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A mini-review on the safety profile of essential oils



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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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):3336. 33
©2022 Singh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which
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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,
Received: January 22, 2022 | Published: February 22, 2022
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
©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):3336.
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
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
A mini-review on the safety prole of essential oils 35
©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):3336.
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 Dlimonene 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.
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.
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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DOI: 10.15406/mojbm.2022.07.00162
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... However, frequent and prolonged use of OH-based disinfectants may be harmful to health and the environment [7][8][9]. EOs in the form of natural products are generally recognized as safe (GRAS) by the FDA (Food and Drug Administration, Silver Spring, MD, USA), and their use is permitted [27]. Many studies have explored using EOs as potential antibacterial and antifungal alternatives to commercial disinfectants [14,28]. ...
... The envelope has 90 head-to-tail dimers of the E protein organized in a herringbone, with the M protein bound at the dimer interface [32]. On the other hand, CHIKV assembles and budding occurs at the cytoplasmic membrane, and the viral envelope comprises the E1 and E2 glycoproteins and a peptide (E3) arranged in trimers to make 80 E1/E2 spikes [27]. A recent study [18] showed differences in the sensitivity of enveloped viruses (human and feline coronaviruses) to treatment with a mixture of tea tree oil and ethanol. ...
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The large-scale use of alcohol (OH)-based disinfectants to control pathogenic viruses is of great concern because of their side effects on humans and harmful impact on the environment. There is an urgent need to develop safe and environmentally friendly disinfectants. Essential oils (EOs) are generally recognized as safe (GRAS) by the FDA, and many exhibit strong antiviral efficacy against pathogenic human enveloped viruses. The present study investigated the virucidal disinfectant activity of solutions containing EO and OH against DENV-2 and CHIKV, which were used as surrogate viruses for human pathogenic enveloped viruses. The quantitative suspension test was used. A solution containing 12% EO + 10% OH reduced > 4.0 log10 TCID50 (100% reduction) of both viruses within 1 min of exposure. In addition, solutions containing 12% EO and 3% EO without OH reduced > 4.0 log10 TCID50 of both viruses after 10 min and 30 min of exposure, respectively. The binding affinities of 42 EO compounds and viral envelope proteins were investigated through docking analyses. Sesquiterpene showed the highest binding affinities (from −6.7 to −8.0 kcal/mol) with DENV-2 E and CHIKV E1-E2-E3 proteins. The data provide a first step toward defining the potential of EOs as disinfectants.
... EOs are lipophilic complex mixtures of hydrocarbon compounds of 10 to 15 carbon atoms with different functional groups, such as phenols, aldehydes, ketones, alcohols and hydrocarbons [24]. Lipophilicity is among the most important parameters to take into account when selecting bioactive compounds and the methods to test them, because the insect cuticle forms a physical defense barrier [41][42][43]. Thus, the lipophilicity property of EOs makes it easier for them to reach their target within the body [43][44][45][46]. ...
... Lipophilicity is among the most important parameters to take into account when selecting bioactive compounds and the methods to test them, because the insect cuticle forms a physical defense barrier [41][42][43]. Thus, the lipophilicity property of EOs makes it easier for them to reach their target within the body [43][44][45][46]. It is widely known that organophosphate insecticides, such as Dichlorvos (DDVP), penetrate through the integument until they reach the hemolymph and, subsequently, their site of action [47,48]. ...
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Spodoptera frugiperda is a major pest of maize crops. The application of synthetic insecticides and the use of Bt maize varieties are the principal strategies used for its control. However, due to the development of pesticide resistance and the negative impact of insecticides on the environment, natural alternatives are constantly being searched for. Accordingly, the objective of this review was to evaluate the use of essential oils (EOs) as natural alternatives for controlling S. frugiperda. This review article covers the composition of EOs, methods used for the evaluation of EO toxicity, EO effects, and their mode of action. Although the EOs of Ocimum basilicum, Piper marginatum, and Lippia alba are the most frequently used, Ageratum conyzoides, P. septuplinervium. O. gratissimum and Siparuna guianensis were shown to be the most effective. As the principal components of these EOs vary, then their mode of action on the pest could be different. The results of our analysis allowed us to evaluate and compare the potential of certain EOs for the control of this insect. In order to obtain comparable results when evaluating the toxicity of EOs on S. frugiperda, it is important that methodological issues are taken into account.
... Terpenes also provide for flexibility in the route of administration and the reduction of side effects in addition to these qualities. Terpenes are natural substances that are unlikely to harm healthy cells or have any negative side effects, which attracts many researchers to explore their potential as a cancer treatment [138]. Castilhos et al. conducted toxicity research of essential oils in 2017, and the findings show that these compounds exhibit relative selectivity to the predator Chrysoperla externa; nevertheless, some compounds also showed sublethal effects on reproduction. ...
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Breast cancer is the second highest cancer-related death worldwide. The treatment for breast cancer is via chemotherapy; however, occurrences of multidrug resistance, unselective targets, and physicochemical problems suggest that chemotherapy treatment is ineffective. Therefore, there is a need to find better alternatives. Essential oil is a plant secondary metabolite having promising bioactivities and pharmacological effects, including anti-breast cancer capabilities. This review intends to discuss and summarize the effect of essential oils on anti-breast cancer from published journals using keywords in PubMed, Scopus, and Google Scholar databases. Our findings reveal that the compositions of essential oils, mainly terpenoids, have excellent anti-breast cancer pharmacological effects with an IC50 value of 0.195 μg/mL. Hence, essential oils have potential as anti-breast cancer drugs candidates with the highest efficacy and the fewest side effects.
... Therefore, alternative strategies such as the use of nano-based delivery systems encapsulating biosourced terpenes from essential oils (EOs) such as thymol (THY) have aroused as impressive control strategies with remarkable antibiofilm effectiveness against a wide range of pathogenic microorganisms [5,7,[15][16][17]. THY is recognized as safe to be used in food industries by the Food and Drug Administration (FDA) [18,19]. Its encapsulation could be a promising tool to overcome the different obstacles arising not only from free terpenes as their high volatility and low stability but also from the biofilm structures barriers and their resistance mechanisms to microorganisms [12,20]. ...
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In food industries, microbial contaminations are difficult to control due to the recurrent formation of biofilms that hinders antimicrobials penetration and efficiency. An understanding of Salmonella Enteritidis biofilms behavior under flow conditions is a key to develop efficient preventive and control strategies. S. Enteritidis biofilms displayed 5.96, 6.28 and 6.80 log CFU cm⁻² under 0.006 cm s⁻¹, 0.045 cm s⁻¹, and 0.087 cm s⁻¹ flow velocities, respectively. Biofilms exposed to higher nutrient conditions under greater flow rates, induced significantly more biofilm biomass. To control biofilms, the disinfection efficiency of thymol (THY) was assessed under dynamic conditions by encapsulation it into two types of nanocapsules: monolayer (ML) nanocapsules prepared with a single carrier material (maltodextrin), and layer-by-layer (LBL) nanocapsules prepared by combining two carrier materials (maltodextrin and pectin). A combined mixture of ML and LBL nanocapsules at ½ their minimal inhibitory concentrations induced 99.99% eradication of biofilms developed under the highest flow conditions, after 5 h. ML nanocapsules decreased significantly bacterial counts during the first 0.5 h, while LBL nanocapsules eliminated the remaining bacterial cells and ensured a protection from bacterial contamination for up to 5 h by releasing THY in a sustained manner over time due to the thicker shell wall structure.
... Regarding the safety issue related to the usage of EOs, negative side effects such as allergic dermatitis, neurological complications, spasmolytic issues, and dysregulations related to endocrine systems are reported in the literature (Kuttan & Liju, 2016;Oliviu et al., 2020;Singh et al., 2022). These safety concerns force a proper regulation condition by authorities before their wider applications as preservatives. ...
According to the definition given in literature, essential oils (EOs) are defined as an aromatic volatile fraction isolated from different parts of plants such as leaves, fruits, bark etc using different extraction processes. They are synthesized by all plant parts and are principally complex mixture of terpenes and their oxygenated derivatives. Due to their antimicrobial properties, now they are representing an interesting source of natural antimicrobials for food preservation. The side effects caused by synthetic preservatives have pushed the scientific community to find an alternative that covers the same antimicrobial efficacies without affecting the organoleptic properties of food products and supports the trend of green consumerism. In this search, essential oils became a potent candidate in food preservation and now‐a‐days, play momentous role in food preservation. This review noticeably focuses on the applications of EOs as food preservatives along with the current prospects and limitations.
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Discovery of new drugs with high therapeutic potential but having poor solubility and poor membrane permeation characteristics leads to use of bioenhancers in drug delivery. In general, bioenhancers have been identified as chemical entities of natural origin that can increase the quantity of unchanged drug that appears in the systemic blood circulation by means of modulating membrane permeation and/or pre-systemic metabolism. Since antiquity, various herbs and spices were used for the treatment of different ailments and drug formulations. In modern pharmacopoeias also, approximately 25 % of drugs have been documented as plant origin drugs [1-3]. Pepper fruit of Piperaceae family is one of them which have been established as bioenhancer for some selected drugs. Piper species have a special and importance place in Ayurvedic literature and formulations. Out of 370 drug formulations, about 210 drug formulation contained ‘Trikatu’ as one of the ingredients [4]. Black pepper is one of the three ingredients of ‘Trikatu’. The other two ingredients are ginger and long pepper (Piper longum). Certain studies proved that ‘Trikatu’ was acting as bioenhancer for the accompanying drugs. This action is referred as Yogvahi in ancient classic literature. The concept of bioenhancer appears too late in allopathic practice as compared to Ayurveda [5].
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Geraniol is a natural monoterpene showing anti-inflammatory, antioxidant, neuroprotective and anticancer effects. No pharmacokinetic and bioavailability data on geraniol are currently available. We therefore performed a systematic study to identify the permeation properties of geraniol across intestinal cells, and its pharmacokinetics and bioavailability after intravenous and oral administration to rats. In addition, we systematically investigated the potential hepatotoxic effects of high doses of geraniol on hepatic phase I, phase II and antioxidant enzymatic activities and undertook a hematochemical analysis on mice. Permeation studies performed via HPLC evidenced geraniol permeability coefficients across an in vitro model of the human intestinal wall for apical to basolateral and basolateral to apical transport of 13.10 ± 2.3 × 10-3 and 2.1 ± 0.1⋅× 10-3 cm/min, respectively. After intravenous administration of geraniol to rats (50 mg/kg), its concentration in whole blood (detected via HPLC) decreased following an apparent pseudo-first order kinetics with a half-life of 12.5 ± 1.5 min. The absolute bioavailability values of oral formulations (50 mg/kg) of emulsified geraniol or fiber-adsorbed geraniol were 92 and 16%, respectively. Following emulsified oral administration, geraniol amounts in the cerebrospinal fluid of rats ranged between 0.72 ± 0.08 μg/mL and 2.6 ± 0.2 μg/mL within 60 min. Mice treated with 120 mg/kg of geraniol for 4 weeks showed increased anti-oxidative defenses with no signs of liver toxicity. CYP450 enzyme activities appeared only slightly affected by the high dosage of geraniol.
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Essential oil has performed a variety of indirect services used as insect/pest repellent. The present study investigated the acute and subchronic toxicity of eucalyptus oil emulsion in water (EOE). In addition, we conduct safety pharmacology evaluation of EOE to supplement the toxicity tests and provide a basis for a comprehensive understanding of the toxicity of EOE. Acute administration of EOE was done as single dose from 2772 mg to 5742 mg of EOE per kg/bodyweight (b.wt.) and subchronic toxicity study for thirty days was done by daily oral administration of EOE at doses of 396, 792 and 1188 mg/kg b.wt. In SPF SD rats. The acute toxicity study showed the LD50 of EOE was 3811.5 mg/kg. The subchronic toxicity study suggested the high-dose and middle-dose EOE slowed down the growth of male rats. The clinical pathology showed the high-dose and middle-dose EOE could cause damage to liver and kidney. The safety pharmacology indicated that EOE had no side effects on rats. These results suggest that EOE is a safe veterinary medicine for external use.
A scientific definition of the term volatile oils is not possible, although several practical definitions exist. The most frequently used definition describe a volatile or an essential oil as a more or less volatile material isolated from an odorous plant of a single botanical species by a physical process. They are usually liquids which will evaporate or volatize when exposed to ordinary temperature and so they are called ethereal oils. A few of them are solid or resinous, and showing different colors ranging from pale yellow to emerald green and from blue to dark brownish red. These volatile oils are also called essential oils (EOs) because they were believed to represent the quintessence of odor and flavor from the flower kingdom – differ in composition properties from fatty or fixed oils, which consist for the most part of glycerides and from mineral or hydrocarbon oils. They are synthesized by all plant organs, i.e., buds, flowers, leaves, stems, twigs, seeds, fruits, roots, wood or bark, and are stored in secretory cells, cavities, canals, epidermic cells or glandular trichomes. There are several extraction methods for volatile oils extraction, comprising steam distillation, hydrodistillation, organic solvent extraction, expression, enfleurage, microwave-assisted distillation, microwave hydrodiffusion and gravity, high-pressure solvent extraction, supercritical carbon dioxide extraction, ultrasonic extraction, solvent-free microwave extraction, and the phytonic process. Volatile oils are mainly comprises of biosynthetically related groups which includes terpenes and their oxygenated derivatives such as aldehydes, ketones, alcohols, phenols, acids, ethers and esters having low molecular weight. Monoterpenes and sesquiterpenes are usually the main group of compounds found in essential oils. Moreover, some essential oils may also contain phenylpropanoids, fatty acids and their esters and, more rarely, nitrogen and sulfur derivatives. These oils find applications mainly in the flavor and fragrance industry, pharmaceutical industries. In recent years field of aromatherapy is evolved, which is the science of applying the controlled use of naturally plant extracted essences to promote physical and psychological well-being. The knowledge of these oils has been constantly developed and updated in the long stream of history thanks to a growing number of studies in multidisciplinary fields. Although some compositions and mechanisms are not completely understood, the fascinating odor of EOs and their interesting biological activities are of great interest, which have been pushing the progress of the EOs’ research in recent years. This chapter documents the conventional as well as novel extraction techniques for volatile oils with their specification in terms of their principles, benefits and disadvantages. The chapter also comprehensively reviews the chemistry of volatile oils and discusses their synthetic route.
Meat and meat products are perishable products that require the use additives to prevent the spoilage by foodborne microorganisms and pathogenic bacteria. Current trends for products without synthetic preservatives have led to the search for new sources of antimicrobial compounds. Essential oils (EOs), which has been used since ancient times, meet these goals since their effectiveness as antimicrobial agents in meat and meat products have been demonstrated. Cinnamon, clove, coriander, oregano, rosemary, sage, thyme, among others, have shown a greater potential to control and inhibit the growth of microorganisms. Although EOs are natural products, their quality must be evaluated before being used, allowing to grant the Generally Recognized as Safe (GRAS) classification. The bioactive compounds (BAC) present in their composition are linked to their activity, being the concentration and the quality of these compounds very important characteristics. Therefore, a single mechanism of action cannot be attributed to them. Extraction technique plays an important role, which has led to improve conventional techniques in favour of green emerging technologies that allow to preserve better target bioactive components, operating at lower temperatures and avoiding as much as possible the use of solvents, with more sustainable processing and reduced energy use and environmental pollution. Once extracted, these compounds display greater inhibition of gram-positive than gram-negative bacteria. Membrane disruption is the main mechanism of action involved. Their intense characteristics and the possible interaction with meat components make that their application combined with other EOs, encapsulated and being part of active film, increase their bioactivity without modifying the quality of the final product.
Essential oils (EOs) are natural, volatile and aromatic liquids extracted from special plants. EOs are complex mixture of secondary metabolites (terpenes, phenolic compounds, alcohol). EOs possess a wide range of biological activities including antioxidant, antimicrobial and anti-inflammatory ones. Particularly, EOs exhibit pronounced antibacterial and food preservative properties that represent a real potential for the food industry. Numerous EOs have the potential to be used as a food preservative for meat and meat products, vegetables and fruits as well as for dairy products. The main obstacles for using EOs as food preservatives are their safety limits, marked organoleptic effects and possible contamination by chemical products such as pesticides. This review aims to provide an overview of current knowledge about EOs food preservative properties with special emphasis on their antibacterial activities and to support their uses as natural, eco-friendly, safe and easily biodegradable agents for food preservation.
This chapter mainly deals with the toxicological aspects of essential oils (EOs). The use of EOs is growing rapidly amongst most of the countries in food industries, production of soaps, detergents, cosmetics, nonalcoholic beverages, agriculture, oral care products, aromatherapy and pharmacology. Long history of the usage of EOs in preservatives, food additives and traditional toxicology approaches has been pointed out to establish the safety of the EOs. Toxicity evaluations of EOs are essential for their safe use to mankind. The phototoxicity study in cell line showed, EO isolated from Orange is probably phototoxic in the presence of UV. The acute toxicity of EO from Piper vicosanum leaves was evaluated by administration to female rats at a single dose of 2 g/kg body weight orally. EO are usually devoid of mutagenicity and carcinogenicity in lower concentration. Studies of EO from Piper vicosanum showed no genotoxicity and mutagenicity in mice.