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PHAR 303 > L14. Skin, Eye, & Household Hazards > Flashcards

L14. Skin, Eye, & Household Hazards Flashcards

1
Q

Why is skin an important organ to talk about in terms of toxicology?

A
  • Skin is 6% of your body weight -> really important mechanism of exposure.
  • Occupational skin diseases are the 2nd most common type of occupational disease.
  • 13 million U.S. workers are exposed to chemicals that can be absorbed through skin.
  • We are exposed to many household elements through our skin.
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2
Q

Why do we have skin?

A
  1. Mechanical support (keeps all organs in)
  2. Neurosensory reception
  3. Environmental barrier
  4. Many physiological roles
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3
Q

What are some examples of physiological roles of the skin?

A
  • Thermal regulation
  • Regulation of blood flow, fur and hair, sweat
  • Metabolism
  • Electrolyte regulation
  • Immune function
  • Hormone function
  • etc
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4
Q

What are the 3 primary layers of the skin? What are found throughout the layers of the skin?

A

3 primary layers:

  1. Epidermis (outer layer & barrier)
  2. Dermis
  3. Hypodermis

Throughout the layers of skin, there are:

  • hair follicles
  • sweat glands
  • innervation & circulation
  • vascular supply
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5
Q

What are difference cell types found in the epidermis? Describe their purpose.

A
  1. Langerhans cells:
    - part of the immune system (take up and process antigens)
  2. Melanocytes:
    - make pigment to insert into keratinocytes.
  3. Merkel cells:
    - respond to touch (i.e. mechanosensors) ->make you feel pressure
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6
Q

What is the top layer of the epidermis called? What’s it made of? Describe it.

A 
Stratum corneum
• superficial (top) layer of epidermis
• made of dead keratinocytes called
corneocytes
• we continually shed this layer
• keratinocyte lifetime = 4 weeks -> every 4 weeks there is a new layer
• keratinocytes make their way up to
the top of epidermis as they grow and divide and eventually die.
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7
Q

What makes corneocytes a good barrier?

A

Corneocytes are connected with desmosomes (really strong cell-cell adhesion proteins) very tightly. This makes it a good barrier. It also allows us to keep our moisture in. They are also held by lipids.

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8
Q

Why does the biology of the epidermis matter for toxicology?

A

Thickness varies in different parts of the body:
• palms of hands/soles of feet have thick stratum corneum to resist abrasion
• thinnest region is behind the ear (drugs readily absorbed)
• thin skin has many hair follicles

Children have thinner skin
• vulnerable to damage and absorption of molecules

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9
Q

Why is the dermis important?

A
  • Thermoregulation
  • It supplies the avascular epidermis with nutrients. Since the dermis is innervated by vasculature, if things get into the dermis they will get all over.
  • The dermis contains mostly fibroblasts which are responsible for secreting collagen, elastin, and ground substance that give the support and elasticity of the skin.
  • Fibroblasts are also important for wound healing.
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10
Q 
What type of cells are present in the epidermis and are part of the immune system?
A. Merkel cells
B. Corneocytes
C. Langerhans
D. Stratum coreum
E. Desmosomes
A

C. Langerhans

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11
Q

How can toxicants be absorbed through your skin?

A
  1. Intercellularly: small or non-polar molecules can pass in between the cells or other molecules can pass through if the barrier gets damaged.
  2. Transcellularly: molecules that are lipid soluble
  3. Via hair or glands
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12
Q

What types of molecules can get through the stratum corneum? Give some examples.

A

Most compounds cannot get through the stratum corneum. BUT! Small, lipophilic molecules can enter! Examples include: Toluene; benzene; carbon tetrachloride.

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13
Q

What can cause an impaired stratum corneum barrier?

A
  • disease
  • abrasion
  • elevated water content (i.e. swimming) -> Our skin is approx. 7% hydrated, but if it gets more hydrated it can allow slightly more polar molecules to go through (like 5X more).
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14
Q

Why are solvents dangerous? What are some examples?

A

Many industrial solvents are small, lipophilic molecules (and get absorbed!)
Some are particular dangerous because they:
• Cause local irritation
• Dissolve the lipid barrier→damaging the skin and making us more susceptible
• Systemically absorbed (i.e. effect on nervous system)

Examples:

  1. Toluene (used in paint thinner and permanent markers)
  2. turpentine (used for wood polish or in some waxes - found at hardware store)
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15
Q

Describe how the nicotine patch works.

A
  • The nicotine is slowly and steadily absorbed through skin (make sure to out on specific areas of skin that have good absorption. Ex: stratum corneum on sole of the foot is way too thick)
  • Gets directly into blood stream
  • No first pass effect through liver (also known as first pass metabolism)

Note: There is a first pass effect from skin!

  • Phase I several cytochrome P450s
  • Phase I flavin monooxygenase
  • Some Phase II metabolism as well
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16
Q

What are some skin disorders caused by exposure?

A
  • Irritant dermatitis
  • Allergic dermatitis
  • Photosensitivity
  • Urticaria (hives)
  • Skin cancer
  • Eczema (Atopic dermatitis)
  • Pigment disturbances
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17
Q

What is contact dermatitis? What are the 2 sub-groups?

A

Contact dermatitis: inflammation of the skin through contact with toxicants

Sub-groups:
1. Irritant dermatitis
(80% of dermatitis cases)
2. Allergic dermatitis

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18
Q

What is irritant dermatitis?

A

A general inflammatory response to a sensitized molecule or chemical. There is no single mechanism of action because many cytokines are involved. Intensity is related to dose, therefore more exposure = more intense reaction. There is a lot of variability between individuals.

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19
Q

What are the 2 sub-groups of irritant dermatitis? Explain them.

A
  1. Chronic cumulative irritation (most of the time):
    • repeated exposures (causing redness, dryness, etc.)
    • mild irritants such as soaps, detergents,
    solvents
  2. Acute irritation (less individual variability):
    • also called 2nd-degree chemical burn
    • substantially disrupts the cornified layer
    • strong acids, alkalies, oxidizing & reducing
    agents
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20
Q

Give an example of a substance that causes acute irritant dermatitis.

A

Wet cement:
• Very alkaline (i.e. basic): pH 12-14
• Sand and small particles = skin irritation
• Can’t feel burn from basic substances right away so a lot of damage can be done before you notice!

Note: It’s also extra bad because it is sandy/grainy so it causes damage to your skin barrier so the burns can get even deeper past the epidermis.

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21
Q

What is allergic dermatitis? How does it occur (general)? Example of a substance that can cause this?

A

A delayed T-cell mediated hypersensitive reaction. Occurs when a molecule (called a hapten) generates an allergic reaction. Dose does not relate to the effect. You can have a very small exposure and still have a crazy response.

Ex: poison oak. Upon first exposure, there is no allergic reaction, but upon second exposure, you will get a reaction because your body was induced after the first exposure.

22
Q

What is the first step of allergic dermatitis? What type of reaction is it?

A

Step 1: Induced sensitization through the skin upon 1st exposure
Type 4 reaction:
• haptens penetrate the lipid barrier and become attached to carrier proteins
• hapten + carrier protein = antigen
• antigens are processed by Langerhans cells (which are the APC’s)
• Langerhans cells present antigen to T cells in lymph nodes
• T cells become “activated” and proliferate
• over a 1–3 week period, activated T cells are generated and enter the circulation

23
Q

What is the second step of allergic dermatitis?

A

Upon 2nd contact, activated T cells induce inflammatory reaction:
• T cells release a barrage of cytokines.
• cytokines recruit macrophages + other cells to generate reaction.
• allergic reaction is limited to area where 2nd exposure occurred.

24
Q

What can cause allergic dermatitis?

A
  • Cosmetics, skin creams, perfumes
  • Plants: Poison oak, Poison ivy, Henna
  • Metals: Nickel (it’s a cheap metal) in watchbands, jewelry, glasses
  • Rubber: E.g. latex in boots and gloves. Latex contains hundreds of different proteins that can cause allergic dermatitis.
  • Glue: E.g. in bandaids
  • Drugs: antibiotics (e.g. neomycin antibiotic/topical ointment)
25
Q

Compare/contrast irritant contact dermatitis and allergic contact dermatitis.

A

Irritant contact dermatitis:

  1. Accounts for approx. 80% of all contact dermatitis
  2. Immediate result from a local toxic effect
  3. Affects everyone, no sensitization required
  4. Reaction soon after contact (minuted to hours)
  5. Dose response relationship
  6. Burning prominent
  7. Lesions are restricted to the area where the irritant damaged the tissue

Allergic contact dermatitis:

  1. Accounts for the remaining 20% of all contact dermatitis.
  2. It is a delayed-type 4 hypersensitivity reaction Th1 response.
  3. Prior sensitization is required
  4. Reaction is delayed for hours to days
  5. A small amount of allergen is enough to elicit the reaction
  6. Burning not prominent
  7. Localized, but may be more diffuse.
26
Q

How can skin exposure to light result in toxicity? What is it called?

A

Phototoxicology.
Phototoxicology = light exposure + interaction (from a xenobiotic that gets activated from light exposure) = toxic effect.

27
Q

Where does exposure from light come from?

A
  • The sun (ozone depletion)
  • Indoor tanning
  • Mainly UVA and UVB light
  • UVC from the sun doesn’t reach us
28
Q

What’s the difference between UVA and UVB light?

A

UVA is the worst because it gets deep past the epidermis and into the dermis and causes long-term damage that we start to see skin cancer from, aging, and wrinkles.

UVB is higher energy and we get sun-burns from it. Acts at top layer.

Remember E = hc/lambda
therefore, more energy means more reactions when the light comes into contact with the oxygen in the ozone which gets rid of the wavelength since the energy is absorbed in the reaction. This means that the higher energy rays wont penetrate through the atmosphere or skin as deep. UVB has more energy (shorter wavelength) than UVA (longer wavelength).

29
Q

What are the 3 branches of phototoxicology?

A
  • Phototoxicity
  • Photocarcinogenicity
  • Photo allergy
30
Q

What is phototoxicity? Give examples of what can cause this.

A

Phototoxicity can occur when certain compounds react with sunlight and damage skin
• not an immunologic response
→meaning no prior exposure to the photosensitizing agent is required.

Examples:

  1. Tattoo ink
  2. Pharmaceuticals: antibiotics like tetracyclines, chlorpromazine (for schizophrenia)
  3. Plants: Carrot family, citrus family, mulberry family, legume family -> therefore if you’re a farmer who works with these plants and you get them on your hands you can have a phototoxic reaction.
31
Q

What is the main compound in plants that can cause phototoxicity? What is the mechanism?

A

Furanocoumarins (ex:psoralen):
→activated by long-wavelength UVA light.

Mechanism:
Furanocoumarins are flat molecules so they can easily intercolate into DNA. This can disturb hydrogen bonds but not usually actually cause damage, but with light it can cause a reaction of these molecules with the DNA which causes DNA damage.

After reaction with UVA light: It’s basically a giant adduct: ex thymine is now covalently attached to a giant molecule which is bad for replication, transcription, etc.

32
Q

What is photocarcinogenicity?

A

Photocarcinogen: substance which causes cancer when an organism is exposed to it + light.

Chemical (not a carcinogen) + UV light = photocarcinogenic

  • after illumination, compound transitions to an excited state
  • compound becomes more chemically reactive
  • light can also cleave photocarcinogens, resulting in free radicals (could contribute to ROS and lead to cancer)
33
Q

What are different effects of photocarcinogenicity?

A
  • Photoageing is skin damage from UV light
  • Genetic changes (DNA damage and mutation)
  • Pigment changes (due to inflammation)
  • Degradation of collagen in the dermis layer which usually keeps the skins structural integrity.
34
Q

What is photoallergy? Give examples of substances

A

Photocontact dermatitis occurs upon exposure to sunlight.
Compound absorbs UV light→converts to hapten→ type 4 reaction as in allergic contact dermatitis

Examples (can be activated by UV light):
• antibacterial soaps (hexachlorophene)
• drugs (antihistamines such as diphenhydramine)
• ingredients in cosmetics (musk, sandalwood oil, ..)

35
Q 
Which of the following is not a skin toxicology disorder?
A. Skin cancer
B. Eczema
C. Pigment disturbances
D. Anaphylaxis
E. Photo products
A

E. Photo products -> what’s made when UV light interacts with a molecule.

36
Q

Draw a summary chart of contact dermatitis and its many forms.

A

Slide 46

37
Q

What is urticaria immunology? Why is it different than allergic dermatitis?

A

Urticaria = hives
• urticaria arise from a different hypersensitivity reaction
• type I or “anaphylactic” reaction
• mediated by IgE
• results in release of histamines -> generic release is why it’s more systemic
• histamine increases the permeability of capillaries to white blood cells/proteins (to engage pathogens in infected tissues)

Difference from allergic dermatitis because it is a more systemic reaction rather than a more local reaction.

38
Q

What are the different symptoms of urticaria immunology and what are some allergen examples?

A

Skin reaction composed of :

  • “wheals” (red bumps)
  • itching feeling

Other symptoms:

  • hayfever
  • bronical asthma

Example Allergens:

  • plants
  • latex
  • antibiotics
39
Q

How do we determine sensitization using animals and cells?

A
  1. In the past, the guinea pig maximization test was used. Now we use the local murine lymph node assay instead. When animal models are necessary for the testing, the thickness of the skin needs to be considered. Certain animals are not good to use in terms of skin thickness compared to humans (ex: rabbits are not good).
  2. In vitro cell culture with keratinocytes or langerhans cells.
  3. In vitro skin irritancy tests using EpiSkin or SkinEthic models.
40
Q

Which part(s) of the eye are most susceptible to toxicant injury?

A

The anterior part of the eye (which faces out to world) is most susceptible to toxicant injury
• Cornea, conjunctiva and eyelids

41
Q

What happens when compounds that are toxic to the retina, optic nerve, or visual cortex come into contact with these parts? What are examples of toxic substances?

A

It can lead to visual impairments. Examples are small metals like lead, methanol, and methyl mercury.

42
Q

Is the eye able to metabolize things?

A

The eye also has metabolizing enzymes!

  • Minimal compared to liver
  • Both Phase I and II
  • Different enzymes are found in different components of the eye.
  • Important to know in case certain compounds can be activated by these enzymes and cause toxic effects.
43
Q

What is cataracts?

A
  • Cataracts results from toxicant exposure (chronic)
  • Cataracts is damage to the lens causing it to become opaque
  • Examples of toxicants include:
  • UV light • Steroids • Tobacco • smoke
44
Q

What are different tests used for toxicology testing in the eye?

A
  • Previously, the draize test was done on rabbits but it is not used anymore and is a very inhumane testing method.

Accepted alternatives fro the Draize test that were approved by the OECD:
1. Isolated chicken eye that came from slaughter houses.

  1. Bovine corneal opacity permeability:
    They mount the cornea and can see within 10mins-2 hours, whether a chemical causes a swelling or damage.
    They can use light to see how opaque the cornea becomes indicating swelling, they can also if it starts to thin out and get destroyed.
    They can also add fluorescein (yellow dye) to look for dryness etc.
    Can also use spectrophotometry assays: shine light through and take fast measurements to see if the molecules are causing damage to the cornea.
3. Short time exposure in vitro test:
Method for Identifying
i) Chemicals Inducing Serious Eye
Damage
ii) Chemicals Not Requiring
Classification for Eye Irritation or Serious Eye Damage

Test consists of:
• monolayer of Statens Seruminstitut Rabbit Cornea (SIRC) cells
• 96-well plate MTT assay

45
Q

What kind of household hazards can be found in a garage/basement?

A
  • Paint thinners (solvents) -> Small, lipophilic and can go through barrier and cause irritation.
  • Cement -> Very basic & can cause physical damage
46
Q

What kind of household hazards can be found in a garden?

A
  • Plants (can be activated by light to cause DNA damage)
  • UV light
  • Insecticides and herbicides (e.g. atrazine-> Endocrine disrupter. Not typically absorbed through skin, you can get it from drinking water.)
  • Insects that sting (bee stings hurt because of apamin: smallest neurotoxin polypeptide known. The only way for it to get into the skin is if you’re punctured by the bee because it’s too bulky.)
  • Weeds (Solanum dulcamara red berries contain solanine). Solanum is very big so touching it is probably not a big deal but eating it could be a problem. Looks like cholesterol so mechanism of toxicity is probably related to destructing membranes.
47
Q

What kind of household hazards can be found in a bathroom?

A
  • Drano (NaOH)
  • Other cleaning products (ammonium)
  • Bleach
  • Medicine (Oral & topical that can cause contact, allergic, or photoactivated dermatitis)
  • Antibacterial soaps
  • Neosporin
  • Bandaids
48
Q

What kind of household hazards can be found in a kitchen?

A
  • Latex

* Oven cleaners contain sodium hydroxide

49
Q

What kind of household hazards can be found in a bedroom?

A
  • Cosmetics
  • Houseplants
  • Nickel (in jewlery?)
  • Carpets accumulate toxins (e.g. smoke) (especially for children) -> Or molds that can grow that emit secondary metabolites that are toxins.
50
Q

Explain how the following substances are/are not toxicants:

  1. Air fresheners
  2. Toilet bowl cleaner
  3. Mold & Mildew remover
  4. Drano
  5. Antibacterial cleaner
  6. Petrolium jelly
  7. Baby oil
  8. Oatmeal bath
A

1) Air fresheners are irritants to eyes and skin
2) Toilet bowl cleaner has bleach
3) Mold & mildew remover
contains fungicides and
corrosive
4) Drano has NaOH
5) Antibacterial cleaner
can be an irritant
6) Petroleum jelly is all
good
7) Baby oil is fine
8) Oatmeal bath is fine

PHAR 303 (21 decks)

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