P-Asarone

P-Asarone Daucus carota (Apiaceae), Acorns calamus OD-R [carcinogen, insect... 

These detectors are commonly used in HPLC analysis. The absorption of the substances in the eluate by a specific wavelength normally between 190 and 700 nm is proportional to their concentration. This technique is widely used for quality control of flavourings, e.g. for the quantification of the vanillin/p-hydroxybenzaldehyde ratio for natural vanilla products, for the determination of caffeine in extracts and drinks, or for the detection and quantification of restricted ingredients such as quassine, coumarin or p-asarone in natural extracts [11-12[. 

A list of 89 flavouring substances and 13 groups of substances without limitations is given (similar to the Japanese list). A restrictive list with 14 limited substances mentions e.g. P-asarone 0.1 ppm, coumarin in beverages 2 ppm, pulegone 100 ppm, quassine 5 ppm, quinine 85 ppm, safrole 1 ppm, a- and P-thujones 0.5 ppm etc. Propylene glycol and glycerol are mentioned as carrier solvents. 

There are four varieties of Acorns calamus based on content of isoasarone (P-asarone c/s-isoasarone), which has been shown to cause duodenal tumors in rats (Tyler, 1993). Type I is found in North America and contains practically no isoasarone (Anonymous, 1996). Type II is found in Europe and the oil contains <10% isoasarone, while the oils of types III and IV contain up to 96% isoasarone. 

Calamus oil in a dose of 0.005 mL fed daily in powdered chow for 35 d was found to be genotoxic in Swiss mice (Balachandran et al., 1991). These effects were attributed to P-asarone, which was previously demonstrated to cause chromosomal aberrations and an increase in the rate of sister chromatid exchanges in human lymphocytes. 

Diploid race 2.7%-5% essential oil, p-asarone absent or in low concentration ... 

The hexane extracts of the plant showed in vitro nematocidal activity. The activity was shown to be due to a- and P-asarone (168, 169)... 

Sharma, J.D. etal. 1961. Pharmacodynam-ical effects of asarone and p-asarone Nature 192 1299-1300. 

Animal and in vitro studies have indicated that the compound P-asarone has carcinogenic, mutagenic, and chromo-some-damaging properties (Abel 1987 Balachandran et al. 1991 EAO/WHO 1981 Goggelmann and Schimmer 1983 Habermann 1971 Hasheminejad and Caldwell 1994). 

No teratogenic effects were observed in chicken eggs injected with calamus essential oil at doses of 0.12,0.60,3.00, 15.00, or 75.00 mg/egg (Yabiku et al. 1979). Similarly, no teratogenic effects were observed in chicken eggs injected with a-asarone at doses up to 4 mg/egg. In eggs injected with P-asarone, 43% of embryos survived a dose of 0.04 mg/egg, while none survived a dose of 4 mg/egg (Yabiku et al. 1979). 

In rats fed diets containing 0,500,1000,2500, or 5000 ppm (0, 0.05, 0.1, 0.25, and 0.5%) Jammu calamus essential oil (-75% P-asarone) daily for 2 years, all of the 5000 ppm group died within 45 weeks, all of the 2500 ppm group died within 68 weeks, and all of the 1000 ppm group died within 104 weeks. Gross abnormalities were observed, including liver damage, fluid in the pleural and or peritoneal cavity, and tumorous masses in the intestines. Cardiac atrophy was observed in both test and control animals but was more severe in test animals (Taylor 1967,1981). 

In rats fed diets containing 0.1,0.5,1.0, or 2.0% European calamus essential oil (-5% P-asarone) daily for 2 years, leiomyosarcomas, hepatocellular adenomas, and hepatocellular adenocarcinomas were observed at the 1 and 2% dose levels. Other dose-dependent adverse effects on the livers were observed, with effects at the 0.1% dose being similar to those in the controls, or slightly increased. Dose-dependent changes observed in the heart included myocardial atrophy, fibrosis, fatty degeneration, and fatty infiltration (Taylor 1981). 

In rats fed diets containing 0, 400, 800, or 2000 ppm (0, 0.04, 0.08, or 0.2%) P-asarone for 2 years, none of the animals receiving 2000 ppm P-asarone survived more than 84 weeks, and mortality was increased at the 800 ppm dose. Gross pathological changes were observed and included serous fluid in the abdominal and pleural cavities, liver and kidney changes, and tumorous masses in the intestinal tract. Occurrence of tumors was dose-related. Ghanges in... 

No mutagenic activity of P-asarone was observed in Salmonella typhimurium strains TA98, TAIOO, TA1535, TA1537, or TA1538 at concentrations of 2 to 200 pg/plate with metabolic activation. Tests without metabolic activation were not completed (Hsia et al. 1979). 

No mutagenic activity of a-asarone was observed in the Ames test with Salmonella typhimurium at concentrations of up to 5000 ppm with or without activation. In a related study, P-asarone was not mutagenic at 50 ppm, but did show mutagenic activity at a concentration of 5000 ppm with activation (Yabiku et al. 1979). 

FAO/WHO. 1981. P-Asarone. FAO/WHO Expert Committee on Food Additives. Toxicological evaluation of certain food additives. WHO Food Additives Series 16. Geneva. 

Subramanian, R., V. Ozaa, P. Parmara, and S. Mehtab. 2008. Rapid determination of P-asarone-free Acorus calamus cytotypes by HPTLC Curr. Trends Biotechnol. Pharm. 2(4) 506-513. 

Widmer, V, A. Schibli, and E. Reich. 2005. Quantitative determination of P-asarone in calamus by high-performance thin-layer chromatography. J. AO AC Int. 88(5) 1562-1567. 

Calamus grows wild in India, China, Europe, and North America, and the phytochemical profile of the plant material varies according to origin. The essential oil of plants from India contains up to 75% p-asarone see Alkenylbenzenes in Appendix 1), while the oil of calamus from Japan and eastern Russia contains 10-40%, oil from European plants contains... 

Different varieties of grass-leaf sweetflag and material of different geographical origin have varying levels of P-asarone (see Alkenylbenzenes in Appendix 1) (Bensky et al. 2004 Sugimoto et al. 1997b). Plant material with low P-asarone is... 

Also see entry for Acorus calamus rhizome of the asarone-con-taining triploid or tetraploid varieties for more information on the toxicity of P-asarone. 

Alkenylbenzenes, also known as allylbenzenes or allylphe-nols, contribute to the flavor of some plants. Alkenylbenzenes found in medicinal plants include, among others, asarone, estragole, safrole, and methyleugenol. p-asarone is found in species of Acorus and Asarum. Traces of estragole can be found in herbs such as tarragon (Artemisia dracunculus),... 

Hagan, E.C., P.M. Jenner, W.l. Jones, et aL 1965. Toxic properties of compounds related to safrole. Toxicol. Appl. Pharmacol. 7 (l) 18-24 Hasheminejad, G., and J. Caldwell. 1994. Genotoxicity of the alkenylbenzenes a- and P-asarone, myristicin and elemicin as determined by the UDS assay in cultured rat hepatocytes. Food Chem. Toxicol. 32 (3) 223-231. 

The essential oil of Acorus calamus (Araceae) contains p-asarone (30) that causes depression of development of the gonads and ovaries of the insect Dysdercus koenigii. Although third and fourth instar larvae molted normally to... 

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