• Dermotoxicants, their toxico kinetics,

mechanisms of toxicity and treatment

•

Contents • Introduction• Anatomy of skin• Percutaneous absorption• Factors effecting stratum corneum• Manifestation • Contact dermatitis• Ulcers UtricariaToxic epidermal necrolysisAcneiform dermatosesPigment disturbancesSkin cancer

Introduction Dermal toxicology

Also known as cutaneous toxicity is the ability of

substance to poison people or animals by contact

with skin. Toxic materials absorb through the skin

to various degrees depending on their chemical

composition and whether they are dissolved in

solvent.

Anatomy of skinSkin is composed of three primary

layers

1. The epidermis

2. The dermis

3. The hypodermis

Percutaneous Absorption• To be absorbed through the skin, a toxicant

must pass through the epidermis or the appendages (sweat and sebaceous glands and hair follicles).

Once absorbed through the skin, toxicants must pass through several tissue layers before entering the small blood and lymph capillaries in the dermis

The rate-determining barrier in the dermal absorption of chemicals is the epidermis—especially the stratum corneum (horny layer), the upper most layer of the epidermis.

• Once a toxicant is absorbed through the stratum corneum, absorption through the other epidermal layers is rapid.

All toxicants move across the stratum corneum by passive diffusion

• Polar substances diffuse through the outer surface of protein filaments of the hydrated stratum corneum.

• Non-polar molecules dissolve and diffuse through the lipid matrix between protein filaments.

• The rate of diffusion is proportional to lipid solubility and inversely proportional to molecular weight.

Once absorbed, the toxicant enters the systemic circulation by-passing first-pass metabolism

Factors that Affect Stratum Corneum Absorption of Toxicants

1. Hydration of the stratum corneum• The stratum corneum is normally 7% hydrated which greatly

increases permeability of toxicants. (10-fold better than completely dry skin)

• On additional contact with water, toxicant absorption can increase by 2- to 3-fold.

2. Damage to the stratum corneum• Acids, alkalis and mustard gases injure the epidermis and increase

absorption of toxicants.• Burns and skin diseases can increase permeability to toxicants. 3. Solvent Administration• Carrier solvents and creams can aid in increased absorption of

toxicants and drugs (e.g. dimethylsulfoxide (DMSO)).

Special Routes of Exposure

Toxicants usually enter the bloodstream after absorption through the skin, lungs or GI tract. Special routes include:

1. Subcutaneous injection (SC) (under the skin)

◦ -by-passes the epidermal barrier, slow absorption but directly into systemic circulation; affected by blood flow

◦ 2. Intramuscular injection (IM) (into muscle)

◦ -slower absorption than IP but steady and directly into systemic circulation; affected by blood flow

◦ 3. Intraperitoneal injection (IP) (into the peritoneal cavity)

◦ -quick absorption due to high vascularization and large surface area

◦ -absorbed primarily into the portal circulation (to liver—first-pass metabolism) as well as directly into the systemic circulation.

4. Intravenous injection (IV) (into blood stream) -directly into systemic circulation

Manifestation Contact dermatitisUlcers UtricariaToxic epidermal necrolysisAcneiform dermatosesPigment disturbancesSkin cancer

Contact dermatitisMost common occupational diseaseSymptoms Hives, reddening of the skin (erythema),

rashes, hyperkeratosis (thickening of the skin), dryness and roughness of skin

Treatment Avoiding the amount of exposure to the

irritantWearing glovesHand washingAvoiding from chemicals

Ulcers Some chemicals cause ulceration of

the skinIt involves sloughing of the

epidermis and damage to the exposed dermis

It is cause byAcids, burns, trauma and can occur

on mucous membranes and skinPlants and trees, rubber products, leather

Treatment

Treatment remove any excess dischargemaintain a moist wound

environmentUsing of antibioticsChange dietRecommended exerciseStop smoking and loose wieght

Utricaria

It is a kind of skin rashThey are frequently caused by allergic

reactionsChronic urticaria (hives lasting longer

than six weeks) is rarely due to an allergy.

Symptoms Wheals appear on the surface of skinEdema of the upper dermis occur

Treatment Don’t eat foods that have been

identified to cause your symptoms.

Avoid harsh soaps. Frequent baths may reduce itching and scratching

Avoid tight clothingWear protective clothing; apply

sunblock.

Toxic epidermal necrolysisalso known as Lyell's syndrome, is a rare,

life-threatening skin condition that is usually caused by a reaction to drugs.

Symptoms ProdromeSkin FindingsMucosal FindingsTreatment intravenous immunoglobulins (IVIG)

treatment is necesaary

Acneiform dermatoses

This belong to dermatoses including acne vulgaris, rosacea, folliculitis, and perioral dermatitis.

Disorders are nails, hair loss, hypertrichosis

Treatment Acne drugsAntibiotics

Pigment disturbances

it includes hyperpigmentary disorders (darkening

of the skin) and hypopigmentary disorders (decrease

in the normal skin color)Disorders Albinism Melasma Pigment loss after skinvitligo

Tratment Avoid sunlightApplying of creamCosmeticsLight sensitive drugs

Skin cancerSkin cancers are cancers that arise

from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body.[

There are three main types: basal-cell cancer (BCC) squamous-cell cancer (SCC) and melanoma

Symptoms Asymmetry: melanomas are

rounded and symmetricBorders: have irregular and

raised borders.Color: Melanomas may be tan,

black or brown in color Diameter: 6 mm

Treatment Surgery. Most basal cell and

squamous cell skin cancers can be successfully treated with surgery. ...

Radiotherapy. ... Chemotherapy. ... Immunotherapy. ... Photodynamic therapy (PDT)

Toxicant present in foods which cause dermal disease

Bleached starch: Can be used in many dairy products. Thought to be related to asthma and skin irritations.

BHTIt cause liver cancerPotassium bromate: Added to breads

to increase volume. Linked to cancer in humans.

Carrageenan: Stabilizer and thickening agent used in many prepared foods. Can cause ulcers and cancer

Tert butylhydroquinone: Used to preserve fish products. Could cause stomach tumors at high doses.

Aluminum: A preservative in some packaged foods that can cause cancer.

Agave nectar: Sweetener derived from a cactus. Contains high levels of fructose, which causes insulin resistance, liver disease and inflammation of body tissues.