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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