Isosafrole

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage. Storage class (TRGS 510): 10: Combustible liquids

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/

ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Soak up with inert absorbent material and dispose of as hazardous waste. Keep in suitable, closed containers for disposal.

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/

SMALL SPILLS AND LEAKAGE: You should dampen the solid spill material with acetone, then transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the adsorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a strong soap and water solution. Do not reenter the contaminate area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U141, 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 Isosafrole (7 total), please visit the HSDB record page.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Avoid contact with skin and eyes. Avoid inhalation of vapor or mist. Normal measures for preventive fire protection.

ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Environmental precautions: Do not let product enter drains.

For more Preventive Measures (Complete) data for Isosafrole (13 total), please visit the HSDB record page.

MINIMUM PROTECTIVE CLOTHING: If Tyvek-type disposable protective clothing is not worn during handling of this chemical, wear disposable Tyvek-type sleeves taped to your gloves.

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

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/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 210(SRC), determined from a structure estimation method(2), indicates that isosafrole is expected to moderate mobility in soil(SRC). Volatilization of isosafrole from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 0.036 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Isosafrole has an estimated vapor pressure of 0.023 mm Hg(SRC), determined from a fragment constant method(2) and exists as a liquid under environmental conditions: therefore, isosafrole may volatilize from dry soil. 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 isosafrole 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 0.036 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 80(SRC), from an estimated log Kow of 3.37(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is moderate(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), isosafrole, which has an estimated vapor pressure of 0.023 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 isosafrole is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-lives for this reaction in air is estimated to be 5 and 4.6 hours(SRC), calculated from rate constants of 7.6X10-11 and 8.4X10-11 cu cm/molecule-sec at 25 °C(SRC), for the cis- and trans- isomers, respectively, that were derived using a structure estimation method(2). Vapor-phase isosafrole is also degraded in the atmosphere by reaction with ozone(SRC); the half-lives for this reaction in air are estimated to be 4 and 2 hours(SRC), calculated from rate constants of 6.8X10-17 and 1.4X10-18 cu cm/molecule-sec(SRC), for the cis- and trans- isomers, respectively, that were derived using a structure estimation method(2). Isosafrole absorbs UV light at wavelengths >380 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: Isosafrole is a colorless liquid. Isosafrole exists as a trans-(E-)isomer (beta-isosafrole) and as a cis-(Z-)isomer (alfa-isosafrole). Isosafrole is used in fragnances, but it is no longer used in foods in the United States. Safrole and isosafrole can be used as precursors for 3,4-methylenedioxymethylamphetamine (MDMA). HUMAN STUDIES: When tested at 8% in petrolatum, it produced no irritation after a 48-hr closed-patch test on human subjects. A maximization test was carried out on 25 volunteers and produced no sensitization reactions. A 19-year-old man developed a schizophrenia-like psychosis after ingesting isosafrole. His use of amphetamines and LSD failed to produce a similar syndrome. ANIMAL STUDIES: Isosafrole applied full strength to intact or abraded rabbit skin for 24 hr under occlusion was moderately irritating. Isosafrole is a weak rodent hepatocarcinogen, the carcinogenicity is probably mediated by a nongenotoxic mechanism. Isosafrole metabolites may give rise to only very low binding to liver DNA in mice. Hepatomas and pulmonary tumors were observed in isosafrole-treated mice. Hepatoma incidence tended to be higher in males than females with isosafrole. Isosafrole (19,7% cis/78.2% trans isomer) did not induce gene mutations in Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, TA 1538 or in Escherichia coli WP 2 uvr A with or without metabolic activation.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of February 4, 2019: http://actor.epa.gov/dashboard/]

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/

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

Of the two isomers (cis- and trans-), trans-isosafrole is more stable and has been isolated in the pure state, most likely occurring in essential oil of ylang-ylang. The compound has been identified in oils of Illicium religiosum and Ligusticum acutilobum Sieb and Zucc(1). Isosafrole occurs naturally as a principal component of the essential oil star anise and also at low concentrations in the essential oils of other spices. Its distribution is generally similar to that of safrole which is found in several essential oils including the essential oils of sassafras, nutmeg, mace, ginger, cinnamon, and black pepper(2).

/HUMAN EXPOSURE STUDIES/ Tested at 8% in petrolatum, it produced no irritation after a 48-hr closed-patch test on human subjects.

/HUMAN EXPOSURE STUDIES/ A maximization test was carried out on 25 volunteers. The material was tested at a concentration of 8% in petrolatum and produced no sensitization reactions.

/CASE REPORTS/ A 19-year-old man developed a schizophrenia-like psychosis after ingesting isosafrole. His use of amphetamines and LSD failed to produce a similar syndrome.

Isosafrole

Group 3: Not classifiable as to its carcinogenicity to humans

Volume 10: (1976) Some Naturally Occurring Substances

1987

1987

The following chemicals have been specifically designated by the Administrator of the Drug Enforcement Administration as the listed chemicals subject to the provisions of this part and parts 1309 and 1313 of this chapter. Each chemical has been assigned the DEA Chemical Code Number set forth opposite it. Isosafrole (DEA Code: 8704) is included on this List I.

List I chemical means a chemical specifically designated by the Administrator in section 1310.02(a) of this chapter that, in addition to legitimate uses, is used in manufacturing a controlled substance in violation of the Act and is important to the manufacture of a controlled substance.

Exempt chemical mixtures. (a) The chemical mixtures meeting the criteria in paragraphs (c) or (d) of this section are exempted by the Administrator from application of sections 302, 303, 310, 1007, 1008, and 1018 of the Act (21 U.S.C. 822, 823, 830, 957, 958, and 971) to the extent described in paragraphs (b) and (c) of this section. (b) No exemption granted pursuant to this section 1310.12 or section 1310.13 affects the criminal liability for illegal possession, distribution, exportation, or importation of listed chemicals contained in the exempt chemical mixture or the civil liability for unlawful acts related to exempt chemical mixtures, including distribution in violation of 21 U.S.C. 842(a)(11). (c) Mixtures containing a listed chemical in concentrations equal to or less than those specified in the "Table of Concentration Limits" are designated as exempt chemical mixtures for the purpose set forth in this section. The concentration is determined for liquid-liquid mixtures by using the volume or weight and for mixtures containing solids or gases by using the unit of weight.[Table#4234]

(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).

U141; As stipulated in 40 CFR 261.33, when isosafrole, 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).

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 100 lb or 45.4 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).