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Toxicology of the Skin

Toxicology of the Skin. Leena A. Nylander-French, Ph.D., CIH 159 Rosenau Hall Tel. 966.3826. Science that studies adverse skin effects and the substances that produce them. Prevalence of Skin Disease. Occupational skin diseases are the second most common types of occupational disease

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Toxicology of the Skin

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  1. Toxicology of the Skin Leena A. Nylander-French, Ph.D., CIH 159 Rosenau Hall Tel. 966.3826 Science that studies adverse skin effects and the substances that produce them

  2. Prevalence 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

  3. Prevalence 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

  4. Acetone 600 µmol Ethyl Acrylate 1.25 µmol TPA 60 µmol TPGDA

  5. Introduction to: • Structure and function of the skin • Percutaneous absorption • Metabolism • Allergic contact dermatitis

  6. Functions of the Skin • Environmental barrier • diffusion barrier • metabolic barrier • Mechanical support • Neurosensory reception

  7. Functions 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

  8. Functions of the Skin 2. Metabolism • keratin • collagen • melanin • lipid • carbohydrate • respiration • biotransformation • vitamin D

  9. Functions of the Skin 3. Apocrine/eccrine/sebaceous glandular secretion 4. Endocrine 5. Immunological affector and effector

  10. Epidermis Dermis Hypodermis Structure of the Skin • Dermal surface area 1.5-2 m2 • Two major components, separated with a basement membrane • epidermis (outer layer) • dermis (underlying epidermis)

  11. Figure 1. The major structures of the skin Mukhtar, H., 1992. Pharmacology of the Skin. CRC Press, Inc., Boca Raton, FL.

  12. Figure 2. Diagram of a cross section of human skin

  13. Epidermis • 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

  14. 1.25 µmol TPA

  15. Figure 3. Structure of the epidermis Mukhtar, H., 1992. Pharmacology of the Skin. CRC Press, Inc., Boca Raton, FL.

  16. Figure 4. Schematic of the Stratum Corneum Mukhtar, H., 1992. Pharmacology of the Skin. CRC Press, Inc., Boca Raton, FL.

  17. 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

  18. Dermis • 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

  19. Figure 1. The major structures of the skin Mukhtar, H., 1992. Pharmacology of the Skin. CRC Press, Inc., Boca Raton, FL.

  20. 1.25 µmol TPA

  21. 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

  22. 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

  23. 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

  24. Hypodermis • 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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