dermal toxicology

DERMAL TOXICOLOGY

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SKIN STRUCTURE

Skin is a water resistant covering of multiple cell layers.

It has three major divisions EpidermisDermisHypodermis


Epidermis has five layers(from superficial to deep)Stratum corneumStratum lucidumStratum granuolosum Stratum spinosumStratum basale (include melanocytes) or stratum germinativum Dermis Supported by network of loose connective tissue containing collagen and elastin.


Supplied by extensive blood vessels that are under active neurogenic control.

Hypodermis(fat storage)OTHER COMPONENETS OF SKIN:Hair folliclesSebaceous glandsSweat glands


BIOTRANSFORMATION OF XENOBIOTICS

The deep layers of the epidermis have significant capability to metabolize foreign compounds. The dermis has no significant xenobiotic metabolizing ability.

Compounds that are biotransformed in other organs are delivered to the skin, where they exert toxic or photodynamic activity that damages the skin.


EXPOSURE TO TOXICANTS

Skin especially the stratum corneum is relatively impermeable to water soluble substances.

Small non polar lipophilic toxicants readily penetrate the epidermis and are absorbed by dermal vasculature.

Axillary, inguinal, mammary and scrotal skin is highly permeable compared with the skin in the dorsal and lateral regions of most of the mammals.


DERMAL HYPERMIA

Increases in environmental temperature may enhances absorption e.g in hot climates, dermal hyperemia may increase the toxicity of organophosphate insecticide to mammals.

Highly lipophilic substances that contain surfactants or detergents.


RESPONSE TO TOXICANTS

Irritation, degeneration and necrosisDirect irritation of the skin by corrosive, caustic and

necrotizing chemicals elicits an inflammatory response. Generally materials with less than pH 2 and Ph 12 are strong irritants. e.g acids, alkalis and metal salts.

a) Agents that damage cell membrane results in irritation followed by the cardinal signs of inflammation(i.e. erythema, swelling , heat and pain) leucocytosis and increased vascular permeability.

Eschar formation, ulceration and necrosis may permanently damage the skin.


Chemicals associated with dermal irritation, degeneration and

necrosis

AcidsAlcoholsAlkalis

Hydrocarbon solvents(minerals, turpentine, kerosene)iodine

ArsenicDetergentsFormaldehyde

Mercuric saltsPhenolsThallium


Allergic Contact Dermatitis

Some chemicals act as antigens by combining with a carrier proteins, eliciting a response from cellular components of the immune system.

Langerhans’ cells in the epidermis process the antigen and interact with appropriate T lymphocytes to form sensitized T lymphocytes.

Sensitized T lymphocytes react to later exposure to the antigen by producing a variety of cytokines. The cytokines initiate a series of changes that characterize the allergic response(i.e. erythema, itching , edema)

Plants associated with allergic contact dermatitis


Photosensitization

Is an increase in susceptibility to ultraviolet lightFree radicals produced by photodynamic reactions

damage cells and lysosomal membranes. Conditions lead to photosensitizationPhotosensitization depends on the absorption of UV

light within the specific range of wavelengths (280-790 nm) and the presence of photodynamic agent in the skin.

Released energy of the photodynamic agents damages epidermal cell membrane and forms free radicals that can initiate a chain reaction of membrane damage. www.mcqsinpharmacology.com

photosensitization is most prominent on areas of the body where protection from sunlight is least effective.

dorsal and lateral areas of the body thin and unpigmented skin of the body photosensitization is most likely to occur in sunny

climates and during the spring and summer when sunlight is more intense or of longer duration each day.


Clinical effects of photosensitization

early signs of erythema and edemapruritis, photophobia and hyperesthesia followserious signs that occur later in the course of the

disease include exudation of serum, formation of vesicles , ulceration, exfoliation of damaged epidermis, and, possibly, blindness.


Types of photosensitization

primary photosensitization occurs when a photodynamic agent is directly ingested, absorbed through the skin, or injected, or when a chemical is biotransformed to a photodynamic metabolite.

the major effects of primary photosensitizers occur in the skin; other organs are usually spared.

prompt removal of the photosensitizer and supportive treatment often results in recovery with new sequelae.

secondary photosensitization occur as a result of compromised liver function, which reduces the excretion of plant pigment metabolites from the body.


several toxic plants are known to cause hepatogenous photosensitization.

normally chlorophyll is metabolized to phylloerythrin by intestinal and colonic bacteria. Phylloerythrin reabsorbed from the gut is conjugated by the liver and excreted in the bile.

failure of the liver to conjugate or excrete phylloerythrin allows it to accumulate in the dermal vasculature, where it is activated to a photodynamic state by ultraviolet light.

Liver damage and involvement of other organ system may accompany the expected skin related signs of photosensitization.


Cutaneous Porphyrias(Vampires disease)

porphyria, which can cause photosensitization, is the presence of abnormal levels of porphyrins in the blood as a result of abnormal heme synthesis.


Hyperkeratosis

is the abnormal proliferation or keratinization of the superficial epidermis .Toxicants include highly chlorinated naphthalenes.

Alopecia

associated with thallium, arsenic, and selenium toxicosis . chemotherapy with cytostatic drugs.

Skin cancer

Skin cancers are named after the type of skin cell from which they arise.

Basal cell carcinoma originates from the lowest layer of the epidermis, and is the most common but least dangerous skin cancer.

Squamous cell carcinoma originates from the middle layer, and is less common but more likely to spread and, if untreated, become fatal.

Melanoma, which originates in the pigment-producing cells (melanocytes), is the least common, but most aggressive, most likely to spread and, if untreated, become fatal.


Basal cell carcinoma Note the pearly translucency to

fleshy color, tiny blood vessels on the surface, and sometime ulceration which can be characteristics. The key term is translucency.

Squamous cell carcinoma Commonly presents as a red,

crusted, or scaly patch or bump. Often a very rapid growing tumor.

Malignant melanoma The common appearance is an

asymmetrical area, with an irregular border, color variation, and often greater than 6 mm diameter.


http://en.wikipedia.org/wiki/Basal_cell_carcinoma

http://en.wikipedia.org/wiki/Squamous_cell_carcinoma

http://en.wikipedia.org/wiki/Squamous_cell_carcinoma

http://en.wikipedia.org/wiki/Malignant_melanoma

http://en.wikipedia.org/wiki/File:Squamous_Cell_Carcinoma1.jpg

http://en.wikipedia.org/wiki/File:Melanoma.jpg

Causes

Ultraviolet radiation from sun exposure is the primary cause of skin cancer.

HPV infections increase the risk of squamous cell carcinoma.

Some genetic syndromesChronic non-healing wounds.Ionizing radiation, environmental carcinogens, artificial

UV radiation (e.g. tanning beds), aging, and light skin color

The use of many immunosuppressive medication increase the risk of skin cancer. Cyclosporin A, increases the risk approximately 200 times, and azathioprine about 60 times


Management

Sunscreen is effective in prevention Surgical excisionRadiation therapySkin grafting


References

Toxicology by Osweilerwww.google.com.pkwww.medmerits.comwww.google.com.pkwww.webmd.comwww.crystalspring.co.ukapps.ashland.eduwww.ncbi.nlm.nih.gov


dermal toxicology

Health & Medicine

skin structure skin

toxicants skin

componenets of skin

scrotal skin

unpigmented skin

body photosensitization

secondary photosensitization

dermal irritation