Absorption, Distribution and Excretion
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/.
Piperonyl butoxide is poorly absorbed from GI tract. In 2 experiments, 78% & 87%, respectively, of dose admin orally to dogs were recovered in feces. The small proportion that was absorbed from GI tract was rapidly excreted in urine. Intratracheal admin led to more prolonged excretion of metabolites in the bile and urine, but even in this instance residues in lung tissue were less than they were following iv admin.
... 48 hr after oral admin of ... (14)C-piperonyl butoxide ... to mice, 76% of (14)C had been excreted in expired air, 7% in urine, and 4% in feces ... In rats, about 40% was excreted as (14)C-CO2 in expired air, 8 hr after iv dose ...
For more Absorption, Distribution and Excretion (Complete) data for Piperonyl butoxide (9 total), please visit the HSDB record page.

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Metabolism / Metabolites
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.

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Biological Half-Life
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. ...

Protein Binding
Piperonyl butoxide is minimally absorbed in humans. Protein binding has not been studied.

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Toxicity Data
LC50 (rat) > 5,900 mg/m3

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Interactions
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.

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Non-Human Toxicity Values
LD50 Rat oral 11.5 g/kg
LD50 Rat (male) acute oral 4570 mg/kg
LD50 Rat (female) acute oral 7220 mg/kg
LD50 Rat percutaneous >7950 mg/kg
For more Non-Human Toxicity Values (Complete) data for Piperonyl butoxide (11 total), please visit the HSDB record page.

Therapeutic Uses
Piperonyl butoxide itself has no known therapeutic use. ... Formulations of pyrethrins containing piperonyl butoxide are used as a pediculicide to control the body louse Pediculus humanus humanus, the head louse, P. humanus capitus, and the crab louse Pthirus pubis ... .

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Pharmacodynamics
Piperonyl butoxide does not affect the mixed-function oxidase system in humans. In small trials in human volunteers, usual doses of piperonyl butoxide had no effect on humans.

C19H30O5

338.44

338.209

51-03-6

Piperonyl butoxide-d9;1329834-53-8

5794

Colorless to light yellow ointment

1.1±0.1 g/cm3

396.2±0.0 °C at 760 mmHg

165.3±27.2 °C

0.0±0.8 mmHg at 25°C

1.503

4.23

0

5

13

24

312

0

CCCC1=C(COCCOCCOCCCC)C=C2OCOC2=C1

FIPWRIJSWJWJAI-UHFFFAOYSA-N

InChI=1S/C19H30O5/c1-3-5-7-20-8-9-21-10-11-22-14-17-13-19-18(23-15-24-19)12-16(17)6-4-2/h12-13H,3-11,14-15H2,1-2H3

5-[2-(2-butoxyethoxy)ethoxymethyl]-6-propyl-1,3-benzodioxole

NSC-8401; NSC 8401; Piperonyl butoxide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Ethanol : ~100 mg/mL (~295.47 mM)
DMSO : ~100 mg/mL (~295.47 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.39 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (7.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)