Dr. Basma Damiri Toxicology Dermal toxicity Dr. Basma Damiri Toxicology

Skin Anatomy

Layers and toxicity absorption Stratum corneum : Primary layer governing the rate of diffusion which is very slow for most chemicals. 2. Epidermis and dermis: viable layers of the skin, poor barriers for toxicants.

Factors influence the diffusions of chemicals across stratum corneum (SC) Hydrophobic agents with low molecular weight>> than hydrophilic with high molecular weight. Reason: low water and high lipid content in SC. Hydrated skin: its effectiveness as a barrier to hydrophilic substances is reduced. Organophosphate pesticides such as parathion: hydrophobic, very potent, can lead to systemic effect ( nerve damage) and lethality after exposure to skin. The skin has reservoir capacity for the chemicals

Rate of diffusion The rate of diffusion through epidermis is not a function of skin thickness. Higher rate of diffusion is through the sole of the foot than the forehead or abdomen even though it is much thicker. Wounded skin has higher rate of diffusion Hydrated skin has greater risk of infection than dry skin. Metabolic activity of chemicals <<< than liver Epidermis have ↑metabolic activity (Phase I and II)

Contact dermatitis Irritant Allergic contact dermatitis ulcer Skin cancer

Irritants Occupational diseases

Highest incidence of chronic irritants dermatitis of hands Food handler Janitorial workers Construction worker Mechanics Metal worker Horticulture Hairdresser Nurses

Response Hives (rashes) wheals. Reddening of the skin (erythema) 1 2 Response Hives (rashes) wheals. Reddening of the skin (erythema) Blistering Eczemas or rashes that weep and ooze Hyperkeratosis ( thickening of the skin) Pustule (abscess) Dryness and roughness 4 3 5 6

Factors that lower the threshold of irritation for a given compound Extremes in Temperature Humidity Sweating Occlusion (blocking)

2- Primary irritant chemicals Cause nonselective damage at the site of contact which is not a result of secondary inflammatory response. Cause damage because of their reactivity e.g acids precipitating proteins and solvents dissolving cell membrane) result: cell damage, death or disruption of the keratin ultrastructure.

Primary irritant chemicals Ammonia acids hydrogen peroxide phenol chlorine sodium hydroxide antiseptic or germicidal agents ( cresol, iodine, boric acids, hexachlorophene, thimerosal) Thimerosal is the mercury vaccine preservative.

3- Allergic contact dermatitis Delayed type IV hypersensitivity reaction that is mediated by a triggered immune response. similar to irritant contact clinically but more sever and not restricted to the site of exposure. first exposure: little to no response second exposure: sensitization Genetics paly a role in it. (e.g. hay fever)

Ulcers sloughing of the epidermis and damaging of the exposed dermis. can occur on mucus membrane and skin cement and chrome are the commonly compounds that induce ulcers.

Acneiform dermatosis the most common causes of acne in work places is petroleum, coal tar, and cutting oil products. Halogenated chemicals – polyhalogenated naphthalene

Pigments disturbances Hyperpigmented inducers: coal tar compounds, mercury, lead, arsenic, petroleum oils. hypopigmentation agents: phenols and catechols

Photosensitivity UVB is 100-foold more potent than UVA. UVB causes erythema Chronic exposure to UV light causes: freckling, wrinkling, precancerous and malignant skin lesions UV light is the primary cause of skin cancer

Skin cancer Inducers of skin cancer UVB light is the most potent inducer of DNA damage. PAHs- coal tar, creosote, pitch and soot. scrotal cancer was found to be prevalent among chimney sweeps in England in 1700s. PAH must be activated ( active epoxide) by P450s in order to cause damage to DNA.

Eye toxicity acids and alkalis organic solvents and detergents methanol