Dermal Toxicology

Jinu Janet Varghese

Group: 4

Year:5

Tbilisi State Medical University

Introduction

Dermal toxicity, also known as cutaneous toxicity is the ability of a

substance to poison people or animals by contact with the skin. Toxic

materials absorb through the skin to various degrees depending on

their chemical composition and whether they are dissolved in a

solvent.

Occupational skin diseases are the second most common types of

occupational disease. Greatest number of occupational skin disease

cases occur in the agricultural and manufacturing industries

Functions of Skin Environmental barrier

diffusion barrier

metabolic barrier

Mechanical support

Neurosensory reception

Physiologically, skin participates directly in

thermal regulation

regulation of blood flow, hair and fur, sweating

Metabolism

keratin, collage, melanin, lipids, and vitamin D synthesis, respiration and

biotransformation

electrolyte and hormonal regulation

apocrine/eccrine/sebaceous glandular secretion

endocrine function

immune regulation

Anatomy of skin

Skin is composed of three primary layers:

1. the epidermis, which provides waterproofing and serves as a barrier to

infection;

2. the dermis, which serves as a location for the appendages of skin; and

3. the hypodermis (subcutaneous adipose layer).

The skin’s color is created by special cells called melanocytes, which produce

the pigment melanin. Melanocytes are located in the epidermis.

Manifestation

Contact Dermatitis

Allergic Contact Dermatitis

Ulcers

Utricaria

Toxic Epidermal Necrolysis

Acneiform Dermatoses

Pigment Disturbances

Photosensitivity

Skin Cancer

Contact Dermatitis

Irritant contact dermatitis is one of the most common occupational diseases.

is confined to the area of irritant exposure. Symptoms are hives (wheals),

reddening of the skin (erythema), blistering, eczemas or rashes that weep

and ooze, hyperkeratosis (thickening of the skin), pustules, and dryness and

roughness of the skin. Treatment is by reducing or avoiding the amount of

exposure to the irritant. Wearing gloves to provide protection against

wetness or chemicals and minimizing wet working conditions and hand

washing can be very helpful. Extremely corrosive and reactive chemicals can

cause immediate coagulative necrosis at the site of contact resulting in

substantial tissue damage. These are called primary irritants that cause

nonselective damage at the site of contact & also causes damage resulting

from their reactivity, such as acids precipitating proteins and solvents

dissolving cell membranes, both resulting in cell damage, death, or disruption

of the keratin ultrastructure.

Allergic Contact Dermatitis

Allergic contact dermatitis is a delayed type IV hypersensitivity reaction that is mediated by a triggered immune response. On first exposure to the allergenic chemical, little or no response occurs. After this first exposure, the individual becomes sensitized to the chemical, and subsequent exposures elicit the typical delayed type IV hypersensitivity reaction. The allergenic agents (haptens) are typically low-molecular-weight chemicals that are electrophilic or hydrophilic. These agents are seldom allergenic alone and must be linked with a carrier protein to form a complete allergen. Some chemicals must be metabolically activated in order to form an allergen. Patch testing is used to try to determine to which agent a person with suspected allergic contact dermatitis may be sensitive. The best treatment, however, is avoidance of the allergen or irritant. Baths and wet compresses, antibiotics, antihistamines, and corticosteroids are used in various combinations to treat contact dermatitis.

Ulcers

Some chemicals can cause ulceration of the skin. This involves sloughing of

the epidermis and damage to the exposed dermis. Ulcers are commonly

triggered by acids, burns, and trauma and can occur on mucous membranes

and the skin. Two commonly encountered compounds that induce ulcers are

cement and chrome.

Utricaria

Triggered by immunity-related mechanisms, and minute quantities of

allergen. Urticaria results in the typical hives, which are pruritic red wheals

that erupt on the skin. Asthma is also a common occurrence after exposure to

an inducer of urticaria. The symptoms often last less than 24 h. In severe

cases, however, anaphylaxis and/or death may occur. Most compounds that

induce urticaria must enter the systemic circulation. Some potential

nonimmune inducers of urticaria are curare, aspirin, azo dyes, and toxins

from plants and animals. A smaller number of agents may cause contact

urticaria on exposure only to the epidermis. Cobalt chloride, benzoic acid,

butylhydroxyanisol (BHA), and methanol have been reported to cause this

form of urticaria. One of the most common inducers of contact urticaria seen

in the medical community is caused by latex rubber products such as gloves.

Toxic Epidermal Necrolysis

Toxic epidermal necrolysis (TEN) is one of the most immediate life-

threatening skin diseases caused by chemicals or drugs. The disease is

characterized by a sudden onset of large, red, tender areas involving a large

percentage of the total body surface area. As the disease progresses, necrosis

of the epidermis with widespread detachment occurs at the affected areas.

Once the epidermis is lost, only the dermis remains, severely compromising

the ability of the skin to regulate temperature, fluid, and electrolyte

homeostasis. Since the epidermis is lost, the remaining dermis posses little

resistance to chemicals entering the systemic circulation and to infection

from microorganisms.

Acneiform Dermatoses

Acne is a very disfiguring ailment & the most common causes of acne are petroleum, coal tar, and cutting oil products. They are termed comedogenicsince they induce the characteristic comedo, which is either open (blackhead) or closed (whitehead). The comedogenic agents produce biochemical and physiological alterations in the hair follicle and cell structure that cause accumulation of compacted keratinocytes in the hair follicles and sebaceous glands. The keratinocytes clog the hair follicles and sebaceous glands. Halogenated chemicals as polyhalogenated naphthalenes, biphenyls, dibenzofurans, polychlorophenol and dichloroaniline—cause a very disfiguring and recalcitrant form of acne called chloracne. It is typically characterized by the presence of many comedones and straw-colored cysts behind the ears, around the eyes, and on the shoulders, back, and genitalia. To prevent exposure to the halogenated chemicals could involve putting up splash guards and other devices to prevent the chemicals from coming into contact with the skin along with changing chemical soaked clothing frequently.

Pigment Disturbances

Some chemicals can cause either an increase or decrease in pigmentation.

These compounds often cause hyperpigmentation (darkening of the skin) by

enhancing the production of melanin or by causing deposition of endogenous

or exogenous pigment in the upper epidermis. Hypopigmentation (loss of

pigment from the skin) can be caused by decreased melanin production

and/or loss, melanocyte damage, or vascular abnormalities. Some common

hyperpigment inducers are coal tar compounds, metals (e.g., mercury, lead,

arsenic), petroleum oils, and a variety of drugs. Phenols and catechols are

potent depigmentors that act by killing melanocytes.

Photosensitivity

Photosensitivity is an abnormal sensitivity to ultraviolet (UV) and visible light and

can be caused by endogenous and exogenous factors. Chromophores, epidermal

thickness, and water content all affect the ability of light to penetrate the skin,

and those parameters vary from region to region on the body. Melanin is the most

significant chromophore, since it can absorb a wide range of radiation from UVB

(290–320 nm) through the visible spectrum. Exposure to intense sunlight causes

erythema. Inflammatory mediators may be released at these areas and have been

implicated in the systemic symptoms of sunburn such as fever, chills, and

malaise. UVB is the most important radiation band in causing erythema. Ionizing

radiation can cause acute changes such as redness, blistering, swelling,

ulceration, and pain. Following a latent period or chronic exposure, epidermal

thickening, freckling, nonhealing ulcerations, and malignancies may occur. and

chemicals. Photoallergy is very similar to contact allergic dermatitis and is a

delayed type IV hypersensitivity reaction. The difference between an allergenic

chemical and a photoallergenic chemical is that the photoallergenic chemical must

be activated by exposure to light—most often UVA.

Skin Cancer

Skin cancer is the most common neoplasm in humans with half a million new

cases occurring per year in the United States. Even though exposure to UV

light is the primary cause of skin cancer, chemicals can also induce

malignancies. UV light and carcinogenic agents induce alterations in

epidermal cell DNA. These alterations can lead to permanent mutations in

critical genes that cause uncontrolled proliferation of the affected cells,

ultimately leading to a cancerous lesion. Since UVB light is the most potent

inducer of DNA damage, utilization of a sunscreen that blocks UVB radiation is

critical in preventing skin cancer along with the other skin effects associated

with UV light exposure. The best characterized chemical inducers of skin

cancer are the polycyclic aromatic hydrocarbons (PAH).

References

http://tools.niehs.nih.gov/srp/research/research5_s7.cfm

http://informahealthcare.com/isbn/9781420079180

http://www.alttox.org/ttrc/toxicity-tests/skin-irritation/

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

https://www.google.ge/search?q=skin&es_sm=122&source=lnms&tbm=isch&s

a=X&ei=q05LUqnvCqKX1AXBj4Fg&ved=0CAkQ_AUoAQ&biw=1352&bih=579&dpr

=1

Principles of Toxicology