DERMAL

TOXICOLOGY
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 SKIN STRUCTURE

 Skin is a water resistant covering of multiple cell layers.

 It has three major divisions
 Epidermis
 Dermis
 Hypodermis

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 Epidermis has five layers(from superficial to deep)
 Stratum corneum
 Stratum lucidum
 Stratum granuolosum
 Stratum spinosum
 Stratum basale (include melanocytes)
or stratum germinativum
 Dermis
 Supported by network of loose
connective tissue containing
collagen and elastin.

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 Supplied by extensive blood vessels that are under active
neurogenic control.
 Hypodermis(fat storage)
 OTHER COMPONENETS OF SKIN:
 Hair follicles
 Sebaceous glands
 Sweat glands

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 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.

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 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.

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 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.

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 RESPONSE TO TOXICANTS

 Irritation, degeneration and necrosis

Direct 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.

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 Chemicals associated with dermal
irritation, degeneration and necrosis
Acids Hydrocarbon solvents(minerals,
Alcohols turpentine, kerosene)
Alkalis iodine

Arsenic Mercuric salts

Detergents Phenols
Formaldehyde Thallium

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 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

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 Photosensitization

 Is an increase in susceptibility to ultraviolet light

 Free radicals produced by photodynamic reactions damage
cells and lysosomal membranes.
 Conditions lead to photosensitization
 Photosensitization 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.

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 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.

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 Clinical effects of photosensitization

 early signs of erythema and edema

 pruritis, photophobia and hyperesthesia follow
 serious 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.

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 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.
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 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.
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 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.

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 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.
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 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. www.mcqsinpharmacology.com
 Causes

 Ultraviolet radiation from sun exposure is the primary

cause of skin cancer.
 HPV infections increase the risk of squamous cell
carcinoma.
 Some genetic syndromes
 Chronic 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
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 Management

 Sunscreen is effective in prevention

 Surgical excision
 Radiation therapy
 Skin grafting

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 References
 Toxicology by Osweiler
 www.google.com.pk
 www.medmerits.com
 www.google.com.pk
 www.webmd.com
 www.crystalspring.co.uk
 apps.ashland.edu
 www.ncbi.nlm.nih.gov

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