PRINCIPLES OF TOXICOLOGY

TABLE 8.2 Potential Inducers of Irritant Contact Dermatitis
AgentExamples
Water —
Cleansers Soaps and detergents
Bases Epoxy resin hardeners, lime, cement, and ammonium
Acids Hydrochloric acid and citric acid
Organic solvents Many petroleum-based products
Oxidants Peroxides, benzoyl peroxide, and cyclohexanone
Reducing agents Thioglycolates
Plants Orange peel, asparagus, and cucumbers
Source: Adapted from Rietschel (1985).
Extremely corrosive and reactive chemicals can cause immediate coagulative necrosis at the site
of contact resulting in substantial tissue damage. These chemicals, called primary irritants, differ from
those 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 resulting
from their reactivity, such as acids precipitating proteins and solvents dissolving cell membranes, both
resulting in cell damage, death, or disruption of the keratin ultrastructure. The resulting damage is in
direct proportion to the concentration of chemical in contact with the tissue. It is important to realize
that primary irritants are not always in a liquid form. Many primary irritants are solid chemicals that
become hydrated on contact with the skin, and gaseous agents are often converted to acids on contact
with water available on the skin and mucous membranes. Ammonia, hydrogen chloride, hydrogen
peroxide, 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 encountered
primary irritants that can cause skin burns.
Allergic Contact Dermatitis
8.3 CONTACT DERMATITIS 161
Allergic contact dermatitis is a delayed type IV hypersensitivity reaction that is mediated by a triggered
immune response. Typical of a true immune reaction, minute quantities of the allergenic agent can
trigger a response. This differentiates it from irritant dermatitis, which is proportional to the dose
applied. Allergic contact dermatitis can be very similar to irritant contact dermatitis clinically, but
allergic contact dermatitis tends to be more severe and is not always restricted to the part of the body
exposed 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 delayed
type IV hypersensitivity reaction. The allergenic agents (haptens) are typically low-molecular-weight
chemicals that are electrophilic or hydrophilic. These agents are seldom allergenic alone and must be
linked with a carrier protein to form a complete allergen. Some chemicals must be metabolically
activated in order to form an allergen, which can occur within the skin as a result of the skin’s phase
I and phase II metabolic activities.
Sensitization occurs when the hapten/carrier protein (antigen) is engulfed by an antigen-presenting
cell (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 cells
that specifically recognize the antigen. The secretion of cytokines also causes inflammation of the
contact area and activation of monocytes into macrophages. The active macrophages are the ultimate
effector cells of the reaction. They act to eliminate the foreign antigen and, through secretion of
additional chemical mediators, enhance the inflammation of the contact site. Keratinocytes also play
a role in the hypersensitivity reaction. They are capable of producing many different cytokines and