- Email: [email protected]
Nutmeg oil, East indian
Fragrance raw materials monographs NUTMEG
631
OIL, EAST INDIAN
Synonym : Myristica oil. Description and physical properties: Food Chemicals Codex (1972).The major componentsof nutmeg
oil, including CL-and /I-pinene,camphene,myristicin, dipenteneand sabinene,have been identified by gas chromatography-massspectrometry(Matthews, Pickering & Robinson, 1974; Sammy & Nawar, 1968).The myristicin fraction of nutmeghas beenshown to include cis and frans isomers of isomyristicin,methylisoeugenol and elemicin(Shulgin,1963). Occurrence: Found in the fruit of Myristica jiqrans Houtt. (Fam. Myristicaceae)(Gildemeister& Hoffman, 1956;Guenther, 1952). Preparation: By steamdistillation of the dried nutmeg(Guenther, 1952). Uses:In public usebefore1900.Usein fragrancesin the USA amountsto approximately10,000lb&r. Concentrationin final product (%): Soap
Detergent
Creams, lotions
Perfume
Usual Maximum Analytical
0.01 ooo1 0.005 0.05 0.1 0.01 0.02 0.3 data: Gas chromatogram,RIFM nos. 71-58, 71-59; infra-red curve, RIFM nos. 71-58,
71-59. status Nutmeg was given GRAS status by FEMA (1965)and is approved by the FDA for food use (GRAS). The Council of Europe(1974)includednutmegin the list of substances, spicesand seasoningsdeemedadmissiblefor use,with a possiblelimitation of the active principle in the tinal product. The Food Chemicals Codex (1972)has a monographon nutmegoil, which has also beenincluded in extensivestudiesin the GRAS review programme(National TechnicalInformation Service(NTIS) publicationsPB221-2228~ PB221-807). . Biologicaldata Acute toxicity. The acute oral LD,, value of nutmegoil in rats has beenreported as2620mg/kg (Jeerer, Hagan,Taylor, Cook & Fitzhugh, 1964)and as 2600 + 220 mg/kg (NTIS, 1972a). The acute oral LD,, value of East Indian nutmegin rats was reportedas 500+ 140mg/kg(Ttuitt, Callaway, Braude & Krantz, 1961).The acute oral LD,, values of nutmeg oil in mice and hamsterswere reportedas 5620+ 520mg/kg and 6000f 230,respectively(NTIS, 1972a).The acute dermal LD,, value in rabbits exceededlOml/kg (Owen, 1971),while lOml/kg injected ip into cats was fatal (Ahmad & Thompson, 1975).The latter authors failed to produce local mydriatic action when they dropped nutmegoil on the corneaof a cat or injected 1ml subconjunctivally. In animals,lethal dosesproducefatty degenerationof tie liver and centralnervoussystemparalysis (Weil, 1965),the liver changesbeingattributable to the myristicin component(Christomanos,1927). Large dosesof nutmeg producevasomotor instability, tachycardia,hypothermia,absenceof saliva flow, constrictedpupilsand emotionallability, due largely but not entirely to the myristicin content (Truitt et al. 1961) and have also been reported to induce narcosis,delirium and death, in man as well as animals,following ingestion(Dale, 1909;Merck Index, 1968). Severalcasesof nutmeg poisoningin man have been reported (Green, 1959; Hamond, 1906; Hinman, 1901; Painter, Shanor & Winek, 1971; Payne, 1963).A group of male prisonersin a New Jerseystate prison attempted to achieve a state of euphoria by eating large quantities of nutmeg.Two of the mendevelopedtoxic psychoses as a result, sufferingfrom disorientation,confusion and auditory and visual hallucinations,but they recoveredwithin 6 months (Weiss,1960). Two instancesof attemptednutmegintoxication have beenreported in’sweden,wherea 17-yr%id girl consumed25g and a 22-yr-old woman 15g of powderednutmeg (Akesson& Walinder, 1965). They both describeddreamlikefeelingswith impaired visual perceptionand reported experiencing musicintensely.The girl sleptcontinuouslyfor 40hr and woke up in a euphoricstate.No abnormal need of sleepor euphoric reaction was reported by the older woman. The duration of nutmeg intoxication is dose-dependent. In the caseof the girl, symptomslastedfor 10 days, but usually they disappearafter 2-3 days. Irritation. Nutmeg oil, EI, applied full strengthto intact or abradedrabbit skin for 24hr under occlusionwasmoderatelyirritating (Owen, 1971).Testedat 2% in petrolatum, it producedno irritation after a 48-hr closed-patchtest on humansubjects(Kligman, 1971). Sensitization. A maximization test (K&man, 1966;K&man & Epstein, 1975)was carried out on 25 volunteers.The material was testedat a concentration of 2% in petrolatum and produced no sensitizationreactions(Kligman, 1971). Metabolism. Nutmegdemonstrates a mild degreeof monoamineoxidase(MAO)-inhibiting activity in vitro and in vivo (Truitt, 1967;Truitt & Ebersberger,1962).In a test basedon interferencewith tryptamine metabolism,nutmegwas shownto possess a weak enzyme-inhibitoryaction, but inhibition by myristicin was approximately one third as powerful as that of iproniazid, a well known
D. L. J. OPDYKE
632
antidepressant of this class(Truitt & Ebersberger, 1962). When oral doses of 0.2 or l.Og/kg nutmeg powder (asan acaciasuspension) were given to mice and rats, the onset of the inhibiting action was first noted 17-24hr after feedingas a loweringof the convulsive thresholdin mice following iv injection of tryptamine. In rats, after the tryptamine injection, the MAO inhibition took the form of an increasein concentrationof 5hydroxytryptamine in the brain (Truitt, Duritz & Ebersberger, 1963). Pharmacology. The principal pharmacolog@ally active component of nutmeg, myristicin, caused ataxia and disorientation in monkeys and enhanced morphine-induced rage in cats (Truitt et al. 1961). Doses of 400mg on alternate days produced in normal volunteers some evidence of slight euphoria, but none resembling the symptoms of excitation seen in acute nutmeg poisoning (Truitt et al. 1961). Teratology. The administration of up to 560mg nutmeg oil/kg body weight to pregnant mice for 10 consecutive days, of up to 26Omg/kg to pregnant rats for 10 consecutive days and of up to 600 mg/kg to pregnant hamsters for 5 consecutive days had no clearly discernible effect on nidation
or on maternalor foetal survival (NTIS, 1972b).The numberof abnormalitiesseenin either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated Additional
published
controls. data
Prolonged storage of nutmeg resulted in changes in the volatile composition, as determined by gas chromatography. The variation in composition of the nutmeg constituents appears to be mainly a function of their volatilization (Sanford & Heinz, 1971). References Ahmad, A. & Thompson, H. S. (1975). Nutmeg mydriasis. J. Am. med. Ass. 234, 274. Akesson, H. 0. & Walinder, J. (1965). Nutmeg intoxication. L.uncet i, 1271. Christomanos, A. A. (1927). Zur Pharmakologie des Apiols und einiger seiner Verwandten. Naunyn-Schmiedebergs Arch. exp. Path.
Pharmak.
123, 252.
Council of Europe (1974). Natural Flavouring Substances, Their Sources, and Added Artificial Flavouring Substances. Partial Agreement in the Social and Public Health Field. List N(l), Series l(b), no. 296, p. 83. Strasbourg. Dale, H. H. (1909). Sot. exp. Biol., N.Y. 23. 69. Flavoring Extract Manufacturers’ Association (1965). Survey of flavoring ingredient usage levels. No. 2793. Fd Technol., Champaign 19 (2), part 2, 155. Food Chemicals Codex (1972). 2nd Ed. Prepared by the Committee on Specifications, Food Chemicals Codex, of the Committee on Food Protection. p. 556. National Academy of Sciences-National Research Council Publ. 1406, Washington, D.C. Gildemeister, E. u. Hoffman, F. (1956). Die jtherischen ale. Vol. IV, p. 666. Akademie Verlag, Berlin. Green, R. C., Jr. (1959). Nutmeg poisoning. J. Am. med. Ass. 171, 1342. Guenther. E. (1952). The Essential Oils. Vol. V, p. 59. D. Van Nostrand, Inc., Princeton, New Jersey. Hamond, P. W. (1906). Nutmeg poisoning. Br. med. J. 2, 778. Hinman. E. E. (1901). A case of nutmeg poisoning. Albany med. Ann. 22, 669. Jenner. P. M., Hagan, E. C., Taylor, J. M., Cook, E. L. & Fitzhugh, 0. G. (1964). Food flavourings and compounds of related structure. I. Acute oral toxicity. Fd Cosmet. Toxicol. 2, 327. Khgman, A. M. (1966). The identification of contact allergens by human assay. III. The maximization test. A procedure for screening and rating contact sensitizers. J. invest. Derm. 47. 393. Kligman, A. M. (1971). Report to RIFM, 17 June. Kligman, A. M. & Epstein, W. (1975). Updating the maximization test for identifying contact allergens. Contact Dermatitis 1, 231. Matthews, W. S. A., Pickering, G. R. & Robinson, F. U. (1974). The distillation and composition of nutmeg oils. VI. Proceedings, International Congress of Essential Oils, San Francisco, California. Merck Index (1968). An Encyclopedia of Chemicals and Drugs. 8th Ed., p. 760. Merck 8~ Co., Rahway, New Jersey. National Technical Information Service (1972a). GRAS (Generally Recognized As Safe) Food Ingredients--Oil of Nutmeg and Myristica Oil. Food and Drua Research Labs., Inc., reuort to the Food and Drug Administration, December, 1972. National Technical Information Service (1972b). Teratologic Evaluation of FDA 71-28 (Oil of Nutmeg). Food and Drug Research Labs, Inc., report to the Food and Drug Administration, February, 1972. Owen, G. (1971). Report to RIFM, 23 August. Painter, J. C., Shanor, S. P. & Winek, C. L. (1971). Nutmeg poisoning-A case report. C/in. Toxicol. 4, 1. Payne, R. B. (1963). Nutmeg intoxication. New Engl. J. Med. 269, 36. Sammy, G. M. & Nawar, W. W. (1968). Identification of the major components of nutmeg oil by gas chromatography and mass spectrometry. Chemy Ind. p. 1279. Sanford, K. J. & Heinz, D. E. (1971). Effects of storage on the volatile composition of nutmeg. Phytochemistry 10, 1245. Shulgin, A. T. (1963). Composition of the myristicin fraction from oil of nutmeg. Nature. Lond. 197, 379. Truitt, E. B. (1967). The pharmacology of myristicin and nutmeg. In Ethnopharmacologic Search for Psychoactive Drugs. Proceedings of a Symposium, 28-30 January 1967. Publ. Hlth Serv. Pubis, Wash. no. 1645, p. 215.
Fragrance
raw materials
monographs
633
Truitt, E. B., Jr.. Callaway, E., III. Braude, M. C. & Krantz, J. C., Jr. (1961). The pharmacology of myristicin. Contribution to the psychopharmacology of nutmeg. J. Newopsychiat. 2. 205. Truitt, E. B., Duritz. G. & Ebersberger, E. M. (1963). Evidence of monoamine oxidase inhibition by myristicin and nutmeg. Proc. Sot. up. Biol. Med. 112. 647. Truitt, E. B., Jr. & Ebersberger, E. M. (1962). Evidence of monoamine oxidase inhibition by myristicin and nutmeg in viuo. Fedn Proc. Fedn Am Sots esp. Biol. 21. 418. Weil, A. T. (1965). Nutmeg as a narcotic. Econ. Bar. 19. 194. Weiss, G. (1960). Hallucinogenic and narcotic-like effects of powdered Myristica (nutmeg). Psyhiar. Q. 34. 346.
631
OIL, EAST INDIAN
Synonym : Myristica oil. Description and physical properties: Food Chemicals Codex (1972).The major componentsof nutmeg
oil, including CL-and /I-pinene,camphene,myristicin, dipenteneand sabinene,have been identified by gas chromatography-massspectrometry(Matthews, Pickering & Robinson, 1974; Sammy & Nawar, 1968).The myristicin fraction of nutmeghas beenshown to include cis and frans isomers of isomyristicin,methylisoeugenol and elemicin(Shulgin,1963). Occurrence: Found in the fruit of Myristica jiqrans Houtt. (Fam. Myristicaceae)(Gildemeister& Hoffman, 1956;Guenther, 1952). Preparation: By steamdistillation of the dried nutmeg(Guenther, 1952). Uses:In public usebefore1900.Usein fragrancesin the USA amountsto approximately10,000lb&r. Concentrationin final product (%): Soap
Detergent
Creams, lotions
Perfume
Usual Maximum Analytical
0.01 ooo1 0.005 0.05 0.1 0.01 0.02 0.3 data: Gas chromatogram,RIFM nos. 71-58, 71-59; infra-red curve, RIFM nos. 71-58,
71-59. status Nutmeg was given GRAS status by FEMA (1965)and is approved by the FDA for food use (GRAS). The Council of Europe(1974)includednutmegin the list of substances, spicesand seasoningsdeemedadmissiblefor use,with a possiblelimitation of the active principle in the tinal product. The Food Chemicals Codex (1972)has a monographon nutmegoil, which has also beenincluded in extensivestudiesin the GRAS review programme(National TechnicalInformation Service(NTIS) publicationsPB221-2228~ PB221-807). . Biologicaldata Acute toxicity. The acute oral LD,, value of nutmegoil in rats has beenreported as2620mg/kg (Jeerer, Hagan,Taylor, Cook & Fitzhugh, 1964)and as 2600 + 220 mg/kg (NTIS, 1972a). The acute oral LD,, value of East Indian nutmegin rats was reportedas 500+ 140mg/kg(Ttuitt, Callaway, Braude & Krantz, 1961).The acute oral LD,, values of nutmeg oil in mice and hamsterswere reportedas 5620+ 520mg/kg and 6000f 230,respectively(NTIS, 1972a).The acute dermal LD,, value in rabbits exceededlOml/kg (Owen, 1971),while lOml/kg injected ip into cats was fatal (Ahmad & Thompson, 1975).The latter authors failed to produce local mydriatic action when they dropped nutmegoil on the corneaof a cat or injected 1ml subconjunctivally. In animals,lethal dosesproducefatty degenerationof tie liver and centralnervoussystemparalysis (Weil, 1965),the liver changesbeingattributable to the myristicin component(Christomanos,1927). Large dosesof nutmeg producevasomotor instability, tachycardia,hypothermia,absenceof saliva flow, constrictedpupilsand emotionallability, due largely but not entirely to the myristicin content (Truitt et al. 1961) and have also been reported to induce narcosis,delirium and death, in man as well as animals,following ingestion(Dale, 1909;Merck Index, 1968). Severalcasesof nutmeg poisoningin man have been reported (Green, 1959; Hamond, 1906; Hinman, 1901; Painter, Shanor & Winek, 1971; Payne, 1963).A group of male prisonersin a New Jerseystate prison attempted to achieve a state of euphoria by eating large quantities of nutmeg.Two of the mendevelopedtoxic psychoses as a result, sufferingfrom disorientation,confusion and auditory and visual hallucinations,but they recoveredwithin 6 months (Weiss,1960). Two instancesof attemptednutmegintoxication have beenreported in’sweden,wherea 17-yr%id girl consumed25g and a 22-yr-old woman 15g of powderednutmeg (Akesson& Walinder, 1965). They both describeddreamlikefeelingswith impaired visual perceptionand reported experiencing musicintensely.The girl sleptcontinuouslyfor 40hr and woke up in a euphoricstate.No abnormal need of sleepor euphoric reaction was reported by the older woman. The duration of nutmeg intoxication is dose-dependent. In the caseof the girl, symptomslastedfor 10 days, but usually they disappearafter 2-3 days. Irritation. Nutmeg oil, EI, applied full strengthto intact or abradedrabbit skin for 24hr under occlusionwasmoderatelyirritating (Owen, 1971).Testedat 2% in petrolatum, it producedno irritation after a 48-hr closed-patchtest on humansubjects(Kligman, 1971). Sensitization. A maximization test (K&man, 1966;K&man & Epstein, 1975)was carried out on 25 volunteers.The material was testedat a concentration of 2% in petrolatum and produced no sensitizationreactions(Kligman, 1971). Metabolism. Nutmegdemonstrates a mild degreeof monoamineoxidase(MAO)-inhibiting activity in vitro and in vivo (Truitt, 1967;Truitt & Ebersberger,1962).In a test basedon interferencewith tryptamine metabolism,nutmegwas shownto possess a weak enzyme-inhibitoryaction, but inhibition by myristicin was approximately one third as powerful as that of iproniazid, a well known
D. L. J. OPDYKE
632
antidepressant of this class(Truitt & Ebersberger, 1962). When oral doses of 0.2 or l.Og/kg nutmeg powder (asan acaciasuspension) were given to mice and rats, the onset of the inhibiting action was first noted 17-24hr after feedingas a loweringof the convulsive thresholdin mice following iv injection of tryptamine. In rats, after the tryptamine injection, the MAO inhibition took the form of an increasein concentrationof 5hydroxytryptamine in the brain (Truitt, Duritz & Ebersberger, 1963). Pharmacology. The principal pharmacolog@ally active component of nutmeg, myristicin, caused ataxia and disorientation in monkeys and enhanced morphine-induced rage in cats (Truitt et al. 1961). Doses of 400mg on alternate days produced in normal volunteers some evidence of slight euphoria, but none resembling the symptoms of excitation seen in acute nutmeg poisoning (Truitt et al. 1961). Teratology. The administration of up to 560mg nutmeg oil/kg body weight to pregnant mice for 10 consecutive days, of up to 26Omg/kg to pregnant rats for 10 consecutive days and of up to 600 mg/kg to pregnant hamsters for 5 consecutive days had no clearly discernible effect on nidation
or on maternalor foetal survival (NTIS, 1972b).The numberof abnormalitiesseenin either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated Additional
published
controls. data
Prolonged storage of nutmeg resulted in changes in the volatile composition, as determined by gas chromatography. The variation in composition of the nutmeg constituents appears to be mainly a function of their volatilization (Sanford & Heinz, 1971). References Ahmad, A. & Thompson, H. S. (1975). Nutmeg mydriasis. J. Am. med. Ass. 234, 274. Akesson, H. 0. & Walinder, J. (1965). Nutmeg intoxication. L.uncet i, 1271. Christomanos, A. A. (1927). Zur Pharmakologie des Apiols und einiger seiner Verwandten. Naunyn-Schmiedebergs Arch. exp. Path.
Pharmak.
123, 252.
Council of Europe (1974). Natural Flavouring Substances, Their Sources, and Added Artificial Flavouring Substances. Partial Agreement in the Social and Public Health Field. List N(l), Series l(b), no. 296, p. 83. Strasbourg. Dale, H. H. (1909). Sot. exp. Biol., N.Y. 23. 69. Flavoring Extract Manufacturers’ Association (1965). Survey of flavoring ingredient usage levels. No. 2793. Fd Technol., Champaign 19 (2), part 2, 155. Food Chemicals Codex (1972). 2nd Ed. Prepared by the Committee on Specifications, Food Chemicals Codex, of the Committee on Food Protection. p. 556. National Academy of Sciences-National Research Council Publ. 1406, Washington, D.C. Gildemeister, E. u. Hoffman, F. (1956). Die jtherischen ale. Vol. IV, p. 666. Akademie Verlag, Berlin. Green, R. C., Jr. (1959). Nutmeg poisoning. J. Am. med. Ass. 171, 1342. Guenther. E. (1952). The Essential Oils. Vol. V, p. 59. D. Van Nostrand, Inc., Princeton, New Jersey. Hamond, P. W. (1906). Nutmeg poisoning. Br. med. J. 2, 778. Hinman. E. E. (1901). A case of nutmeg poisoning. Albany med. Ann. 22, 669. Jenner. P. M., Hagan, E. C., Taylor, J. M., Cook, E. L. & Fitzhugh, 0. G. (1964). Food flavourings and compounds of related structure. I. Acute oral toxicity. Fd Cosmet. Toxicol. 2, 327. Khgman, A. M. (1966). The identification of contact allergens by human assay. III. The maximization test. A procedure for screening and rating contact sensitizers. J. invest. Derm. 47. 393. Kligman, A. M. (1971). Report to RIFM, 17 June. Kligman, A. M. & Epstein, W. (1975). Updating the maximization test for identifying contact allergens. Contact Dermatitis 1, 231. Matthews, W. S. A., Pickering, G. R. & Robinson, F. U. (1974). The distillation and composition of nutmeg oils. VI. Proceedings, International Congress of Essential Oils, San Francisco, California. Merck Index (1968). An Encyclopedia of Chemicals and Drugs. 8th Ed., p. 760. Merck 8~ Co., Rahway, New Jersey. National Technical Information Service (1972a). GRAS (Generally Recognized As Safe) Food Ingredients--Oil of Nutmeg and Myristica Oil. Food and Drua Research Labs., Inc., reuort to the Food and Drug Administration, December, 1972. National Technical Information Service (1972b). Teratologic Evaluation of FDA 71-28 (Oil of Nutmeg). Food and Drug Research Labs, Inc., report to the Food and Drug Administration, February, 1972. Owen, G. (1971). Report to RIFM, 23 August. Painter, J. C., Shanor, S. P. & Winek, C. L. (1971). Nutmeg poisoning-A case report. C/in. Toxicol. 4, 1. Payne, R. B. (1963). Nutmeg intoxication. New Engl. J. Med. 269, 36. Sammy, G. M. & Nawar, W. W. (1968). Identification of the major components of nutmeg oil by gas chromatography and mass spectrometry. Chemy Ind. p. 1279. Sanford, K. J. & Heinz, D. E. (1971). Effects of storage on the volatile composition of nutmeg. Phytochemistry 10, 1245. Shulgin, A. T. (1963). Composition of the myristicin fraction from oil of nutmeg. Nature. Lond. 197, 379. Truitt, E. B. (1967). The pharmacology of myristicin and nutmeg. In Ethnopharmacologic Search for Psychoactive Drugs. Proceedings of a Symposium, 28-30 January 1967. Publ. Hlth Serv. Pubis, Wash. no. 1645, p. 215.
Fragrance
raw materials
monographs
633
Truitt, E. B., Jr.. Callaway, E., III. Braude, M. C. & Krantz, J. C., Jr. (1961). The pharmacology of myristicin. Contribution to the psychopharmacology of nutmeg. J. Newopsychiat. 2. 205. Truitt, E. B., Duritz. G. & Ebersberger, E. M. (1963). Evidence of monoamine oxidase inhibition by myristicin and nutmeg. Proc. Sot. up. Biol. Med. 112. 647. Truitt, E. B., Jr. & Ebersberger, E. M. (1962). Evidence of monoamine oxidase inhibition by myristicin and nutmeg in viuo. Fedn Proc. Fedn Am Sots esp. Biol. 21. 418. Weil, A. T. (1965). Nutmeg as a narcotic. Econ. Bar. 19. 194. Weiss, G. (1960). Hallucinogenic and narcotic-like effects of powdered Myristica (nutmeg). Psyhiar. Q. 34. 346.