Skip to main content
NCBI home page
Molecules logoLink to Molecules
. 2023 Oct 10;28(20):7014. doi: 10.3390/molecules28207014

Chemical Composition, Market Survey, and Safety Assessment of Blue Lotus (Nymphaea caerulea Savigny) Extracts

Noura S Dosoky 1, Sara A Shah 2, Joseph T Dawson 2, Sushant Sharma Banjara 1, Ambika Poudel 1, Cécile Bascoul 2, Prabodh Satyal 1,*
Editors: Lucia Panzella, Zhi Na
PMCID: PMC10609367  PMID: 37894493

Abstract

Blue lotus, also known as Nymphaea caerulea (Nymphaeaceae), is a water lily found globally in lakes and rivers. With its long history of use in Egyptian culture, blue lotus has been associated with spiritual rituals and health benefits. Nowadays, blue lotus is still consumed as a tea or tincture to induce relaxation and heightened spiritual awareness. In this study, six authentic N. caerulea extracts from trusted sources and eleven commercial products were analyzed using gas chromatography−mass spectrometry (GC-MS). Authentic blue lotus extracts were produced in industrial settings. Overall, the extracts were a mixture of aliphatic hydrocarbons, aromatic alcohols, fatty acids, phenyl derivatives, diterpenoids, phytosterols, and stigmastanes. Apomorphine and nuciferine, which are responsible for psychoactive effects of the blue lotus flower, were virtually absent from the authentic blue lotus extract. Although blue lotus has a long history of use, the safety data on the plant and its extracts is limited; however, together with the analytical data, the available information does not indicate major safety concerns for the topical application of authentic blue lotus flower concrete or absolute when diluted as a fragrance ingredient.

Keywords: blue lotus, water lily, Nymphaea caerulea, aquatic plants

1. Introduction

Blue lotus, water lily, and Egyptian lotus are common names of Nymphaea caerulea Savigny (Nymphaeaceae). It is an aquatic perennial plant that grows globally along rivers and lakes at altitudes ranging from sea level to 2700 m asl [1]. N. caerulea is a recognized synonym of N. nouchali var. caerulea (Sav.) Verdc. [2]. The plant is characterized by its floating round or oval flat leaves (up to 40 cm in diameter) that arise from a perennial spongy rhizome submerged in the mud of pond habitats. The leaves stay afloat because of their top surface, which is covered with a smooth, waxy cuticle and slightly rolled-up margins [1]. The flowers of N. caerulea are its characteristic feature. Blooming in September until February, the flowers are presented in a star-like pattern when fully open, measuring about 15–20 cm in diameter. The flowers close in the afternoon after opening in mid-morning and can be found in a range of colors, such as blue, white, and pink, with blue being the most common.

Blue lotus has long-standing historical and cultural significance. Drawings and paintings of the blue lotus flower were reported on Egyptian papyri and tombs from the 14th century B.C., indicating its use in shamanistic rituals and health-related practices [3,4]. Nymphaea species were revered as the epitome of holiness and beauty in ancient Greece and Rome. Based on its regional distribution, the plant is classified into tropical and hardy water lilies [5]. Blue lotus is a popular ornamental plant used in landscaping and is used in water purification. The flowers, stems, and roots are used for health-related purposes [6,7]. In traditional medicine, N. caerulea is reputed to have calming and soothing effects. In Ayurvedic medicine, it is used for a variety of health-related issues [8]. The family Nymphaeaceae has been studied extensively in the field of pharmacognosy due to their ability to produce aminogenic secondary metabolites. These metabolites have been found to have a range of pharmacological activities including analgesic, anti-inflammatory, and antimicrobial properties. N. caerulea is a rich source of different secondary metabolites such as anthocyanins, anthraquinones, fatty acids, flavonoids, leuecoanthocyanins, phenols, coumarins, tannins, and triterpenoids [9,10,11,12]. The leaf and flower extracts are excellent sources of phytoconstituents when compared with the rhizome and root [11]. The flavonoid composition has been reported to determine the flower color. Cultivars with amaranth flowers contain delphinidin 3-galactoside, blue flowers contain delphinidin 3-O-galactoside, red flowers contain derivatives of delphinidin and cyanidin, while white and yellow flowers lack anthocyanins [13]. Because of its high content of polyphenols, blue lotus is recognized as a natural source of antioxidants that can delay food spoilage, slow down the aging process, support healthy cell growth, and promote cardiovascular health [12,14]. Kaempferol, quercetin, quercitin, chalcone, and gallic acid have been identified from the plant [12,15,16]. According to Agnihotri et al. [7], the ethyl acetate fraction of N. caerulea flowers and nine isolated compounds can be used as a natural solution for oxidative stress. The blue lotus flower has been chiefly utilized in relation to relaxation and sleep in modern times. At high doses, some users might experience hallucinations and euphoria [4]. In a case series, five active-duty patients presented to the emergency department with altered mental status following the use of blue lotus products, four after vaping and one after making an infused beverage [4]. Although the case series did not include confirmatory analytical data, the effects were attributed to two compounds, apomorphine and nuciferine, which were previously found to be present in these types of products [17]. Interestingly, these two compounds have been studied and used as therapeutic agents using oral doses in the range of 15–150 mg/day [18,19]. Little is known about industrially produced blue lotus extracts. Currently, various blue lotus products are accessible online including dried leaves, teas, plant resins, flower extracts, oils, concentrated alkaloids, and electronic cigarette liquids [17]. These products are labeled as natural, but mostly have not been approved by the Federal Drug Administration (FDA) for human consumption. Therefore, we aimed to investigate the chemical composition of industrially produced floral extracts of N. caerulea and compare the composition to the commercial products available in the U.S. market. Moreover, we assessed the safety of N. caerulea extracts.

2. Results and Discussion

2.1. Authentic Blue Lotus Extracts

Authentic blue lotus extracts were produced in industrial settings. The average yields were 0.18% and 0.09% for the concrete and absolute, respectively. The aroma of N. caerulea extracts can be described as floral, fruity, sweet, fig-like, leathery, and slightly herbaceous. The volatile fraction ranged from 38.7–65.1% of the total extract. Table 1 summarizes the chemical compositions of authentic N. caerulea extracts. Overall, the extracts were a mixture of aliphatic hydrocarbons, aromatic alcohols, fatty acids, phenyl derivatives, diterpenoids, phytosterols, and stigmastanes. The chemical makeup of the flower is quite complex. Fossen and coworkers identified seven flavonoids and five anthocyanins, including three acylated anthocyanins from the methanolic extract of the flower [20,21]. Agnihotri and colleagues isolated and identified several compounds from the flower ethanolic extract with a considerable antioxidant activity [7]. In a study using headspace solid-phase microextraction (HS-SPME) followed by GC-MS analysis, the vapor phase of a trapped N. caerulea live flower contained benzyl acetate (10.4%), pentadecane (15.5%), 6,9-heptadecadiene (40.1%), and 8-heptadecene (15.3%) as the main components [22]. When the stamens, pistils, and petals were compared, it was reported that the majority of volatiles were produced by the stamens, with alkanes, alkenes, aldehydes, and ketones being the most abundant [23].

Table 1.

Chemical composition of authentic blue lotus extracts.

RIexp a RT Compound Name Concrete (Area %) Absolute (Area %)
1 2 3 Avg SD 1 2 3 Avg SD
1038 13.253 Benzyl alcohol 7.94 8.20 6.61 7.58 0.85 12.09 9.74 9.53 10.46 1.42
1166 19.126 Benzyl acetate 0.21 0.10 0.17 0.16 0.05 0.28 0.20 0.13 0.20 0.07
1284 24.686 p-Anisyl alcohol 0.59 0.41 0.15 0.38 0.23 1.15 0.79 0.80 0.91 0.20
1435 31.304 (E)-α-Bergamotene 0.28 0.28 0.36 0.30 0.05 0.27 0.37 0.38 0.34 0.06
1454 32.119 (E)-β-Farnesene 1.43 1.27 1.48 1.39 0.11 1.44 1.59 1.87 1.63 0.22
1500 34.135 Pentadecane 4.24 4.16 5.53 4.64 0.77 3.41 4.40 5.01 4.27 0.81
1504 34.275 (E,E)-α-Farnesene 0.73 0.63 0.78 0.71 0.08 0.73 0.86 1.04 0.88 0.16
1525 35.084 β-Sesquiphellandrene 0.64 0.63 0.83 0.70 0.11 0.59 0.80 0.82 0.74 0.13
1670 40.752 6,9-Heptadecadiene 11.10 10.89 13.85 11.95 1.65 9.80 11.96 12.75 11.50 1.53
1674 40.901 (Z,Z,Z)-1,8,11,14-Heptadecatetraene 0.48 0.46 0.61 0.52 0.08 0.45 0.55 0.62 0.54 0.08
1678 41.058 Tetradecanol 5.51 5.46 7.01 5.99 0.88 4.56 5.37 6.04 5.32 0.74
1697 41.823 2-Pentadecanone 0.21 0.15 0.21 0.19 0.03 0.31 0.31 0.31 0.31 0.00
1700 41.932 Heptadecane 0.50 0.87 1.15 0.84 0.33 0.71 0.78 0.84 0.78 0.07
1837 46.789 Neophytadiene 0.52 0.42 0.48 0.47 0.05 0.23 0.25 0.26 0.25 0.01
1900 48.999 Nonadecane 4.78 4.45 4.72 4.65 0.18 4.51 3.10 2.90 3.50 0.88
1908 49.234 (E,E)-7,11,15-Trimethyl-3-methylene-hexadeca-1,6,10,14-tetraene 0.34 0.26 0.28 0.29 0.04 0.38 0.32 0.33 0.34 0.03
1959 50.907 Palmitic acid 2.22 1.81 1.91 1.98 0.22 3.11 2.57 2.28 2.65 0.42
1993 52.041 Ethyl Palmitate 0.44 0.69 0.52 0.55 0.13 1.31 1.16 1.33 1.27 0.09
2008 52.512 Hexadecyl acetate 0.87 0.94 1.27 1.03 0.21 0.83 1.39 1.03 1.08 0.28
2101 55.438 Heneicosane 4.52 4.47 5.55 4.85 0.61 1.88 2.20 2.57 2.22 0.35
2104 55.544 2-Nonadecanone 1.50 1.63 1.78 1.64 0.14 0.17 0.10 0.20 0.16 0.05
2108 55.649 Phytol 1.92 1.46 1.23 1.53 0.35 2.74 2.09 2.21 2.35 0.35
2129 56.277 Linoleic acid 3.26 2.61 2.57 2.81 0.38 4.77 3.50 3.52 3.93 0.73
2135 56.454 Oleic Acid 4.29 4.26 4.10 4.22 0.10 6.12 4.42 4.38 4.97 1.00
2159 57.189 Ethyl Stearate 1.16 1.42 1.01 1.20 0.21 2.75 1.09 1.45 1.76 0.87
2165 57.363 Ethyl linoleate 0.85 1.15 0.85 0.95 0.17 2.34 2.14 1.51 2.00 0.43
2180 57.832 Tetrapenol 3.12 3.12 2.69 2.98 0.25 4.42 3.30 3.32 3.68 0.64
2287 60.929 (E,E,E)-2,6,10,14-Hexadecatetraen-1-ol 3,7,11,15-tetramethyl acetate 0.49 0.47 0.41 0.46 0.04 0.56 0.48 0.54 0.53 0.04
2301 61.34 n-Tricosane 7.84 8.06 8.19 8.03 0.18 1.39 2.27 2.62 2.09 0.63
2400 64.105 n-Tetracosane 0.23 0.24 0.22 0.23 0.01
2501 66.78 n-Pentacosane 3.04 3.19 2.91 3.05 0.14 0.23 0.56 0.58 0.46 0.19
2577 68.726 Benzyl hexadecanoate 0.81 0.73 0.81 0.78 0.04 1.06 1.49 1.59 1.38 0.28
2600 69.344 n-Hexacosane 0.12 0.14 0.19 0.15 0.04
2683 71.394 n- Heptacosane 1.54 1.69 1.51 1.58 0.10 0.51 0.71 0.48 0.57 0.12
2749 73.056 Benzyl linoleate 1.36 1.23 1.22 1.27 0.08 1.73 2.27 2.00 0.38
2757 73.256 Benzyl linolenate 0.83 0.71 0.82 0.79 0.06 1.17 1.58 1.73 1.49 0.29
2779 73.833 Benzyl stearate 0.20 0.13 0.18 0.17 0.04 0.22 0.24 0.28 0.25 0.03
2790 74.114 Octacosane 0.12 0.09 0.14 0.12 0.03
2803 74.447 (E)-Squalene 3.67 4.09 3.78 3.85 0.22 2.30 2.23 2.16 2.23 0.07
2880 76.512 3-((8Z,11Z)-Heptadeca-8,11-dien-1-yl)-5-methoxyphenol 2.53 2.97 1.09 2.20 0.98 2.79 2.48 2.60 2.62 0.16
3023 80.457 β-Sitosterol acetate 0.25 0.35 0.14 0.25 0.10 0.20 0.13 0.17 0.05
3055 81.361 Vitamin E 0.22 0.21 0.21 0.21 0.00 0.26 1.02 1.12 0.80 0.47
3123 83.327 Methyl cholesterol 1.047 1.11 0.99 1.05 0.06 1.18 1.29 1.28 1.25 0.06
3142 83.885 Stigmasterol 0.97 1.12 1.11 1.07 0.08 1.20 1.28 1.28 1.25 0.05
3184 85.156 γ-Sitosterol 2.83 2.13 2.14 2.37 0.40 3.34 3.90 3.87 3.70 0.32
Total identified % 91.73 90.85 93.76 89.47 87.28 87.52
Open in a new tab

RIexp = experimental retention index, RT = retention time, a retention index determined with respect to a homologous series of n-alkanes on a ZB-5ms column.

2.2. Alkaloids

Alkaloids are mainly found in lotus leaves [24,25]. Nuciferine is insoluble in water and soluble in acidic aqueous solutions and organic solvents such as chloroform, ethanol, and methanol [24]. While acid-ethanol extraction was traditionally used to extract nuciferine, ultrasound-assisted acid-ethanol extraction seemed to improve the results [24]. In the current study, blue lotus concretes and absolutes were free of apomorphine and contained negligible traces of nuciferine (10–72 ppb). This finding indicates that the extraction conditions to produce concrete and absolute using hexane followed by ethanol were not optimal for their extraction.

2.3. Commercial Products

Eleven commercially available blue lotus products were purchased online. Interestingly, the aroma varied greatly between the commercial products and none of these products resembled the original aroma. More than 150 compounds were identified from the obtained products (Table 2). All of the tested samples contained synthetic fragrance components. Unlike the authentic samples, terpenes were among the identified compounds. C1, C2, and C7 showed signs of a Citrus oil, Lavandula oil, and Geranium oil addition, respectively. It was hard to recognize which oil was added to C8-C11. Furthermore, there is evidence that herculyn D was used as a fragrance fixative in C4, C8, and C9, as indicated by the presence of abietic acid derivatives.

Table 2.

Chemical composition of commercial (C) samples.

RI Compounds C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 C11
778 Isobutyl acetate 0.12
931 α-Pinene 0.06 0.09 0.04 0.04 tr 0.07 0.07
948 Camphene 0.01 0.03 0.01
962 Benzaldehyde 0.02 0.17 0.01
967 Glycerin 58.33
971 Sabinene 0.06 0.01 0.02 0.03
978 β-Pinene 0.37 0.18 0.14 0.03 0.36 0.38
983 3-Octanone 0.05
988 Myrcene 0.05 0.05 0.04 0.05
991 2,6-Dimethyl-2-heptanol 0.05 0.01 0.01 0.04 0.05
997 Diethyl diglycol 0.24 0.84 0.78 0.42 0.33
1010 Hexyl acetate 0.04
1013 1,4-Cineole 0.06 0.04 0.04
1019 p-Methyl anisole 0.15
1023 p-Cymene 0.09 6.92 3.00 2.17
1024 Dipropylene glycol 1 0.69 2.61
1026 Dipropylene glycol 2 6.03 0.90 6.04
1027 Limonene 3.08 0.80 3.48 0.03 0.29 0.04 0.06 3.75 4.21
1031 1,8-Cineole 0.05 0.21 0.07 0.28 0.28 0.09
1033 (Z)-β-Ocimene 0.17 0.37
1034 Benzyl alcohol 0.01
1043 Dipropylene glycol 3 0.64 1.91 4.66
1044 (E)-β-Ocimene 0.01
1045 (E)-β Ocimene 0.01
1046 Dipropylene glycol 4 4.67 6.04 1.11
1049 Dipropylene glycol 5 1.06 0.73
1056 Dipropylene glycol 6 4.66
1057 γ-Terpinene 0.22 0.11 0.23 0.38 0.55
1069 (Z)-Linalool oxide (furanoid) 0.29 0.01
1069 Dihydro myrcenol 3.22 3.40 3.62 3.42
1080 Dipropylene glycol 7 0.66
1085 Terpinolene 0.05 0.02 0.02 0.10
1086 (E)-Linalool oxide (furanoid) 0.27 0.01
1090 3-(Z)-Hexenyl methyl carbonate 0.04 0.03 0.04
1094 Methyl benzoate 0.31
1098 Linalool 6.85 12.38 12.33 4.73 2.22 2.64 2.64 12.75 11.69
1114 Phenyl ethyl alcohol 0.31 1.87 7.01 7.74 4.11 3.79
1118 3-Octanol acetate 0.37
1127 allo-Ocimene 0.01
1127 (E)-Rose oxide 0.02
1134 Dihydro linalool 0.07 0.08 0.04 0.02
1149 Camphor 2.47 0.02 0.29 0.29
1151 Citronellal 0.04
1157 Menthone 0.30
1161 Benzyl acetate 0.55 1.23 2.26 2.07 1.16 1.23
1164 Borneol
1166 Isomenthone 0.15
1170 Isononyl acetate 0.19 0.19 0.18
1174 2-Phenyl ethyl formate 0.07
1178 (Z)-Pinocamphone 0.02
1181 Terpinen-4-ol 0.18 0.07 0.37 0.12 0.12
1192 Methyl salicylate 0.31
1194 Dihydro citronellol 0.01
1195 α-Terpineol 0.08 0.09 0.16 0.01 0.15 0.15 0.08 0.08
1198 Florosa 0.44 0.32 0.77 0.48 0.41
1215 (E)-Rozanol 1.52 1.29 3.93 2.20 2.03
1225 Citronellol 0.69 1.39 3.12 8.55 11.77 4.68 4.18
1225 Nerol 0.81 1.71
1226 Sabinene hydrate acetate 0.02
1239 Neral 0.02
1247 Linalyl acetate 7.78 2.92 5.14 1.70 3.53 2.43 2.36 5.19 5.10
1248 Geraniol 0.40 1.72 3.23 2.15 1.37
1267 Dihydro linalyl acetate 0.10 0.05 0.03 0.07 0.07
1267 Geranial 0.03 0.03
1269 1-Isoprpyl-3-tert-butylbenzene 0.04 0.04
1272 Citronellyl formate 0.79
1275 Neryl formate 0.04
1279 Lavandulyl acetate 0.14
1286 Hydroxy citronellal 7.43 0.19 2.01 3.59 4.07 2.39 2.38 0.18 0.20
1288 (Z)-2-tert-butyl cyclohexanol acetate 1.01
1292 Indole 0.07 0.09 0.09 0.08 0.09
1297 Geranyl formate 0.16
1330 2-Propanol, 1,1’-[(1-methyl-1,2-ethanediyl)bis 2.51
1345 α-Terpinyl acetate 0.06 0.03 0.03 0.03
1347 Citronellyl acetate 0.22
1354 Neryl acetate 0.16 0.21 0.05 0.20 0.07 0.06 0.02
1374 Geranyl acetate 0.29 0.52 0.34 0.11 0.12 0.21 0.16 0.15 0.34 0.36
1377 α-Copaene 0.2
1380 α-α-α-2-Trimethyl benzeneacetic 0.02 0.03
1388 (E)-α-Damascone 0.17 0.03 0.02 0.03
1395 Vanillin 0.63
1408 β-Maaliene 0.17
1410 Calone 0.15 0.27 0.27 0.32
1421 β-Caryophyllene 1.10 0.08 0.42 0.01 0.11 0.11
1423 Allyl cyclohexyl propanoate 0.06 0.05 0.07
1438 Coumarin 0.22
1442 Dihydro curcumene 0.23 1.47
1443 (E)-Cinnamyl acetate 0.29
1446 (E)-Isoeugenol 0.21
1447 1-(4-tert-Butylphenyl)propan-2-one 0.16 0.05 0.24 0.28 0.10 0.10
1449 (E)-β-farnesene 0.25
1458 α-humulene 0.09
1460 Cyclamanal 0.76 1.86 1.73 0.94 0.94
1465 γ-Decalactone 0.55 0.93
1472 Isomethyl-α-(Z)-ionone 1.15
1478 (E)-β-Ionone 0.29 0.27 0.31
1480 Sandal mysore core 1.81
1501 Butylated hydroxy toluene 0.22 0.21 0.26
1502 α-Bulnesene 0.08
1513 6-Methyl α-ionone 0.34
1527 (Z)-Nerolidol 0.08
1529 Lilial 5.65 13.68 9.34 16.93 15.43 9.69 10.13 13.79 14.04
1538 (E)-α-Bisabolene 0.07
1549 Raspberry ketone 0.19
1553 Geranyl butyrate 0.01
1560 (E)-Nerolidol 0.15 0.31 0.29 0.28 0.30
1565 Tropional 0.88
1569 Methyl-β-ionone 0.13
1570 γ-Undecalactone 0.18 0.19 0.19
1585 Caryophyllene oxide 0.28
1625 γ-Eudesmol 0.07
1626 Cedryl methyl ether 0.25 0.25 0.31
1649 (Z)-Methyl dihydro jasmonate 2.29 10.26 21.79 6.75 12.73 12.02 7.34 7.30 21.37 20.66
1656 (7-α-Isopropenyl-4,5-dimethyl octahydroinden-4-yl)methanol 2.54
1659 Lyral 1.71 9.70 6.67 9.29 9.38 5.46 5.41
1669 3-(Z)-Hexenyl salicylate 0.47 5.83
1669 Iso-(E)-γ-Super 2.17 2.20 0.58
1675 (E)-Methyl dihydro jasmonate 0.27 1.41 2.34 0.80 2.16 0.05 0.86 0.84 2.49 2.65
1678 Salicylic acid hexyl ester 1.94 9.74
1693 Iso-(E)-α-Super 0.44 0.53
1696 2-(Z)-6-(Z)-Farnesol 0.35
1729 2-Methoxy ethoxy cyclododecane 0.86 1.73 1.74 0.97 0.98
1746 2-Hexyl-(E)-cinnamaldehyde 11.84 2.56 4.34 8.29 0.47 4.86 4.85 2.62 2.95
1756 Cosmone isomer II 0.04 0.07 0.04
1768 Ambroxide 0.26 0.21 0.18 0.18
1768 Benzyl benzoate 0.56
1769 Methyl cedryl ketone 2.41
1770 2-Hexyl-(Z)-cinnamaldehyde 0.16 0.45 0.34 0.32 0.11 0.16
1802 (Z, E)-Farnesyl acetate 0.08
1827 (E,E)-Farnesyl acetate
1844 Acetyl methyl tetralin 10.15 5.03 4.72 5.96
1870 Galaxolide 1 0.24 0.16 0.15 0.21
1871 Benzyl salicylate 0.39
1875 Galaxolide 2 0.18 0.14 0.13 0.19
1892 Galaxolide 3 0.31 0.2 0.18 0.25
1903 Galaxolide 4 0.31 0.19 0.18 0.23
2011 Ethylene brassylate 1.10 1.89 1.83 2.02
2057 Ricenalidic acid lactone 8.40
2098 Benzyl cinnamate 0.03
2234 Methyl Pimarate 0.09 0.13 0.11
2249 Methyl pimar-8(14)-en-18-oate 1.72 2.02 6.08
2290 Methyl pimaran-18-oate 2.24 2.89 2.96
2300 Methyl-8-piramen-18-oate isomer I 2.64
2311 trans-3-Phenylpropyl cinnamate 0.54
2315 Methyl 13-abieten-18-oate 2.98 3.03 2.99
2324 Methyl-8-piramen-18-oate isomer II 23.82 5.84
2330 Methyl 7-isopimaren-18-oate 0.29 0.20 0.20
2338 Methyl dehydroabietate 6.47 6.17
2360 Methyl abiet-7-en-18-oate 0.56 0.58 0.62
2387 Methyl abietate 1.82 1.87 2.07
2420 Cinnamyl cinnamate 0.95
2435 Methyl neoabietate 0.18 0.23 0.25
2695 Verdantiol isomer II 0.07 0.05 0.05 0.09
2927 Tricaprylin Triglyceride 1.68
3084 β-Sitosterol acetate 7.54
3116 Caprin Biscaprylin Triglyceride 3.19
3301 Caprylin Biscaprin Triglyceride 1.82
3325 β-Amyrone 0.17
3376 Lupenone 2.85
3486 Tricaprin Triglyceride 0.40
Total 66.81 70.84 97.76 97.06 74.27 91.82 91.99 77.66 68.39 97.83 97.59
Unidentified 33.2 28.8 2.19 2.75 25.69 8.18 7.88 22.24 31.59 2.13 2.38
Open in a new tab

2.4. Safety Assessment

N. caerulea is not GRAS classified, and no published safety data were found on the plant or the extracts as a whole. However, the plant has a long history of use. The safety data for all constituents present at 1% and above are presented in Table 3. The three main constituents detected in the concrete were 6,9-heptadecadiene (11.95 ± 1.65%), n-tricosane (8.03 ± 0.18%), and benzyl alcohol (7.58 ± 0.85%). The three main constituents identified in the absolute were 6,9-heptadecadiene (11.05 ± 1.53%), benzyl alcohol (10.46 ± 1.42%), and tetradecanol (5.32 ± 0.74%). Tsai et al. [22] studied the volatile compounds of N. caerulea (water lily) flowers using GC-MS and reported four main compounds: 6,9-heptadecadiene (40.1%), pentadecane (15.5%), 8-heptadecene (15.3%), and benzyl acetate (10.4%). This is different from our GC-FID results, except that the main compound, 6,9-heptadecadiene, was identified as the most abundant compound, although at a substantially lesser concentration in the flower extracts.

Table 3.

Toxicological reference values from CIR, RIFM, and ECHA for compounds ≥1% identified in authentic blue lotus extracts.

Compound Name CAS Number Average Concentration (%) CIR RIFM ECHA Ref.
Max Use Concentration Genotoxicity Phototoxicity NOAEL (mg/kg/day) NESIL (ug/cm2) LD50 Repeated Dose ±
Concrete Absolute Repeated Dose Developmental & Reproductive Oral (mg/kg) Dermal (mg/kg) Inhalation (mg/L) Oral NOAEL (mg/kg/d) Inhalation NOAEC (mg/m3)
6,9-Heptadecadiene - 11.95% 11.50% - - - - - - - - - - - N.A.
n-Tricosane 638-67-5 8.03% 2.09% - NIG - - - - - - - - - [26]
Benzyl alcohol 100-51-6 7.58% 10.46% ≤10% NG NPT/A 100 † 500 5900 1620 >2000 >4.2 400 * 1072 ‡ [27,28,29]
Tetradecanol 112-72-1 5.99% 5.32% <5% NIG - - - - >2000 8000 >1.5 3548 ‡ 1000 † [30,31,32]
Heneicosane 629-94-7 4.85% 2.22% - NIG - - - - - - - - - [33]
Nonadecane 629-92-5 4.65% 3.50% - NIG - - - - - - - - - [34]
Pentadecane 629-62-9 4.64% 4.27% - NIG - - - - >5000 # >2000 # >6.0 # ≥500 #,† ≥6000 #,† [35,36]
Oleic acid 112-80-1 4.22% 4.97% ≤20.9% NIG - - - - - - - - - [37,38]
(E)-Squalene 111-02-4 3.85% 2.23% ≤10% - - - - - >5000 - 13,800 >600 ‡ - [39,40]
n-Pentacosane 629-99-2 3.05% 0.46% - - - - - - - - - - - N.A.
Tetrapenol 24034-73-9 2.98% 3.68% - - - - - - - - - - - N.A.
Linoleic acid 60-33-3 2.81% 3.93% ≤21.8% NIG - - - - - - - - - [37,41]
γ-Sitosterol 83-47-6 2.37% 3.70% ≤10% - - - - - - - - - - [42]
3-((8Z,11Z)-Heptadeca-8,11-dien-1-yl)-5-methoxyphenol - 2.20% 2.62% - - - - - - - - - - - N.A.
Palmitic acid 57-10-3 1.98% 2.65% ≤21% NG NPT/A - - - >5000 >2000 # >0.15 # 1000–5000 #,† - [37,43,44]
2-Nonadecanone 629-66-3 1.64% 0.16% - - - - - - - - - - - N.A.
Heptacosane 593-49-7 1.58% 0.57% - - - - - - - - - - - N.A.
Phytol 150-86-7 1.53% 2.35% - NG # NPT/A 333 #,† - 2700 # >10,000 >4000 - 100 - [45]
(E)-β-Farnesene 18794-84-8 1.39% 1.63% - NG # NPT/A # - - 3700 # >5000 >5000 >2.06 ≥1000 † - [46,47]
Benzyl linoleate 47557-83-5 1.27% 2.00% - - - - - - - - - - - N.A.
Ethyl Stearate 111-61-5 1.20% 1.76% - NIG - - - - - - - - - [48]
Stigmasterol 83-48-7 1.07% 1.25% ≤10% - - - - - - - - - - [42]
Methyl cholesterol 4651-51-8 1.05% 1.25% - - - - - - - - - - - N.A.
Hexadecyl acetate 629-70-9 1.03% 1.08% ≤12.6% - - - - - >40 mL/kg >5000 - - - [49,50]
Ethyl linoleate 544-35-4 0.95% 2.00% - NIG - - - - >2000 # >2000 # - - - [51,52]
Benzyl linolenate 77509-02-5 0.79% 1.49% - - - - - - - - - - - N.A.
Benzyl hexadecanoate 41755-60-6 0.78% 1.38% - - - - - - - - - - - N.A.
Ethyl Palmitate 628-97-7 0.55% 1.27% - NIG - - - - >2000 # >2000 # - 1000 # - [53,54]
Open in a new tab

CIR = Cosmetic Ingredient Review, RIFM = Research Institute for Fragrance Materials, Inc., ECHA = European Chemical Agency, CAS = Chemical Abstracts Service, NOAEL = No Observed Adverse Effect Level, LD50 = Lethal Dose 50, NESIL = No Expected Sensitization Induction Level, Ref. = References, N.A. = Not Available, NG = Not Genotoxic, NIG = No Indication of Genotoxicity, NPT/A = not phototoxic/photoallergenic, # = read-across, † = sub-acute study, ‡ = sub-chronic study, * = chronic study, - = not available, ± = No ECHA Dermal Repeated Dose NOAEL was available for the compounds listed.

As these are absolute and concrete materials, they may contain an unknown and significant portion of nonvolatile compounds. As such, quantification through GC-FID may not be accurate and compounds present in the absolute and concrete may not be detected and therefore not evaluated as part of this assessment. Since the safety of unidentified compounds cannot be guaranteed, this presents an unknown safety risk.

Of the 28 compounds investigated (making up 85.43% of the concrete and 80.52% of the absolute), safety information was not found for 10 compounds (making up 27.29% of the concrete and 25.11% of the absolute) including 6.9-heptadecadiene, n-pentacosane, tetrapenol, 3-((8Z,11Z)-heptadeca-8,11-dien-1-yl)-5-methoxyphenol, 2-nonadecanone, heptacosane, benzyl linoleate, methyl cholesterol, benzyl linolenate, and benzyl hexadecanoate. We were able to gather safety information for the remaining 18 compounds (making up 58.69% of the concrete and 56.68% of the absolute) including n-tricosane, benzyl alcohol, tetradecanol, heneicasane, nonadecane, pentadecane, oleic acid, E-squalene, linoleic acid, γ-sitosterol, palmitic acid, phytol, E-β-farnesene, ethyl stearate, stigmasterol, hexadecyl acetate, ethyl linoleate, and ethyl palmitate. According to the data available from CIR, all of the assessed compounds, except two, were found to be at concentrations considered safe in accordance with current usage practices, as indicated in Table 3. Benzyl alcohol and tetradecanol are slightly above the maximum concentrations; however, when blue lotus extracts are used as part of a formulation, the concentration of these compounds will be reduced. For compounds with data on genotoxicity, there was no indication of genotoxicity risks. Very limited information was available on acute or chronic toxicity and phototoxicity or photoallergenicity. However, the data are not indicative of major safety risks.

3. Materials and Methods

3.1. Plant Material and Extraction

Authentic blue lotus absolutes and concrete samples were prepared using industrial extraction methods. Cultivated blue lotus plants were collected from Hainan and Guangdong, China (Figure 1). The plant prefers high temperatures, humidity, and sunlight. Fresh flowers were shredded with a flower-cutting machine. About 1000 Kg of the shredded material was extracted twice with hexane (1: 2, w/v) in an enamel extraction tank with continuous stirring for 12 h. After soaking, the hexane was discharged and filtered with 120 mesh stainless steel mesh. The collected extracts were allowed to settle for 4 h, then filtered. The solvent was then recovered by heating with jacketed steam. The extract was concentrated under atmospheric pressure with a spherical concentrator until all of the hexane was evaporated. The concentrated extract is called concrete. To prepare the absolute, the blue lotus concrete was dewaxed with 95% ethanol (1:5, w/v) in a stainless-steel barrel, stirred carefully, and placed in the freezer for more than 12 h. The resulting extract was filtered and the floral was separated. The filtrate was concentrated under low pressure in a spherical concentrator until all of the solvent was evaporated. Samples of both the concrete and absolute were tested for solvent residue. Eleven commercially available blue lotus oil products were purchased online (Amazon and Etsy). The product labels of these samples contained the information listed in Table 4.

Figure 1.

Figure 1

Open in a new tab

Fresh Nymphaea caerulea flowers harvested from the field.

Table 4.

Available information on commercial blue lotus products.

Sample Oil Name Description Botanical Name
C1 Egyptian Sahasrana 100%
Blue Lotus Oil Euphoria		 100% Blue Lotus Oil Euphoria NA
C2 Blue Lotus Oil Therapeutic grade NA
C3 Lotus Blue Oil Pure essential oil, steam distilled Nymphaea caerulea
C4 Blue Lotus Extra Strength Euphoric mood + dream tonic and liquid tincture, glycerin, alcohol, filtered water Nymphaea c. 200:1
C5 Blue Lotus Absolute 100% pure, natural, and undiluted EO Nymphaea caerulea
C6 Blue Lotus EO 100% natural ingredients NA
C7 Blue Lotus Oil 100% pure EO NA
C8 Blue Lotus EO NA NA
C9 Blue Lotus absolute Oil Organic • 100% PURE • Absolute NA
C10 Blue Lotus essential Oil NA NA
C11 Blue Lotus essential Oil NA NA
Open in a new tab

NA = not applicable.

3.2. Gas Chromatography−Mass Spectrometry (GC–MS) Analysis

Authentic and commercial samples were analyzed using a gas chromatograph coupled to a mass spectrometer QP2010 Ultra (Shimadzu Scientific Instruments, Columbia, MD, USA) with electron impact (EI) mode with 70 eV, as previously described [55]. The components were identified by comparing the mass spectral fragmentation patterns (over 80% similarity match) and retention indices (RI) based on a series of homologous C8-C20 n-alkanes with those reported in databases (NIST database, and our in-house library) using the Lab Solutions GCMS post-run analysis software version 4.45 (Shimadzu Scientific Instruments, Columbia, MD, USA).

3.3. Gas Chromatography–Flame Ionization Detection (GC–FID) Analysis

Analysis of E. purpurea essential oil was carried out using a Shimadzu GC 2010 equipped with a flame ionization detector (Shimadzu Scientific Instruments, Columbia, MD, USA), as previously described [56], with a ZB-5 capillary column (Phenomenex, Torrance, CA, USA).

3.4. Detection and Quantification of Nuciferine and Apomorphine

LCMS-grade methanol, LCMS-grade water, and HPLC-formic acid were purchased from Sigma-Aldrich (St. Louis, MO, USA). Nuciferine and apomorphine were purchased from Cayman Chemical (Ann Arbor, MI, USA). Stock solutions of each standard at a concentration of 10 ppm were prepared by diluting the powder in methanol. Nuciferine and apomorphine were quantified using a NEXERA UPLC system (Shimadzu Corp., Kyoto, Japan) equipped with a mass spectrometer (Triple quadrupole, LCMS8060, Shimadzu, Kyoto, Japan) as previously described [18,25]. The detection was completed in multiple reaction monitoring mode (MRM) (Table 5). Samples were run in triplicate with external standards in between and the injection volume was 1 μL. The acquired chromatographic results were processed in LabSolutions Insight software version 3.2 (Shimadzu). For each compound, calibration curves (0.005–0.1 ppm) were created by linking the peak area and the concentration.

Table 5.

Multiple reaction monitoring mode parameters (MRM).

Name CAS # Precursor
(m/z)		 Product 1
(m/z)		 Product 2
(m/z)		 Product 3
(m/z)		 RT (min) r2
Apomorphine 58117-94-5 309.05 268.20 237.15 191.1 1.47 0.9995
Nuciferine 475-83-2 296.00 265.10 250.10 235.15 2.87 0.9995
Open in a new tab

r2, equation and coefficient of determination.

3.5. Safety Assessment

The safety assessment of blue lotus extracts was conducted by applying standard toxicology and risk assessment methods using the analytical results (Table 2), published safety data on the raw material as a whole plant, plant extract, and the constituents identified in the extracts. The information considered for the safety assessment included the historical use of the plant and extracts, safety and toxicology data on the plant and extracts, and safety and toxicology data of all constituents present at 1% and above. This safety assessment is based solely on the available literature. The documents collected and reviewed included scientific articles from books and scientific journals on botany and the safety of natural complex substances, fragrances, and flavors. Studies using different degrees of evidence from in vitro methods, pre-clinical models, clinical trials, and case reports were used as evidence of the safety or toxicity of the raw material as a whole. The sources of information used to evaluate the safety of individual constituents included the RIFM (Research Institute for Fragrance Materials, Inc.) Fragrance and Flavor Database, CIR (Cosmetic Ingredient Review) assessments, and ECHA (European Chemical Agency) REACH (Registration, Evaluation, Authorization, and Restriction of Chemicals) registrations. The main endpoints of interest included genotoxicity, developmental and reproductive toxicity, skin irritation and sensitization, photoirritation and photoallergenicity, as well as acute and chronic toxicity for oral, dermal, and inhalation routes of exposure.

4. Conclusions

In this study, we analyzed the chemical composition of six authentic blue lotus extracts and eleven commercial products. The extracts were a mixture of aliphatic hydrocarbons, aromatic alcohols, fatty acids, phenyl derivatives, diterpenoids, phytosterols, and stigmastanes. The main constituents in the authentic concrete were 6,9-heptadecadiene (11.95 ± 1.65%), n-tricosane (8.03 ± 0.18%), and benzyl alcohol (7.58 ± 0.85%), while the main constituents of the authentic absolute were 6,9-heptadecadiene (11.05 ± 1.53%), benzyl alcohol (10.46 ± 1.42%), and tetradecanol (5.32 ± 0.74%). Surprisingly, none of the investigated commercial products resembled authentic extracts in aroma or composition. Nuciferine and apomorphine were found in traces or were absent, respectively, from the studied authentic extracts, suggesting that the risk of psychoactive effects associated with these compounds would be virtually absent for a small dose of either of these extracts applied topically. Other than the psychoactive effects associated with nuciferine and apomorphine, the available safety data from the literature are limited and do not show major safety concerns for the authentic extracts. Surprisingly, none of the investigated commercial products resembled authentic extracts in aroma or composition.

Acknowledgments

We would like to thank Tim Valentiner, Simon Zhou, and Emilie Bell for kindly providing the authentic samples and photos. Special thanks to Megan Bean for purchasing the commercial blue lotus products.

Author Contributions

Conceptualization, N.S.D., C.B. and P.S.; methodology, N.S.D., S.S.B., A.P. and C.B.; validation, N.S.D.; formal analysis, N.S.D., P.S. and A.P.; safety investigation, S.A.S., J.T.D. and C.B.; data curation, N.S.D., P.S. and A.P.; writing—original draft preparation, N.S.D. and S.A.S.; writing—review and editing, N.S.D., S.A.S., J.T.D., P.S., C.B. and A.P.; supervision, P.S. and C.B. All authors have read and agreed to the published version of the manuscript.

Data Availability Statement

Data are contained within the article.

Conflicts of Interest

The authors declare no conflict of interest.

Funding Statement

This research received no external funding.

Footnotes

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

References

  • 1.South African National Biodiversity Institute Nymphaea nouchali Var. Caeruleae. [(accessed on 24 April 2023)]. Available online: https://pza.sanbi.org/nymphaea-nouchali-var-caerulea.
  • 2.The World Flora Online Nymphaea caerulea Savigny. [(accessed on 25 April 2023)]. Available online: http://www.worldfloraonline.org/taxon/wfo-0000382331.
  • 3.Emboden W. The Sacred Journey in Dynastic Egypt: Shamanistic Trance in the Context of the Narcotic Water Lily and the Mandrake. J. Psychoact. Drugs. 1989;21:61–75. doi: 10.1080/02791072.1989.10472144. [DOI] [PubMed] [Google Scholar]
  • 4.Schimpf M., Ulmer T., Hiller H., Barbuto A.F. Toxicity from Blue Lotus (Nymphaea caerulea) After Ingestion or Inhalation: A Case Series. Mil. Med. 2021;188:e2689–e2692. doi: 10.1093/milmed/usab328. [DOI] [PubMed] [Google Scholar]
  • 5.Huang G.Z., Deng H.Q., Li Z.X., Li G. Water Lily. Forestry Publishing House; Beijing, China: 2009. [Google Scholar]
  • 6.Daboor S.M., Haroon A.M. In Vitro: Antimicrobial Potential and Phytochemical Screening of Some Egyptian Aquatic Plants. Egypt. J. Aquat. Res. 2012;38:233–239. doi: 10.1016/j.ejar.2013.01.005. [DOI] [Google Scholar]
  • 7.Agnihotri V.K., ElSohly H.N., Khan S.I., Smillie T.J., Khan I.A., Walker L.A. Antioxidant Constituents of Nymphaea caerulea Flowers. Phytochemistry. 2008;69:2061–2066. doi: 10.1016/j.phytochem.2008.04.009. [DOI] [PubMed] [Google Scholar]
  • 8.Brown D. Encyclopedia of Herbs and Their Uses. DK Publishing; London, UK: 1995. [Google Scholar]
  • 9.Gibbs R. Chemotaxonomy of Flowering Plants. Volume 1 McGill-Queen’s University Press; London, UK: 1974. [Google Scholar]
  • 10.Makkar H.P.S., Blümmel M., Borowy N.K., Becker K. Gravimetric Determination of Tannins and Their Correlations with Chemical and Protein Precipitation Methods. J. Sci. Food Agric. 1993;61:161–165. doi: 10.1002/jsfa.2740610205. [DOI] [Google Scholar]
  • 11.Prasad K.S., Savithramma N. Screening of Phytochemical Constituents of Nymphaea caerulea Savigny. An Aquatic Plant Resource for Drug Development. Am. J. Adv. Drug Deliv. 2016;4:45–54. [Google Scholar]
  • 12.Zhao J., Xu F., Ji T.F., Gu Z.Y., Li C.Y. Advances in the Study on Chemical Constituents and Biological Activities in Nymphaea Genus. Nat. Prod. Res. Dev. 2014;26:142–147. [Google Scholar]
  • 13.Zhu M., Zheng X., Shu Q., Li H., Zhong P., Zhang H., Xu Y., Wang L., Wang L. Relationship between the Composition of Flavonoids and Flower Colors Variation in Tropical Water Lily (Nymphaea) Cultivars. PLoS ONE. 2012;7:e34335. doi: 10.1371/journal.pone.0034335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Kerio L.C., Wachira F.N., Wanyoko J.K., Rotich M.K. Total Polyphenols, Catechin Profiles and Antioxidant Activity of Tea Products from Purple Leaf Coloured Tea Cultivars. Food Chem. 2013;136:1405–1413. doi: 10.1016/j.foodchem.2012.09.066. [DOI] [PubMed] [Google Scholar]
  • 15.Nafisi S., Hashemi M., Rajabi M., Tajmir-Riahi H.A. DNA Adducts with Antioxidant Flavonoids: Morin, Apigenin, and Naringin. DNA Cell Biol. 2008;27:433–442. doi: 10.1089/dna.2008.0735. [DOI] [PubMed] [Google Scholar]
  • 16.Yagura T., Motomiya T., Ito M., Honda G., Iida A., Kiuchi F., Tokuda H., Nishino H. Anticarcinogenic Compounds in the Uzbek Medicinal Plant, Helichrysum maracandicum. J. Nat. Med. 2008;62:174–178. doi: 10.1007/s11418-007-0223-y. [DOI] [PubMed] [Google Scholar]
  • 17.Poklis J.L., Mulder H.A., Halquist M.S., Wolf C.E., Poklis A., Peace M.R. The Blue Lotus Flower (Nymphea caerulea) Resin Used in a New Type of Electronic Cigarette, the Re-Buildable Dripping Atomizer. J. Psychoact. Drugs. 2017;49:175–181. doi: 10.1080/02791072.2017.1290304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Chen Y.-L., Shi L., Agbo F., Yong S.H., Tan P.-S., Ngounou Wetie A.G. LC-MS/MS Simultaneous Quantification of Apomorphine and Its Major Metabolites in Human Plasma: Application to Clinical Comparative Bioavailability Evaluation for the Apomorphine Sublingual Film and a Subcutaneous Product. J. Pharm. Biomed. Anal. 2020;190:113493. doi: 10.1016/j.jpba.2020.113493. [DOI] [PubMed] [Google Scholar]
  • 19.Apomorphine Dosage. [(accessed on 5 August 2023)]. Available online: https://www.drugs.com/apomorphine.html#dosage.
  • 20.Fossen T., Larsen P., Kiremire B., Andersen O. Flavonoids from Blue Flowers of Nymphaèa caerulea. Phytochemistry. 1999;51:1133–1137. doi: 10.1016/S0031-9422(99)00049-7. [DOI] [Google Scholar]
  • 21.Fossen T., Andersen Ø.M. Delphinidin 3′-Galloylgalactosides from Blue Flowers of Nymphaéa caerulea. Phytochemistry. 1999;50:1185–1188. doi: 10.1016/S0031-9422(98)00649-9. [DOI] [Google Scholar]
  • 22.Tsai F.-J., Liu H.-J., Lee M.-Y., Lin C.-C. Determination of Volatile Components from Live Water Lily Flowers by an Orthogonal-Array-Design-Assisted Trapping Cell. Appl. Sci. 2019;9:1269. doi: 10.3390/app9071269. [DOI] [Google Scholar]
  • 23.Yuan R., Li S., Zheng X., Wu Q., Zhang H., Wang L. Determination of Volatiles in Water Lily Flowers Using Gas Chromatography–Mass Spectrometry. Anal. Lett. 2014;47:1541–1551. doi: 10.1080/00032719.2013.878840. [DOI] [Google Scholar]
  • 24.Du X., Pan X., Guo L., Zhu Y. Extractions and Purification of Nuciferine from Lotus Leaves. Adv. J. Food Sci. Technol. 2016;10:153–159. doi: 10.19026/ajfst.10.1817. [DOI] [Google Scholar]
  • 25.Gu S., Zhu G., Wang Y., Li Q., Wu X., Zhang J., Liu G., Li X. A Sensitive Liquid Chromatography–Tandem Mass Spectrometry Method for Pharmacokinetics and Tissue Distribution of Nuciferine in Rats. J. Chromatogr. B. 2014;961:20–28. doi: 10.1016/j.jchromb.2014.04.038. [DOI] [PubMed] [Google Scholar]
  • 26.RIFM Fragrance and Flavor Database, Version 2.0.7. Research Institute for Fragrance Materials. n.d. Tricosane (CAS RN: 638-67-5) [(accessed on 18 June 2023)]. Available online: https://rifmdatabase.rifm.org.
  • 27.REACH Database. European Chemical Agency. n.d. Benzyl Alcohol (CAS RN: 100-51-6) [(accessed on 4 June 2023)]. Available online: https://echa.europa.eu/en/home.
  • 28.Api A.M., Belsito D., Bhatia S., Bruze M., Calow P., Dagli M.L., Dekant W., Fryer A.D., Kromidas L., La Cava S., et al. RIFM Fragrance Ingredient Safety Assessment, Benzyl Alcohol, CAS Registry Number 100-51-6. Food Chem. Toxicol. 2015;84:S1–S14. doi: 10.1016/j.fct.2015.09.005. [DOI] [PubMed] [Google Scholar]
  • 29.Johnson W., Bergfeld W.F., Belsito D.V., Hill R.A., Klaassen C.D., Liebler D.C., Marks J.G., Shank R.C., Slaga T.J., Snyder P.W., et al. Safety Assessment of Benzyl Alcohol, Benzoic Acid and Its Salts, and Benzyl Benzoate. Int. J. Toxicol. 2017;36:5S–30S. doi: 10.1177/1091581817728996. [DOI] [PubMed] [Google Scholar]
  • 30.REACH Database. European Chemical Agency. n.d. Tetradecanol (CAS RN 112-72-1) [(accessed on 14 June 2023)]. Available online: https://echa.europa.eu/en/home.
  • 31.RIFM Fragrance and Flavor Database, Version 2.0.7. Research Institute for Fragrance Materials. n.d. 1-Tetradecanol (CAS RN: 112-72-1) [(accessed on 19 June 2023)]. Available online: https://rifmdatabase.rifm.org.
  • 32.Cosmetic Ingredient Review Final Report on the Safety Assessment of Cetearyl Alcohol, Cetyl Alcohol, Isostearyl Alcohol, Myristyl Alcohol, and Behenyl Alcohol. J. Am. Coll. Toxicol. 1988;7:359–413. doi: 10.3109/10915818809023137. [DOI] [Google Scholar]
  • 33.RIFM Fragrance and Flavor Database, Version 2.0.7. Research Institute for Fragrance Materials. n.d. Heneicosane (CAS RN: 629-94-7) [(accessed on 19 June 2023)]. Available online: https://rifmdatabase.rifm.org.
  • 34.RIFM Fragrance and Flavor Database, Version 2.0.7. Research Institute for Fragrance Materials. n.d. Nonadecane (CAS RN: 629-92-5) [(accessed on 19 June 2023)]. Available online: https://rifmdatabase.rifm.org.
  • 35.REACH Database. European Chemical Agency. n.d. Pentadecane (CAS RN: 629-62-9) [(accessed on 4 June 2023)]. Available online: https://echa.europa.eu/en/home.
  • 36.RIFM Fragrance and Flavor Database, Version 2.0.7. Research Institute for Fragrance Materials. n.d. Pentadecane (CAS RN: 629-62-9) [(accessed on 19 June 2023)]. Available online: https://rifmdatabase.rifm.org.
  • 37.Cosmetic Ingredient Review Safety Assessment of Fatty Acids & Fatty Acid Salts as Used in Cosmetics. Tentative Report for Public Comment. 2019. [(accessed on 19 June 2023)]. Available online: https://www.cir-safety.org/sites/default/files/facids122018tent.pdf.
  • 38.RIFM Fragrance and Flavor Database, Version 2.0.7. Research Institute for Fragrance Materials. n.d. Oleic Acid (CAS RN: 112-80-1) [(accessed on 19 June 2023)]. Available online: https://rifmdatabase.rifm.org.
  • 39.REACH Database. European Chemical Agency. n.d. 2,6,10,15,19,23-Hexamethyltetracosa-2,6,10,14,18,22-Hexaene (CAS RN: 111-02-4) [(accessed on 4 June 2023)]. Available online: https://echa.europa.eu/en/home.
  • 40.Cosmetic Ingredient Review Safety Assessment of Squalane and Squalene as Used in Cosmetics. Re-Review for Panel Review. 2019. [(accessed on 19 June 2023)]. Available online: https://www.cir-safety.org/sites/default/files/Squalene%20and%20Squalane.pdf.
  • 41.RIFM Fragrance and Flavor Database, Version 2.0.7. Research Institute for Fragrance Materials. n.d. Linoleic Acid (CAS RN: 60-33-3) [(accessed on 19 June 2023)]. Available online: https://rifmdatabase.rifm.org.
  • 42.Cosmetic Ingredient Review Safety Assessment of Phytosterols as Used in Cosmetics. Draft Report for Panel Review. 2013. [(accessed on 19 June 2023)]. Available online: https://www.cir-safety.org/sites/default/files/phytosterols_0.pdf.
  • 43.REACH Database. European Chemical Agency. n.d. Palmitic Acid (CAS RN: 57-10-3) [(accessed on 19 June 2023)]. Available online: https://echa.europa.eu/en/home.
  • 44.RIFM Fragrance and Flavor Database, Version 2.0.7. Research Institute for Fragrance Materials. n.d. Palmitic Acid (CAS RN: 57-10-3) [(accessed on 19 June 2023)]. Available online: https://rifmdatabase.rifm.org.
  • 45.RIFM Fragrance and Flavor Database, Version 2.0.7. Research Institute for Fragrance Materials. n.d. Phytol (CAS RN: 150-86-7) [(accessed on 19 June 2023)]. Available online: https://rifmdatabase.rifm.org.
  • 46.REACH Database. European Chemical Agency. n.d. (E)-7,11-Dimethyl-3-Methylenedodeca-1,6,10-Triene (CAS RN: 18794-84-8) [(accessed on 19 June 2023)]. Available online: https://echa.europa.eu/en/home.
  • 47.RIFM Fragrance and Flavor Database, Version 2.0.7. Research Institute for Fragrance Materials. n.d. β-Farnesene (CAS RN: 18794-84-8) [(accessed on 19 June 2023)]. Available online: https://rifmdatabase.rifm.org.
  • 48.RIFM Fragrance and Flavor Database, Version 2.0.7. Research Institute for Fragrance Materials. n.d. Ethyl Octadecanoate (CAS RN: 111-61-5) [(accessed on 19 June 2023)]. Available online: https://rifmdatabase.rifm.org.
  • 49.REACH Database. European Chemical Agency. n.d. Hexadecyl Acetate (CAS RN: 629-70-9) [(accessed on 19 June 2023)]. Available online: https://echa.europa.eu/en/home.
  • 50.Heldreth B., Bergfeld W.F., Belsito D.V., Hill R.A., Klaassen C.D., Liebler D., Marks J.G., Shank R.C., Slaga T.J., Snyder P.W., et al. Final Report of the Cosmetic Ingredient Review Expert Panel on the Safety Assessment of Methyl Acetate. Int. J. Toxicol. 2012;31:112S–136S. doi: 10.1177/1091581812444142. [DOI] [PubMed] [Google Scholar]
  • 51.REACH Database. European Chemical Agency. n.d. Ethyl Linoleate (CAS RN: 544-35-4) [(accessed on 5 June 2023)]. Available online: https://echa.europa.eu/en/home.
  • 52.RIFM Fragrance and Flavor Database, Version 2.0.7. Research Institute for Fragrance Materials. n.d. Ethyl Linoleate (CAS RN: 544-35-4) [(accessed on 19 June 2023)]. Available online: https://rifmdatabase.rifm.org.
  • 53.RIFM Fragrance and Flavor Database, Version 2.0.7. Research Institute for Fragrance Materials. n.d. Ethyl Palmitate (CAS RN: 628-97-7) [(accessed on 19 June 2023)]. Available online: https://rifmdatabase.rifm.org.
  • 54.REACH Database. European Chemical Agency. n.d. Ethyl Palmitate (CAS RN: 628-97-7) [(accessed on 5 June 2023)]. Available online: https://echa.europa.eu/en/home.
  • 55.Dosoky N.S., Poudel A., Satyal P. Authentication and Market Survey of Sweet Birch (Betula lenta L.) Essential Oil. Plants. 2022;11:2132. doi: 10.3390/plants11162132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Decarlo A., Johnson S., Ouédraogo A., Dosoky N.S., Setzer W.N. Chemical Composition of the Oleogum Resin Essential Oils of Boswellia dalzielii from Burkina Faso. Plants. 2019;8:223. doi: 10.3390/plants8070223. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

Data are contained within the article.

Articles from Molecules are provided here courtesy of Multidisciplinary Digital Publishing Institute (MDPI)

RESOURCES