity reaction. They are capable of producing many different cytokines and