PRINCIPLES OF TOXICOLOGY - Biology East Borneo

164 DERMAL AND OCULAR TOXICOLOGYkeratinocytes in the hair follicles and sebaceous glands. The keratinocytes clog the hair follicles andsebaceous glands and become bathed in sebum (released from the sebaceous glands).Halogenated chemicals—especially polyhalogenated naphthalenes, biphenyls, dibenzofurans, andcontaminants of herbicides such as polychlorophenol and dichloroaniline—cause a very disfiguringand recalcitrant form of acne called chloracne. Chloracne is typically characterized by the presenceof 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 dischargedue to hypersecretion of the Meibomian glands around the eyelids, hyperpigmentation, and increasedhair in atypical locations. Since chloracne is a very persistent disease, the best method of treatment isto prevent exposure to the halogenated chemicals. This could involve putting up splash guards andother devices to prevent the chemicals from coming into contact with the skin along with changingchemical soaked clothing frequently.Pigment DisturbancesSome chemicals can cause either an increase or decrease in pigmentation. These compounds oftencause hyperpigmentation (darkening of the skin) by enhancing the production of melanin or by causingdeposition of endogenous or exogenous pigment in the upper epidermis. Hypopigmentation (loss ofpigment from the skin) can be caused by decreased melanin production and/or loss, melanocytedamage, 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 arepotent depigmentors that act by killing melanocytes.PhotosensitivityPhotosensitivity is an abnormal sensitivity to ultraviolet (UV) and visible light and can be caused byendogenous and exogenous factors. Wavelengths outside the UV and visible light ranges are seldominvolved, since the earth’s atmosphere significantly filters those wavelengths or they are not sufficientlyenergetic 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 abilityof light to penetrate the skin, and those parameters vary from region to region on the body. Melanin isthe most significant chromophore, since it can absorb a wide range of radiation from UVB (290–320nm) through the visible spectrum.Exposure to intense sunlight causes erythema (redness or sunburn) due to vasodilation of theexposed areas. Inflammatory mediators may be released at these areas and have been implicated in thesystemic symptoms of sunburn such as fever, chills, and malaise. UVB is the most important radiationband in causing erythema. Sunlight has up to 100-fold greater UVA (320–400 nm), but UVA is 1000times less potent than UVB in causing erythema. UVB exposure causes darkening of the skin throughenhanced melanin production or through oxidation of melanin. Oxidation of melanin occurs immediately,but offers no additional protection against sun damage. Enhanced melanin production isnoticeable within 3 days of exposure. UV exposure also enhances thickening of the skin, primarily inthe stratum corneum, which further retards subsequent UV absorption. Chronic exposure to UV lightcan induce a number of skin changes such as freckling, wrinkling, and precancerous and malignantskin lesions. UV light is not the only type of radiation that can induce skin changes. Depending on thedose 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 symptomsare very similar to severe sunburn and include reddening and blistering of the skin. Chronic exposurecan result in hyperpigmentation and thickening of the affected areas. Unlike sunburn, phototoxicityoften results from exposure to the UVA band, but the UVB band is sometimes involved. Phototoxicchemicals are protoxicants (i.e., they are not toxic in their native form) and must be activated by UV