Inhalation of Cananga odorata essential oil relieves anxiety behaviors in autism-like rats via regulation of serotonin and dopamine metabolism.

OBJECTIVE: Anxiety is one of the most common symptoms associated with autistic spectrum disorder. The essential oil of Cananga odorata (Lam.) Hook. f. & Thomson, usually known as ylang-ylang oil (YYO), is often used in aromatherapy as a mood-regulating agent, sedative, or hypotensive agent. In the present study, the effects and mechanisms of YYO in alleviating anxiety, social and cognitive behaviors in autism-like rats were investigated. METHODS: The prenatal valproic acid (VPA) model was used to induce autism-like behaviors in offspring rats. The effectiveness of prenatal sodium valproate treatment (600 mg/kg) on offspring was shown by postnatal growth observation, and negative geotaxis, olfactory discrimination and Morris water maze (MWM) tests. Then three treatment groups were formed with varying exposure to atomized YYO to explore the effects of YYO on the anxiety, social and cognitive behaviors of the autistic-like offspring through the elevated plus-maze test, three-chamber social test, and MWM test. Finally, the monoamine neurotransmitters, including serotonin, dopamine and their metabolites, in the hippocampus and prefrontal cortex (PFC) of the rats were measured using a high-performance liquid chromatography. RESULTS: Offspring of VPA exposure rats showed autism-like behaviors. In the VPA offspring, medium-dose YYO exposure significantly elevated the time and entries into the open arms in the elevated plus-maze test, while low-dose YYO exposure significantly enhanced the social interaction time with the stranger rat in session 1 of the three-chamber social test. VPA offspring treated with YYO exposure used less time to reach the platform in the navigation test of the MWM test. YYO exposure significantly elevated the metabolism of serotonin and dopamine in the PFC of VPA offspring. CONCLUSION: YYO exposure showed the effects in alleviating anxiety and improving cognitive and social abilities in the offspring of VPA exposure rats. The role of YYO was related to the regulation of the metabolism of serotonin and dopamine. Please cite this article as: Zhang N, Wang ST, Yao L. Inhalation of Cananga odorata essential oil relieves anxiety behaviors in autism-like rats via regulation of serotonin and dopamine metabolism. J Integr Med. 2023; 21(2): 205-214.

Comparison of chemometric assisted targeted and untargeted approaches for the prediction of radical scavenging activity of ylang-ylang essential oils.

Essential oils have been used for centuries for their preservative properties. An example is ylang-ylang Cananga odorata [Lam.] Hook. f. & Thomson essential oil, which exists in four different distillation grades, where the fraction with the longest distillation time has the highest radical scavenging activity (RSA). Gas chromatography mass spectrometry (GC-MS) followed by multivariate statistical analysis is a powerful approach for determination of RSA. Herein the performance of such multivariate statistical analysis using three data sets derived from gas chromatography mass spectrometry (GC-MS) analysis, is compared to that achieved using two direct and fast spectroscopic techniques, for the prediction of RSA using partial least squares (PLS) regression analysis. The three GC-MS data sets were, 'full chemical composition', 'total chromatogram average mass spectra (TCAMS)' and 'segment average mass spectra (SAMS)', whilst two spectroscopic techniques, namely attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and Raman spectroscopy, provided the spectroscopic data sets for comparison. PLS models created using ATR-FTIR and 'full chemical composition' data sets provided the lowest relative error of prediction (REP) and mean error of prediction (MEP) in validation, whilst in independent test sets, the PLS models created using ATR-FTIR and SAMS data sets delivered the lowest REP and MEP. The three GC-MS derived data sets were further compared for value in determination of compounds contributing to the RSA. PLS regression analysis of the full chemical composition data set revealed that germacrene D and (E,E)-α-farnesene were the major contributors to the RSA, whilst average mass spectrum based data sets, TCAMS and SAMS, also highlighted eugenol as another contributor to the RSA.

Radical scavenging activity and metabolomic profiling study of ylang-ylang essential oils based on high-performance thin-layer chromatography and multivariate statistical analysis.

Ylang-ylang (YY) essential oil (EO) is distilled from the fresh-mature flowers of the Annonaceae family tropical tree Cananga odorata [Lam.] Hook. f. & Thomson, and is widely used in perfume and cosmetic industries for its fragrant character. Herein, two different metabolomic profiles obtained using high-performance thin-layer chromatography (HPTLC), applying different stains, namely 2,2-diphenyl-1-picrylhydrazyl (DPPH·) and p-anisaldehyde, were used for discrimination of 52 YY samples across geographical origins and distillation grades. The first profile is developed using the DPPH· stain based on the radical scavenging activity (RSA) of YY EOs. Results of the HPTLC-DPPH· assay confirmed that RSA of YY EOs is in proportion to the length of distillation times. Major components contributing to the RSA of YY EOs were tentatively identified as germacrene D and α-farnesene, eugenol and linalool, by gas chromatography-mass spectrometry (GC-MS) and GC-flame ionisation detector (GC-FID). The second profile was developed using the general-purpose p-anisaldehyde stain based on the general chemical composition of YY EOs. Untargeted metabolomic discrimination of YY EOs from different geographical origins was performed based on the HPTLC-p-anisaldehyde profiles, followed by principal component analysis (PCA). A discrimination and prediction model for identification of YY distillation grade was developed using PCA and partial least squares regression (PLS) based on binned HPTLC-ultraviolet (254 nm) profiles, which was successfully applied to distillation grade determination of blended YY Complete EOs.

Assessment of nanoencapsulated Cananga odorata essential oil in chitosan nanopolymer as a green approach to boost the antifungal, antioxidant and in situ efficacy.

In this study, a comparative efficacy of Cananga odorata EO (CoEO) and its nanoencapsulated formulation into chitosan nanoemulsion (CoEO-CsNe) against a toxigenic strain of Aspergillus flavus (AF-M-K5) were investigated for the first time in order to determine its efficacy in preservation of stored food from fungal, aflatoxin B1 (AFB1) contamination and lipid peroxidation. GC and GC-MS analysis of CoEO revealed the presence of linalool (24.56%) and benzyl acetate (22.43%) as the major components. CoEO was encapsulated into chitosan nanoemulsion (CsNe) through ionic-gelation technique and characterized by High Resolution-Scanning Electron Microscopy (HR-SEM), Fourier Transform Infrared spectroscopy (FTIR), and X-Ray Diffraction (XRD) analysis. The CoEO-CsNe during in vitro investigation against A. flavus completely inhibited the growth and AFB1 production at 1.0 µL/mL and 0.75 µL/mL, respectively. Additionally, CoEO-CsNe showed improved antioxidant activity against DPPH• and ABTS•+ with IC50 value 0.93 and 0.72 µL/mL, respectively. Further, CoEO-CsNe suppressed fungal growth, AFB1 secretion and lipid peroxidation in Arachis hypogea L. during in situ investigation without causing any adverse effect on seed germination. Overall results demonstrated that the CoEO-CsNe has potential of being utilized as a suitable plant based antifungal agent to improve the shelf-life of stored food against AFB1 and lipid peroxidation mediated biodeterioration.

Comprehensive characterisation of ylang-ylang essential oils according to distillation time, origin, and chemical composition using a multivariate approach applied to average mass spectra and segmented average mass spectral data.

Analyses of the complex essential oil samples using gas chromatography hyphenated with mass spectrometry (GC-MS) generate large three-way data arrays. Processing such large data sets and extracting meaningful information in the metabolic studies of natural products requires application of multivariate statistical techniques (MSTs). From the GC-MS raw data several different input data sets for the MSTs can be created, including total chromatogram average mass spectra (TCAMS), segmented average mass spectra (SAMS) and chemical composition. Herein, we compared the performance of MSTs on average mass spectrum based data sets, TCAMS and SAMS, against chemical composition and attenuated total reflectance - Fourier transformation infrared (ATR-FTIR) spectroscopy in the evaluation of quality of ylang-ylang essential oils, based on their grade, geographical origin and chemical composition, using principal component analysis (PCA), partial least squares regression (PLS) and discriminatory analysis (PLS-DA). PCA based on TCAMS, SAMS and chemical composition showed clear trends amongst the samples based on increase in grade (distillation time). PLS-DA applied to TCAMS, SAMS and ATR-FTIR discriminated between all geographical origins. Predicted relative abundances of the 18 most important compounds, using PLS regression models on TCAMS, SAMS and ATR-FTIR, were successfully applied to ylang-ylang essential oil quality assessment based on comparison with the ISO 3063:2004 standard, where the SAMS data set showed superior performance, compared to other data sets.

Chemical components of the volatile oil from leaves of Cananga odorata and its anti-oxidant activity.

Cananga odorata (Lamk.) Hook. f. et Thoms., belonging to Annonaceae, is an evergreen tree. The oils extracted from its flower are a famous perfume and used in daily chemical and food industry. Although this plant has been widely cultivated in tropical regions of the world, the yield of oils from its flower is very limited. In order to develop the other parts of this plant, the chemical constituents of the volatile oils from the leaves of C. odorata was analyzed by gas chromatography/flame ionization detector (GC-FID) and GC/mass spectrometry (GC-MS). And the volatiles showed nitric oxide (NO) inhibitory activity with an IC50 value of 37.61µg/mL and anti-oxidant activity with an IC50 value of 3.84mg/mL, respectively.

Antiviral Activity of Cananga odorata Against Hepatitis B Virus.

Chronic hepatitis B virus (HBV) infection can lead to liver cirrhosis and hepatocellular carcinoma. Current therapeutic drugs for chronic hepatitis B using pegylated interferons and nucleos(t)ide analogs have limited efficacy. Therefore, the development of novel and safe antivirals is required. Natural products including medicinal plants produce complex and structurally diverse compounds, some of which offer suitable targets for antiviral screening studies. In the present study, we screened various crude extracts from Indonesian plants for anti-HBV activity by determining their effects on the production of extracellular HBV DNA in Hep38.7-Tet cells and HBV entry onto a HBV-susceptible cell line, HepG2-NTCP, with the following results: (1) In Hep38.7-Tet cells, Cananga odorata exhibited the highest anti-HBV activity with a 50% inhibitory concentration (IC50) of 56.5 µg/ml and 50% cytotoxic concentration (CC50) of 540.2 µg/ml (Selectivity Index: 9.6). (2) The treatment of HepG2-NTCP cells with Cassia fistula, C. odorata, and Melastoma malabathricum at concentrations of 100 µg/ml lowered the levels of HBsAg production to 51.2%, 58.0%, and 40.1%, respectively, compared to untreated controls, and IC50 and CC50 values of C. odorata were 142.9 µg/ml and >400 µg/ml. In conclusion, the C. odorata extract could be a good candidate for the development of anti-HBV drugs.

Essential Oils, Part VI: Sandalwood Oil, Ylang-Ylang Oil, and Jasmine Absolute.

In this article, some aspects of sandalwood oil, ylang-ylang oil, and jasmine absolute are discussed including their botanical origin, uses of the plants and the oils and absolute, chemical composition, contact allergy to and allergic contact dermatitis from these essential oils and absolute, and their causative allergenic ingredients.

The anxiolytic effect of essential oil of Cananga odorata exposure on mice and determination of its major active constituents.

BACKGROUND: Essential oil from Cananga odorata (ylang-ylang essential oil, YYO) is usually used in reducing blood pressure, improving cognitive functioning in aromatherapy in human. Few reports showed its effect on anxiety behaviors. HYPOTHESIS/PURPOSE: To investigate the anxiolytic effects of YYO exposure on anxiety animal models, determine the major active constituents and investigate the change of neurotransmitters after odor exposure. STUDY DESIGN AND METHODS: ICR mice were subjected to three anxiety models including open field, elevated plus maze and light-dark box tests after acute and chronic YYO exposure. Main constituents of YYO were defined using GC/MS. These compounds were then tested on the male mice separately on three anxiety models. The monoamines neurotransmitters and their metabolites were analyzed after acute odor exposure and elevated plus maze test. RESULTS: YYO exposure only showed significant anxiolytic effect on the male mice. It increased the time that mice visited open arms and light box area in elevated plus maze and light-dark box tests after acute and chronic YYO exposures. Three main constituents of YYO, benzyl benzoate, linalool and benzyl alcohol showed anxiolytic effect on the male mice individually. YYO exposure brought changes of neurotransmitters on the male mice more significantly than the female mice. It decreased the dopamine (DA) concentration in the striatum and increased the 5-hydroxytryptamine (5-HT) concentration in the hippocampus of the male mice. The major constituent benzyl benzoate changed neurotransmitters concentration in accordance with the YYO. Moreover, it decreased the ratio of 5-HIAA/5-HT in the hippocampus. CONCLUSION: Both acute and chronic YYO exposure showed anxiolytic effect on the male mice. YYO and its major constituent benzyl benzoate might act on the 5-HTnergic and DAnergic pathways.

Canangalias C-H, juvenile hormone III analogues from the roots of Cananga latifolia.

Chemical investigation of the roots of Cananga latifolia led to the isolation and purification of thirteen juvenile hormone III analogues. Six new analogues, canangalias C-H (1-6) and a new natural product, (2E,6E,10R)-10-acetoxy-11-hydroxy-3,7,11-trimethyldodeca-2,6-dienoic acid methyl ester (7), were isolated. In addition, six known juvenile hormone III analogues were isolated. Their structures were established by spectroscopic methods including 1D and 2D NMR, IR and mass spectrometry.

Efficacy of essential oil from Cananga odorata (Lamk.) Hook.f. & Thomson (Annonaceae) against three mosquito species Aedes aegypti (L.), Anopheles dirus (Peyton and Harrison), and Culex quinquefasciatus (Say).

The essential oil of Cananga odorata flowers was evaluated for oviposition-deterrent, ovicidal, insecticidal, and repellent activities toward three mosquito species: Aedes aegypti, Anopheles dirus, and Culex quinquefasciatus. Oviposition deterrence of the oil was evaluated on gravid females using oviposition deterrence bioassay. The results showed that 10 % Ca. odorata exhibited high percent effective repellency against oviposition at 99.4 % to Ae. aegypti, 97.1 % to An. dirus, and 100 % to Cx. quinquefasciatus. Ca. odorata oil was tested for ovicidal activity. Regression equations revealed that the ovicidal rates were positively correlated with the concentrations of the essential oil. As the concentration of essential oil increased from 1, 5, and up to 10 % concentration, the ovicidal rate increased accordingly. Larvicidal activity of the oils was used on immature stages (third and fourth instar lavae and pupae). The maximum larval mortality was found with 10 % Ca. odorata against immature stages, and there were LC50 values ranged from 10.4 to 10.5 % (for Ae. aegypti), <1 % (for An. dirus), and <1 % (for Cx. quinquefasciatus). Adulticidal properties were evaluated with unfed females. Ten percent Ca. odorata oil had high knockdown rates against the three mosquito species at 96 % (for Ae. aegypti), 98.4 % (for An. dirus), and 100 % (for Cx. quinquefasciatus), with EC50 values of 6.2, 4.7, and 5.4 %, respectively. It gave moderate mortality rates after 24 and 48 h of exposure. Ca. odorata oil was assessed for repellency to females by using the modified K&D module. Ten percent Ca. odorata oil gave the strongest value against Ae. aegypti, An. dirus, and Cx. quinquefasciatus, with percentage repellency of 66, 92, and 90 %, respectively. This study demonstrates the potential for the essential oil of Ca. odorata essential oil to be used as a botanical insecticide against three mosquito species.

Structure of constituents isolated from the flower buds of Cananga odorata and their inhibitory effects on aldose reductase.

Three new terpenoid derivatives, canangaterpenes IV-VI, were isolated from the flower buds of Cananga odorata, cultivated in Thailand, together with eight known flavonoids. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effects of the isolated compounds on aldose reductase were also investigated. Several terpenoid derivatives and flavonoids were shown to inhibit aldose reductase.

Plant-derived juvenile hormone III analogues and other sesquiterpenes from the stem bark of Cananga latifolia.

Juvenile hormone III (JH III) is a larval metamorphosis-regulating hormone present in most insect species. JH III was first isolated from the plant, Cyperus iria L., but the presence of JH III has not been reported in other plant species. In the present study, proof of the existence of JH III and its analogues from Cananga latifolia was established. From an aqueous MeOH extract of C. latifolia stem bark, six compounds were isolated along with nine known compounds. These were identified by using spectroscopic analyses as: (2E,6E,10R)-11-butoxy-10-hydroxy-3,7,11-trimethyldodeca-2,6-dienoic acid methyl ester, (2E,6E)-3,7,11-trimethyl-10-oxododeca-2,6-dienoic acid methyl ester, (2E)-3-methyl-5-[(1S,2R,6R)-1,2,6-trimethyl-3-oxocyclohexyl]-pent-2-enoic acid methyl ester, 1ß-hydroxy-3-oxo-4ß, 5α,7α-H-eudesmane 11-O-α-l-rhamnopyranoside, 4-epi-aubergenone 11-O-2',3'-di-O-acetyl-α-l-rhamnopyranoside and 4-epi-aubergenone 11-O-2',4'-di-O-acetyl-α-l-rhamnopyranoside. Three of the previously known compounds, (2E,6E,10R)-10-hydroxy-3,7,11-trimethyldodeca-2,6,11-trienoaic acid methyl ester, (2E,6E,10R)-10,11-dihydroxy-3,7,11-trimethyldodeca-2,6-dienoic acid and (2E,6S)-3-methyl-6-hydroxy-6-[(2R,5R)-5-(2-hydroxypropan-2-yl)-2-methyltetrahydrofuran-2-yl]-hex-2-enoaic acid methyl ester have now been found in a plant species. Ultra performance liquid chromatography-quadruple time-of-flight mass spectroscopy (UPLC-QTOF/MS) analysis of the chemical constituents of C. latifolia showed that several were predominant in the sub-fractions of a C. latifolia stem bark extract.

Aroma helps to preserve information processing resources of the brain in healthy subjects but not in temporal lobe epilepsy.

PURPOSE: Inhalation of ylang-ylang aroma has been shown to reduce the auditory P300, an event-related potential thought to reflect higher-order processing. Because olfactory function is sometimes disturbed in temporal lobe epilepsy (TLE), the objective of the present study was to determine whether the effect of ylang-ylang aroma on the auditory P300 was impaired in patients with TLE. METHOD: Fourteen subjects with TLE and 14 healthy controls participated in this study. Electroencephalograms were recorded during an auditory oddball task, and ylang-ylang aroma or odorless air was delivered through a mask. RESULTS: We found that the ylang-ylang aroma prolonged the latencies of P300 in both groups. The ylang-ylang aroma significantly reduced the P300 amplitudes of healthy subjects as described previously. However, in TLE patients, the P300 was unaffected by the aroma. CONCLUSION: The current results show that exposure to the ylang-ylang aroma reduced information processing resources in healthy subjects but had limited effects in patients with TLE. We suggest that impaired higher-order olfactory processing in TLE patients may inhibit the effects of the ylang-ylang aroma on the P300.

Cananginones A­I, linear acetogenins from the stem bark of Miliusa velutina [corrected].

Nine linear C23 and C21 acetogenins, named cananginones A-I (1-9), were isolated from stem bark of Miliusa velutina [corrected] . Their structures were established by spectroscopic methods. These compounds showed cytotoxicity against three cancer cell lines (KB, MCF7 and NCI-H187) with IC50 values in the range 16.6-129.7 µM. Only 5 showed weak antimalarial activity against Plasmodium falciparum. In addition, 8 and 9 exhibited weak antifungal activity against Candida albicans.

Repellent activity of essential oils and some of their individual constituents against Tribolium castaneum herbst.

A tool for integrated pest management is the use of essential oils (EOs) and plant extracts. In this study, EOs from Tagetes lucida , Lepechinia betonicifolia , Lippia alba , Cananga odorata , and Rosmarinus officinalis , species grown in Colombia, were analyzed by gas chromatography-mass spectrometry. These oils as well as several of their constituents were tested for repellent activity against Tribolium castaneum , using the area preference method. The main components (>10%) found in EOs were methylchavicol, limonene/α-pinene, carvone/limonene, benzyl acetate/linalool/benzyl benzoate, and α-pinene, for T. lucida, L. betonicifolia, L. alba, C. odorata, and R. officinalis, respectively. All EOs were repellent, followed a dose-response relationship, and had bioactivity similar to or better than that of commercial compound IR3535. EOs from C. odorata and L. alba were the most active. Compounds from EOs, such benzyl benzoate, ß-myrcene, and carvone, showed good repellent properties. In short, EOs from plants cultivated in Colombia are sources of repellents against T. castaneum.

[Effects of aromatherapy on changes in the autonomic nervous system, aortic pulse wave velocity and aortic augmentation index in patients with essential hypertension].

PURPOSE: To investigate the effectiveness of aromatherapy on blood pressure, heart rate variability, aortic pulse wave velocity and the aortic augmentation index of essential hypertensive patients. METHODS: Using a coin toss, 22 participants were assigned to the experimental group and 20 to the control. The experimental group was given a blend of oils of lemon (Citrus limonum), lavender (Lavandula angustifolia), and ylang ylang (Cananga odorata) which were prepared in the ratio of 2:2:1, respectively. The control group was given an artificial lemon fragrance of Limonene (35 cc) and Citral (15 cc) mixture. The experiment, inhalation, was conducted for 3 weeks (2 min per inhalation, 2 times per day) to both groups. RESULTS: There was a noticeable difference in systolic blood pressure between the groups (p=.001), however the difference in diastolic blood pressure between the two groups was not significant. There was a notable difference in sympathetic nerve system activity of heart rate variability (p=.047). However, the differences in aortic pulse wave velocity or the aortic augmentation index were not significant. CONCLUSION: Aromatherapy is effective in lowering systolic blood pressure and sympathetic nerve system activity.

Effects of Aromatherapy on Changes in the Autonomic Nervous System, Aortic Pulse Wave Velocity and Aortic Augmentation Index in Patients with Essential Hypertension

PURPOSE: To investigate the effectiveness of aromatherapy on blood pressure, heart rate variability, aortic pulse wave velocity and the aortic augmentation index of essential hypertensive patients. METHODS: Using a coin toss, 22 participants were assigned to the experimental group and 20 to the control. The experimental group was given a blend of oils of lemon (Citrus limonum), lavender (Lavandula angustifolia), and ylang ylang (Cananga odorata) which were prepared in the ratio of 2:2:1, respectively. The control group was given an artificial lemon fragrance of Limonene (35 cc) and Citral (15 cc) mixture. The experiment, inhalation, was conducted for 3 weeks (2 min per inhalation, 2 times per day) to both groups. RESULTS: There was a noticeable difference in systolic blood pressure between the groups (p=.001), however the difference in diastolic blood pressure between the two groups was not significant. There was a notable difference in sympathetic nerve system activity of heart rate variability (p=.047). However, the differences in aortic pulse wave velocity or the aortic augmentation index were not significant. CONCLUSION: Aromatherapy is effective in lowering systolic blood pressure and sympathetic nerve system activity.

Modulation of olfactory information processing in the antennal lobe of Manduca sexta by serotonin.

The nervous system copes with variability in the external and internal environment by using neuromodulators to adjust the efficacy of neural circuits. The role of serotonin (5HT) as a neuromodulator of olfactory information processing in the antennal lobe (AL) of Manduca sexta was examined using multichannel extracellular electrodes to record the responses of ensembles of AL neurons to olfactory stimuli. In one experiment, the effects of 5HT on the concentration-response functions for two essential plant oils across a range of stimulus intensities were examined. In a second experiment, the effect of 5HT on the ability of ensembles to discriminate odorants from different chemical classes was examined. Bath application of 5HT enhanced AL unit responses by increasing response duration and firing rate, which in turn increased the amount of spike time cross-correlation and -covariance between pairs of units. 5HT had the greatest effect on overall ensemble activation at higher odorant concentrations, resulting in an increase in the gain of the dose-response function of individual units. Additionally, response thresholds shifted to lower odorant concentrations for some units, suggesting that 5HT increased their sensitivity. Serotonin enhanced ensemble discrimination of different concentrations of individual odorants as well as discrimination of structurally dissimilar odors at the same concentration. Given the known circadian fluctuations of 5HT in the AL of this species, these findings support the hypothesis that 5HT periodically enhances sensitivity and responsiveness in the AL of Manduca to maximize efficiency when the requirement for olfactory acuity is the greatest.

Safety assessment of Ylang-Ylang (Cananga spp.) as a food ingredient.

Ylang-Ylang oil is used in the food industry as a flavor ingredient. It is a complex chemical mixture in the form of an essential oil extracted by water or water-and-steam distillation from the fresh flowers of Cananga odorata Hook. f. & Thomson. Ylang-Ylang oil has been reported to cause dermal sensitization reactions in animals and humans, but it is unclear what constituent(s) within the essential oil comprise the offending agent(s) and whether some Ylang-Ylang oils that have had certain constituent(s) removed are any less prone to cause such allergic reactions. There is no indication in the literature that food exposure to Ylang-Ylang oil has caused allergic reactions. One subchronic inhalation toxicity study, involving Ylang-Ylang oil as part of a larger fragrance raw materials mixture, gave no indication of causing adverse effects, but the relevance to risk assessment of oral food flavoring use exposures is likely minimal. No further toxicity data for Ylang-Ylang oil have been reported. Notwithstanding the foregoing, Ylang-Ylang oil has a long history of fragrance and food flavoring use, with no indication that its estimated consumption from food flavoring use (0.0001 mg/kg/day) has led to any adverse human health effects. These data indicate that at the current level of intake as a food ingredient, Ylang-Ylang oil does not pose a health risk to humans.