11/3/10 Toxicology of the Skin
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Toxicology of the SkinToxicology of the Skin
Leena A. Nylander-French, Ph.D., CIH159 Rosenau HallTel. 966.3826
Science that studies adverse skin effects and the substances
that produce them
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Prevalence of Skin DiseasePrevalence of Skin Disease
Occupational skin diseases are the second most common types of occupational disease
45,000 reported cases of occupational skin disease in 2002
15% of all occupational diseases in the US
1983-1994: occupational skin diseases increased by 26%, and 75% of workers with occupational skin disease developed a chronic skin disease
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Prevalence of Skin DiseasePrevalence of Skin Disease
Greatest number of occupational skin disease cases occur in the agricultural and manufacturing industries
Occupational skin diseases are believed to be severely underreported and the true rate may be many fold higher
Estimated total annual costs (including lost work days and loss of productivity) associated with occupational skin disease may reach $1 billion
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Acetone 600 µmol Ethyl Acrylate
60 µmol TPGDA 1.25 µmol TPA
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Introduction to:Introduction to:
Structure and function of the skin Percutaneous absorption Metabolism Allergic contact dermatitis
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Functions of the Skin Functions of the Skin
Environmental barrier– diffusion barrier– metabolic barrier
Mechanical support Neurosensory reception
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Functions of the SkinFunctions of the Skin
Physiologically, skin participates directly in thermal, metabolic, electrolyte, hormonal, and immune regulation
1. Temperature regulation– regulation of blood flow– hair and fur– sweating
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Functions of the Skin Functions of the Skin
2. Metabolism– keratin– collagen– melanin– lipid– carbohydrate– respiration– biotransformation– vitamin D
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Functions of the Skin Functions of the Skin
3. Apocrine/eccrine/sebaceous glandular secretion
4. Endocrine
5. Immunological
affector and effector
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Structure of the SkinStructure of the Skin
Dermal surface area 1.5-2 m2
Two major components, separated with a basement membrane– epidermis (outer layer)
– dermis (underlying epidermis)
Dermis
Hypodermis
Epidermis
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Figure 1. The major structures of the skin
Mukhtar, H., 1992. Pharmacology of the Skin. CRC Press, Inc., Boca Raton, FL.
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Figure 2. Diagram of a cross section of human skin
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EpidermisEpidermis
Stratified squamous epithelium Keratinocytes the major cell type– > 90% of all cells
Programmed process of differentiation
Divided into several layers based on the state of keratinocyte differentiation
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1.25 µmol TPA
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Figure 3. Structure of the epidermis
Mukhtar, H., 1992. Pharmacology of the Skin. CRC Press, Inc., Boca Raton, FL.
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Figure 4. Schematic of the Stratum Corneum
Mukhtar, H., 1992. Pharmacology of the Skin. CRC Press, Inc., Boca Raton, FL.
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Cell Types in Epidermis Keratinocytes Merkel cells
– type I mechanoreceptor (sensory reception)
Melanocytes– pigment-producing (melanin granules) cells that originate in the neural crest
Langerhan’s cells– bone marrow derived antigen presenting cells that are localized in the viable epidermis
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DermisDermis
Largest fraction of the skin– approximately 90%
Provides structural strength– high content of collagen and elastin
Nerve and vascular networks and appendages required to support the epidermis
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Figure 1. The major structures of the skin
Mukhtar, H., 1992. Pharmacology of the Skin. CRC Press, Inc., Boca Raton, FL.
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1.25 µmol TPA
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1. Papillary Layer
Underlies the epidermis Fibroblasts Major synthetic product is type III collagen
Organized into small fiber bundles that contrast with the larger type I collagen fiber bundles found in the reticular dermis
Collagenase activity
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2. Reticular Layer
Superficial to the hypodermis Composed primarily of type I collagen; organized in large fibrillar bundles
Contains large, fully matured elastic bundles that extend between the collagen fiber bundles
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Cell Types in Dermis Fibroblast Macrophages
– phagocytize and neutralize foreign cells and chemicals
– process and present antigen to immunocompetent lymphoid cells
Mast cells– respond to light, cold, acute trauma, vibration, and pressure
– initiate chemotaxis or vasodilation
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HypodermisHypodermis Layer of mesenchymally derived adipose cells that form the connective tissue layer of the reticular dermis
Innermost layer of the skin Provides cushion between the external skin layers and the internal structures such as bone and muscle
Energy reserve Allows for skin mobility and molds body contours
Insulates the body
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