A mini-review on the safety profile of essential oils

Abstract

Essential oils (EOs) are defined as secondary metabolites of plants that are volatile in nature and synthesized by various parts of plants such as buds, trichomes, bark, leaves, flowers, twigs, etc. They are generally extracted through steam and hydro distillation processes. The chemistry of these essential oils is very complex and mainly consists of terpenes and their oxygenated derivatives. The color, aroma, volatility, lipophilicity are some of the salient features of these essential oils. Primarily, they are used for flavoring purposes, but with the advancement in science and scientific tools, many properties such as antioxidant, antimicrobial, and anti-inflammatory were explored by the scientific community. Their role as natural food preservatives has evolved in recent years, like biofilms and nano encapsulation in the active packaging of food products. The pharmaceutical industries also look at these essential oils as one of the potent candidates in ameliorating various ailments. The significant components of many essential oils such as piperine of pepper family, eugenol, thymoquinone, curcuminoids were found to have promising therapeutic effects and provide wider research scope for pharmaceutical industries. Besides all these applications, the safety profiling of these EOs is a matter of concern. This mini-review documented the updated published data related to the various aspects related to toxicity and safety issues of EOs.

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Introduction
In European and Asian traditional medicine literature, the use of
essential oils (EOs) for the prevention and treatment of several diseases
was well documented. More than 3000 EOs are known to date, among
which approximately 300 are commercially exploited by the food,
beverages, and pharmaceutical markets. Some commonly known
commercially available EOs are Caraway (Carum carvi),Cinnamon
(Cinnamomum zeylanicum), Neroli (Citrus aurantium var.
Amara), Lemongrass (Cymbopogon citrate), Cardamom (Elettaria
cardamomum), Fennel (Foeniculum vulgare), Ginger (Zingiber
ocinale), Juniper (Juniperus communis), Thyme (Thymus
vulgaris), Tea tree (Melaleuca alternifolia), Peppermint (Mentha
x piperita), and Rosemary (Rosmarinus ocinalis).1 The bioactive
components present in these EOs are responsible for the antioxidant,
anti-inammatory, anticarcinogenic, anti-diabetic, antimutagenic,
and antiproliferative properties,2 which are exploited in the avor,
fragrance, and pharma sectors. Especially in pharmaceutical sectors,
the bioactive components present in EOs have an ability to interact
with several pharmacological targets such as enzymes, receptors
and help in the development of potent drug options for the industry.
In recent years, piperine, curcumin, and thymoquinone are also
considered bio-enhancers used in drug delivery systems to enhance
the availability of drugsin the body.3
The chemistry of EOs is very complex, and the bioactive
components found in EOs range from 20 to 60 in number.4,5 The
chemical prole of EOs showed the presence of more than 300 polar
and non-polar fractions of components at variable percentages.4,5
Major components contribute more than 85% in the chemical prole
of EOs, while other components are present in trace amounts.6
However, based on chemical moieties, these components of EOs
are classied into terpenes/ terpenoids (oxygenated derivative of
terpenes) and phenylpropanoids. The basic unit of terpenes comprises
isoprene units (C5H8)n. These groups are synthesized through separate
metabolic pathways.7 The complexity of the EOs composition is due
to dierent geographical conditions, harvesting time, and extraction
techniques. The notion that being natural is always safe and risk-free
also gets wells with usage EOs. But in recent years, there have been
many reports regarding the toxicity and safety issues related to the
exposure of these EOs. There is a strong need for proper awareness
among the people regarding the usage of these EOs. This mini-review
accounts for the published data available with toxicity-related issues
associated with the use of EOs.
General use of EOs
EOs are one of the constituents in the products related to
perfumery, cosmetics, sprayers, deodorants, food products, beverages,
soaps, fumigants, and detergents.8,9 EOs of tea tree is eective in
controlling the growth of pathogens because of which they are
widely used in hand washes and antiseptics liquids.10 Eucalyptus,
thyme, and menthol are generally used in mouthwashes for providing
refreshing fragrance as well as antiseptic properties.8,11,12 EOs derived
from Species of Ocimum, Eucalyptus, Cymbopogon are widely used
as mosquito repellants.13 There are many patents regarding these
repellants containing EOs around the world. Chemical moieties
mainly responsible for the repellant properties are monoterpenes and
sesquiterpenes.14 Cinnamomum camphora, Syzygium aromaticum L.,
Lavandula angustifolia, Cinnamomum zeylanicum are also known for
their mosquito repellency properties.14 Synergism among dierent
constituents also plays an inuential role in the properties of Eos.15
Camphor, vanillin, limonene, thymol, citronellol, and alpha-pinene are
some of the major components of EOs having insecticidal properties.8
These EOs derived repellants have no side eects and are eco-friendly
options of mosquito repellants.15
Different routes for EOs systemic absorption
Due to their lipophilic nature, EOs can easily pass through the
biological barriers, permitting a possibility of systemic absorption
of the chemical components present in them, which allows their
administration easier through oral, pulmonary, or cutaneous pathways
but comes with toxicological implications and complications.1,16 In
one of the works reported, it was observed that more than 90% of
MOJ Biol Med. 2022;7(1):33‒36. 33
©2022 Singh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and build upon your work non-commercially.
A mini-review on the safety prole of essential oils
Volume 7 Issue 1 - 2022
Sunita Singh,1 Pankaj Kumar Chaurasia,2
Shashi Lata Bharati,3 Upendarrao Golla4,5
1Department of Chemistry, Navyug Kanya Mahavidyalaya,
University of Lucknow, Lucknow, India
2PG Department of Chemistry, LS College, BRA Bihar
University, Muzaffarpur, India
3Department of Chemistry, North Eastern Regional Institute of
Science and Technology, Nirjuli, Arunachal Pradesh, India
4Division of Hematology and Oncology, Department of
Medicine, Pennsylvania State University College of Medicine,
Hershey, PA, United States
5Penn State Cancer Institute, Pennsylvania State University
College of Medicine, Hershey, PA, United States
Correspondence: Sunita Singh, Department of Chemistry,
Navyug Kanya Mahavidyalaya, University of Lucknow,
Lucknow-226004, Uttar Pradesh, India,
Email
Received: January 22, 2022 | Published: February 22, 2022
Abstract
Essential oils (EOs) are dened as secondary metabolites of plants that are volatile in nature
and synthesized by various parts of plants such as buds, trichomes, bark, leaves, owers,
twigs, etc. They are generally extracted through steam and hydro distillation processes.
The chemistry of these essential oils is very complex and mainly consists of terpenes and
their oxygenated derivatives. The color, aroma, volatility, lipophilicity are some of the
salient features of these essential oils. Primarily, they are used for avoring purposes, but
with the advancement in science and scientic tools, many properties such as antioxidant,
antimicrobial, and anti-inammatory were explored by the scientic community. Their
role as natural food preservatives has evolved in recent years, like biolms and nano
encapsulation in the active packaging of food products. The pharmaceutical industries
also look at these essential oils as one of the potent candidates in ameliorating various
ailments. The signicant components of many essential oils such as piperine of pepper
family, eugenol, thymoquinone, curcuminoids were found to have promising therapeutic
eects and provide wider research scope for pharmaceutical industries. Besides all these
applications, the safety proling of these EOs is a matter of concern. This mini-review
documented the updated published data related to the various aspects related to toxicity and
safety issues of EOs.
Keywords: essential oils, terpenes, safety, toxicity
MOJ Biology and Medicine
Mini Review Open Access

A mini-review on the safety prole of essential oils 34
Copyright:
©2022 Singh et al.
Citation: Singh S, Chaurasia PK, Bharati SL, et al. A mini-review on the safety prole of essential oils. MOJ Biol Med. 2022;7(1):33‒36.
DOI: 10.15406/mojbm.2022.07.00162
trans-anethole was absorbed from the digestive tract into the blood of
rats and being metabolized and excreted with fecal waste and urine.1,17
Orally administered geraniol showed a systemic absorption of about
92% in Sprague-Dawley rats.1,18 In aromatherapy, EOs are one of
the signicant components, and there is a possibility of systemic
absorption because the skin is in direct contact with EOs. Components
like limonene, camphor, and α–pinene were systemically absorbed
transdermally, crossing the skin barriers.1,16 One of the studies
reported inhaling ingredients of EOs such as menthol, camphor, and
α-pineneduring pulmonary administration for treating respiratory
diseases. Inhalation occurs due to the volatility property of EOs,
which makes them readily available to get absorbed at the alveolar
level.1,16
Toxicity related to EOs
EOs in the form of natural preservatives are generally recognized
as safe (GRAS) as recommended by the FDA and allowed their
permitted use.19 Figure 1 demonstrates some of the components of
EOs with toxicity.1,8 Since these EOs are required to use in higher
concentrations, the issues related to their toxicity cannot be ignored.
Presently applied toxicity and safety evaluations are available with
dierent variables for EOs. One of the most used methods for
evaluating EOs safety and toxicity is the acute oral test in which LD50
or Median Lethal Dose value is determined.20 In various reported
works done in animal models, the acceptable range of EOs and their
chemical components with LD50 is 1-20 g/kg body weight.8,19 These
evaluations are needed because of the side eects reported in recent
years such as oestrogenic, carcinogenic, and abortifacient eects.21
EOs derived from Salvia lavandifula, Mentha pulegium, Satureja
hortensis, Chenopodium, and Thuja were found to have signicant
toxic eects with LD50 value ranges between 0.1-1 g/kg in the animal
model (rats) and requires prescribed precautions before their use.8,21
Figure 1 Some of the components present in EOs are reported to be toxic
in nature.
Acute and oral toxicity related with EOs
The data relating to EOs toxicity in mammals are relatively low
compared to animal models. The dose of Eucalyptus EO (2772 mg/
kg b.wt) is toxic in one of the investigations, and the administration
of EO causes reduced growth with damage in the liver and kidney of
rats.8,22 A dose of 400 mg/kg of Syzygium aromaticum signicantly
reduces the body weight in rats. The LD50 value for oral dose was
found to be 4500 mg/kg approximately.8,23 Commonly known EOs
derived from lemongrass, marjoram, eucalyptus, clove, chamomile,
anise have oral LD50 values ranging from 2000 to 5000 mg/kg body
weight in rats.8,13 EOs of Eupatorium cannabinum L. containing
germacrene D and neryl acetate as one of the major components
have an oral dose of LD50 value equal to 16.3–22.0 μg/mL.8 Fourteen
days toxicity study was conducted in Wistar rats using Ocimum
basilicum, Ocimum gratissimum, Cymbopogon citratus EOs, which
showed dose dependent (>1500 mg/kg body weight) adverse eects
and caused damage in stomach and liver.8,24 Recently, in the US and
Australia, acute intoxication cases were reported with symptoms such
as vomiting, convulsions, polypnea, and nausea.1 Clove, Tea tree oil,
eucalyptus cinnamon, and wintergreen oils are responsible for these
acute intoxication cases.25 Oral consumption of 0.6–5 mL of pure
eucalyptus EO is found to cause severe symptoms in young children,
even a fatal case being reported in an infant of an 8-month-old.26
Dermatological toxicity related to EOs
In recent years, aromatherapy with some EOs and their components
is known to cause allergic dermatitis infrequent use, due to their
lipophilic nature and capacity to penetrate the skin. Especially in
aromatherapy, EOs are diluted with carrier oils and applied directly
to the skin. Skin irritation, sensitization, and photosensitization are
some of the adverse eects with topical administration of these EOs.
Factors such as method of application, adulteration in EOs, exposure
area, environmental condition play an essential role in developing the
various adverse reactions on the skin.
Skin irritation
EOs derived from Cuminum cyminum, Origanum vulgare,
Cinnamomum zeylanicum, Syzygium aromaticum, Thymus
vulgaris, Tagetes minuta are some of the common skin irritant
oils.1 Components like carvacrol, thymol, eugenol, anethole, and
cinnamaldehyde are some of the constituents causing skin irritation.
Mode of action involves the disruption of the skin barrier, causing
destruction at cellular levels involving the oxidative stress factor.
EOs of Cananga odourata, Melaleuca species, Lavandula spica,
and Mentha species were found to show severe adverse eects while
applied in aromatherapy.8,27,28
Skin sensitization
Skin sensitization is a cumulative response of the immune system
to certain foreign particles or chemicals that come in contact with the
skin in the form of an allergic response. The use of EOs can cause
modication in proteins of the skin and induce a delayed response of the
T-cell mediated system.Components such as citral, cinnamaldehyde,
geraniol, eugenol, coumarin, linalool, citronellol, limonene,
benzyl cinnamate, farnesol, anisyl alcohol, cinnamyl alcohol, and
hydroxycitronellal are responsible for allergic reactions.1,29,30
Photosensitization or phototoxicity
Some chemical moieties absorb light which causes changes in
structural level and causing toxic eects. This phenomenon is known
as photosensitization. In the case of EOs, the chemical components
present in EOs absorb light and cause skin irritation. This interaction
will be either phototoxic or photoallergic in nature. Psoralens or
Furanocoumarins are a class of phototoxic compounds, mainly
present in EOs derived from citrus species, parsley leaf, cumin,
and marigold.1,8,31 The most common compounds are bergapten and
psoralen, producing phototoxicity.1,8,31
HO
carvacrol
O
pulegone
O
O
safrole
O O
O
psoralen
OO O
O
Bergapten
O
thujone
O
H
H
Pinocamphone
O
camphor
O
cinnamaldehyde

A mini-review on the safety prole of essential oils 35
Copyright:
©2022 Singh et al.
Citation: Singh S, Chaurasia PK, Bharati SL, et al. A mini-review on the safety prole of essential oils. MOJ Biol Med. 2022;7(1):33‒36.
DOI: 10.15406/mojbm.2022.07.00162
Other physiological toxicities related with EOs
Some EOs are found to be abortifacients and can induce
miscarriages orabortion during pregnancy. EOs derived from Mentha
pulegium, Petroselinum sativum, Salvia lavandulifolia, Juniperus
sabina, containing pulegone, apiole and sabinyl acetate as major
component respectively is generally avoided in pregnancy. Some
works also reported toxicity issues such as damage to kidney and
liver to conceiving mother.1,21,32 The lipophilic nature of EOs make
them able to cross the placenta and even disturbs the fetal circulation
system.1,25,32 It was recommended that EOs containing components
such as (E)-anethole, β-eudesmol, thujone, apiole, methyl salicylate,
and thuja should be avoided during pregnancy and breastfeeding.1,21,32
In recent years some EOs have been reported to cause genotoxicity
and carcinogenicity.8 In an experiment conducted on rodents, estragole
containing EOs of Ocimum basilicum and Artemisia dracunculus were
carcinogenic in nature.8,33,34 Pulegone and safrole components showed
carcinogenicity after getting activated in metabolic channels.8,35
Estrogen-related cancer can be induced by EOs of Salvia sclarea and
Melaleuca quinquenervia, which can stimulate estrogen production.8
In rodents, methyl eugenol and D‐limonene in EOs of Laura nobilis
and citrus plants, respectively, have been reported as carcinogenic in
nature.36,37 Eugenolis one of the major components of clove EOs is
found to be genotoxic and causes aberration at the chromosomal level
in cells.38 In higher doses EOs of peppermint Pinus densiora and
Anethum graveolens have been reported to be cytotoxic and genotoxic
in lymphocytes of humans.39
In recent years, there have been enough pieces of evidence
suggesting that some EOs can disrupt the endocrine system. Topical
administration of tea tree and lavender EOs causes prepubertal
gynecomastia in patients.1,40 They are found to be involved in
activating estrogenicreceptors (ER).
During systemic absorption of EOs, they can quickly reach to the
central nervous system. In one of the experimental studies done on
rats, EOs of Hyssopus ocinalis and Salvia ocinalis at the doses
of 0.5 g/kg and 0.13 g/kg given intraperitoneally is found to involve
developing convulsions.1,41 Studies on human done with EOs of
Mentha pulegium, Thuja plicata, Eucalyptus spp, Salvia ocinalis,
and Anethum graveolens induces seizures, especially in children.42,43
Standard convulsant evoking components of EOs are pulegone,
camphor, pinocamphone, and thujone.1,42 One of the studies reported
some EOs with pentylentetrazole having convulsive eect.44 The
usage of EOs aects the mechanism related to GABA and brings
modication in the action of Na/K ions at neuron levels.
Conclusion
In recent years there has been an increased awareness among
the consumers’ approach towards the product of natural origin.
EOs comes as a potential candidate for perfumery, cosmetics,
fragrance, and pharmaceutical sectors. Advancement in extraction
techniques to separate bioactive components present in EOs has
opened new horizons for many sectors. The widespread applications
such as antioxidant, anti-diabetic, antiproliferative, antimutagenic,
anticarcinogenic were experimentally investigated in vitro and in
vivo models. Even though various agencies recommend the EOs as
safe additive, their toxicological and safety issues cannot be ignored.
Investigation on the toxicological assessment is limited to the animal
model, which should be expanded more and more. In vivo evidences
are very scarce in the literature. These toxicological assessments are
also needed and helpful in exploring the therapeutic potentials of EOs.
Acknowledgments
The authors are grateful to their respective Departments and
Institutions/universities for their unconditional support.
Conicts of interest
The authors declared no have conict interest for the study.
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Copyright:
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Citation: Singh S, Chaurasia PK, Bharati SL, et al. A mini-review on the safety prole of essential oils. MOJ Biol Med. 2022;7(1):33‒36.
DOI: 10.15406/mojbm.2022.07.00162
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