Generic placeholder image

Mini-Reviews in Organic Chemistry

Editor-in-Chief

ISSN (Print): 1570-193X
ISSN (Online): 1875-6298

Review Article

Occurrence, Isolation, Pharmacological Potential, Metabolism, and Toxicity of Myristicin: A Naturally Occurring Alkoxy-Substituted Allylbenzene

Author(s): Vishaldeep Kaur, Sonia Kaushal*, Heena and Divya Utreja

Volume 21, Issue 4, 2024

Published on: 27 April, 2023

Page: [477 - 493] Pages: 17

DOI: 10.2174/1570193X20666230314105024

Price: $65

Abstract

Background: Natural products are secondary metabolites obtained from plants, animals, and microorganisms with diverse chemical structures resulting in diverse biological functions and drug-like properties.

Objective: This review article summarizes in detail the occurrence, detection, isolation, various pharmacological properties, metabolism, and toxicity of a natural compound i.e., 5-Allyl-1-methoxy- 2,3-methylenedioxybenzene commonly known as Myristicin.

Methods: A relevant literature search was made using the keywords essential oil, mace, myristicin, nutmeg, and pharmacological activities from different databases such as PubMed, Sci Finder, Science Direct, and Google Scholar. The literature search results presented articles from 1963 to 2022. Thereafter, the articles were carefully screened and selected for review.

Results: Myristicin, an alkoxy-substituted allylbenzene is present in major to minor amounts in the essential oils obtained from different plant parts and exhibits various pharmacological properties such as antimicrobial, antioxidant, antiproliferative, anti-inflammatory, insecticidal, and hepatoprotective. It forms 10 metabolites by reduction, demethylation, hydroxylation, ring formation, ring-opening, and conjugate formation. In the liver, myristicin has been metabolized by Cytochrome P450 complex enzymes to generate active metabolite (1ˈ hyroxymyristicin) responsible for cytotoxic, genotoxic and apoptotic effects (150 μM). But, myristicin at 600 μM does not produce enough 1ʼ-hydroxymyristicin to give the final toxicant.

Conclusion: Myristicin poses no major risk to human health through the consumption of herbs and spices due to its presence in low amounts. It has great potential to be used in the traditional system of medicine. We hope that this review will provide complete knowledge about myristicin on a single platform.

Keywords: Myristicin, isolation, pharmacological potential, essential oil, toxicity, metabolism.

« Previous
Graphical Abstract
[1]
Calixto, J.B. The role of natural products in modern drug discovery. An. Acad. Bras. Cienc., 2019, 91(Suppl. 3), e20190105.
[http://dx.doi.org/10.1590/0001-3765201920190105] [PMID: 31166478]
[2]
Alves, R.R.N.; Rosa, I.M.L. Biodiversity, traditional medicine and public health: Where do they meet? J. Ethnobiol. Ethnomed., 2007, 3(1), 14.
[http://dx.doi.org/10.1186/1746-4269-3-14] [PMID: 17376227]
[3]
Brixius, D. A hard nut to crack: Nutmeg cultivation and the application of natural history between the Maluku islands and Isle de France (1750s–1780s). Br. J. Hist. Sci., 2018, 51(4), 585-606.
[http://dx.doi.org/10.1017/S0007087418000754] [PMID: 30566063]
[4]
Marabini, L.; Neglia, L.; Monguzzi, E.; Galli, C.L.; Marinovich, M. Assessment of toxicity of myristicin and 1ʼ hydroxymyristicin in hepG2 cell line. J. Pharmacol. Toxicol., 2017, 12(4), 170-179.
[http://dx.doi.org/10.3923/jpt.2017.170.179]
[5]
Barceloux, D.G. Nutmeg (Myristica fragrans Houtt.). In: Medical Toxicology of Natural Substances: Foods, fungi, medicinal herbs, plants, and venomous animals; Barceloux, D.G., Ed.; John Wiley and Sons, Inc.: USA, 2008, pp. 67-70.
[http://dx.doi.org/10.1002/9780470330319.ch9]
[6]
Seneme, E.F.; dos Santos, D.C.; Silva, E.M.R.; Franco, Y.E.M.; Longato, G.B. Pharmacological and therapeutic potential of myristicin: A literature review. Molecules, 2021, 26(19), 5914.
[http://dx.doi.org/10.3390/molecules26195914] [PMID: 34641457]
[7]
Götz, M.E.; Sachse, B.; Schäfer, B.; Eisenreich, A. Myristicin and Elemicin: Potentially toxic alkenylbenzenes in food. Foods, 2022, 11(13), 1988.
[http://dx.doi.org/10.3390/foods11131988] [PMID: 35804802]
[8]
Alajlouni, A.M. Mode of action based risk assessment of the botanical food-borne alkenylbenzenes apiol and myristicin., PhD Thesis, Wageningen University: Netherlands., 2017.
[9]
Qin, W.; Huang, S.; Li, C.; Chen, S.; Peng, Z. Biological activity of the essential oil from the leaves of Piper sarmentosum Roxb. (Piperaceae) and its chemical constituents on Brontispa longissima (Gestro) (Coleoptera: Hispidae). Pestic. Biochem. Physiol., 2010, 96(3), 132-139.
[http://dx.doi.org/10.1016/j.pestbp.2009.10.006]
[10]
Santos, A.L.M.; Araújo, F.A.M.; Matisui, É.S.; Costa, L.A.M.A.; Macêdo, A.J.; Lucena, J.M.V.M. Antimicrobial and antibiofilm properties of essential oils from Piper marginatum Jacq. Res. Society Develop., 2021, 10(11), e514101119967.
[http://dx.doi.org/10.33448/rsd-v10i11.19967]
[11]
Alizadeh, A.; Abdollahzadeh, H. Essential oil constituents and antimicrobial activity of Pycnocycla bashagardiana Mozaff. from Iran. Nat. Prod. Res., 2017, 31(17), 2081-2084.
[http://dx.doi.org/10.1080/14786419.2016.1274890] [PMID: 28092983]
[12]
Jabrane, A.; Ben Jannet, H.; Mastouri, M.; Mighri, Z.; Casanova, J. Chemical composition and in vitro evaluation of antioxidant and antibacterial activities of the root oil of Ridolfia segetum (L.) Moris from Tunisia. Nat. Prod. Res., 2010, 24(6), 491-499.
[http://dx.doi.org/10.1080/14786410802228520] [PMID: 20397101]
[13]
Zhao, Y.; Yang, Y.H.; Ye, M.; Wang, K.B.; Fan, L.M.; Su, F.W. Chemical composition and antifungal activity of essential oil from Origanum vulgare against Botrytis cinerea. Food Chem., 2021, 365, 130506.
[http://dx.doi.org/10.1016/j.foodchem.2021.130506] [PMID: 34237567]
[14]
Elsadek, M.F.; Almoajel, A.; Farahat, M.F. Ameliorative effects of ribes rubrum oil against gastric ulcers caused by indomethacin in experimental models. Saudi J. Biol. Sci., 2022, 29(1), 30-34.
[http://dx.doi.org/10.1016/j.sjbs.2021.10.029] [PMID: 35002392]
[15]
Benarfa, A.; Gourine, N.; Harrat, M.; Yousfi, M. Composition and biovariability of Deverra scoparia volatile oil and its potential use as a source of bioactive phthalide components. Biochem. Syst. Ecol., 2020, 90, 104019.
[http://dx.doi.org/10.1016/j.bse.2020.104019]
[16]
Ghimire, B.K.; Yoo, J.H.; Yu, C.Y.; Chung, I.M. GC–MS analysis of volatile compounds of Perilla frutescens Britton var. Japonica accessions: Morphological and seasonal variability. Asian Pac. J. Trop. Med., 2017, 10(7), 643-651.
[http://dx.doi.org/10.1016/j.apjtm.2017.07.004] [PMID: 28870340]
[17]
Brazao, M.A.B.; Brazao, F.V.; Maia, J.G.S.; Monteiro, M.C. Antibacterial activity of the Piper aduncum oil and dill apiole, its main constituent, against multidrug-resistant strains. B. Latinoam. Caribe. Pl., 2014, 13(6), 517-526.
[18]
Cook, W.B.; Howard, A.S. The essential oil of Illicium anisatum Linn. Can. J. Chem., 1966, 44(21), 2461-2464.
[http://dx.doi.org/10.1139/v66-371]
[19]
Stahl, E. Variation of myristicin content in cultivated parsnip roots (Pastinaca sativa subspecies sativa var hortensis. J. Agric. Food Chem., 1981, 29(4), 890-892.
[http://dx.doi.org/10.1021/jf00106a055] [PMID: 7276395]
[20]
Kubeczka, K.H.; Stahl, E. [On the essential oils from the Apiaceae (Umbelliferae). I. The oil of roots from Pastinaca sativa. Planta Med., 1975, 27(3), 235-241.
[http://dx.doi.org/10.1055/s-0028-1097792] [PMID: 1161888]
[21]
Abourashed, E.A.; El-Alfy, A.T. Chemical diversity and pharmacological significance of the secondary metabolites of nutmeg (Myristica fragrans Houtt.). Phytochem. Rev., 2016, 15(6), 1035-1056.
[http://dx.doi.org/10.1007/s11101-016-9469-x] [PMID: 28082856]
[22]
Ansory, H.M.; Putri, P.K.K.; Hidayah, N.A.; Nilawati, A. The analysis of nutmeg mace essential oil compound using GC-MS and antibacterial activity test toward Eschericia coli and Staphylococcus aureus. Majalah Farmaseutik, 2020, 16(1), 1-8.
[23]
Shafiq, M.I.; Ahmed, M.; Rasul, A.; Samra, Z.Q.; Qadir, M.A.; Mazhar, S.; Ali, A. Chemical composition of the essential oils of] ] nutmeg and mace by GC-FID/MS indigenous to Pakistan and evaluation of their biological activities. Lat. Am. J. Pharm., 2016, 35(10), 2176-2184.
[24]
Has, A.T.C.; Islam, M.R.; Baburin, I.; Hering, S.; Osman, H.; Mohamad, H.; Abdullah, J.M. The inhibitory activity of nutmeg essential oil on GABAA α1β2γ2s receptors. Biomed. Res., 2014, 25(4), 543-550.
[25]
Jose, H.; Arya, K.R.; Sindhu, T.J.; Syamjith, P.; Vinod, K.R.; Sandhya, S. A descriptive review on Myristica fragrans Houtt. Hygeia. J. D. Med, 2016, 8(1), 35-43.
[26]
Sipahelut, S.G.; Patty, J.A.; Patty, Z.; Kastanja, A.Y.; Lekahen, V.N.J. The antibacterial and antifungal activity of essential oil derived from the flesh of nutmeg fruit. Eurasia. J. Biosci, 2019, 13, 93-98.
[27]
Suwarda, R.; Suneth, R.F. Potential and opportunities of nutmeg pericarp as functional foods, The First International conference on assessment and development of agricultural innovation. E3S Web of Conferences, Bogor City (virtual), Indonesia 2021, p. 04007.
[28]
Nurdjanah, N. Nutmeg Processing Technology; Agricultural Research and Development Agency, Center for Agricultural Postharvest Research and Development: Bogor, 2007.
[29]
Ashokkumar, K.; Vellaikumar, S.; Muthusamy, M.; Dhanya, M.K.; Aiswarya, S. Compositional variation in the leaf, mace, kernel, and seed essential oil of nutmeg (Myristica fragrans Houtt.) from the Western Ghats, India. Nat. Prod. Res., 2022, 36(1), 432-435.
[http://dx.doi.org/10.1080/14786419.2020.1771713] [PMID: 32515616]
[30]
Rameshkumar, K.B.; Nandu, T.G.; Anu Aravind, A.P.; Mathew, S.P.; Shiburaj, S. Chemical composition and FtsZ GTPase inhibiting activity of the essential oil of Piper sarmentosum from Andaman Islands, India. J. Essent. Oil Res., 2017, 29(5), 430-435.
[http://dx.doi.org/10.1080/10412905.2017.1303405]
[31]
Marín, I.; Sayas-Barberá, E.; Viuda-Martos, M.; Navarro, C.; Sendra, E. Chemical composition, antioxidant and antimicrobial activity of essential oils from organic fennel, parsley, and lavender from Spain. Foods, 2016, 5(4), 18.
[http://dx.doi.org/10.3390/foods5010018] [PMID: 28231113]
[32]
Linde, G.A.; Gazim, Z.C.; Cardoso, B.K.; Jorge, L.F.; Tešević, V.; Glamoćlija, J.; Soković, M.; Colauto, N.B. Antifungal and antibacterial activities of Petroselinum crispum essential oil. Genet. Mol. Res., 2016, 15(3)
[http://dx.doi.org/10.4238/gmr.15038538] [PMID: 27525894]
[33]
Sohilait, M.R.; Sohilait, H.J.; Kainama, H. Comparison of chemical compositions of seed and mace nutmeg (Myristica Fragrans) essential oils from Amboina Island, Moluccas, Indonesia and their antioxidant activities. Nat. Volatiles Essent. Oils, 2021, 8(6), 5537-5545.
[34]
Rahardiyan, D.; Poluakan, M.; Moko, E.M. Physico-chemical properties of nutmeg (Myristica fragranshoutt) of North Sulawesi nutmeg. Fullerene J. Chem., 2020, 5(1), 23-31.
[http://dx.doi.org/10.37033/fjc.v5i1.146]
[35]
Saputro, M.A.; Andarwulan, N.; Didah Nur Faridah, D.N. Physical characterization and essential oil properties of West Sumatra mace and nutmeg seed (Myristica fragrans Houtt) at different ages. J. Pharmacogn. Phytochem., 5(6), 371-376.
[36]
Srinivas, Y.; Mathew, S.M.; Kothakota, A.; Sagarika, N.; Pandiselvam, R. Microwave assisted fluidized bed drying of nutmeg mace for essential oil enriched extracts: An assessment of drying kinetics, process optimization and quality. Innov. Food Sci. Emerg. Technol., 2020, 66, 102541.
[http://dx.doi.org/10.1016/j.ifset.2020.102541]
[37]
Flamini, G.; Smaili, T.; Zellagui, A.; Gherraf, N.; Cioni, P.L. Effect of growth stage on essential-oil yield and composition of Daucus sahariensis. Chem. Biodivers., 2013, 10(11), 2014-2020.
[http://dx.doi.org/10.1002/cbdv.201300052] [PMID: 24243610]
[38]
Hamed, A.N.E.; Moustafa, Y.M.M.; Tawfike, A.F.; Bishr, M.M.; Abdelmohsen, U.R. GC/MS of volatile oils and horticultural characteristics of four curled and non curled Netherlands’ parsley genotypes grown under the conditions of Middle Egypt in clay soil for the first time. J. Adv. Biomed. Pharm. Sci, 2021, 4, 7-11.
[http://dx.doi.org/10.2139/ssrn.3776668]
[39]
Rattan, S.; Partap, M. Kanika; Kumar, S.; Warghat, A.R. Nutrient feeding approach enhances the vegetative growth biomass, volatile oil composition, and myristicin content in hydroponically cultivated Petroselinum crispum (Mill.). Nyman. J. Appl. Res. Med. Aromat. Plants, 2022, 26, 100359.
[http://dx.doi.org/10.1016/j.jarmap.2021.100359]
[40]
Piras, A.; Rosa, A.; Marongiu, B.; Atzeri, A.; Dessì, M.A.; Falconieri, D.; Porcedda, S. Extraction and separation of volatile and fixed oils from seeds of Myristica fragrans by supercritical CO2: chemical composition and cytotoxic activity on Caco-2 cancer cells. J. Food Sci., 2012, 77(4), C448-C453.
[http://dx.doi.org/10.1111/j.1750-3841.2012.02618.x] [PMID: 22429024]
[41]
Dong, X.; Jiang, Z.T.; Jiang, S.; Li, R. Composition comparison of essential oils extracted by hydrodistillation and microwave-assisted hydrodistillation from Petroselinum crispum grown in China. J. Essent. Oil-Bear. Plants, 2017, 20(2), 368-374.
[http://dx.doi.org/10.1080/0972060X.2017.1321504]
[42]
Lung, I.; Stan, M.; Opriş, O.; Soran, M.L. Determination of myristicin and linalool in plants exposed to microwave radiation by high-performance liquid chromatography. Anal. Lett., 2015, 48(4), 567-574.
[http://dx.doi.org/10.1080/00032719.2014.954120]
[43]
Stan, M.; Opriş, O.; Lung, I.; Soran, M.L. High-performance thin-layer chromatographic quantification of myristicin and linalool from leaf extracts of microwave-irradiated parsley, dill, and celery. J. Planar Chromatogr. Mod. TLC, 2014, 27(2), 97-101.
[http://dx.doi.org/10.1556/JPC.27.2014.2.5]
[44]
Pandey, R.; Rameshkumar, K.B.; Kumar, B. Ultra high performance liquid chromatography tandem mass spectrometry method for the simultaneous determination of multiple bioactive constituents in fruit extracts of Myristica fragrans and its marketed polyherbal formulations using a polarity switching. J. Sep. Sci., 2015, 38(8), 1277-1285.
[http://dx.doi.org/10.1002/jssc.201401297] [PMID: 25631526]
[45]
Saputri, F.A. Mutakin; Lestari, K.; Levita, J. Development and validation of a RP-HPLC method to determine dehydrodiisoeugenol, myristicin, and safrole in ethanol extract of nutmeg (Myristica fragrans Houtt). Res. J. Pharm. Biol. Chem. Sci., 2017, 8, 75-79.
[46]
Dawidowicz, A.L.; Dybowski, M.P. Determination of myristicin in commonly spices applying SPE/GC. Food Chem. Toxicol., 2012, 50(7), 2362-2367.
[http://dx.doi.org/10.1016/j.fct.2012.04.013] [PMID: 22525861]
[47]
Dawidowicz, A.L.; Dybowski, M.P. Simple and rapid determination of myristicin in human serum. Forensic Toxicol., 2013, 31(1), 119-123.
[http://dx.doi.org/10.1007/s11419-012-0151-8] [PMID: 23440626]
[48]
Nowak, J.; Woźniakiewicz, M.; Gładysz, M.; Sowa, A.; Kościelniak, P. Development of advance extraction methods for the extraction of myristicin from Myristica fragrans. Food Anal. Methods, 2016, 9(5), 1246-1253.
[http://dx.doi.org/10.1007/s12161-015-0300-x]
[49]
Guenther, E. Essential oils, 1st ed; Universitas Indonesia Press: Jakarta, Indonesia, 1987.
[50]
Nilawati, A.; Atmajaningtyas, A.T.J.; Ansory, H.M. The influence of myristicin lost in Myristica fragrans volatile oils to antimicrobial activity against B. subtilis, E. coli and S. aureus. Adv. Health Sci. Res., 2019, 26, 143-145.
[51]
Ansory, H.M.; Sari, E.N.; Nilawati, A.; Handayani, S.; Aznam, N. Sunscreen and antioxidant potential of myristicin in nutmeg essential oils (Myristica fragrans). Adv. Health Sci. Res, 2019, 26, 138-142.
[52]
Suprihatin, D.; Ketaren, S.; Ngudiwaluyo, S.; Friyadi, A. Isolation of myristicin from nutmeg oil with steam distillation method. J. Tek. Ind. Pert., 1968, 17, 23-28.
[53]
Sudradjat, S.E.; Timotius, K.H.; Mun’im, A.; Anwar, E. The isolation of myristicin from nutmeg oil by sequences distillation. J. Young Pharm., 2018, 10(1), 20-23.
[http://dx.doi.org/10.5530/jyp.2018.10.6]
[54]
Wulf, L.W.; Nagel, C.W.; Branen, A.L. High-pressure liquid chromatographic separation of the naturally occurring toxicants myristicin, related aromatic ethers and falcarinol. J. Chromatogr. A, 1978, 161(21), 271-278.
[http://dx.doi.org/10.1016/S0021-9673(01)85236-5] [PMID: 730800]
[55]
Narasimhan, B.; Dhake, A.S. Antibacterial principles from Myristica fragrans seeds. J. Med. Food, 2006, 9(3), 395-399.
[http://dx.doi.org/10.1089/jmf.2006.9.395] [PMID: 17004905]
[56]
Al-Jumaily, E.F.; Al-Amiry, M.H.A. Extraction and purification of terpenes from nutmeg (Myristica fragrans). Biotechnology, 2012, 15(3), 151-160.
[http://dx.doi.org/10.22401/JNUS.15.3.21]
[57]
Srivastava, S.; Gupta, M.M.; Prajapati, V.; Tripathi, A.K.; Kumar, S. Insecticidal activity of myristicin from Piper mullesua. Pharm. Biol., 2001, 39(3), 226-229.
[http://dx.doi.org/10.1076/phbi.39.3.226.5933]
[58]
Pineda, R.; Vizcaíno, S.; García, C.M.; Gil, J.H.; Durango, D.L. Antifungal activity of extracts, essential oil and constituents from Petroselinum crispum against Colletotrichum acutatum. Rev. Fac. Nac. Agron., 2018, 71(3), 8563-8572.
[http://dx.doi.org/10.15446/rfnam.v71n3.68284]
[59]
Lee, C.J.; Huang, C.W.; Chen, L.G.; Wang, C.C. (+)-Erythro-∆8̍-7S,8R-Dihydroxy-3,3̍,5̍-Trimethoxy-8-O-4̍-Neolignan, an anti-acne component in degreasing Myristica fragrans Houtt. Molecules, 2020, 25(19), 4563.
[http://dx.doi.org/10.3390/molecules25194563] [PMID: 33036279]
[60]
Stefano, V.; Pitonzo, R.; Schillaci, D. Antimicrobial and antiproliferative activity of Athamanta sicula L. (Apiaceae). Pharmacogn. Mag., 2011, 7(25), 31-34.
[http://dx.doi.org/10.4103/0973-1296.75893] [PMID: 21472076]
[61]
Zhang, H.; Chen, F.; Wang, X.; Yao, H.Y. Evaluation of antioxidant activity of parsley (Petroselinum crispum) essential oil and identification of its antioxidant constituents. Food Res. Int., 2006, 39(8), 833-839.
[http://dx.doi.org/10.1016/j.foodres.2006.03.007]
[62]
Yoon, K.D.; Chin, Y.W.; Kim, J. Centrifugal partition chromatography: application to natural products in 1994–2009. J. Liq. Chromatogr. Relat. Technol., 2010, 33(9-12), 1208-1254.
[http://dx.doi.org/10.1080/10826076.2010.484374]
[63]
Rattarom, R.; Sakpakdeejaroen, I.; Hansakul, P.; Itharat, A. Cytotoxic activity against small cell lung cancer cell line and chromatographic fingerprinting of six isolated compounds from the ethanolic extract of Benjakul. J. Med. Assoc. Thai., 2014, 97(8)(Suppl. 8), S70-S75.
[PMID: 25518296]
[64]
Valente, V.M.M.; Jham, G.N.; Jardim, C.M.; Dhingra, O.D.; Ghiviriga, I. Major antifungals in nutmeg essential oil against Aspergillus flavus and A. ochraceus. J. Food Res., 2014, 4(1), 51-57.
[http://dx.doi.org/10.5539/jfr.v4n1p51]
[65]
Hallström, H.; Thuvander, A. Toxicological evaluation of myristicin. Nat. Toxins, 1997, 5(5), 186-192.
[http://dx.doi.org/10.1002/19970505NT3] [PMID: 9496377]
[66]
Eisenreich, A.; Götz, M.E.; Sachse, B.; Monien, B.H.; Herrmann, K.; Schäfer, B. Alkenylbenzenes in foods: Aspects impeding the evaluation of adverse health effects. Foods, 2021, 10(9), 2139.
[http://dx.doi.org/10.3390/foods10092139] [PMID: 34574258]
[67]
Raffo, A.; D’Aloise, A.; Magrì, A.L.; Leclercq, C. Quantitation of tr-cinnamaldehyde, safrole and myristicin in cola-flavoured soft drinks to improve the assessment of their dietary exposure. Food Chem. Toxicol., 2013, 59, 626-635.
[http://dx.doi.org/10.1016/j.fct.2013.06.058] [PMID: 23845511]
[68]
Cao, X.; Xie, Q.; Zhang, S.; Xu, H.; Su, J.; Zhang, J.; Deng, C.; Song, G. Fabrication of functionalized magnetic microspheres based on monodispersed polystyrene for quantitation of allyl-benzodioxoles coupled with gas chromatography and mass spectrometry. J. Chromatogr. A, 2019, 1607, 460402.
[http://dx.doi.org/10.1016/j.chroma.2019.460402] [PMID: 31378533]
[69]
Al-Malahmeh, A.J.; Al-ajlouni, A.M.; Wesseling, S.; Vervoort, J.; Rietjens, I.M.C.M. Determination and risk assessment of naturally occurring genotoxic and carcinogenic alkenylbenzenes in basil-containing sauce of pesto. Toxicol. Rep., 2017, 4, 1-8.
[http://dx.doi.org/10.1016/j.toxrep.2016.11.002] [PMID: 28959619]
[70]
Alajlouni, A.M.; Al-Malahmeh, A.J.; Isnaeni, F.N.; Wesseling, S.; Vervoort, J.; Rietjens, I.M.C.M. Level of alkenylbenzenes in parsley and dill based teas and associated risk assessment using the margin of exposure approach. J. Agric. Food Chem., 2016, 64(45), 8640-8646.
[http://dx.doi.org/10.1021/acs.jafc.6b03650] [PMID: 27771948]
[71]
Alajlouni, A.M.; Al-Malahmeh, A.J.; Wesseling, S.; Kalli, M.; Vervoort, J.; Rietjens, I.M.C.M. Risk assessment of combined exposure to alkenylbenzenes through consumption of plant food supplements containing parsley and dill. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess., 2017, 34(12), 2201-2211.
[http://dx.doi.org/10.1080/19440049.2017.1338837] [PMID: 28580843]
[72]
Swain, S.S.; Paidesetty, S.K.; Padhy, R.N. Development of antibacterial conjugates using sulfamethoxazole with monocyclic terpenes: A systematic medicinal chemistry based computational approach. Comput. Methods Programs Biomed., 2017, 140, 185-194.
[http://dx.doi.org/10.1016/j.cmpb.2016.12.013] [PMID: 28254074]
[73]
Oo, T.; Saiboonjan, B.; Srijampa, S.; Srisrattakarn, A.; Sutthanut, K.; Tavichakorntrakool, R.; Chanawong, A.; Lulitanond, A.; Tippayawat, P. Inhibition of bacterial efflux pumps by crude extracts and essential oil from Myristica fragrans Houtt. (Nutmeg) seeds against methicillin-resistant Staphylococcus aureus. Molecules, 2021, 26(15), 4662.
[http://dx.doi.org/10.3390/molecules26154662] [PMID: 34361815]
[74]
Felicetti, T.; Cannalire, R.; Pietrella, D.; Latacz, G.; Lubelska, A.; Manfroni, G.; Barreca, M.L.; Massari, S.; Tabarrini, O.; Kieć-Kononowicz, K.; Schindler, B.D.; Kaatz, G.W.; Cecchetti, V.; Sabatini, S. 2-Phenylquinoline S. aureus NorA afflux pump inhibitors: Evaluation of the importance of methoxy group introduction. J. Med. Chem., 2018, 61(17), 7827-7848.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00791] [PMID: 30067360]
[75]
Torbati, M.; Nazemiyeh, H.; Lotfipour, F.; Asnaashari, S.; Nemati, M.; Fathiazad, F. Composition and antibacterial activity of heracleum transcaucasicum and heracleum anisactis aerial parts essential oil. Adv. Pharm. Bull., 2013, 3(2), 415-418.
[PMID: 24312869]
[76]
Piaru, S.P.; Mahmud, R.; Abdul Majid, A.M.S.; Ismail, S.; Man, C.N. Chemical composition, antioxidant and cytotoxicity activities of the essential oils of Myristica fragrans and Morinda citrifolia. J. Sci. Food Agric., 2012, 92(3), 593-597.
[http://dx.doi.org/10.1002/jsfa.4613] [PMID: 25520982]
[77]
Al-Jumaily, E.; Al-Massody, A. Cytogenetic study of the pure myristicin from nutmeg (Myristica fragrans) on Rhabdomyosarrcoma cell line (In vitro). Dav Int. J. Sci., 2012, 1, 2277-2355.
[78]
Ahmad, H.; Tijerina, M.T.; Tobola, A.S. Preferential overexpression of a class MU glutathione S-transferase subunit in mouse liver by myristicin. Biochem. Biophys. Res. Commun., 1997, 236(3), 825-828.
[http://dx.doi.org/10.1006/bbrc.1997.7053] [PMID: 9245741]
[79]
Zheng, G.; Kenney, P.M.; Zhang, J.; Lam, L.K.T. Inhibition of benzo[ a]pyrene-induced tumorigenesis by myristicin, a volatile aroma constituent of parsley leaf oil. Carcinogenesis, 1992, 13(10), 1921-1923.
[http://dx.doi.org/10.1093/carcin/13.10.1921] [PMID: 1423855]
[80]
Jeong, H.G.; Yun, C.H. Induction of rat hepatic cytochrome P450 enzymes by myristicin. Biochem. Biophys. Res. Commun., 1995, 217(3), 966-971.
[http://dx.doi.org/10.1006/bbrc.1995.2864] [PMID: 8554622]
[81]
Lee, B.K.; Kim, J.H.; Jung, J.W.; Choi, J.W.; Han, E.S.; Lee, S.H.; Ko, K.H.; Ryu, J.H. Myristicin-induced neurotoxicity in human neuroblastoma SK-N-SH cells. Toxicol. Lett., 2005, 157(1), 49-56.
[http://dx.doi.org/10.1016/j.toxlet.2005.01.012] [PMID: 15795093]
[82]
Zhao, Q.; Liu, C.; Shen, X.; Xiao, L.; Wang, H.; Liu, P.; Wang, L.; Xu, H. Cytoprotective effects of myristicin against hypoxia-induced apoptosis and endoplasmic reticulum stress in rat dorsal root ganglion neurons. Mol. Med. Rep., 2017, 15(4), 2280-2288.
[http://dx.doi.org/10.3892/mmr.2017.6258] [PMID: 28260107]
[83]
Seneme, E.F.; dos Santos, D.C.; de Lima, C.A.; Zelioli, Í.A.M.; Sciani, J.M.; Longato, G.B. Effects of myristicin in association with chemotherapies on the reversal of the Multidrug Resistance (MDR) mechanism in cancer. Pharmaceuticals (Basel), 2022, 15(10), 1233.
[http://dx.doi.org/10.3390/ph15101233] [PMID: 36297344]
[84]
Martins, C.; Doran, C.; Laires, A.; Rueff, J.; Rodrigues, A.S. Genotoxic and apoptotic activities of the food flavourings myristicin and eugenol in AA8 and XRCC1 deficient EM9 cells. Food Chem. Toxicol., 2011, 49(2), 385-392.
[http://dx.doi.org/10.1016/j.fct.2010.11.013] [PMID: 21087650]
[85]
Martins, C.; Doran, C.; Silva, I.C.; Miranda, C.; Rueff, J.; Rodrigues, A.S. Myristicin from nutmeg induces apoptosis via the mitochondrial pathway and down regulates genes of the DNA damage response pathways in human leukaemia K562 cells. Chem. Biol. Interact., 2014, 218, 1-9.
[http://dx.doi.org/10.1016/j.cbi.2014.04.014] [PMID: 24792648]
[86]
Lee, J.Y.; Park, W. Anti-inflammatory effect of myristicin on RAW 264.7 macrophages stimulated with polyinosinic-polycyti-dylic acid. Molecules, 2011, 16(8), 7132-7142.
[http://dx.doi.org/10.3390/molecules16087132] [PMID: 21991618]
[87]
de Cássia da Silveira e Sá. R.; Andrade, L.; dos Reis Barreto de Oliveira, R.; de Sousa, D. A review on anti-inflammatory activity of phenylpropanoids found in essential oils. Molecules, 2014, 19(2), 1459-1480.
[http://dx.doi.org/10.3390/molecules19021459] [PMID: 24473208]
[88]
Qiburi, Q.; Ganbold, T.; Bao, Q.; Da, M.; Aoqier, A.; Temuqile, T.; Baigude, H. Bioactive components of ethnomedicine Eerdun Wurile regulate the transcription of pro-inflammatory cytokines in microglia. J. Ethnopharmacol., 2020, 246, 112241.
[http://dx.doi.org/10.1016/j.jep.2019.112241] [PMID: 31533078]
[89]
Badr, G.; Elsawy, H.; Amalki, M.A.; Alfwuaires, M.; El-Gerbed, M.S.A.; Abdel-Moneim, A.M. Protective effects of myristicin against ulcerative colitis induced by acetic acid in male mice. Food Agric. Immunol., 2020, 31(1), 435-446.
[http://dx.doi.org/10.1080/09540105.2020.1739626]
[90]
Lim, H.J.; Woo, K.W.; Lee, K.R.; Lee, S.K.; Kim, H.P. Inhibition of pro-inflammatory cytokine generation in lung inflammation by the leaves of Perilla frutescens and its constituents. Biomol. Ther. (Seoul), 2014, 22(1), 62-67.
[http://dx.doi.org/10.4062/biomolther.2013.088] [PMID: 24596623]
[91]
Kuropakornpong, P.; Itharat, A.; Panthong, S.; Sireeratawong, S.; Ooraikul, B. In vitro and in vivo anti-inflammatory activities of Benjakul: A potential medicinal product from Thai traditional medicine. Evid. Based Complement. Alternat. Med., 2020, 2020, 1-8.
[http://dx.doi.org/10.1155/2020/9760948] [PMID: 32733593]
[92]
Sumiwi, S.A.; Sihombing, O.S.; Subarnas, A.; Abdassah, M.; Levita, J. A study to predict anti-inflammatory activity of eugenol, myristicin, and limonene of Cinnamomum Sintoc. Int. J. Pharm. Pharm. Sci., 2015, 7, 51-54.
[93]
Ai, S.; Lin, G.; Bai, Y.; Liu, X.; Piao, L. QSAR classification-based virtual screening followed by molecular docking identification of potential COX-2 inhibitors in a natural product library. J. Comput. Biol., 2019, 26(11), 1296-1315.
[http://dx.doi.org/10.1089/cmb.2019.0142] [PMID: 31233340]
[94]
Morita, T.; Jinno, K.; Kawagishi, H.; Arimoto, Y.; Suganuma, H.; Inakuma, T.; Sugiyama, K. Hepatoprotective effect of myristicin from nutmeg (Myristica fragrans) on lipopolysaccharide/d-galactosamine-induced liver injury. J. Agric. Food Chem., 2003, 51(6), 1560-1565.
[http://dx.doi.org/10.1021/jf020946n] [PMID: 12617584]
[95]
Goswami, P.K.; Samant, M.; Srivastava, R. Natural sunscreen agents : A review. Sch. Acad. J. Pharm, 2013, 2(6), 458-463.
[96]
Boulebd, H. DFT study of the antiradical properties of some aromatic compounds derived from antioxidant essential oils: C–H bond vs. O–H bond. Free Radic. Res., 2019, 53(11-12), 1125-1134.
[http://dx.doi.org/10.1080/10715762.2019.1690652] [PMID: 31694416]
[97]
Niu, G.; Pollock, H.S.; Lawrance, A.; Siegel, J.P.; Berenbaum, M.R. Effects of a naturally occurring and a synthetic synergist on toxicity of three insecticides and a phytochemical to navel orangeworm (Lepidoptera: Pyralidae). J. Econ. Entomol., 2012, 105(2), 410-417.
[http://dx.doi.org/10.1603/EC10194] [PMID: 22606811]
[98]
Passreiter, C.M.; Akhtar, Y.; Isman, M.B. Insecticidal activity of the essential oil of Ligusticum mutellina roots. Z. Naturforsch. C J. Biosci., 2005, 60(5-6), 411-414.
[http://dx.doi.org/10.1515/znc-2005-5-608] [PMID: 16042341]
[99]
Song, H.Y.; Yang, J.Y.; Suh, J.W.; Lee, H.S. Acaricidal activities of apiol and its derivatives from Petroselinum sativum seeds against Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Tyrophagus putrescentiae. J. Agric. Food Chem., 2011, 59(14), 7759-7764.
[http://dx.doi.org/10.1021/jf201945y] [PMID: 21688847]
[100]
de Morais, S.M.; Facundo, V.A.; Bertini, L.M.; Cavalcanti, E.S.B.; Anjos Júnior, J.F.; Ferreira, S.A.; de Brito, E.S.; de Souza Neto, M.A. Chemical composition and larvicidal activity of essential oils from Piper species. Biochem. Syst. Ecol., 2007, 35(10), 670-675.
[http://dx.doi.org/10.1016/j.bse.2007.05.002]
[101]
Swiech, K.; Polec, I. Comparison of the insecticidal effectiveness of synthetic and natural myristicin against housefly (Musca domestica L.) and oriental cockroach (Blatta orientalis). Chemik., 2013, 67, 1115-1120.
[102]
You, C.X.; Jiang, H.Y.; Zhang, W.J.; Guo, S.S.; Yang, K.; Lei, N.; Ma, P.; Geng, Z.F.; Du, S.S.; Athanassiou, C. Contact toxicity and repellency of the main components from the essential oil of Clausena anisum-olens against two stored product insects. J. Insect Sci., 2015, 15(1), 87-102.
[http://dx.doi.org/10.1093/jisesa/iev071] [PMID: 26136499]
[103]
Heshmati Afshar, F.; Maggi, F.; Iannarelli, R.; Cianfaglione, K.; Isman, M.B. Comparative toxicity of Helosciadium nodiflorum essential oils and combinations of their main constituents against the cabbage looper, Trichoplusiani (Lepidoptera). Ind. Crops Prod., 2017, 98, 46-52.
[http://dx.doi.org/10.1016/j.indcrop.2017.01.004]
[104]
Pavela, R.; Maggi, F.; Cianfaglione, K.; Bruno, M.; Benelli, G. Larvicidal activity of essential oils of five Apiaceae taxa and some of their main constituents against Culex quinquefasciatus. Chem. Biodivers., 2018, 15(1), e1700382.
[http://dx.doi.org/10.1002/cbdv.201700382] [PMID: 28990348]
[105]
Benelli, G.; Pavela, R.; Iannarelli, R.; Petrelli, R.; Cappellacci, L.; Cianfaglione, K.; Afshar, F.H.; Nicoletti, M.; Canale, A.; Maggi, F. Synergized mixtures of Apiaceae essential oils and related plant-borne compounds: Larvicidal effectiveness on the filariasis vector Culex quinquefasciatus Say. Ind. Crops Prod., 2017, 96, 186-195.
[http://dx.doi.org/10.1016/j.indcrop.2016.11.059]
[106]
Liu, X.C.; Liu, Z.L. Analysis of the essential oil of Illicium henryi Diels root bark and its insecticidal activity against Liposcelis bostrychophila Badonnel. J. Food Prot., 2015, 78(4), 772-777.
[http://dx.doi.org/10.4315/0362-028X.JFP-14-407] [PMID: 25836404]
[107]
Qi, X.J.; Pang, X.; Cao, J.Q.; Du, S.S. Comparative analysis on bioactivity against three stored insects of Ligusticum pteridophyllum Franch. rhizomes essential oil and supercritical fluid (SFE-CO2) extract. Environ. Sci. Pollut. Res. Int., 2020, 27(13), 15584-15591.
[http://dx.doi.org/10.1007/s11356-020-08043-5] [PMID: 32078128]
[108]
Dorla, E.; Gauvin-Bialecki, A.; Deuscher, Z.; Allibert, A.; Grondin, I.; Deguine, J.P.; Laurent, P. Insecticidal activity of the leaf essential oil of Peperomia borbonensis miq. (Piperaceae) and its major components against the melon fly Bactrocera cucurbitae (Diptera: Tephritidae). Chem. Biodivers., 2017, 14(6), e1600493.
[http://dx.doi.org/10.1002/cbdv.201600493] [PMID: 28273402]
[109]
Lichtenstein, E.P.; Casida, J.E. Naturally occurring insecticides, myristicin, an insecticide and synergist occurring naturally in the edible parts of parsnips. J. Agric. Food Chem., 1963, 11(5), 410-415.
[http://dx.doi.org/10.1021/jf60129a017]
[110]
Jaiswal, P.; Kumar, P.; Singh, V.K.; Singh, D.K. Biological effects of Myristica fragrans. Annu. Rev. Biomed. Sci., 2009, 11, 21-29.
[111]
Seo, S.M.; Jung, C.S.; Kang, J.; Lee, H.R.; Kim, S.W.; Hyun, J.; Park, I.K. Larvicidal and acetylcholinesterase inhibitory activities of apiaceae plant essential oils and their constituents against aedes albopictus and formulation development. J. Agric. Food Chem., 2015, 63(45), 9977-9986.
[http://dx.doi.org/10.1021/acs.jafc.5b03586] [PMID: 26500081]
[112]
Abou-Elnaga, Z.S. Insecticidal bioactivity of eco-friendly plant origin chemicals against Culex pipiens and Aedes aegypti (Diptera: Culicidae). J. Entomol. Zool. Stud., 2014, 2, 340-347.
[113]
Cossolin, J.F.S.; Pereira, M.J.B.; Martínez, L.C.; Turchen, L.M.; Fiaz, M.; Bozdoğan, H.; Serrão, J.E. Cytotoxicity of Piper aduncum (Piperaceae) essential oil in brown stink bug Euschistus heros (Heteroptera: Pentatomidae). Ecotoxicology, 2019, 28(7), 763-770.
[http://dx.doi.org/10.1007/s10646-019-02072-8] [PMID: 31254186]
[114]
Pavela, R.; Maggi, F.; Cianfaglione, K.; Canale, A.; Benelli, G. Promising insecticidal efficacy of the essential oils from the halophyte Echinophora spinosa (Apiaceae) growing in Corsica Island, France. Environ. Sci. Pollut. Res. Int., 2020, 27(13), 14454-14464.
[http://dx.doi.org/10.1007/s11356-019-04980-y] [PMID: 30963429]
[115]
Jaiswal, P.; Singh, D.K. Molluscicidal activity of Nutmeg and Mace (Myristica fragrans Houtt.) against the vector snail Lymnaea acuminata. Herbs, Spices Med. Plants, 2009, 15, 177-186.
[116]
Rahman, N.A.A.; Fazilah, A.; Effarizah, M.E. Toxicity of nutmeg (myristicin): A review. Int. J. Adv. Sci. Eng. Inf. Technol., 2015, 5(3), 61-64.
[117]
Bourgeois, J.A.; Parthasarathi, U.; Hategan, A. Taking the spice route: Psychoactive properties of culinary spices. Curr. Psychiatr., 2014, 13(4), 21-32.
[118]
Warsito, M.F. A review on chemical composition, bioactivity, and toxicity of Myristica fragrans Houtt. essential oil. Indones. J. Pharm., 2021, 32(3), 304-313.
[http://dx.doi.org/10.22146/ijp.1271]
[119]
Truitt, E.B., Jr; Duritz, G.; Ebersberger, E.M. Evidence of monoamine oxidase inhibition by myristicin and nutmeg. Exp. Biol. Med. (Maywood), 1963, 112(3), 647-650.
[http://dx.doi.org/10.3181/00379727-112-28128] [PMID: 13994372]
[120]
Stein, U.; Greyer, H.; Hentschel, H. Nutmeg (myristicin) poisoning-Report on a fatal case and a series of cases recorded by a poison information centre. Forensic Sci. Int., 2001, 118(1), 87-90.
[http://dx.doi.org/10.1016/S0379-0738(00)00369-8] [PMID: 11343860]
[121]
Gupta, A.D.; Rajpurohit, D. Antioxidant and antimicrobial activity of nutmeg (Myristica fragrans). In: Nuts and seeds in health and disease prevention; Preedy, V.R.; Watson, R.R.; Patel, V.B. Elsevier Inc., Amsterdam, 2011, 1, pp. 831-839
[122]
Ehrenpreis, J.E.; DesLauriers, C.; Lank, P.; Armstrong, P.K.; Leikin, J.B. Nutmeg poisonings: a retrospective review of 10 years experience from the Illinois Poison Center, 2001-2011. J. Med. Toxicol., 2014, 10(2), 148-151.
[http://dx.doi.org/10.1007/s13181-013-0379-7] [PMID: 24452991]
[123]
Leiter, E.; Hitchcock, G.; Godwin, S.; Johnson, M.; Sedgwick, W.; Jones, W.; McCall, S.; Ceremuga, T.E. Evaluation of the anxiolytic properties of myristicin, a component of nutmeg, in the male Sprague-Dawley rat. AANA J., 2011, 79(2), 109-114.
[PMID: 21560973]
[124]
NTP technical report on the toxicity studies of myristicin (CASRN 607-91-0) administered by Gavage to F344/NTac rats and B6C3F1/N mice. Natl. Toxicol. Program Tech. Rep. Ser., 2019, 95.
[http://dx.doi.org/10.22427/NTP-TOX-95]
[125]
Hasheminejad, G.; Caldwell, J. Genotoxicity of the alkenylbenzenes α− and β-asarone, myristicin and elemicin as determined by the UDS assay in cultured rat hepatocytes. Food Chem. Toxicol., 1994, 32(3), 223-231.
[http://dx.doi.org/10.1016/0278-6915(94)90194-5] [PMID: 8157216]
[126]
Casida, J.E.; Engel, J.L.; Essac, E.G.; Kamienski, F.X.; Kuwatsuka, S. Methylene-C14-dioxyphenyl compounds: Metabolism in relation to their synergistic action. Science, 1966, 153(3740), 1130-1133.
[http://dx.doi.org/10.1126/science.153.3740.1130] [PMID: 4162081]
[127]
Al-Malahmeh, A.J.; Al-Ajlouni, A.; Wesseling, S.; Soffers, A.E.M.F.; Al-Subeihi, A.; Kiwamoto, R.; Vervoort, J.; Rietjens, I.M.C.M. Physiologically based kinetic modeling of the bioactivation of myristicin. Arch. Toxicol., 2017, 91(2), 713-734.
[http://dx.doi.org/10.1007/s00204-016-1752-5] [PMID: 27334372]
[128]
Kamienski, F.X.; Casida, J.E. Importance of demethylenation in the metabolism in vivo and in vitro of methylenedioxyphenyl synergists and related compounds in mammals. Biochem. Pharmacol., 1970, 19(1), 91-112.
[http://dx.doi.org/10.1016/0006-2952(70)90331-X] [PMID: 4396245]
[129]
Zhu, X.; Wang, Y.K.; Yang, X.N.; Xiao, X.R.; Zhang, T.; Yang, X.W.; Qin, H.B.; Li, F. Metabolic activation of myristicin and its role in cellular toxicity. J. Agric. Food Chem., 2019, 67(15), 4328-4336.
[http://dx.doi.org/10.1021/acs.jafc.9b00893] [PMID: 30912427]
[130]
Lee, H.S.; Jeong, T.C.; Kim, J.H. In vitro and in vivo metabolism of myristicin in the rat. J. Chromatogr., Biomed. Appl., 1998, 705(2), 367-372.
[http://dx.doi.org/10.1016/S0378-4347(97)00531-8] [PMID: 9521577]
[131]
Beyer, J.; Ehlers, D.; Maurer, H.H. Abuse of nutmeg (Myristica fragrans Houtt.): studies on the metabolism and the toxicologic detection of its ingredients elemicin, myristicin, and safrole in rat and human urine using gas chromatography/mass spectrometry. Ther. Drug Monit., 2006, 28(4), 568-575.
[http://dx.doi.org/10.1097/00007691-200608000-00013] [PMID: 16885726]
[132]
Smith, R.L.; Adams, T.B.; Doull, J.; Feron, V.J.; Goodman, J.I.; Marnett, L.J.; Portoghese, P.S.; Waddell, W.J.; Wagner, B.M.; Rogers, A.E.; Caldwell, J.; Sipes, I.G. Safety assessment of allylalkoxybenzene derivatives used as flavouring substances — methyl eugenol and estragole. Food Chem. Toxicol., 2002, 40(7), 851-870.
[http://dx.doi.org/10.1016/S0278-6915(02)00012-1] [PMID: 12065208]
[133]
Zhou, G.D.; Moorthy, B.; Bi, J.; Donnelly, K.C.; Randerath, K. DNA adducts from alkoxyallylbenzene herb and spice constituents in cultured human (HepG2) cells. Environ. Mol. Mutagen., 2007, 48(9), 715-721.
[http://dx.doi.org/10.1002/em.20348] [PMID: 17948277]
[134]
Randerath, K.; Putman, K.L.; Randerath, E. Flavor constituents in cola drinks induce hepatic DNA adducts in adult and fetal mice. Biochem. Biophys. Res. Commun., 1993, 192(1), 61-68.
[http://dx.doi.org/10.1006/bbrc.1993.1381] [PMID: 8476434]
[135]
Bergau, N.; Herfurth, U.M.; Sachse, B.; Abraham, K.; Monien, B.H. Bioactivation of estragole and anethole leads to common adducts in DNA and hemoglobin. Food Chem. Toxicol., 2021, 153, 112253.
[http://dx.doi.org/10.1016/j.fct.2021.112253] [PMID: 34015424]
[136]
Randerath, K.; Haglund, R.E.; Phillips, D.H.; Reddy, M.V. 32 P-Post-labelling analysis of DNA adducts formed in the livers of animals treated with safrole, estragole and other naturally-occurring alkenylbenzenes. I. Adult female CD-1 mice. Carcinogenesis, 1984, 5(12), 1613-1622.
[http://dx.doi.org/10.1093/carcin/5.12.1613] [PMID: 6499112]
[137]
Martins, C.; Rueff, J.; Rodrigues, A.S. Genotoxic alkenylbenzene flavourings, a contribution to risk assessment. Food Chem. Toxicol., 2018, 118, 861-879.
[http://dx.doi.org/10.1016/j.fct.2018.06.020] [PMID: 29913232]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy