Leena A. Nylander-French, Ph.D., CIH 11/3/00 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 9/23/2018 Dermal Toxicology

Prevalence of Skin Disease Leena A. Nylander-French, Ph.D., CIH 11/3/00 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 9/23/2018 Dermal Toxicology

Prevalence of Skin Disease Leena A. Nylander-French, Ph.D., CIH 11/3/00 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 9/23/2018 Dermal Toxicology

Leena A. Nylander-French, Ph.D., CIH 11/3/00 9/23/2018 Dermal Toxicology

Leena A. Nylander-French, Ph.D., CIH 11/3/00 9/23/2018 Dermal Toxicology

Leena A. Nylander-French, Ph.D., CIH 11/3/00 9/23/2018 Dermal Toxicology

Leena A. Nylander-French, Ph.D., CIH 11/3/00 9/23/2018 Dermal Toxicology

Leena A. Nylander-French, Ph.D., CIH 11/3/00 Acetone 600 µmol Ethyl Acrylate 1.25 µmol TPA 60 µmol TPGDA 9/23/2018 Dermal Toxicology

Leena A. Nylander-French, Ph.D., CIH 11/3/00 Introduction to: Structure and function of the skin Percutaneous absorption Metabolism Allergic contact dermatitis 9/23/2018 Dermal Toxicology

Functions of the Skin Environmental barrier Mechanical support diffusion barrier metabolic barrier Mechanical support Neurosensory reception 9/23/2018

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 9/23/2018

Functions of the Skin 2. Metabolism keratin collagen melanin lipid carbohydrate respiration biotransformation vitamin D 9/23/2018

Functions of the Skin 3. Apocrine/eccrine/sebaceous glandular secretion 4. Endocrine 5. Immunological affector and effector 9/23/2018

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) Epidermis Dermis Hypodermis 9/23/2018

Figure 1. The major structures of the skin Mukhtar, H., 1992. Pharmacology of the Skin. CRC Press, Inc., Boca Raton, FL. 9/23/2018

Figure 2. Diagram of a cross section of human skin 9/23/2018

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 9/23/2018

1.25 µmol TPA 9/23/2018

Figure 3. Structure of the epidermis Mukhtar, H., 1992. Pharmacology of the Skin. CRC Press, Inc., Boca Raton, FL. 9/23/2018

Figure 4. Schematic of the Stratum Corneum Leena A. Nylander-French, Ph.D., CIH 11/3/00 Figure 4. Schematic of the Stratum Corneum Mukhtar, H., 1992. Pharmacology of the Skin. CRC Press, Inc., Boca Raton, FL. 9/23/2018 Dermal Toxicology

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 9/23/2018

Dermis Largest fraction of the skin Provides structural strength approximately 90% Provides structural strength high content of collagen and elastin Nerve and vascular networks and appendages required to support the epidermis 9/23/2018

Figure 1. The major structures of the skin Mukhtar, H., 1992. Pharmacology of the Skin. CRC Press, Inc., Boca Raton, FL. 9/23/2018

1.25 µmol TPA 9/23/2018

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 9/23/2018

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 9/23/2018

Cell Types in Dermis Fibroblast Macrophages Mast cells 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 9/23/2018

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 9/23/2018