This document discusses dermal toxicity and its effects on the skin. It begins by defining dermal toxicity as the ability of substances to poison through skin contact. It then describes the three main layers of skin - the epidermis, dermis and hypodermis - and their functions. Various manifestations of dermal toxicity are outlined, including contact dermatitis, ulcers, pigment disturbances and skin cancer. Specific toxic chemicals that can cause these effects are also mentioned.

1. Dermal Toxicology
Jinu Janet Varghese
Group: 4
Year:5
Tbilisi State Medical University

2. 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

3. 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

4. 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.

6. Manifestation
 Contact Dermatitis
 Allergic Contact Dermatitis
 Ulcers
 Utricaria
 Toxic Epidermal Necrolysis
 Acneiform Dermatoses
 Pigment Disturbances
 Photosensitivity
 Skin Cancer

7. 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.

9. 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.

11. 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.

13. 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.

15. 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.

17. 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 comedogenic
since 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.

19. 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.

21. 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.

23. 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).

25. 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