PRINCIPLES OF TOXICOLOGY

164 DERMAL AND OCULAR TOXICOLOGY
keratinocytes in the hair follicles and sebaceous glands. The keratinocytes clog the hair follicles and
sebaceous glands and become bathed in sebum (released from the sebaceous glands).
Halogenated chemicals—especially polyhalogenated naphthalenes, biphenyls, dibenzofurans, and
contaminants of herbicides such as polychlorophenol and dichloroaniline—cause a very disfiguring
and recalcitrant form of acne called chloracne. Chloracne is typically characterized by the presence
of many comedones and straw-colored cysts behind the ears, around the eyes, and on the shoulders,
back, and genitalia. Other symptoms that may or may not occur include conjunctivitis and eye discharge
due to hypersecretion of the Meibomian glands around the eyelids, hyperpigmentation, and increased
hair in atypical locations. Since chloracne is a very persistent disease, the best method of treatment is
to prevent exposure to the halogenated chemicals. This could involve putting up splash guards and
other devices to prevent the chemicals from coming into contact with the skin along with changing
chemical soaked clothing frequently.
Pigment Disturbances
Some chemicals can cause either an increase or decrease in pigmentation. These compounds often
cause hyperpigmentation (darkening of the skin) by enhancing the production of melanin or by causing
deposition of endogenous or exogenous pigment in the upper epidermis. Hypopigmentation (loss of
pigment from the skin) can be caused by decreased melanin production and/or loss, melanocyte
damage, or vascular abnormalities. Some common hyperpigment inducers are coal tar compounds,
metals (e.g., mercury, lead, arsenic), petroleum oils, and a variety of drugs. Phenols and catechols are
potent depigmentors that act by killing melanocytes.
Photosensitivity
Photosensitivity is an abnormal sensitivity to ultraviolet (UV) and visible light and can be caused by
endogenous and exogenous factors. Wavelengths outside the UV and visible light ranges are seldom
involved, since the earth’s atmosphere significantly filters those wavelengths or they are not sufficiently
energetic to cause skin damage. In order for any form of electromagnetic radiation to produce an effect,
it must first be absorbed. Chromophores, epidermal thickness, and water content all affect the ability
of light to penetrate the skin, and those parameters vary from region to region on the body. Melanin is
the most significant chromophore, since it can absorb a wide range of radiation from UVB (290–320
nm) through the visible spectrum.
Exposure to intense sunlight causes erythema (redness or sunburn) due to vasodilation of the
exposed areas. Inflammatory mediators may be released at these areas and have been implicated in the
systemic symptoms of sunburn such as fever, chills, and malaise. UVB is the most important radiation
band in causing erythema. Sunlight has up to 100-fold greater UVA (320–400 nm), but UVA is 1000
times less potent than UVB in causing erythema. UVB exposure causes darkening of the skin through
enhanced melanin production or through oxidation of melanin. Oxidation of melanin occurs immediately,
but offers no additional protection against sun damage. Enhanced melanin production is
noticeable within 3 days of exposure. UV exposure also enhances thickening of the skin, primarily in
the stratum corneum, which further retards subsequent UV absorption. Chronic exposure to UV light
can induce a number of skin changes such as freckling, wrinkling, and precancerous and malignant
skin lesions. UV light is not the only type of radiation that can induce skin changes. Depending on the
dose delivered, ionizing radiation can cause acute changes such as redness, blistering, swelling,
ulceration, and pain. Following a latent period or chronic exposure, epidermal thickening, freckling,
nonhealing ulcerations, and malignancies may occur.
Phototoxicity results from systemic or topical exposure to exogenous chemicals. The symptoms
are very similar to severe sunburn and include reddening and blistering of the skin. Chronic exposure
can result in hyperpigmentation and thickening of the affected areas. Unlike sunburn, phototoxicity
often results from exposure to the UVA band, but the UVB band is sometimes involved. Phototoxic
chemicals are protoxicants (i.e., they are not toxic in their native form) and must be activated by UV