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

2. Skin Anatomy

3. 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.

4. 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

5. 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)

6. Contact dermatitis Irritant Allergic contact dermatitis ulcer
Skin cancer

7. Irritants Occupational diseases

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

9. 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

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

11. 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.

12. 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.

13. 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)

15. 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.

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

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

18. 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

19. 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.

20. Eye toxicity acids and alkalis organic solvents and detergents
methanol