Toxicology Unit 2: Essential Oils

What are products obtained from raw vegetable material, either by distillation with water or steam, from the epicarp of citrus fruit through a mechanical process or by dry distillation?

Essential oils

What is the natural role of essential oils?

Protect the plant from pathogenic microorganisms, repel or attract insects, or discourage consumption by herbivores (unpleasant taste)

Methods of essential oil application

(1) Topical

(2) Inhalation

(3) Ingestion (oral)

(4) Diffusion

Active vs passive diffusion methods of use

Active = vapor devices

Passive = reed diffusers and fan devices

What is a product intended only to cleanse the body or make a person more attractive (fragrance and make-up)?

Cosmetic

Is the cost of essential oils always a direct correlation with quality?

NO

Which essential oil functional groups can be a skin irritant when they get old?

Monoterpenes (citrus oils, pine, cypress, fir, spruce, and juniper)

Which essential oil functional groups are a skin and mucus membrane irritant and possibly hepatotoxic?

Phenols (aniseed, star anise, cinnamon, clove, fennel, and thyme

Ingestion of a high dose of Eugenol (clove) can cause what?

Severe liver injury

But a therapeutic dose has not been implicated to cause liver injury

Which essential oil functional groups are skin and respiratory irritants?

aldehydes (lemongrass, lemon verbena, and cinnamon

Which essential oil functional groups are hepatotoxic and neurotoxic?

Ketones

Which essential oil functional groups are phototoxic?*

Furanocoumarins

Topical application of essential oils increases the risk for what?

Irritation, allergy (long-term use), and phototoxicity

If applying an essential oil topically, what do you need to make sure you always do?

Dilute!!

What are the usual side effects with inhalation of essential oils?

Headache and nausea

Which method of EO application is not FDA approved?

Internal/ingestion (due to risk of exposure to contaminants and there is no industry standard or quality checking

Oral vs dermal administration bioavailability

Oral = highly variable with limited data

Dermal:

— may remain in the skin for up to 72 hours before crossing into the blood

— routes of entry = intracellular, transcellular, and hair follicles

Which types of essential oils cross into the body more easily?

Lipophilic compounds

BUT...need some degree of water-solubility to be transported in the blood

Essential Oil solubility is measured as what?

Octanol/water values (Log10P)

How do you interpret Log10P values? (Does a higher or lower value have a greater or lesser solubility) **TQ!!

Estimated that Log10P values between 2-4 have the best chance of making it through the dermis into the bloodstream

Lower values = greater water solubility

Higher values = greater lipid solubility

Many essential oils contain constituents that enhance permeability by what possible mechanisms?

(1) Stimulating capillary blood flow

(2) Disrupting integrity of intercellular lipid bilayers (mixes with skin lipids, decreasing barrier function and increasing passage)

What other factors impact dermal absorption of essential oils?

(1) Hydration and Temperature (increased absorption following a hot shower or bath)

(2) Pressure (massaging area prior to application increases absorption)

(3) Volatility

(4) Trauma (increases absorption due to decreased barrier)

(5) Age

How does volatility affect essential oil dermal absorption?

More volatile = less likely absorbed

How does age affect essential oil dermal absorption?

Older skin is thicker than young skin = less absorption

What should you use to dilute essential oils?

Always use a neutral carrier oil (coconut or avocado oil)

Ensure that they are fresh!

Which population is it recommended to never use any essential oils on?

Premature infants (even on other infants there is a very small dose recommendation and maximum)

Can you use essential oils on a wound?

Should NOT unless directed by a trained aromatherapist

Inhaled essential oils enter the blood stream through what?

Lungs and olfactory epithelium

Absorption is generally about 60-70%

Which administration route of essential oils has the highest likelihood of toxicity?

Oral

Nearly all reported cases of poisoning are due to the oral route

What is the level of risk with inhalation of essential oils?

Considered lower level of risk compared to oral administration (lower toxicity likelihood)

What is the risk with oral administration of essential oils?

Many constituents irritate gastric mucosa and co-administration with food has unpredictable effects on absorption

Aspiration of as little as 2 mL may cause chemical pneumonitis

How are essential oils distributed throughout the body?

Based on solubility >> lipophilic are more readily taken up and can accumulate in adipose

Note: little is known about transport of the essential oils on binding proteins

Can essential oils cross the BBB?

Yes

Phase 1 of essential oil metabolism includes which reactions?

(1) Hydrolysis

(2) Oxidation (CYP 450)

(3) Reduction (minor)

Phase II of essential oil metabolism includes which reactions?

(1) Glucuronidation**

(2) Sulfation

(3) Glutathione conjugation

Which EO should not be taken with Warfarin?

Birch and wintergreen

Methyl salicylate inhibits platelet aggregation = increased risk of bleeding

What are some common EO's that contain CYP inhibitors?

Safrole = CYP inhibitor

Essential oils that can inhibit CYP: birch, wintergreen, camphor, sassafras, betel, tansy, yarrow, mugwort, chamomile, balsam poplar, myrtle, lemongrass, may change, tea tree

What is the route of excretion for essential oils that have been administered orally?

(1) Urine (primary route)

(2) Exhaled air and feces (secondary)

(3) Sweat, saliva, breast milk (minor)

What is the route of excretion for essential oils that have been inhaled?

(1) Exhaled air (primary)

(2) Urine (very minor)

Essential Oil toxicity depends on what 4 main factors?

(1) Dose and concentration applies

(2) Route of administration

(3) Bioavailability

(4) Mechanism of toxicity

Who is at a higher risk for essential oil toxicity?

Massage therapists (due to consistent exposure with inhalation and dermally)

Camphor is used for what?

Aromatic properties, insect repellant, embalming fluids, and topical skin preparations (Vicks Vaporub)

What is the risk with using Camphor?

Skin and mucous membrane, respiratory, and eye irritant

Toxicity targets CNS and kidneys (initial excitatory phase followed by CNS depression)

Do NOT put into the nostrils

Nearly all cases of essential oil poisoning are due to what?

Oral ingestion of undiluted oil in quantities significantly higher than therapeutic doses

What is the most common age of essential oil poisoning?

1-3 years old

75% of all accidental poisonings occur in kids <6 years of age

What term is used for when the action and potency of an essential oil mix is as predicted from known action and quantities?

Additivity

5 + 2 = 7

What is the term used from when the essential oil mixture's action is significantly greater than would be expected?

Syngery

5 + 2 = 19

What is the term for when an essential oil mixture's observed action is less than anticipated?

Antagonism

5 + 2 = 3

What is the LD1 and LD50?

The dose that kills 1% and 50% of the test population

LD >> lethal dose

What is the TD1 and TD50?

Dose that causes a toxic effect in 1% and 50% of the test population

TD >> toxic dose

What is the ED50 and ED99?

Dose that causes a therapeutic effect in 50% and 99% of the test population

ED >> effective dose

How do you calculate the therapeutic index?

LD50/ED50 or TD50/ED50

How do you calculate the standard margin of safety?

LD1/ED99 or TD1/ED99

What is the LD50 for an EO rated non-toxic?

More than 5 g/kg

What is the LD50 for an EO rated slightly toxic?

1-5 g/kg

What is the LD50 for an EO rated moderately toxic?

100-999 mg/kg

What is the LD50 for an EO rated very toxic?

10-99 mg/kg

What is the LD50 for an EO rated extremely toxic?

9 mg/kg or less

Which essential oils can cause an immune system reaction triggered by the sun (phototoxic)?*

(1) Grapefruit

(2) Lemon (expressed)

(3) Lime (expressed)

(4) Mandarin Leaf

(5) Orange (bitter and expressed)

(6) Bergamot (slightly)

*CITRUS FAMILY*

Which two EO contain 98% salicylate?*

Birch and wintergreen

Which EO is 80-90% eugenol and can cause metabolic acidosis, CNS depression, seizures, and hepatotoxicity?

Clove oil

Which EO is a hallucinogen when smoked and is at high risk for skin sensitization?

Cinnamon oil

Which EO has a toxic dose of 5 mL and can cause epigastric burning and CNS depression when ingested?

Eucalyptus oil

Which EO can cause photosensitization?

Lavender oil

Ingestion of which EO can cause vomiting, tremor, and CNS depression?

Menthol

Teat tree oil storage instructions

Old or oxidized oils should be discarded

Store it in a dark, air-tight container in the refrigerator

Pennyroyal (mint) oil has moderate to severe toxicity with dose >10 mL. What can help prevent liver damage with this?

N-acetylcysteine

Peppermint oil contains 50% what?

50% menthol (metabolic acidosis and CNS depression; oral mucosa irritant

What are the first aid procedures for EO ingestion?

(1) Don't induce vomiting

(2) Rinse mouth with water if awake and not convulsing

(3) Take to hospital

What are the first aid procedures for EO inhalation?

(1) Remove to fresh air

(2) Mouth-to-mouth if not breathing

(3) Seek medical attention

What are the first aid procedures for EO eye contact?

(1) Flush eyes with water for >15 minutes

(2) Seek medical attention if irritation persists after 20-30 minutes

Note: give at least 5 minutes of rinsing before remove contacts

What are the first aid procedures for EO skin contact?

(1) Remove contaminated clothing

(2) Wash skin for 15-2o minutes

(3) Expose skin to air (no direct sunlight)

(4) Lukewarm oatmeal baths

(5) Barrier cream and oral antihistamines

(6) Seek medical attention if irritation persists

How long do EO last?

Look for a "use by" date

General rule = use within 12 months of first opening

BUT discard oxidation-prone oils that are more than 6 months old or when 90% gone)

EO waste disposal

All waste containers, unused materials, or paper towel used to clean up an EO spill should be placed in closed, metal containers

EO use with cancer

Avoid EO use 1 week before and through to 1 month after chemo/radiation

EO use with surgery

Do not use for 1 week before and after surgery

Can act as a blood thinner

EO have the greatest risk of harm to what pets?

Cats and birds

For most EO, signs of pet toxicity develops within what time?

6-8 hours (quickly for especially toxic oils like tea tree)

Which pets are at highest risk for inhalation of EO causing respiratory and eye irritation? Why?

Cats with pre-existing respiratory conditions (asthma)

Cats lack the major phenol UDP-glucuronosyltransferase enzymes needed for phase II metabolism

Which EOs are very toxic to dogs?

(1) Tea tree

(2) Pennyroyal

(3) Wintergreen

(4) Pine

Pet EO toxicity first aid procedures

(1) Don't induce vomiting

(2) bathe pet if dermal; dilute with food and water if ingestion; fresh air if respiratory

(3) watch and wait for mild cases

(4) more concerning cases a vet will administer fluid therapy and GI support