2-(2-Butoxyethoxy)ethyl-6-propylpiperonylether

Pesticides -> Other Insecticides

Pesticide

Pesticide (Piperonyl butoxide) -> USDA PDB

Pesticide

log Kow = 4.75

4.29

ODORLESS

Mild odor

1.04 to 1.07 at 68 °F (NTP, 1992)

1.06 at 20 °C

Relative density (water = 1): 1.1

1.04-1.07

1.06 @ 20°C

Colorless liquid

Pale yellowish liquid

Light brown liquid

less than 1 mg/mL at 64 °F (NTP, 1992)

Miscible with methanol, ethanol, benzene, Freons, Geons, petroleum oils, and other organic solvents

In water, 14.3 mg/L at 25 °C

Solubility in water: none

340 °F (NTP, 1992)

171 °C

340 °F (171 °C) (open cup)

171 °C

340 °F

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Warning

H319: Causes serious eye irritation [Warning Serious eye damage/eye irritation]

P261, P264+P265, P271, P273, P280, P304+P340, P305+P351+P338, P319, P337+P317, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for 1.8% (5 of 279) of reports.

Warning

H319 (31.9%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

Chemical: 1,3-Benzodioxole, 5-[[2-(2-butoxyethoxy)ethoxy]methyl]-6-propyl-

1,3-Benzodioxole, 5-[[2-(2-butoxyethoxy)ethoxy]methyl]-6-propyl- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of 1,3-Benzodioxole, 5-[[2-(2-butoxyethoxy)ethoxy]methyl]-6-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)

Piperonyl butoxide is listed in the dataset of EPA Human Health Benchmarks for Pesticides under the Safe Drinking Water Act (40 eCFR 141)

Status: Active Update: 28-03-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/10134

Piperonyl butoxide: HSNO Approval: HSR002869 Approved with controls

This chemical is combustible. (NTP, 1992)

Combustible.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed over-the-counter drug products, incl piperonyl butoxide, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: the combination of pyrethrum extract (formerly named pyrethrins) and piperonyl butoxide in an aerosol dosage formulation is included in pediculicide drug products.

Pediculicide active ingredients. The active ingredients of the product consist of the combination of pyrethrum extract (providing a concentration of pyrethrins of 0.17 to 0.33 percent) with piperonyl butoxide (2 to 4 percent) in a nonaerosol dosage formulation.

USEPA/Office of Pesticide Programs; Reregistration Eligibility Decision Document - Piperonyl Butoxide (PBO). EPA 738-R-06-005 (June 2006). The RED summarizes the risk assessment conclusions and outlines any risk reduction measures necessary for the pesticide to continue to be registered in the U.S.[Available from, as of October 7, 2009: http://www.epa.gov/pesticides/reregistration/status.htm]

Bioassay of Piperonyl Butoxide for Possible Carcinogenicity (1979) Technical Rpt Series No. 120 DHEW Pub No. (NIH) 79-1375, U.S. Department of Health Education and Welfare, National Cancer Institute, Bethesda, MD 20014

Tolerances for residues of the insecticide piperonyl butoxide [(butyl carbityl)(6-propyl piperonyl)ether] are established in or on the following food commodities: [Table#3540]

Piperonyl butoxide may be safely used in accordance with the following prescribed conditions: (i) It is used or intended for use in combination with pyrethrins for control of insects: (A) In cereal grain mills and in storage areas for milled cereal grain products, whereby the amount of piperonyl butoxide is at least equal to but not more than 10 times the amount of pyrethrins in the formulation. (B) On the outer ply of multiwall paper bags of 50 pounds or more capacity in amounts not exceeding 60 milligrams per square foot, whereby the amount of piperonyl butoxide is equal to 10 times the amount of pyrethrins in the formulation. Such treated bags are to be used only for food, dried. (C) On cotton bags of 50 pounds or more capacity in amounts not exceeding 55 milligrams per square foot of cloth, whereby the amount of piperonyl butoxide is equal to 10 times the amount of pyrethrins in the formulation. Such treated bags are constructed with waxed paper liners and are to be used only for food, dried that contain 4 percent fat or less. (D) In two-ply bags consisting of cellophane/polyolefin sheets bound together by an adhesive layer when it is incorporated in the adhesive. The treated sheets shall contain not more than 50 milligrams of piperonyl butoxide per square foot (538 milligrams per square meter). Such treated bags are to be used only for packaging plum, prune, dried; grape, raisin; and other fruit, dried and are to have a maximum ratio of 3.12 milligrams of piperonyl butoxide per ounce of fruit (0.10 milligram of piperonyl butoxide per gram of product). (E) In food processing and food storage areas: Provided, That the food is removed or covered prior to such use.

Piperonyl butoxide may be safely used in accordance with the following prescribed conditions: It is used or intended for use in combination with pyrethrins and N-octylbicycloheptene dicarboximide for insect control in accordance with 21 CFR 178.3730.

Piperonyl butoxide may be safely used in accordance with the following prescribed conditions: A tolerance of 10 parts per million is established for residues of piperonyl butoxide in or on: (A) Grain, cereal, milled fractions when present therein as a result of its use in cereal grain mills and in storage areas for milled cereal grain products. (B) Food, dried when present as a result of migration from its use on the outer ply of multiwall paper bags of 50 pounds or more capacity. (C) Food treated in accordance with 21 CFR 178.3730. (D) Food, dried that contain 4 percent fat, or less, when present as a result of migration from its use on the cloth of cotton bags of 50 pounds or more capacity constructed with waxed paper liners. (E) Food treated in accordance with paragraph (a)(2)(i)(D) and (E) of this section.

For more FIFRA Requirements (Complete) data for Piperonyl butoxide (13 total), please visit the HSDB record page.

Fires involving this material should be controlled using a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Use foam, powder, carbon dioxide.

Fresh air, rest.

Remove contaminated clothes. Rinse and then wash skin with water and soap.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Give one or two glasses of water to drink. Rest. Refer for medical attention .

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.

Safe Storage of Pesticides. Always store pesticides in their original containers, complete with labels that list ingredients, directions for use, and first aid steps in case of accidental poisoning. Never store pesticides in cabinets with or near food, animal feed, or medical supplies. Do not store pesticides in places where flooding is possible or in places where they might spill or leak into wells, drains, ground water, or surface water.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

This product is toxic to aquatic organisms, including fish and invertebrates. Do not discharge effluent containing this product into lakes, streams, ponds, estuaries, oceans or other waters unless in accordance with the requirements of a National Pollutant Discharge Elimination System (NPDES) permit and the permitting authority has been notified in writing prior to discharge. Do not discharge effluent containing this product to sewer systems without previously notifying the local sewage treatment plant authority. For guidance contact your State Water Board or Regional Office of the EPA. Do not contaminate water when disposing of equipment wash-waters.

If a spill occurs, clean it up promptly. Don't wash it away. Instead, sprinkle the spill with sawdust, vermiculite, or kitty litter. Sweep it into a plastic garbage bag, and dispose of it as directed on the pesticide product label.

After Applying a Pesticide, Indoors or Outdoors. To remove pesticide residues, use a bucket to rinse tools or equipment three times, including any containers or utensils that you used when mixing the pesticide. Then pour the rinsewater into the pesticide sprayer and reuse the solution by applying it according to the pesticide product label directions. After applying any pesticide wash your hands and any other parts of your body that may have come in contact with the pesticide. To prevent tracking pesticides inside, remove or rinse your boots or shoes before entering your home. Wash any clothes that have been exposed to a lot of pesticide separately from your regular wash.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, FIRST REMOVE ALL SOURCES OF IGNITION. Then, use absorbent paper to pick up all liquid spill material. Your contaminated clothing and absorbent paper should be sealed 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: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Safe Disposal of Pesticides. The best way to dispose of small amounts of excess pesticides is to use them - apply them - according to the directions on the label. If you cannot use them, ask your neighbors whether they have a similar pest control problem and can use them. If all of the remaining pesticide cannot be properly used, check with your local solid waste management authority, environmental agency, or health department to find out whether your community has a household hazardous waste collection program or a similar program for getting rid of unwanted, leftover pesticides. These authorities can also inform you of any local requirements for pesticide waste disposal.

Safe Disposal of Pesticides. An empty pesticide container can be as hazardous as a full one because of residues left inside. Never reuse such a container. When empty, a pesticide container should be rinsed carefully three times and the rinsewater thoroughly drained back onto the sprayer or the container previously used to mix the pesticide. Use the rinsewater as a pesticide, following label directions. Replace the cap or closure securely. Dispose of the container according to label instructions. Do not puncture or burn a pressurized container like an aerosol - it could explode. Do cut or puncture other empty pesticide containers made of metal or plastic to prevent someone from reusing them. Wrap the empty container and put it in the trash after you have rinsed it.

SRP: Contaminated protective clothing should be segregated in a manner that results in no direct personal contact by personnel who handle, dispose of, or clean the clothing. Quality assurance procedures to confirm the efficacy of the cleaning procedures should be implemented prior to the decontaminated protective clothing being returned for reuse by the workers. Contaminated clothing (including shoes/socks) should not be taken home at end of shift, but should remain at employee's place of work for cleaning.

Users should wash hands before eating, drinking, chewing gum, using tobacco, or using the toilet. Users should remove clothing/PPE immediately if pesticide gets inside. Then wash thoroughly and put on clean clothing. Users should remove PPE immediately after handling this product. Wash the outside of gloves before removing. As soon as possible, wash thoroughly and change into clean clothing.

Follow manufacturer's instructions for cleaning/maintaining PPE. If no such instructions for washables exist, use detergent and hot water. Keep and wash PPE separately from other laundry. Discard clothing and other absorbent material that have been drenched or heavily contaminated with the product's concentrate. Do not reuse them.

Do not apply directly to water, to areas where surface water is present or to intertidal areas below the mean high water mark. Do not contaminate water when disposing of equipment wash-waters or rinsate.

For more Preventive Measures (Complete) data for Piperonyl butoxide (8 total), please visit the HSDB record page.

Inhibition of metab of drugs has also been demonstrated ... Piperonyl butoxide competitively inhibits n-demethylation of ethylmorphine and o-demethylation of p-nitroanisole...

... Mouse trials indicate that it can dramatically incr toxicity of freons and griseofulvin or vice versa.

In the case of certain sulfur-containing organophosphorus insecticides, which require metabolic activation ... /it is/ antagonistic to development of normal insecticidal potency.

Pyrethrin synergists such as piperonyl butoxide ... are effective for DDT, ...for carbamates, ... and for diazinon, trichlorfon, and other phosphates, ... but they are antagonistic for malathion ...

For more Interactions (Complete) data for Piperonyl butoxide (11 total), please visit the HSDB record page.

LC50; Species: Anas platyrhynchos (Mallard duck, age 10 days) diet >5620 ppm for 8 days

LC50; Species: Colinus virginianus (Northern bobwhite, age 10 days) diet >5620 ppm for 8 days

LD50; Species: Colinus virginianus (Northern bobwhite, age 39 weeks) oral via capsule >2250 mg/kg

LC50; Species: Coturnix japonica (Japanese quail, 14 days old) oral (5 day ad libitum in diet) >5,000 ppm /Technical grade, 100% active ingedient/

For more Ecotoxicity Values (Complete) data for Piperonyl butoxide (38 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values ranging from 399-830(2) indicate that piperonyl butoxide is expected to have moderate to low mobility in soil(SRC). Volatilization of piperonyl butoxide from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 8.9X10-11 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Piperonyl butoxide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.2X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). A half-life in aerobic soils of 14 days(2) suggests that biodegradation may be an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), Koc values ranging from 399-830(2) indicate that piperonyl butoxide is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 8.9X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 27(SRC), from a log Kow of 4.75(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). A half-life in aerobic soils of 14 days(2) suggests that biodegradation may be 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), piperonyl butoxide, which has an estimated vapor pressure of 2.6X10-7 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase piperonyl butoxide 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 3.6 hours(SRC), calculated from its rate constant of 1.1X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase piperonyl butoxide may be removed from the air by wet or dry deposition(SRC). Piperonyl butoxide contains chromophores that absorb at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC); it was rapidly degraded (half-life 8.4 hours) in aqueous solution when illuminated with sunlight(5).

In a study in which 531 samples of grain and beans from the U.S., Japan, Australia, Korea, Canada and other countries were analyzed, the following food products detected piperonyl butoxide: 3 wheat from the U.S. (max concentraion 1.4 ppm); 1 barley from the U.S. (0.8 ppm); 2 barley from Australia (max concn 1.4 ppm); it was not detected (0.1 ppm detection limit) in hulled and unhulled rice, buck wheat, rye, oats, corn, milo, soy beans or red beans(1). Piperonyl butoxide was identified, not quantified (0.20 ppm limit of quantitation), in domestic and imported pears(2). Piperonyl butoxide was detected in 46 out of 769 domestic apples at a max concentration of 1.6 ppm and in 52 out of 1,062 imported apples at a maximum concentration of 0.47 ppm(3). The NY State Department of Agriculture detected piperonyl butoxide in three sweet potato samples at concentrations of 0.0003, 0.00017 and 0.007 ppm(4).

/BIRDS and MAMMALS/ PBO is practically nontoxic to birds on an acute basis. There were no mortalities observed at the highest concentration tested for acute oral (2250 mg/kg bw) or for the sub-acute dietary studies (5620 ppm). EPA did not calculate Reportable Quantities from the acute toxicity data because no mortality was seen at very high concentrations indicting minimal adverse acute effects to birds. From chronic avian toxicity data, a NOEC of 300 ppm was estimated from an avian reproduction study in which adult and hatchling body weight and food consumption, number of eggs laid, number of eggs cracked, and eggshell thickness effects were observed at the lowest observed effect concentration (LOEC) of 1200 ppm.

/AQUATIC SPECIES/ Freshwater Fish. PBO is moderately toxic to freshwater fish on an acute basis (LC50 = 1.9 ppm). A no observed effect concentration (NOEC) of 0.04 ppm was estimated from a chronic early life stage of fish study with fathead minnow in which embryo survival at hatch and length and weight of larvae was observed at the lowest observed effect concentration (LOEC) of 0.11 ppm. Freshwater invertebrates. PBO ranges from moderately toxic (LC50 = 12.0 ppm) to highly toxic (LC50 = 0.51 ppm) to freshwater invertebrates on an acute basis. The species selected for RQ calculation was Daphnia magna with an LC50 of 0.51 ppm. A NOEC of 0.030 ppm was estimated from a chronic life cycle study where Daphnia magna exhibited reproduction affects at the lowest observed effect concentration (LOEC) of 0.047 ppm. Estuarine fish. PBO is moderately toxic (LC50 = 3.94 ppm) to estuarine/marine fish based on observed effects to sheepshead minnow on an acute basis. There are no chronic data available for estuarine fish. Estuarine/Marine invertebrates. PBO is highly toxic to estuarine invertebrates (LC50 = 0.49 ppm). There are no chronic data available for estuarine/marine invertebrates. Amphibians. PBO is highly toxic to amphibians on an acute basis (LC50 = 0.21 ppm).

/AQUATIC SPECIES/ Freshwater Fish. Fathead minnow (Pimephales promelas). Exposure scenario: Chronic. NOEC= 0.04 ppm, LOEC = 0.11 ppm. Effect: Survival and growth /from table/

/AQUATIC SPECIES/ Freshwater Invertebrates. Waterflea (Daphnia magna). NOEC = 0.03 ppm LOEC = 0.047 ppm. Effect: reproduction Exposure scenario chronic. /from table/

For more Ecotoxicity Excerpts (Complete) data for Piperonyl butoxide (9 total), please visit the HSDB record page.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=51-03-6]

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed over-the-counter drug products, incl piperonyl butoxide, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: the combination of pyrethrum extract (formerly named pyrethrins) and piperonyl butoxide in an aerosol dosage formulation is included in pediculicide drug products.

Pediculicide active ingredients. The active ingredients of the product consist of the combination of pyrethrum extract (providing a concentration of pyrethrins of 0.17 to 0.33 percent) with piperonyl butoxide (2 to 4 percent) in a nonaerosol dosage formulation.

Tolerances for residues of the insecticide piperonyl butoxide [(butyl carbityl)(6-propyl piperonyl)ether] are established in or on the following food commodities: [Table#3540]

Piperonyl butoxide may be safely used in accordance with the following prescribed conditions: (i) It is used or intended for use in combination with pyrethrins for control of insects: (A) In cereal grain mills and in storage areas for milled cereal grain products, whereby the amount of piperonyl butoxide is at least equal to but not more than 10 times the amount of pyrethrins in the formulation. (B) On the outer ply of multiwall paper bags of 50 pounds or more capacity in amounts not exceeding 60 milligrams per square foot, whereby the amount of piperonyl butoxide is equal to 10 times the amount of pyrethrins in the formulation. Such treated bags are to be used only for food, dried. (C) On cotton bags of 50 pounds or more capacity in amounts not exceeding 55 milligrams per square foot of cloth, whereby the amount of piperonyl butoxide is equal to 10 times the amount of pyrethrins in the formulation. Such treated bags are constructed with waxed paper liners and are to be used only for food, dried that contain 4 percent fat or less. (D) In two-ply bags consisting of cellophane/polyolefin sheets bound together by an adhesive layer when it is incorporated in the adhesive. The treated sheets shall contain not more than 50 milligrams of piperonyl butoxide per square foot (538 milligrams per square meter). Such treated bags are to be used only for packaging plum, prune, dried; grape, raisin; and other fruit, dried and are to have a maximum ratio of 3.12 milligrams of piperonyl butoxide per ounce of fruit (0.10 milligram of piperonyl butoxide per gram of product). (E) In food processing and food storage areas: Provided, That the food is removed or covered prior to such use.

Piperonyl butoxide may be safely used in accordance with the following prescribed conditions: It is used or intended for use in combination with pyrethrins and N-octylbicycloheptene dicarboximide for insect control in accordance with 21 CFR 178.3730.

Piperonyl butoxide may be safely used in accordance with the following prescribed conditions: A tolerance of 10 parts per million is established for residues of piperonyl butoxide in or on: (A) Grain, cereal, milled fractions when present therein as a result of its use in cereal grain mills and in storage areas for milled cereal grain products. (B) Food, dried when present as a result of migration from its use on the outer ply of multiwall paper bags of 50 pounds or more capacity. (C) Food treated in accordance with 21 CFR 178.3730. (D) Food, dried that contain 4 percent fat, or less, when present as a result of migration from its use on the cloth of cotton bags of 50 pounds or more capacity constructed with waxed paper liners. (E) Food treated in accordance with paragraph (a)(2)(i)(D) and (E) of this section.

For more FIFRA Requirements (Complete) data for Piperonyl butoxide (13 total), please visit the HSDB record page.

Piperonyl butoxide is not a pesticide, but acts as a synergist to increase the activity of pesticides such as carbamates, pyrethrins, pyrethroids, and rotenone. Piperonyl butoxide inhibits the mixed-function oxidase (MFO) system of an insect. The MFO system is the insects natural defense system and causes the oxidative breakdown of insecticides. Thus, by inhibiting this system piperonyl butoxide promotes higher levels of insecticide and allows for lower doses to be used for a lethal effect.

To clarify the mechanism of piperonyl butoxide (PBO)-induced hepatocarcinogenesis in mice, male mice were subjected to a two-thirds partial hepatectomy, N-diethylnitrosamine (DEN) initiation, and a diet containing 0.6% PBO for eight weeks. The incidence of gamma-glutamyl transpeptidase (GGT)-positive foci and PCNA-positive cells was significantly increased in the DEN + PBO group compared with the DEN-alone group. Real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis showed up-regulation of genes related to metabolism, such as cytochrome P450 1A1 and 2B10, and metabolic stress, such as Por, Nqo1, Nrf2, abcc3, and abcc4. Early responsive genes downstream of mitogen-activated protein kinase (MAPK), such as c-fos, c-jun, c-myc, and activating transcription factor 3 (ATF3), were also up-regulated in this group. Positive immunohistochemical staining for ATF3 was diffusely observed in nonproliferating hepatocytes of the DEN + PBO group, but altered foci were negative or weakly positive for ATF3. The nuclei of hepatocytes within ATF3-negative foci were positive for cyclin D. Thus PBO can induce oxidative stress, activate the MAPK pathway, and increase ATF3 transcript levels in hepatocytes outside the altered foci during the early stage of PBO-induced hepatocarcinogenesis in mice. .

... Male F344 rats were administered piperonyl butoxide mixed in the diet at concentrations of 0 (negative control), 0.05, 0.2 or 2% for 2 days, 1, 2, and 4 weeks. As a positive control, phenobarbital was administered to rats for up to 4 weeks as a 0.1% solution in the drinking water. Increased liver weight, centrilobular hepatocellular hypertrophy due to increased smooth endoplasmic reticulum, decreased numbers and areas of connexin 32-positive spots per hepatocyte, and increased cell proliferation were observed in rats treated with 0.2 and 2% piperonyl butoxide. Similar results were obtained for 0.1% phenobarbital treated rats. Hepatocellular necrosis suggestive of hepatotoxicity was also observed in the 2% piperonyl butoxide group. These results indicate that the promoting mechanism of piperonyl butoxide in hepatocarcinogenesis is similar to that of phenobarbital, involving an ability to induce CYP isoenzymes and inhibit gap junctional intercellular communication. In addition, increased cell proliferation following hepatocellular necrosis may also play a role at high doses.

Piperonyl butoxide (PBO) is an insecticide synergist known to inhibit the activity of cytochrome P450 enzymes. ... Little is known about how insects respond to PBO exposure at the gene transcription level. The authors have characterized the transcriptional response of the Drosophila melanogaster genome after PBO treatment, using both a custom-designed 'detox' microarray, containing cytochrome P450 (P450), glutathione S-transferase (GST) and esterase genes, and a full genome microarray. A subset of P450 and GST genes is identified, along with additional metabolic genes, that are induced by PBO. The gene set is an extremely similar gene set to that induced by phenobarbital, a compound for which pretreatment is known to confer tolerance to a range of insecticide compounds.

Piperonyl butoxide (PBO), alpha-[2-(2-butoxyethoxy)ethoxy]-4,5-methylene-dioxy-2-propyltoluene, is widely used as a synergist for pyrethrins. In order to clarify the possible mechanism of non-genotoxic hepatocarcinogenesis induced by PBO, molecular pathological analyses consisting of low-density microarray analysis and real-time reverse transcriptase (RT)-PCR were performed in male ICR mice fed a basal powdered diet containing 6000 or 0 ppm PBO for 1, 4, or 8 weeks. The animals were sacrificed at weeks 1, 4, and 8, and the livers were histopathologically examined and analyzed for gene expression using the microarray at weeks 1 and 4 followed by real-time RT-PCR at each time point. Reactive oxygen species (ROS) products were also measured using liver microsomes. At each time point, the hepatocytes of PBO-treated mice showed centrilobular hypertrophy and increased lipofuscin deposition in Schmorl staining. The ROS products were significantly increased in the liver microsomes of PBO-treated mice. In the microarray analysis, the expression of oxidative and metabolic stress-related genes--cytochrome P450 (Cyp) 1A1, Cyp2A5 (week 1 only), Cyp2B9, Cyp2B10, and NADPH-cytochrome P450 oxidoreductase (Por) was over-expressed in mice given PBO at weeks 1 and 4. Fluctuations of these genes were confirmed by real-time RT-PCR in PBO-treated mice at each time point. In additional real-time RT-PCR, the expression of Cyclin D1 gene, key regulator of cell-cycle progression, and Xrcc5 gene, DNA damage repair-related gene, was significantly increased at each time point and at week 8, respectively. These results suggest the possibility that PBO has the potential to generate ROS via the metabolic pathway and to induce oxidative stress, including oxidative DNA damage, resulting in the induction of hepatocellular tumors in mice.

32 hours.

In order to determine the human in vivo percutaneous absorption of piperonyl butoxide, a commercial formulation containing (14C)piperonyl butoxide (3.4 mCi/uM) was applied to the ventral forearm of six human volunteers. The formulation contained 3.0% piperonyl butoxide. Spreadability studies showed that concn 75.8 ug piperonyl butoxide/sq cm (used in this study) would be consistent with levels found in actual use. The forearms were thoroughly cleansed with soap and water 30 min after application (as recommended for actual use). Percutaneous absorption was determined by urinary cumulative excretion following dose application. With a 7 day urinary accumulation, ... 2.1+/- 0.6% of the dose of piperonyl butoxide applied was absorbed through the forearm skin. 1 hr after application blood samples contained no detectable radioactivity. The percutaneous absorption ... of piperonyl butoxide from the scalp was calculated to be 8.3%. ... The calculated half life of (14)C excretion was 32 hr for piperonyl butoxide. ...

Piperonyl butoxide is minimally absorbed in humans. Metabolism has not been studied.

[14C]-piperonyl butoxide (PBO) was administered to male and female rats by gavage at a dose rate of 50 or 500 mg/kg body weight. In all cases, the radioactivity was rapidly excreted with 87-99% being found in the 0-48-hr excreta and the majority of the dose (64.1-85.0%) being eliminated in feces. The metabolism of PBO was complex with over 25 peaks of radioactivity being seen by radio-high-performance liquid chromatography (HPLC). Using HPLC/tandem mass spectrometry (MS/MS) and nuclear magnetic resonance (NMR), 12 urine metabolites were assigned structures together with four plus PBO in feces. Metabolism occurred at two sites: the methylenedioxy ring, which opened to form a catechol that could then undergo methylation, and the 2-(2-butoxyethoxy)ethoxymethyl side-chain, which underwent sequential oxidation to a series of alcohols and acids. The identified metabolites accounted for approximately 60% of the administered dose.

In mice, the major metabolic pathway for piperonyl butoxide ... incl cleavage of the methylenedioxyphenol residue and exhalation of methylene carbon atom as CO2. Products in urine ... comprise many compounds without methylenedioxyphenyl residue plus small amt of 6-propylpiperonylic acid and its glycine conjugate ...

In mammals (and also in insects), oxidative attack on the carbon atom of the methylenedioxy group leads to the formation of the dihydroxyphenyl compound. Oxidative degradation of the side-chain also occurs.

In a metabolism study, a mixture of non-radiolabeled (93.4% a.i.) and phenyl labeled 14C-piperonyl butoxide (100% radiochemical purity) was administered to 4 CRL:CD rats/sex/dose by single gavage exposure at dose levels of 50 or 500 mg/kg body weight. The main route of excretion was via feces which contained 82.9-85.1% of the administered radioactivity at the low dose level and 64.1-75.9% at the high dose level at 168 hours. The percent radioactive dose excreted in the urine during 168 hours was 11.1-14.4% in low dose group and 19.5-30.2% in the high dose group. The majority of the administered radioactivity was excreted in 0-48 hour urine and feces samples in both dose groups. The percent of administered dose in carcass was below 0.5% in either low dose or high dose groups. The total percent of radioactive dose recovered in both dose groups ranged between 97.4% and 99.6%. There is no significant difference in the excretion pattern either between two dose groups or between sexes in the same dose group. M1 and M3 are the major metabolites excreted in feces. M1 was identified as unchanged PBO corresponding to 15.6-23.9% of administered dose. M3 was identified as PBO with methylenedioxy ring opened to form catechol and found at 17.4-19.7% of the administered dose. M2 and M4/M5 were also identified but were present in low amounts (4-6% of administered radioactivity) in high dose group. Several radioactive peaks (~20 peaks) were observed in urine samples and none of these individual peaks exceeded 5% of the administered radioactivity. The significant metabolite in male urine was found to be M14 which occurred at 3% of the administered dose. In females, the significant urinary metabolites identified were M6 and the combined M7/M8 which contained 5 and 9% of the administered dose, respectively. Although there was no significant difference in the excretion of metabolites between two dose groups, metabolites M5, M8, M9 and M10 were predominantly found in female urine samples and M14 was reported only in male urine samples. Based on the identification of metabolites, the authors proposed three major reactions in the metabolism of PBO: 1) Opening of the methylenedioxy ring to form the catechol; 2) Sequential cleavage of the 2-(2-butoxyethoxy)ethoxymethyl side chain to produce series of alcohols and acids; 3) Conjugation of one of the phenolic groups to yield glucuronide, sulfate or methoxy derivative.

Piperonyl butoxide is applied topically. In a study evaluating the 7-day urinary accumulation of piperonyl butoxide after topical application, it was found that approximately 2% of the dose was absorbed through the skin. The percutaneous absorption when applied to the scalp was found to be 8.3%.

In an absorption study in human volunteers, it was found that, if absorbed, piperonyl butoxide was eliminated in urine.

Piperonyl butoxide is minimally absorbed in humans. Volume of distribution has not been studied.

Clearance of piperonyl butoxide has not been studied.

No ... significant percutaneous absorption /in test mammals/.

Distribution of radioactivity showed that the brain and thoracic ganglia, fore- and hind-gut, and Malpighian tubules of the kidney contained greatest amt of ... /(14)C-labeled piperonyl butoxide/ per unit wt ... /in Madeira roaches/.

Used as a synergist to increase the effectiveness of pyrethrins and other insecticides; [EPA Pesticides]

Farming (Pesticides) [Category: Industry]

For Piperonyl butoxide (USEPA/OPP Pesticide Code: 067501) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Insecticide synergist, esp for pyrethrum and rotenone

Synergist for the pyrethrins and related insecticides

Synergist ... used in these four general ways: preharvest and postharvest uses on many agricultural crops; direct and indirect treatments of livestock animals and premises; treatments of commercial and industrial facilities and storage areas where raw and processed food/feed commodities are stored or processed; and mosquito abatement areas ... Used with insecticides such as the pyrethrins, pyrethroids, and some organophosphates to target a large numbers of pests including ants, worms, beetles, mites, flies, gnats, spiders, weevils, caterpillars, grubs, moths, ticks, lice, wasps, aphids, midges, and fish.

2023: 250,000 - <550,000 lb

(1975) 4.54X10+8 grams (consumption)

(1976) Probably greater than 2.27x10+6 grams

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#3541]

Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: 1,3-Benzodioxole, 5-[[2-(2-butoxyethoxy)ethoxy]methyl]-6-propyl-. Aggreated National Production Volume: <500,000 lbs.[US EPA; Non-Confidential 2006 Inventory Update Reporting. National Chemical Information. 1,3-Benzodioxole, 5-[

Synergist with insecticides, of which 80% is used in household, commercial, and industrial applications and 20% in agriculture for livestock and poultry (1975)

Approximately 5,000 to 10,000 pounds of PBO are used annually in the U.S. on agricultural crops, with highest usage on potatoes (30% crop treated).

Reaction of the chloromethyl derivative of dihydrosafrole with the sodium salt of butyl carbitol

... By condensing 5-chloromethyl-6-propyl-1,3-benzodioxole with sodium-2(2-butoxyethoxy)ethoxide ...

H. Wachs, US patents, 2,485,681; 2,550,737 (1949, 1951, both to US Industrial Chemicals); Science 105, 530 (1947).

Formulation Types: Aerosol, liquid, ready-to-use solution, dust, wettable powder, microencapsulate, impregnated material, pressurized gas, pressurized liquid, pressurized spray, combustible coil, micro-emulsion, dilutable concentrate, shampoo, towelette, pour-on (spot-on), and water-based concentrate. PBO is usually formulated with insecticides and other synergists.

A complete list of currently registered active pesticide products can be found in the National Pesticide Information Retrieval System's USEPA/OPP Registered and Cancelled Pesticide Product Database. These pesticide products are registered for use in the U.S. but approved products may change periodically and so federal, state and local authorities must be consulted for currently approved products.

Final Fly-T: Active Ingredients: 15.0% Butoxypolypropylene glycol, 1.0% Piperonyl butoxide, 0.1% Pyrethrins

Automist Insect Killer: Active Ingredients 3.0% N-Octyl bicycloheptene dicarboximide, 2.0% Piperonyl butoxide,1.0% Pyrethrins

For more Formulations/Preparations (Complete) data for Piperonyl butoxide (167 total), please visit the HSDB record page.

Adjuvants

SYNERGISTS

Pesticide, Fertilizer, and Other Agricultural Chemical Manufacturing

1,3-Benzodioxole, 5-[[2-(2-butoxyethoxy)ethoxy]methyl]-6-propyl-: ACTIVE

First registered in the United States in the 1950s. Currently there are approximately 1500 end-use products registered in the United States containing /piperonyl butoxide/ as a synergist with other active ingredients for use on agricultural and residential sites.

PBO is a classified as a synergist. As a synergist, PBO works by inhibiting the detoxification of the pesticide by the insect pests.

Piperonyl butoxide was first registered in the 1950's and acts as a synergist. Synergists are chemicals that primarily enhance the pesticidal properties of other active ingredients, such as pyrethrins and synthetic pyrethroids. PBO is a registered active ingredient in over 1500 products used to control many different types of flying and crawling insects and arthropods, although there are no products that contain only PBO. It is registered for use in agricultural, residential, commercial, industrial, and public health sites. Approximately 100,000-200,000 pounds are sold every year for non-agricultural uses, with only about 5,000-10,000 pounds used in agriculture.

Anvil is a pesticide product that is used to control mosquitoes in outdoor residential and recreational areas. It contains sumithrin, piperonyl butoxide and petroleum solvents. ... Piperonyl butoxide does not directly kill insects on its own but acts to increase the ability of sumithrin to kill insects. Other pesticide products containing these ingredients are used indoors and on pets to control insects such as fleas, ticks, and ants.