5-Propyl-1,3-benzodioxol

Dihydrosafrole

HCID 7197CAS 94-58-6

Grundinformationen

Standard-SMILES
CCCc1ccc2c(c1)OCO2
InChIKey
MYEIDJPOUKASEC-UHFFFAOYSA-N
Summenformel
C10H12O2
Durchschnittliche Molmasse
164,2 g/mol
Monoisotopische Masse
164,08372962

Überblick

Dihydrosafrole can cause cancer according to an independent committee of scientific and health experts.

Namen und Bezeichner

Bevorzugter Name
Dihydrosafrole
IUPAC
5-propyl-1,3-benzodioxole
Lokaler Name
5-Propyl-1,3-benzodioxol
Englischer Name
DIHYDROSAFROL
Summenformel
C10H12O2
Molmasse
164.2

Namen und Synonyme

Dihydrosafrole5-Propyl-1,3-benzodioxole94-58-6Safrole, dihydro-1,3-Benzodioxole, 5-propyl-2',3'-Dihydrosafrole1,2-(METHYLENEDIOXY)-4-PROPYLBENZENE4-Propyl-1,2-methylenedioxybenzene2ML63PLH7GBenzene, 1,2-methylenedioxy-4-propyl-NSC-27867DTXSID7020475
Weitere Namen anzeigen
NSC 33707AKOS 208-12Dihydroisosafrolercrawastenumberu0902’,3’-dihydrosafrole
RefChem:133927DTXCID30475202-344-9Dihydrosafrol5-Propylbenzo[d][1,3]dioxoleRCRA waste number U090NSC 278675-propyl-2H-1,3-benzodioxole

Datenbank-Bezeichner

CAS
94-58-6
PubChem CID
7197
DTXSID
DTXSID7020475
ChEBI
CHEBI:82319
UNII
2ML63PLH7G
EC Number
202-344-9
Nikkaji
J15.552G

Eigenschaften

Berechnete Struktureigenschaften

XLogP
3,2
Polarare Oberfläche (TPSA)
18,5 Ų
H-Brücken-Donoren
0
H-Brücken-Akzeptoren
2
Frei drehbare Bindungen
2
Schwere Atome
12

Experimentelle und physikochemische Eigenschaften

Chemical Classes · 2 Einträge

Biological Agents -> Plant Toxins

Carcinogens

CosmeticsCosmetics ingredient -> Fragrance
OdorOdor reminiscent of sassafras
Density1.065 at 25 °C/25 °C
Color/Form · 3 Einträge

Oily liquid

Colorless liquid

Colorless to yellowish liquid

Solubility · 3 Einträge

Miscible with ethanol, ether, acetic acid, benzene

Somewhat soluble in alcohol

Soluble in carbon tetrachloride

Physikochemische Eigenschaften

Siedepunkt
251.67 °C · 251.67°C (rough estimate)
Dichte
1.0326 · 1.0326 (rough estimate)
Brechungsindex
1.532 · 1.5320 (estimate)
Löslichkeit
Chloroform (Slightly), Ethyl Acetate (Slightly)
Aggregatzustand
Oil
Farbe
Colourless to Brown

Sicherheit und Regulatorisches

GHS-Klassifizierung

GHS Classification · 6 Einträge

This chemical does not meet GHS hazard criteria for 63.4% (92 of 145) of all reports.

Warning

H351 (26.9%): Suspected of causing cancer [Warning Carcinogenicity]

P203, P280, P318, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 145 reports by companies from 5 notifications to the ECHA C&L Inventory.

Warning

Gefahrenhinweise

Regulatory Information · 6 Einträge

Chemical: 1,3-Benzodioxole, 5-propyl-

Hazard Traits - Carcinogenicity

1,3-Benzodioxole, 5-propyl- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 1,3-Benzodioxole, 5-propyl- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 08-03-2019 https://echa.europa.eu/registration-dossier/-/registered-dossier/12771

1,3-Benzodioxole, 5-propyl-: Does not have an individual approval but may be used under an appropriate group standard

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

Other Safety InformationIMAP assessments - 1,3-Benzodioxole, 5-propyl-: Environment tier I assessment
DOT LabelClass 9
Fire HazardsExcerpt from ERG Guide 171 [Substances (Low to Moderate Hazard)]:
Health HazardsExcerpt from ERG Guide 171 [Substances (Low to Moderate Hazard)]:
Hazards Summary · 1 Eintrag

Emergency treatment: Sassafras oil; Safrole is the toxic agent in sassafras oil; Safrole is classified as 2B (possible human carcinogen) by IARC; Safrole is metabolized in the body to 1'-hydroxysafrole; Ingestion of 5 ml of sassafras oil can cause severe symptoms (tachycardia, hypotension, and respiratory paralysis) or death; Large doses may damage the liver; Drinking 10 cups of sassafras tea caused sweating in one adult subject; [HSDB] Sassafras is an abortifacient and narcotic; [Olson, p. 389] Used as a stimulant, antispasmodic, and purifier, sassafras has potential hepatotoxic and carcinogenic effects; [Goldfrank, p. 643] The lethal dose of sassafras oil is about 5 mL; The oil contains about 80% saffrole; [Leikin, p. 955] A skin irritant; [MSDSonline] See Safrole.

Sicherheit und Schutzausrüstung

Fire FightingExcerpt from ERG Guide 171 [Substances (Low to Moderate Hazard)]:
First AidExcerpt from ERG Guide 171 [Substances (Low to Moderate Hazard)]:
Storage Conditions · 1 Eintrag

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

Cleanup Methods · 1 Eintrag

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

Nonfire Spill ResponseExcerpt from ERG Guide 171 [Substances (Low to Moderate Hazard)]:
Disposal Methods · 5 Einträge

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U090, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for Dihydrosafrole (6 total), please visit the HSDB record page.

Toxikologische Informationen

Interactions · 4 Einträge

Safrole, isosafrole and dihydrosafrole have been shown experimentally to be active synergists for pyrethrum and 1-naphthyl methyl carbamate (Sevin) in common with other methylene-dioxyphenyl cmpd. As class, these substances act as competitive inhibitors of microsomal mixed-function oxidases in houseflies.

Pyrethrin synergists such as ... /certain/ methylenedioxyphenyl compounds serve to synergize many of modern insecticides against houseflies that have become resistant to them. They are thus effective for DDT, ... carbamates, ... diazinon, trichlorfon, & other phosphates ... they inhibit ... microsomal hydroxylation. /Methylenedioxyphenyl cmpd/

Methylenedioxybenzenes (MDBs) and structurally related alkenylbenzenes were compared for their effectiveness in preventing carbon tetrachloride (CCl4)-induced liver necrosis in mice. Pretreatment with isosafrole, safrole, dihydrosafrole, and benzodioxole at dosages as low as 10 mg/kg significantly prevented the increase in plasma transaminase levels and histochemical changes associated with CCl4-induced liver necrosis, whereas piperonyl butoxide (PBO), eugenol, isoeugenol, sesamol, and curcumin did not prevent CCl4 hepatotoxicity even at 200 mg/kg. However, isosafrole was only partly hepatoprotective if administered 10 min after the toxicant. Liver microsomes isolated 1 hr after isosafrole but not after PBO administration had a markedly decreased CYP2E1 activity. Isosafrole, safrole, dihydrosafrole, and benzodioxole in vitro also inhibited CYP2E1-dependent metabolism more effectively than eugenol and isoeugenol, whereas PBO did not inhibit CYP2E1 activity. The protective effects of isosafrole, safrole, and benzodioxole were therefore predominantly attributed to their ability to inactivate CYP2E1, the major isozyme involved in CCl4 bioactivation. The marked potentiation of CCl4 hepatotoxicity in CYP2E1-induced mice was also completely prevented by isosafrole but not PBO pretreatment, supporting the hypothesis that CYP2E1 inhibition by isosafrole contributes to its hepatoprotective effect against CCl4. Isosafrole and safrole also prevented bromotrichloromethane (BrCCl3)-induced hepatocyte cytotoxicity, whereas PBO was ineffective.

1. Inhibitory activity of dihydrosafrole towards benzo[a]pyrene (BP) hydroxylase activity in hepatic microsomes from beta-naphthoflavone (BNF)-induced rats, and in reconstituted systems containing cytochrome P-450c, increased dramatically on preincubation of the inhibitor with NADPH; no inhibition occurred without preincubation. The level of BP hydroxylase inhibition was associated with the progressive formation of the 456 nm dihydrosafrole metabolite-cytochrome P-450c spectral complex during preincubation. 2. Inhibition of BP hydroxylase by dihydrosafrole in control microsomes, and inhibition of ethoxyresorufin O-deethylase (EROD) in microsomes (control or BNF-induced) and in reconstituted systems with cytochrome P-450c, did not require preincubation and apparently was not dependent on prior formation of the dihydrosafrole metabolite-cytochrome P-450 complex. 3. Kinetic studies established that, following preincubation with NADPH, dihydrosafrole was a noncompetitive inhibitor of both BP hydroxylase and EROD activities. In the absence of preincubation, dihydrosafrole was an effective competitive inhibitor of EROD in BNF-induced microsomes and in reconstituted systems with cytochrome P-450c. 4. Both ethoxyresorufin and benzo[a]pyrene inhibited the development of the type I optical difference spectrum of dihydrosafrole in reconstituted systems containing cytochrome P-450c. Inhibition by ethoxyresorufin was competitive while that caused by benzo[a]pyrene was noncompetitive in nature. 5. The type II ligand phenylimidazole was an effective noncompetitive inhibitor of EROD activity but failed to exert any inhibitory effect on cytochrome P-450c-mediated BP hydroxylase activity. Phenylimidazole inhibited formation of the dihydrosafrole type I optical difference spectrum non-competitively. 6. The results indicate that ethoxyresorufin and benzo[a]pyrene may occupy different binding sites on cytochrome P-450c and that dihydrosafrole binds primarily to the site utilized by ethoxyresorufin.

Environmental Fate · 3 Einträge

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 210(SRC), determined from a structure estimation method(2), indicates that dihydrosafrole is expected to have moderate mobility in soil(SRC). Volatilization of dihydrosafrole from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 0.17 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Dihydrosafrole has an estimated vapor pressure of 0.055 mm Hg(SRC), determined from a fragment constant method(2) and exists as a liquid under environmental conditions; therefore, dihydrosafrole may volatilize from dry soil(SRC). Biodegradation data in soil were not available(SRC, 2018).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 210(SRC), determined from a structure estimation method(2), indicates that dihydrosafrole is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 0.17 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 4 hrs and 5 days, respectively(SRC). According to a classification scheme(4), an estimated BCF of 110(SRC), from an estimated log Kow of 3.58(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is high(SRC). Biodegradation data in water were not available(SRC, 2018).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), dihydrosafrole, which has an estimated vapor pressure of 0.055 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase dihydrosafrole is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 8 hrs(SRC), calculated from its rate constant of 5.1X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Dihydrosafrole absorbs UV light at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Adverse EffectsNeurotoxin - Other CNS neurotoxin
Toxicity Summary · 1 Eintrag

IDENTIFICATION AND USE: Dihydrosafrole is a colorless oily liquid. It is used in fragrances. The FDA does not permit dihydrosafrole to be used in foods. HUMAN STUDIES: Tested at 12% in petrolatum, it produced no irritation after a 48 hr closed-patch test in 25 human subjects. It was not sensitizing in the maximization test in volunteers. ANIMAL STUDIES: Applied full strength on intact or abraded rabbit skin it was mildly irritating. Dihydrosafrole 1000 ppm fed to rats in the diet for 2 yr retarded growth in females and caused macroscopic and microscopic liver changes. Tumors of esophagus (papillomas and epidermoid carcinomas) developed in 75% of rats fed 5000 or 10,000 mg/kg of diet levels and in 20% of rats fed 2500 mg/kg of diet. Hepatomas, pulmonary tumors and lymphomas were observed in dihydrosafrole-treated mice. Hepatoma incidence tended to be higher in males than females with dihydrosafrole. No significant mutagenic activity was noted in Salmonella typhimurium strains TA1535 and TA100 with or without metabolic activation.

Medical Surveillance · 1 Eintrag

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

Soil Adsorption/Mobility · 1 Eintrag

Using a structure estimation method based on molecular connectivity indices(1), the Koc of dihydrosafrole can be estimated to be 210(SRC). According to a classification scheme(2), this estimated Koc value suggests that dihydrosafrole is expected to have moderate mobility in soil(SRC).

Regulatorische Informationen

FDA Requirements · 1 Eintrag

(a) Safrole is the chemical 4-allyl-1,2-methylenedioxy-benzene, C10H10O2. It is a natural constituent of the sassafras plant. Oil of sassafras is about 80 percent safrole. Isosafrole and dihydrosafrole are derivatives of safrole, and have been used as flavoring compounds. (b) Food containing any added safrole, oil of sassafras, isosafrole, or dihydrosafrole, as such, or food containing any safrole, oil of sassafras, isosafrole, or dihydrosafrole, e.g., sassafras bark, which is intended solely or primarily as a vehicle for imparting such substances to another food, e.g., sassafras tea, is deemed to be adulterated in violation of the act based upon an order published in the Federal Register of December 3, 1960 (25 FR 12412).

RCRA Requirements · 1 Eintrag

U090; As stipulated in 40 CFR 261.33, when dihydrosafrole, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

CERCLA Reportable Quantities · 1 Eintrag

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 10 lb or 4.54 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

Sicherheitsdaten

tsca
TSCA listed
hs_code
29329990
Giftige Stoffe Daten
94-58-6(Hazardous Substances Data)

Chemie und Industrie

Pharmakologische Informationen

Metabolism/Metabolites · 5 Einträge

In mice, major metabolic pathway for ... dihydrosafrole ... incl cleavage of methylenedioxyphenol residue & exhalation of methylene carbon atom as CO2.

Dihydrosafrole yields 4-propylcatechol probably in mouse & fly. /From table/

Treatment of rats with safrole, isosafrole, dihydrosafrole, or methylenedioxystyrylamyl ketone (150 mg/kg, ip daily for 3 days) resulted in the formation of 455-nm cytochrome P450-methylenedioxyphenyl metabolite complex.

... Clearance of dihydrosafrole and its metabolites from both the ethmoid (olfactory) and maxillary (respiratory) turbinate regions of Beagle dogs and Cynomolgus monkeys was examined. Nasopharyngeal mucus was collected at frequent intervals during periodic instillation of dihydrosafrole (and, for the dogs, 24 hr after instillation). Blood, urine and feces were collected to examine dihydrosafrole clearance from the nose during instillations and up to 48 hr after completion of the nasal instillations of (3)H-dihydrosasfrole. ... Most of the recovered radioactivity was in urine and blood samples over the first 24 hr. Radioactivity was recovered from the nasopharyngeal mucus in both organic extractable and water soluble forms. ... (3)H-dihydrosafrole instilled in either turbinate region was metabolized to 2-methoxy-4-propylphenol, 2-methoxy-4-propenylphenol and 1-(3,4-methylenedioxyphenyl)propan-1-ol. A number of minor metabolites were produced in both species. One mucus sample from an ethmoid-instilled dog contained 1-(3,4-methylenedioxyphenyl)propene (isosafrole) as a metabolite. ... interspecies, inter-individual and inter-regional differences occur in the metabolism of nasally deposited dihydrosafrole in monkeys and dogs.

For more Metabolism/Metabolites (Complete) data for Dihydrosafrole (6 total), please visit the HSDB record page.

Absorption, Distribution and ExcretionIn mice given ... (14)C-labeled safrole or dihydrosafrole orally, 96% and 101% of radioactivity ... recovered; 64 and 61% were found in CO2, 18 & 23% in urine, 6 and 5% in feces and intestine, 2 & 2.5% in liver & 6 and 9% in carcasses ...

Verwendung und Herstellung

Uses · 6 Einträge

Used in essential oil compositions; Formerly used as a fragrance in cosmetics and a flavoring agent in root beer; Used outside the US to make piperonyl butoxide; [HSDB]

Essential oil compositions.

FRAGRANCE IN COSMETICS (FORMER USE); FLAVORING AGENT IN ROOT BEER (FORMER USE); CHEM INT FOR PIPERONYL BUTOXIDE (NON-USA USE).

In public use since the 1950s. Use if fragrances in the USA amounts to less than 2000 lb/yr.

Table: Concentration in final product (%) [Table#4304]

Prohibited for use in food.

U.S. Production · 5 Einträge

2023: 50,000 - <250,000 lb

(1977) AT LEAST 1.82X10+8 G

(1982) NOT PRODUCED COMMERCIALLY IN USA.

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#4302]

Non-confidential 2016 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: 1,2-(Methylenedioxy)-4-propylbenzene:

Industry UsesNot Known or Reasonably Ascertainable
Methods of Manufacturing · 2 Einträge

CATALYTIC HYDROGENATION OF SAFROLE OR ISOSAFROLE.

From safrole or isosafrole by hydrogenation over nickel at 200 °C; by hyrdogenation of either safrole in alcoholic solution in the presence of palladium or activated carbon or of 3,4-methylenedioxy cinnamic aldehyde.

Household ProductsCosmetics product ingredient: Dihydrosafrole
General Manufacturing Information · 3 Einträge

Pesticide, Fertilizer, and Other Agricultural Chemical Manufacturing

1,3-Benzodioxole, 5-propyl-: ACTIVE

Although there is no evidence that ... /it/ is produced commercially in USA, it is known to be produced as intermediate in the prodn of piperonyl butoxide ...

Anwendungen

OccurrenceHas apparently not been reported to occur in nature.

VerwendenSafrole derivative. Carcinogenic.

Darstellung

synthetischeBy catalytic hydrogenation of safrole (Arctander, 1969).

Zugehörige Reaktionen

3

Verknüpfte Notizen

Wird geladen…