PRINCIPLES OF TOXICOLOGY

8.3 CONTACT DERMATITIS 165
light to a toxic form. Phototoxic chemicals readily absorb UV light and become excited to a
higher-energy state. Once the excited chemical returns to the ground state, it releases its energy, which
can lead to production of reactive oxygen species and other reactive products that damage cellular
components and macromolecules, ultimately causing cell death. The resulting damage is similar to
that caused by irritant chemicals (discussed in Section 8.3) that cause cell death. Phototoxicant-induced
cell death triggers an inflammatory response that produces the clinical signs of phototoxicity. Dyes
(eosin, acridine orange), polycyclic aromatic hydrocarbons (anthracene, fluoranthene), tetracyclines,
sulfonamides, and furocoumarins (trimethoxypsoralen, 8-methoxypsoralen) are commonly encountered
phototoxic drugs and chemicals.
Photoallergy is very similar to contact allergic dermatitis and is a delayed type IV hypersensitivity
reaction. The difference between an allergenic chemical and a photoallergenic chemical is that the
photoallergenic chemical must be activated by exposure to light—most often UVA. Once activated, the
photoallergen complexes with cellular protein to form a complete allergen that triggers the delayed type
IV hypersensitivity reaction. Since it is a hypersensitivity reaction, previous exposure to the phototoxic
chemical is required for a response. Subsequent topical or systemic exposure to the photoallergen may
induce the hypersensitivity reaction, which has clinical manifestations similar to allergic contact
dermatitis (see the subsection on allergic contact dermatitis). Testing for photoallergy is similar to the
patch testing used for regular allergens, but the potential allergens are tested in duplicate. One set of the
patches is removed during the test and irradiated with UV light. By comparing duplicate samples, the
physician can determine whether the compound is allergenic and is also a photoallergen.
Skin Cancer
Skin cancer is the most common neoplasm in humans with half a million new cases occurring per year
in the United States. Even though exposure to UV light is the primary cause of skin cancer, chemicals
can also induce malignancies. UV light and carcinogenic agents induce alterations in epidermal cell
DNA. These alterations can lead to permanent mutations in critical genes that cause uncontrolled
proliferation of the affected cells, ultimately leading to a cancerous lesion. UVB rays are the most
potent inducers of DNA damage and work by inducing pyrimidine dimers. In addition to inducing
DNA damage, UV light also has an immunosuppressive effect that may reduce the surveillance and
elimination of cancerous cells by the immune system. Since UVB light is the most potent inducer of
DNA damage, utilization of a sunscreen that blocks UVB radiation is critical in preventing skin cancer
along with the other skin effects associated with UV light exposure. Ionizing radiation is also a potent
inducer of skin cancer. Fortunately, ionizing radiation is no longer used for treatment of skin ailments
such as acne and psoriasis, as was done in the recent past.
The best characterized chemical inducers of skin cancer are the polycyclic aromatic hydrocarbons
(PAH). In the 1700s, scrotal cancer was found to be prevalent among chimney sweeps in England. The
compounds that induced the cancer were later determined to be PAHs present in high concentrations
in coal tar, creosote, pitch, and soot. PAHs must be bioactivated within the skin, often to a reactive
epoxide, by cytochrome P450 metabolism (discussed in Section 8.2) in order to cause DNA damage.
The epoxides are electrophilic and can form DNA adducts that may produce gene mutations. Other
carcinogenic agents may cause DNA damage through different mechanisms, but the ultimate lesion is
a gene mutation that leads to a cancerous lesion.
Eye Toxicity
The eye is a very complex organ composed of many different types of cells. Disease, drugs, and
chemicals can injure various parts of the eye with many different manifestations of injury. The most
common cause of injury in an occupational setting is exposure of the cornea and conjunctiva to agents
that are splashed onto the eye. Many other effects can occur to other parts of the eye such as the retina
and optic nerve (see Figure 8.2), but they are usually limited to effects caused by drugs and various
diseases. This section therefore focuses on external exposure of the eye to chemicals.