Download Dermal Toxicity File

DERMAL TOXICITY
Dr. Basma Damiri
Toxicology
Skin Anatomy
Layers and toxicity absorption
1. 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
1. Irritant
2. Allergic contact dermatitis
3. ulcer
4. 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
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2
Response
1. Hives (rashes) wheals.
2. Reddening of the skin (erythema)
4
3
3. Blistering
4. Eczemas or rashes that weep
and ooze
5. Hyperkeratosis ( thickening of
the skin)
6. Pustule (abscess)
7. Dryness and roughness
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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