Botanical oils contain complex mixtures of saturated and unsaturated fatty acids, typically esterified in triglycerides. These fatty acids act as powerful lipophilic solvents to selectively extract and accumulate non-polar secondary metabolites produced by the source plants.

Although data is limited, the most efficient solvent-like molecules in the fixed (oleic and linoleic acids) and essential (limonene) botanical oils are likely low toxicity. However, these compounds may cause mild skin irritation, while their oxidation products may produce dermal sensitization in humans.

The potentially detrimental effects may also vary with dose, form (water or fat-soluble), and site of application (sebaceous gland, hair follicles), which will define absorption rates and accumulation of the bioactive compounds in various layers of the skin and systemic circulation.

Most botanical oils are generally well tolerated in adults, with occasional allergic skin reactions occurring, and are “generally recognized as safe” as a food. This designation, however, does not require the manufacturer to prove the safety and efficacy of the product before marketing. Botanical oils produced by different manufacturers may also contain other ingredients that do not match the actual ingredients or their amounts listed on the label. As such, botanical oils are an alternative to supplement conventional medicines’ perceived failures and side effects.

Site of Application

Regional permeability of the human body is not uniform and is typically ranked as follows: scrotum > face/scalp > trunk/extremities > palm/sole > nail. Within those regions, further variations in stratum corneum thickness, the number of sebaceous glands, and hydration status can all affect the absorption and metabolism of botanical oils and their bioactive components.

Understanding the parameters that affect the permeability of the skin barrier is essential for achieving correct dosing and adherence regimens to reach therapeutic targets within the local skin environment (ointment or cream) or systemic uptake via dermal capillary beds.

The use of botanical oils as vehicles for therapeutic drug delivery provides various choices between achieving optimal drug potency and therapeutic effectiveness. As well as the risk of over-added toxicity, the same drug may appear in different potency classes when formulated in different vehicles or applied to a different target site.

Genotoxicity and Photosensitivity

Some secondary metabolites coextracted with botanical oils may form genotoxic DNA adducts or activate detoxification enzymes, such as safrole and quinones in sassafras oil or epoxides found in pennyroyal oil. Other botanical oils and their constituents may exhibit a dual genotoxic and antigenotoxic effect, as shown for β-caryophyllene.

Adverse cutaneous responses to the combined action of the botanical oil or its bioactive constituent and UV radiation may cause phototoxic reactions that result in sunburn, edema, hyperpigmentation, photoaging, and cancer. However, some of these effects may be beneficial in alleviating multiple symptoms of psoriasis, vitiligo, and cutaneous T-cell lymphoma.

Secondary Metabolites and Biological Reactive Intermediates

While most botanical oils can be considered safe, a few contain compounds, which can be converted to biological reactive intermediates causing toxicity. Although health-promoting effects of secondary metabolites coextracted into the botanical oils may be beneficial, they may also have potentially toxic products and local higher levels of exposure due to topical application.

Let’s take several examples, rosemary oil has demonstrated its ability to induce lipid and protein oxidation at high doses. High doses of the monoterpenoid phenols, carvacrol, and thymol increase malondialdehyde levels, resulting in membrane damage, and 8-hydroxy-deoxyguanosine, causing cell DNA damage.

Eugenol present in clove oil can oxidize phenoxyl radicals that induce reactive oxygen species-mediated apoptosis in human cells. Borage plant parts contain pyrrolizidine alkaloids that are toxic to the liver and lungs and maybe coextracted into borage seed oil. Raw botanical oil materials often originate from different sources and storage timeframes, complicating comparisons of bioactive ingredients and lack of potentially toxic contaminants in them.

Overdose in Pregnant Women and Children

Some commercially marketed hemp seed oils could lead to mild cannabinoid poisoning in children and pregnant women in rare instances. While food-grade hemp strains must contain less than 0.3% tetrahydrocannabinol (THC) by weight (whole plant), hemp seeds or stems used to produce hemp oil may become contaminated by THC-rich trichomes of hemp flowers and thus acquire THC. Due to the polymorphic nature of cytochrome P450 enzymes that can be further affected by age, liver impairment, or potential drug interactions in the body, they result in potentially higher concentrations.

Neonatal Skin Sensitization

Infant skin is susceptible to dryness and irritation from external factors, including topical skincare products not formulated for the infant’s skin. However, topical products with adverse effects on skin barrier function can develop atopic dermatitis or eczema. The practice of recommending and using topical oils to prevent or treat dry baby skin or massage, including the increased societal interest in natural interventions, often ignores the fact that specific topical oils may hurt skin barrier function.

While oils with the lowest oleic acid content provide a lower risk of irritant contact dermatitis, sunflower-based oils may also retard postnatal skin barrier maturation in infants. Skin ointments containing components of food origin also carry the risk of possible percutaneous sensitization to food proteins that may promote the development of contact dermatitis and persistent eczema, as was shown for almond oil.