Piperonal

log Kow = 1.05

1.05

Heliotrope odor

Floral odor

Sweet, flowery odor reminiscent of heliotrope

Sweet-floral, slightly spicey, heliotrope-like odor

Colorless, lustrous crystals

White or colorless crystals

Turns brown on exposure to light

Forms white crystals (MP 37 °C)

This chemical does not meet GHS hazard criteria for 15.9% (329 of 2063) of reports.

Warning

H317 (81.6%): May cause an allergic skin reaction [Warning Sensitization, Skin]

P261, P272, P280, P302+P352, P321, P333+P317, P362+P364, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 2063 reports by companies from 14 notifications to the ECHA C&L Inventory.

Danger

Chemical: 1,3-Benzodioxole-5-carboxaldehyde

List I Chemical: A chemical specified by regulation 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. (21 eCFR 1310.02)

Commission Regulation (EC) No 1565/2000 (Repealed by Com. Implementing Reg. (EU) No 872/2012)

1,3-Benzodioxole-5-carboxaldehyde is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 1,3-Benzodioxole-5-carboxaldehyde 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: 08-07-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/5265

Piperonal: Does not have an individual approval but may be used under an appropriate group standard

A skin irritant; May cause CNS depression; Emergency treatment: Irritants; [HSDB] An irritant; May cause CNS depression; [CAMEO] Safe when used as a flavoring agent in food; [JECFA] Caused hepatocellular necrosis in rats receiving intermittent doses for 6 weeks at >2100 mg/kg; [RTECS]

Synthetic flavoring substances and adjuvants /for animal drugs, feeds, and related products/ that are generally recognized as safe for their intended use, within the meaning of section 409 of the Act. Piperonal is included on this list.

Synthetic flavoring substances and adjuvants /for human consumption/ that are generally recognized as safe for their intended use, withn the meaning of section 409 of the Act. Piperonal is included on this list.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329. Effective date: 9/30/91; Reporting date: 11/27/91.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 1,3-Benzodioxole-5-carboxaldehyde is included on this list. Effective date: 9/30/91; Sunset date: 6/30/98.

PIPERONAL is an aldehyde. Aldehydes are frequently involved in self-condensation or polymerization reactions. These reactions are exothermic; they are often catalyzed by acid. Aldehydes are readily oxidized to give carboxylic acids. Flammable and/or toxic gases are generated by the combination of aldehydes with azo, diazo compounds, dithiocarbamates, nitrides, and strong reducing agents. Aldehydes can react with air to give first peroxo acids, and ultimately carboxylic acids. These autoxidation reactions are activated by light, catalyzed by salts of transition metals, and are autocatalytic (catalyzed by the products of the reaction). The addition of stabilizers (antioxidants) to shipments of aldehydes retards autoxidation. This compound is sensitive to light. This compound may react with oxidizing materials. (NTP, 1992)

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. Light sensitive. Storage class (TRGS 510): Non Combustible Solids

Keep in cool place protected from light.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Contaminated packaging: Dispose of as unused product.

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.

Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.

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

For more Preventive Measures (Complete) data for Piperonal (6 total), please visit the HSDB record page.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Eye/face protection: Safety glasses with side-shields conforming to EN166. 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: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

SCOPE: Piperonal is an aromatic compound found in vanilla and has a floral odor resembling vanillin. This study was aimed to test whether piperonal attenuates visceral adiposity induced by a high-fat diet (HFD) in mice and to explore the underlying molecular mechanisms. METHODS AND RESULTS: Male C57BL/6N mice were fed a normal diet, HFD, or 0.05% piperonal-supplemented HFD (PSD) for 10 weeks. PSD-fed mice showed attenuation of body weight gain, total visceral fat pad weights, and plasma lipid levels compared to HFD-fed mice. Piperonal supplementation of the HFD increased the mRNA expression of certain isotypes of adenylate cyclase (Adcy) and protein kinase A (PKA) in the white adipose tissue (WAT) of mice. The adipogenesis-related genes were downregulated, whereas fatty acid oxidation- and thermogenesis-related genes were upregulated in the WAT of PSD-fed mice compared to those in HFD-fed mice. Piperonal directly activated Adcy by decreasing the Km for its substrate (ATP) in plasma membranes prepared from the WAT of mice. Furthermore, piperonal-induced inhibition of adipocyte differentiation and elevation of Adcy and PKA activities in 3T3-L1 cells were abrogated by an Adcy inhibitor. CONCLUSION: The anti-adipogenic effect of piperonal in mice fed the high-fat diet appears to be associated with increased Adcy-PKA signaling in WAT.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 24(SRC), determined from a log Kow of 1.05(2) and a regression-derived equation(3), indicates that piperonal is expected to have very high mobility in soil(SRC). Volatilization of piperonal from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.6X10-7 atm-cu m/mole(SRC), derived from its vapor pressure, 0.01 mm Hg(4), and water solubility, 3,500 mg/L(5). Piperonal has a vapor pressure of 0.01 mm Hg(4) and exudes a floral odor under environmental conditions: therefore, piperonal may volatilize from dry soil(SRC). Utilizing the Japanese MITI test, 88% of the Theoretical BOD was reached in 2 weeks(6) indicating that biodegradation is an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 24(SRC), determined from a log Kow of 1.05(2) and a regression-derived equation(3), indicates that piperonal is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 5.6X10-7 atm-cu m/mole(SRC), derived from its vapor pressure, 0.01 mm Hg(5), and water solubility, 3,500 mg/L(6). According to a classification scheme(7), an estimated BCF of 2.3(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Utilizing the Japanese MITI test, 88% of the Theoretical BOD was reached in 2 weeks(8) indicating that biodegradation is an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), piperonal, which has a vapor pressure of 0.01 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase piperonal 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 14 hrs(SRC), calculated from its rate constant of 2.9X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Piperonal contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Piperonal was identified, not quantified, as a volatile component of the aqueous phase of cooked chicken broth(1).

Piperonal has been reported as found in the essential oils of Robinia pseudo-acacia and Eryngium poterium. It has also been detected in the oils of Spirea ulmaria and of leaves of Doryphora sassafras as well as Tahitian and Bourbon vanilla, camphor wood oil, and violet flowers cincrete and absolute, burley tobacco, rabbiteye blueberry, melon, pepper, cooked chicken, sherry and dill(1).

IDENTIFICATION AND USE: Piperonal is a solid. It is used in perfumery, flavors, and organic syntheses. A constituent of vanilla and cherry flavors. It has also been used for the treatment of head lice. HUMAN STUDIES: Ten grams of piperonal were ingested by man without any adverse effect. ANIMAL STUDIES: When rats were given 13-115 mg piperonal perorally for 5-9 days, fatty infiltration of the liver parenchymal cells was noted. Intragastric administration of 900 mg/kg bw per day to 3 male and 3 female rats for 4 days produced slight gross liver damage in some animals. Groups of 20 male and 20 female rats were fed on diets containing 0, 0.1 and 0.5 % piperonal for 2 years without any specific adverse effect. Based of a feeding study in rats at 500 mg/kg bw per day for a period of 15 weeks NOAEL of 500 mg/kg bw was determined. Piperonal was positive in the Bacillus subtilis DNA-repair test (Rec assay) without metabolic activation, but it was negative when tested in the Ames Salmonella reversion assay or in the Escherichia coli WP2 uvrA reversion test.

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for piperonal is available.[Available from, as of February 1, 2019: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

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/]

The Koc of piperonal is estimated as 24(SRC), using a log Kow of 1.05(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that piperonal is expected to have very high mobility in soil(SRC).

Piperonal (CAS # 120-57-0) was evaluated for acute dermal toxicity. The test substance was applied at a dose of 5.0 g/kg body weight to the unoccluded scapular region of 8 male and 8 female albino rats (Sprague-Dawley CD strain). No clinical signs or deaths occurred. All of the animals remained healthy and gained weight, except for 1 female who lost 10 grams in 14 days. At necropsy, there were no treatment-related signs. The dermal LD50 was determined to be greater than 5.0 g/kg body weight.

Piperonal (CAS # 120-57-0) was evaluated for primary dermal irritation. The test substance was applied to the cuff of 8 guinea pigs (sex and strain not indicated) at a dose range of 0.25-1.0 mg/kg. Strong skin irritation was evident at 24 hours with slight to gross edema and slight to severe erythema. At 48 hours, slight to moderate edema and erythema was found with eschar formation and necrotic area over part or all of the patch. At 1-week and 2-week observation, desquamation and alopecia was evident.

Piperonal (CAS # 120-57-0) was evaluated for primary eye irritation. Several dry crystals of the test substance were administered to 3 unwashed and 3 washed eyes of rabbits (sex and strain not indicated). Observations after 48 hours indicated that two rabbits (1 unwashed, 1 washed) had slight erythema on the nictating membrane. All animals were normal after 14 days.

/HUMAN EXPOSURE STUDIES/ Ten grams have been ingested by man without any adverse effect.

/EPIDEMIOLOGY STUDIES/ Background. Many families find regular checking of children's heads for head louse infestation too onerous and would prefer to be able to prevent infestation by use of a topical application that deters lice from infesting the head. Identification in the laboratory of a repellent activity for piperonal provided the basis for developing a spray product to repel lice. Methods. A proof of principle field study in Dhaka, Bangladesh, compared the effect of using 2% piperonal spray with that of a placebo in 105 children and adults from three communities with infestation levels close to 100%. All participants were treated for infestation and subsequent incidence of reinfestation monitored daily by investigators. A second randomised, controlled, double blind, study in North London, UK, evaluated the effect of the product in normal use. One hundred and sixty-three children from schools with a high level (20-25%) of infestation were treated and confirmed louse free and randomly divided between 2% piperonal, a placebo spray, and a control group for up to 22 weeks. Parents applied the spray and monitored for infestation. Regular investigator visits confirmed the parental monitoring and replenished supplies of spray. Results. In Dhaka, over 18 days there were only 4 infestations in the piperonal group and 8 in the placebo group. This difference was not significant (p = 0.312). In North London, there were 41 cases of infestation over the course of the study. Although there were fewer infestations in the piperonal group, analysis of time to first infestation showed a no significant (p = 0.4368) difference between groups. Conclusion. Routine use of 2% piperonal spray in communities with a high prevalence of head louse infestation may provide some protection from infestation. However, the difference between use of the product and no active intervention was sufficiently small that regular checking for presence of lice is likely to be a more practical and cost effective approach to prevention of infestation.

Synthetic flavoring substances and adjuvants /for animal drugs, feeds, and related products/ that are generally recognized as safe for their intended use, within the meaning of section 409 of the Act. Piperonal is included on this list.

Synthetic flavoring substances and adjuvants /for human consumption/ that are generally recognized as safe for their intended use, withn the meaning of section 409 of the Act. Piperonal is included on this list.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329. Effective date: 9/30/91; Reporting date: 11/27/91.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 1,3-Benzodioxole-5-carboxaldehyde is included on this list. Effective date: 9/30/91; Sunset date: 6/30/98.

Paths of metabolism: piperonal converted to piperonyl alcohol which is metabolized to glucoside conjugate. /From table/

In houseflies piperonal is metabolized to piperonylic acid which can be converted to a glycine conjugate or to an alanine conjugate or a glutamine conjugate. The alanine conjugate is further converted to a serine conjugate and the glutamine conjugate to a glutamate conjugate. /From table/

In rats piperonal is metabolized to piperonylic acid which is converted to glucuronide or to a glycine conjugate. /From table/

The beta-glucoside of piperonyl alcohol has also been found after injection of...piperonal into houseflies.

For more Metabolism/Metabolites (Complete) data for Piperonal (7 total), please visit the HSDB record page.

Found in various essential oils; Used in fragrances, flavoring agents, and suntan preparations; Also used as a mosquito repellent, laboratory reagent, organic intermediate, and synergist for pyrethrum and rotenone; [HSDB]

Farming (Pesticides) [Category: Industry]

Reported uses (ppm):

Has been used as pediculicide

Perfumery, suntan preparations, mosquito repellent, laboratory reagent, flavoring.

In perfumery, in cherry and vanilla flavors, in organic syntheses.

(1972) 8.92X10+7 G

(1975) 5.97X10+7 G

(1983) 5.0X10+6 g

2023: 8,500,000 - <10,000,000 lb

(1972) 5.63X10+7 G

(1975) GREATER THAN 4.54X10+5 G

Non-confidential 2016 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: Piperonal:

Piperonal (3,4-methylenedioxybenzaldehyde) is prepared in 94% yield via ozonolysis and reduction of isosafrole.

By the oxidation of isosafrole with potassium dichromate and sulfuric acid and subsequent steam distillation of piperonal.

Derivation: By oxidation of isosafrole.

The biotransformation of isosafrole by Cladosporium sphaerospermum yielded piperonal, which is a compound of great commercial importance in the flavor and fragrance industries. The experiments were performed in 500-mL conical flasks containing 100 mL of Czapek-modified medium in an orbital shaker with controlled agitation and temperature. Spores of C. sphaerospermum were used as inocula, and after 96 hr of incubation the substrate was added to the culture. Samples of 2 mL were withdrawn at 24-hr intervals and analyzed by gas chromatography, (GC) and/or GC/MS spectroscopy.

For more Methods of Manufacturing (Complete) data for Piperonal (8 total), please visit the HSDB record page.

Fragrance Ingredients

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavoring Agents -> JECFA Flavorings Index

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Piperonal

A chemical specified by regulation 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. (21 eCFR 1310.02)