Introduction

1


Introduction


This book provides a framework of reference for those interested in the safe and effective use of essential oils in a cosmetic or therapeutic context. The information and guidelines contained herein are intended to help minimize any risk of harm associated with the use of these oils, while optimizing their beneficial effects. We have made rational assessments of risk by critically evaluating and extrapolating from available information relating to both the effects of essential oils and of their individual constituents, from in vivo and in vitro human and animal studies. We have read many excellent reports, as well as some seriously misguided ones.


A considerable amount of information about essential oils can be found in the printed literature, as well as on the internet. Much of the safety information available online is misleading, confusing, wrong or simply absent. Some websites promote potentially dangerous essential oils with no mention of possible dangers, though others make every effort to be safe. Misinformation is not difficult to find, even in the scientific literature. In one ‘systematic review’ of adverse reactions to essential oils, four of the reports cited pertain to fatty oils, not essential oils (Posadzki et al 2012). These are black seed, mustard, neem and tamanu. In the first two cases they are mistakenly referred to as essential oils even in the original research.


The quality of essential oils is an important issue for anyone using them therapeutically. Confidence in their safe use begins with ensuring that the oils have a known botanical origin and composition. In a case of purported tea tree oil allergy that was reported twice, analysis of the allergenic substance showed that it was not in fact tea tree oil (De Groot & Weyland 1992; Van der Valk et al 1994). With the advent of modern analytical techniques, the constituents of an essential oil can be determined with a high degree of accuracy. Despite these advances, many biological studies have been reported using essential oils whose composition has not been clearly stated or even determined. In several publications where essential oil constituents have been studied, low purity is a concern. This can lead to erroneous conclusions being made about the pure constituent. In other cases, the identity of constituents is ambiguous or unknown. This is especially true of compounds that exist as different isomers. Sometimes, mixtures of isomers have been used (e.g., α- + β-thujone), or the nomenclature employed has not been sufficiently specific to identify a single compound (e.g., farnesol, which exists as four different isomers). Such studies are of limited value as reproducibility cannot be guaranteed.


In some studies, observations were made only after administering extremely high doses. Consequently, an impression is created of greater risk than can be reasonably justified. In a carcinogenesis study of β-myrcene (which was only 90% pure), groups of rats and mice were given the equivalent of a human oral dose of 17.5 g, 35 g, or 70 g, every day for two years (National Toxicology Program 2010b). The authors justified the high doses on the basis that β-myrcene was not considered to be very toxic. Many animals died before the end of the study, the findings of which have no relevance to the use of essential oils containing β-myrcene.


Concerns about quality and purity apply to many studies of dermal adverse reactions, the results of which are often extrapolated and interpreted to an extent not justified by the poor standards of the research. The fact that the results of patch testing depend to a significant extent on the brand of patch used is a fundamental concern for the validity of this technique (Suneja and Belsito 2001; Mortz & Andersen 2010). There are also uncertainties about the vehicle used, the dispersion of test substance, and general reproducibility (Chiang & Maibach 2012). Patch testing may be useful for identifying the relative risk of different substances, but it cannot be used as a measure of allergy prevalence.


We are sceptical about the use of local lymph node testing in animals, and in vitro data showing constituent oxidation, as justifications for declaring a substance to be allergenic. Oxidation of certain constituents can and does take place, and it is a concern. However oxidation is a slow process, it does not always increase the risk of skin reactivity, and in commercial products it is easily circumvented by the use of antioxidants, sometimes in combination with use-by or sell-by dates.


The term ‘aromatherapy’ was first coined by René-Maurice Gattefossé (1936). It can be defined as the use of essential oils, applied topically, orally, by inhalation or other means, to promote health, hygiene and psychological wellbeing. Aromatherapy is not a single discipline, but can include almost any application of essential oils to the human body. This would include natural perfumes (mixtures of essential oils, absolutes, etc.) and personal care products that contain them. The fact that essential oils have multiple end uses complicates the safety issue. While cosmetics are expected to encompass virtually zero risk, risk is acceptable in medicine because of potential benefits. There is also a ‘middle ground’, i.e., cosmeceuticals and hygiene products. For example, a small risk of skin reaction might be acceptable if the potential benefit is the prevention of MRSA (methicillin-resistant Staphylococcus aureus) infection. Proving safety is always a challenge, but especially when almost all the funding for research goes to single chemicals, and not to plant-derived products.


Aromatic plants have been used in traditional medicine for thousands of years in numerous forms, from the freshly harvested raw plant and its natural secretions to extracts and distillation products. Herbal preparations are administered by different routes according to the site of disease, most commonly orally, but also topically or by inhalation. A traditional and still popular oral preparation is the hot water infusion, or tea, and includes such plants as chamomile, lemon balm and lime. Topical application includes massage, which takes advantage of transdermal as well as pulmonary absorption, thereby giving oil constituents access to the systemic circulation, and thence to all parts of the body.


In parallel with popular aromatherapy, the application of essential oils is growing in food preservation, in farm animal health, and in agriculture, where many are classified as minimal-risk pesticides. In each case essential oils are replacing chemicals that are more toxic, or to which bacteria or pests have developed resistance. Antibiotic-resistant infectious disease is an area currently attracting significant research interest. Experimental evidence has shown a remarkable potential for essential oils, not only because they can kill resistant bacteria, but also because they can reverse resistance to conventional antibiotics.


The pharmaco-therapeutic potential of essential oils has been reviewed by Edris (2007) and by Bakkali et al (2008). In addition to infectious disease, potential applications include type 2 diabetes, cardiovascular disease, osteoporosis, and the prevention and treatment of cancer. Clinical successes include the treatment of liver cancer with Curcuma aromatica oil (Chen CY et al 2003), irritable bowel disease with peppermint oil (Grigoleit & Grigoleit 2005a), tinea pedis with tea tree oil (Satchell et al 2002a) and anxiety with lavender oil (Kasper et al 2010; Woelk & Schläfke 2010). Common uses of essential oils or their constituents in consumer health products include mouthwashes such as Listerine, liniments such as Tiger Balm, and products for the relief of respiratory symptoms, such as Vicks Vaporub.


We all consume essential oils when we eat food. Pecans, almonds, olives, figs, tomatoes, carrots, cabbages, mangoes, peaches, butter, coffee, cinnamon and peppermint naturally contain essential oils. Fresh aromatic plants typically contain 1–2% by weight of mainly fragrant monoterpenoid volatile compounds. When isolated by distillation as essential oils, the increased concentration of these constituents means that any biological properties are much more evident. Some of these properties may offer therapeutic benefits, but some may manifest as toxicity.


A toxic reaction is any adverse event that occurs following the contact of an external agent with the body. Toxicity in essential oils is an attribute we welcome when we want them to kill viruses, bacteria, fungi or lice, and human cells share some characteristics with these very small organisms. So it should not be totally surprising that some of the most useful antimicrobial essential oils, such as eucalyptus, garlic and savory, possess a degree of human toxicity. Toxicity can manifest in numerous ways. Depending upon the extent of damage and regenerative capacity, individual cells may die due to disruption of normal metabolic processes and inability to maintain cellular homeostasis, or whole organs may fail. Fortunately, most organs have substantial reserve capacity, and can recover.


Adverse reactions include abortion or abnormalities in pregnancy, neurotoxicity manifesting as seizures or retardation of infant development, a variety of skin reactions, bronchial hyperreactivity, hepatotoxicity and more. Interactions with chemotherapeutic or other prescribed drugs are a particular concern. In Chapter 4 and Appendix B we present the first summary of likely risk based on current information. A significant interaction between an essential oil and a drug will only become apparent when a certain dose (of essential oil) is administered. Regrettably, even in the academic literature, this factor is sometimes not properly considered.


Most accidents with essential oils involve young children, and are preventable. In the quantities in which they are most commonly sold (5–15 mL), essential oils can be highly toxic or lethal if drunk by a young child, and there have been a number of recorded fatal cases over the past 70 years. Perhaps the only reason that child fatalities have not increased with the current popularity of aromatherapy is because today most essential oils are sold in bottles with integral drop-dispensers. These make it more difficult for a toddler to drink large amounts. Most urgently, we would like to see ‘open-topped’ bottles (i.e., without drop-dispensers) of undiluted essential oil banned, and appropriate warnings printed on labels.


It is estimated that, in 1994, between 76,000 and 137,000 (a mean of 106,000) hospitalized patients in the USA had fatal adverse drug reactions (ADRs). Even taking the lower estimate of 76,000, fatal ADRs would rank sixth after heart disease (743,460), cancer (529,904), stroke (150,108), pulmonary disease (101,077), and accidents (90,523), and ahead of pneumonia (75,719) and diabetes (53,894). If we take the mean value of 106,000 fatalities from ADRs, this would mean that prescribed drugs had become the fourth leading cause of death in the USA, after heart disease, cancer and stroke. The overall incidence of fatal ADRs was 0.32% (0.23–0.41) and the overall incidence of non-fatal but serious ADRs was 6.7% (5.2–8.2) (Lazarou et al 1998). In the UK, over the years 1996–2000, the total percentage of reported ADRs ranged from 12% to 15% of all ‘hospital episodes’. Fatal ADRs were estimated to be 0.35% of hospital admissions (Waller et al 2005). There has not been a single reported case of poisoning, fatal or non-fatal, from the oral administration of essential oils by a practitioner.


Comparing the safety of conventional medicine to medicinal aromatherapy, the ratio of 106,000 to zero is remarkable, although it must be said that the great majority of users do not ingest the oils. In reviewing the risks presented by essential oils, available evidence suggests that only a relatively small number are hazardous, and many of these, such as mustard and calamus, are not widely used in therapy. However, some commonly used oils do present particular hazards, such as lemongrass (teratogenicity), bergamot (phototoxicity) and ylang-ylang (skin sensitization). By limiting the doses and concentrations they are used in, we can prevent these hazards from presenting significant risk.


It seems to be widely believed that essential oils have not undergone any safety testing at all. It is not unusual to find statements such as ‘The safety of essential oils for human consumption has not undergone the rigorous scientific testing typical of regulated drugs, especially in vulnerable populations such as children or pregnant women’ (Woolf 1999). The assumption here that licensed drugs are extensively tested on children and pregnant women is extremely puzzling, but the idea that essential oils are not rigorously tested seems to be mostly due to ignorance. The information in this text is evidence of a considerable body of toxicology data, both on essential oils and their constituents.


We live in a world replete with toxic substances, yet ‘hazard’ should not be confused with ‘risk’. The presence of a toxic substance (hazard) is only problematic if exposure is sufficiently great (risk). Context is often important too. Roasted coffee contains furan and benzo[a]pyrene, two known carcinogens, acrylamide, a probable carcinogen, in addition to glyoxal, methylglyoxal, diacetyl and hydrogen peroxide, all mutagens. Yet coffee is not considered carcinogenic. Almost all edible fruits contain acetaldehyde, a probable human carcinogen. But bananas and blueberries are not regarded as carcinogenic because the amounts of acetaldehyde are extremely small, and because there are large quantities of antioxidants, antimutagens and anticarcinogens also present in the fruits. It is a similar story with coffee.


Basil herb contains two rodent carcinogens – estragole and methyleugenol. Pesto is a particularly concentrated form of basil, yet the WHO has determined that the amounts of the two carcinogens in basil/pesto are so small that they present no risk to humans. Since that ruling, research has been published demonstrating that basil herb contains anticarcinogenic substances that counter the potential toxicity of the two carcinogens, and is itself anticarcinogenic (Jeurissen et al 2008; Alhusainy et al 2010). Some basil essential oils have been also shown to have anticarcinogenic effects (Aruna & Sivaramakrishnan 1996; Manosroi et al 2005).


Many essential oils, herb extracts and foods contain tiny amounts of single constituents that alone, and in substantial amounts, are toxic, but the parent natural substance is not toxic. However, this scenario is rarely taken into consideration by the cosmetic regulatory bodies responsible for essential oils.


The most common type of dermal adverse reaction to an essential oil is allergic contact dermatitis, which has been reported for cinnamon bark, laurel leaf and tea tree, for example. There is some evidence that occupational exposure to essential oils is hazardous and can cause hand dermatitis. Adverse skin reactions are less emotive issues than poisoning, but they are much more common. The fact that essential oils are usually used in diluted form is not an absolute safeguard because allergic reactions are possible after repeated contact even with small amounts of allergen.


However, the flagging of essential oils or their constituents as allergens is reaching epidemic proportions. Most fragrant substances, under a sufficiently rigorous testing regime, will prove to have some degree of reactivity. If one reaction per 1,250 dermatitis patients patch tested (equivalent to perhaps 1 in 10,000 people using a product containing the same substance) is sufficient justification for labeling limonene as an ‘allergen’ (see Table 5.9) then all essential oils might qualify as allergens. However, regulating them beyond use is unreasonable, irrational and unnecessary. Safety and safety regulations are not always in harmony, in fact they often bear little resemblance. Therefore, the purpose of this text is to inform the reader about the safe use of essential oils, as distinct from simply informing the reader about legal requirements.


In this context, and in an attempt to balance the (in our opinion) dichotomy of sometimes over-regulated and sometimes under-regulated essential oils, many of the safety guidelines in this book are those of its authors. Inevitably, the translation of factual information into recommendations involves subjective judgment. We acknowledge that other interpretations are possible, particularly in the light of new information.


In recommending safe levels of exposure, we have drawn on both experimental animal data and cases of toxicity in humans. Our approach has been to critically review existing quantitative guidelines, to refine them where necessary, and to establish new guidelines where none already exist. To these ends, we have considered a wide range of published data relating to the toxicity of essential oils, and in some cases we have extrapolated from individual constituent data, even though this involves making certain assumptions. Where safe levels for dermal or oral use have been established previously we have tended to follow them, but we have not done so in every instance.


Where there are no established recommendations, we have assumed that oils are safe when diluted for dermal use except where experimental data show a potential risk, which we believe has not yet been appreciated. In some cases we have recommended that the oils should not be taken orally, but are safe to use topically. This is due to the higher dose levels of oral administration. In other cases we have indicated that specific essential oils should be avoided in certain vulnerable conditions, such as pregnancy, or that they should be used with special caution. For an easy reference list of contraindications, we draw the reader’s attention to Appendix A.



References



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