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Monographs of fragrance chemicals and extracts that have caused contact allergy / allergic contact dermatitis
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
Safrole is a colorless to pale yellow clear liquid; its odor type is spicy and its odor at 10% in dipropylene glycol is described as ‘sweet warm spicy woody floral sassafrass anise’ (www.thegoodscentscompany.com). It is not used as fragrance ingredient because of carcinogenicity (4). Examples of essential oils with a high safrole content are Sassafras oil (Sassafras officinale Nees & Eberm.), Ocotea cymbarum oil (Ocotea odorifera (Vell.) Rohwer, synonym: Ocotea pretiosa Mez), nutmeg oil (Myristica fragrans kernel oil, Chapter 6.50), and certain qualities of camphor oils.
Adverse Effects and Intoxication with Essential Oils
Published in K. Hüsnü Can Başer, Gerhard Buchbauer, Handbook of Essential Oils, 2020
Safrole has been demonstrated to be genotoxic and carcinogenic. It produces liver tumors in mice and rats by oral administration, and it produces also liver and lung tumors in male infant mice by subcutaneous application. It has been shown that safrole is able to induce chromosome aberrations, sister chromatid exchanges, and DNA adducts in hepatocytes of F344 rats exposed in vivo (Daimon et al., 1998).
Catalog of Herbs
Published in James A. Duke, Handbook of Medicinal Herbs, 2018
Camphor is cultivated for the essential oil obtained from the wood by distillation. Camphor oil of commerce is oil from which the camphor has been removed. The oil, containing camphor and safrole, is used in the preparation of expensive perfumes. Several oils may be obtained by different processes, white oil — boiling below the camphor fraction, contains mainly cineol, limonene, and pinene; brown oil — obtained after camphor fraction distills over, contains mainly safrole; a terpineol fraction; and blue oil — obtained by direct fire distillation of the residue, made up mainly of sesquiterpene alcohols. Residue after distillation of the leaves may be mixed with guano, ammonium sulfate, lime, and pen manure as fertilizer. Camphor is used extensively (circa 65% of world production) as a plasticizer to make celluloid, and in the preparation of explosives, disinfectants, and other chemicals. Wood, highly esteemed for cabinet making, is easily worked and polished, and resistant to insect attack. It is widely used to make Japanese carved chests. It is also used as a fumigant and quite dangerously as a fumitory.31 According to Purseglove et al., much of the world camphor is now produced synthetically from pinene, a turpentine derivative, or from coal tar. Safrole, produced from the residual oil after camphor extraction, is used to manufacture soap and perfume.64
Risk assessment of herbal supplements containing ingredients that are genotoxic and carcinogenic
Published in Critical Reviews in Toxicology, 2019
Gerhard Prinsloo, Francois Steffens, Jacques Vervoort, Ivonne M.C.M. Rietjens
Alkenylbenzenes (ABs), especially allylalkoxybenzenes including compounds like safrole, methyleugenol and others (Figure 3) occur in a large number of plants including for example basil (Ocimum basilicum), fennel (Foeniculum vulgare), mace (Myristica fragrans), parsley (Petroselinum crispum) and dill (Anethum graveolens) (Rietjens et al. 2014). These plants are used for herbal medicinal products as curing agents in a variety of diseases including for example treatment of gastrointestinal disorders (Farzaei et al. 2013; Mahomoodally and Mothoorah 2014; Rather et al. 2016). ABs have been shown to result in formation of DNA adducts and induction of liver tumors via formation of reactive 1′-sulfoxy metabolites (Boberg et al. 1983; Wiseman et al. 1987; Rietjens et al. 2014). The use of safrole, methyleugenol, and estragole as pure substances in foodstuff has been prohibited in the EU from September 2008 onwards (European Commission 2008). In the USA already in 1960 the US Food and Drug Administration (FDA) prohibited the use of pure safrole and sassafras oil (content of safrole >80%) in food (FDA Ban 21 CFR 189, 180; revised 1 April 2008) due to the potential carcinogenicity of safrole as demonstrated in rodent studies. For the AB estragole DNA adducts produced in V79 cells at 1000 mM were still detected 25-h after the recovery period (Gori et al. 2012). In another study on estragole, a rapid drop in total adduct formation occurred within 7 days after dosing and was followed by a relatively constant level over the next 140 days (Smith et al. 2002).
Identification and analysis of the reactive metabolites related to the hepatotoxicity of safrole
Published in Xenobiotica, 2018
Ai-Hong Yang, Lei Zhang, De-Xian Zhi, Wen-Li Liu, Xue Gao, Xin He
Safrole, as shown in Figure 1 is the main antifungal active ingredient of Asarum volatile oil. The sterilization effect of safrole is four times stronger than 40% formaldehyde. Safrole has a strong broad-spectrum antifungal chemical composition. However, earlier reports showed that safrole is a hepatocarcinogen in mice and rats (Borchert et al., 1973a; Wislocki et al., 1977). It is an allyl-benzene compound that is recognized to be a genotoxic carcinogenic agent in rodents (Shen et al., 2012; Yu et al., 2011). In vivo experiments show that, safrole has been preliminarily presumed to be metabolized by CYP450 enzymes (CYPs) and resulting in the following metabolites, 1,2-dihydroxy-4-allylbenzene, 3′-hydroxysafrole (Benedetti et al., 1977), 1′-hydroxysafrole (Borchert et al., 1973b; Wislocki et al., 1976) and safrole 2′,3′-oxide (Luo & Guenthner, 1996). Of the four metabolites, 1′-hydroxysafrole is further metabolized by sulfotransferase to 1′-hydroxysafrole sulfate, which subsequently reacts with 2-deoxyguanosine to form DNA adducts (Chung et al., 2008; Shen et al., 2012; Ueng et al., 2004), namely N2-(trans-isosafrol-3-yl)-2-deoxyguanosine. The carcinogenicity of safrole is mainly mediated through this pathway by CYP2E1.
Cancer Related to Herbs and Dietary Supplements: Online Table of Case Reports. Part 5 of 5
Published in Journal of Dietary Supplements, 2018
Safrole is extracted from the root-bark and fruit of the sassafras tree (Sassafras albidum) found in North America and Asia. It was frequently used as a flavoring agent in root beer and sassafras tea in North America until animal studies in the 1960s found that it was related to liver cancer in laboratory animals (Table 4). Mouse studies show that it not only crosses the placenta during gestation, but can also be transferred to newborns through the milk of lactating animals, and both scenarios resulted in gender-dependent increased cancer rates (Vesselinovitch, Rao, & Mihailovich, 1979). Safrole was administered by gastric intubation to pregnant and lactating C57 BL/6 J mice (120 ug/g body weight four times during gestation on days 12, 14, 16, and 18). Renal epithelial tumors were observed in 7% of female offspring exposed to safrole in utero. Among breastfed offspring, 34% (28/85) of males developed hepatocellular tumors compared to 2.5% (2/80) of females and 3% (3/100) of male controls by the 92nd week. Direct administration (gastric intubation) of safrole started at weaning age led to hepatocellular tumors in 48% (48/60) of females and 8% (8/60) of males over 92 weeks. The PubMed literature revealed only one reported case of a side effect in humans: excessive sweating after consuming sassafras tea (Haines, 1991).