The Dose Makes the Poison

A dose is regarded as a critical factor that determines whether an exposure will cause a negative response in the body. This concept originates with Paracelsus, who is credited with coining the phrase “the dose makes the poison.” In toxicology, this negative or harmful response is called a toxic response. While in everyday language, a toxin is typically regarded as something that is poisonous, in scientific terminology, there is a distinction between a poison and a toxin. A toxin is a substance that harms the body. 

Toxicologists often refer to a harmful reaction caused by a chemical as a toxic response. The relationship between dose and response can be visualized as a simple graph with dose on the x-axis and response on the y-axis.  Two important points on a dose-response curve that are illustrated in the accompanying figure are the “NOAEL” (No Observed Adverse Effect [or response] Level) and the “LOAEL” (Lowest Observed Adverse Effect Level). These doses are especially important to risk assessors when establishing safe levels of chemicals. These levels differ from the TD50, LD50, or ED50. These levels refer to the points at which adverse effects may be observed. 

 What do we mean by “dose”?

“(A dose) is the amount of a substance administered at one time. However, other parameters are needed to characterize the exposure to xenobiotics. The most important are the number of doses, frequency, and total time period of the treatment.” – NIH 

Xenobiotics are foreign substances that enter the body. These substances can enter the body both intentionally and unintentionally. Unintended exposures often occur from environmental sources. In aromatherapy, environmental exposures such as aromatic diffusion, skincare products, and culinary products often comprise unintended exposures while medicinal inhalation, topical application, or ingestion would comprise intentional exposures. 

Dosing is further classified as the administered dose and the absorbed or internal dose. The administered dose is the total dose over a specified period of time. However, as not everything administered is actually absorbed, the absorbed or internal dose refers to how much actually stays in the body.

Amount x Frequency x Duration = Total dose over a specified period of time. 

A key figure in toxicology is the total dose over a specified period of time. This simply means the total exposure. If a medication is consumed as a 50mg capsule (i.e. the amount) every morning (i.e. the frequency) for one week (i.e. the duration), the formula would be 50mg x 1 x 7 (for 50 mg per dose, once a day, for seven days). The total would be 350mg. 

The internal or absorbed dose requires much more complex calculations. This requires knowledge about the substance itself, absorption and elimination rates, half lives, and other factors about the substance in question. Further complicating the internal dose is the metabolic rate. Metabolism may transform substances by deactivating them or by activating them. Some medicinal substances work only after being activated (metabolized) while other substances no longer work effectively after being deactivated (metabolized). Therefore, calculating internal or absorbed dose is beyond the scope of this handout. 

Route of Exposure 

The dose is further clarified by context, including route of exposure. The measure of the level of exposure is influenced by the absorption route. These routes (or pathways) include barriers which may control how much of the substance can be absorbed or the rate at which the substance is absorbed. Absorption routes include inhalation, ingestion, and topical or dermal application. The systems associated with these routes include the digestive system, the skin, and the respiratory system. Not all exposures can be absorbed through all absorption routes. Some environmental toxins can only be absorbed through certain routes. 

Acute vs Chronic 

One significant area of confusion when interpreting safety of exposures, including essential oils, is in relation to the different calculations for acute and chronic exposures. Acute exposures are exposures with a short duration whereas chronic exposures are repeated or prolonged for a longer duration of time. Substances produce different effects with acute and chronic exposures. The maximum acute exposure will often be much larger than the maximum daily exposure. However, due to routine metabolism and elimination, total exposure over time can be much larger with chronic exposures. 

As an example, a single dose of an essential oil or herbal remedy to relieve short-term pain from an insect bite will often be far larger than what is acceptable for routine, daily applications. Conversely, if the same oil was going to be applied to the skin twice a day for a year, the total dose would typically be required to be much smaller than what is safe for the acute situation. However, the total exposure to each oil during the course of a year would reveal much more total exposure to the oil used chronically than the oil used acutely. 

These calculations differ due to the way the body responds to these exposures and the pharmacokinetics (movement of a drug) within the body. The rate at which the body absorbs, distributes, metabolizes, and eliminates the drug is a key factor which determines the acceptable limits. 

Individual Factors

In addition to what is known about essential oils and herbs and how they are metabolized by the body, individual factors play a role in establishing safe doses. Age, health status, and sex are among the three most significant individual factors. Children have immature metabolic pathways, which means they will often metabolize doses slower than adults. However, this difference is not consistent across all exposures. 

Additionally, genetic and social predispositions may also play a role in safety. Ethnicity, dietary habits, nutritional status, stress levels, and multiple other factors all influence the response to a given dose. There is currently insufficient data to identify how different cultures, ethnic groups, and other populations respond differently to commonly used treatments when using essential oils and herbs–in terms of both safety and efficacy. Future research should prioritize the identification of populations that may require longer or smaller doses or other modifications to overall exposure protocols. 

Evidence-Based Dosing

Store-bought preparations often provide us with the total dose per serving, enabling us to determine proper dispensing. Handmade preparations often result in unpredictable concentrations. There. Children’s products should always be dosed with complete guidelines met. Additionally, even for healthy adults, incomplete dosing may compromise safety or efficacy and may actually inflict harm. Thorough guidelines can ensure optimal safety and efficacy.