Piperonyl butoxide

Piperonyl butoxide
IUPAC name 5-[2-(2-butoxyethoxy)ethoxymethyl] -6-propyl-1,3-benzodioxole
Identifiers
CAS number	51-03-6 Y
	KEGG	C18880 N
ChEMBL	CHEMBL1201131 N
Jmol-3D images	Image 1
SMILES CCCCOCCOCCOCC1=CC2=C(C=C1CCC)OCO2
Properties
Molecular formula	C19H30O5
Molar mass	338.438 g/mol
Density	1.05 g/cm3
Boiling point	180 °C (0.13 kPa)
Hazards
Flash point	170 °C; 338 °F; 443 K
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
Infobox references

Piperonyl butoxide (PBO) is an organic compound used as a component of pesticide formulations. It is a waxy white solid. It is a synergist. That is, despite having no pesticidal activity of its own, it enhances the potency of certain pesticides such as especially for carbamates, pyrethrins, pyrethroids, and rotenone.^[1] It is a semisynthetic derivative of safrole.^[2]

History

PBO was developed in the late 1930s and early 1940s to enhance the performance of the naturally derived insecticide pyrethrum. Pyrethrum is and was an important insecticide against mosquitoes and other disease-carrying vectors, thereby providing public health benefits, e.g., preventing malaria. Although exhibiting little intrinsic insecticidal activity of its own, PBO increases the effectiveness of pyrethrins and were thus are called synergists. PBO was first patented in 1947 in the US by Herman Wachs.^[3]

Uses

PBO was first registered in the United States in the 1950s. PBO is mainly used in combination with insecticides, such as natural pyrethrins or synthetic pyrethroids, in ratios (PBO: pyrethrins) ranging from 3:1 to 20:1. Appearing in over 1,500 U.S. EPA-registered products, PBO is one of the most commonly registered synergists as measured by the number of formulas in which it is present. It is approved for pre-harvest and post-harvest application to a wide variety of crops and commodities, including grain, fruits and vegetables. The application rates are low; the highest single rate is 0.5 lbs PBO/acre.

It is also used extensively with insecticides to control insect pests in and around the home, in food handling establishments such as restaurants as well as for human and veterinary applications against ectoparasites (head lice, ticks, fleas). A wide variety of water-based PBO-containing products such as crack and crevice sprays, total release foggers, and flying insect sprays are produced for and sold to consumers for home use. PBO has an important public health role as a synergist used in pyrethrins and pyrethroid formulations used for mosquito control (e.g. space sprays, surface sprays and bed nets).^[4] Because of its limited, if any, insecticidal properties, PBO is never used alone.^[5]

Mechanism of action

PBO acts as an insecticides synergist by inhibiting the natural defenses of the insects. PBO inhibits enzymes present in insects, most important of which is the mixed function oxidase System (MFOs) also known as the cytochrome P-450 system. The MFOs is the primary route for the detoxification of the insecticides in the insect. By minimizing the oxidative breakdown of insecticides like pyrethrins and the synthetic pyrethroids,^[6] higher levels remain in the insect to exercise their lethal effect.^[7] A important consequence of this property is that, by enhancing the insecticidal activity of a given level of insecticide, less pesticide can be used to achieve the same result.^[3]

PBO does not appear to have a significant effect on the MFOs in humans.^[8]

Other synergists for pyrethroid insecticides include Sesamex and "Sulfoxide" (not to be confused with the funcitonal group).^[2]

Regulatory

PBO is regulated in the United States and some other countries as a pesticide, even though PBO does not have this property. The U.S. Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the law that gives U.S. EPA its authority to regulate pesticides, includes certain synergists in its definition of a “pesticide” and is thus subject to the same approval and registration as products that kill pests, like the insecticides with which PBO is formulated.^[9] Pesticide registration is the process through which U.S. EPA examines the ingredients of a pesticide, where and how the pesticide is used (e.g., whole room fogger, crack-and-crevice, etc.), and the specific use pattern (amount and frequency of its use). U.S. EPA also evaluates the pesticide to ensure that it will not have unreasonable adverse effects on humans, the environment and non-target species. The U.S. EPA must register pesticides before they may be sold or distributed in the U.S. Registration is required for the pesticide itself, as well as for all products containing it. The World Health Organization recognizes the public health value of PBO when used in conjunction with synthetic the pyrethroids deltamethrin or permethrin used in mosquito nets.

Safety and toxicity

Numerous toxicology studies have been conducted over the past 40 years on PBO examining the full range of potential toxic effects.^[10] These studies were conducted in accord with regulatory requirements put forth by the U.S. EPA or other international agencies. Many were conducted following U.S. EPA Good Laboratory Practices (GLPs), a system of processes and controls to ensure the consistency, integrity, quality, and reproducibility of laboratory studies conducted in support of pesticides registration. The following types of studies have been conducted in support of PBO registration:

Acute Toxicity Studies

Acute toxicity studies are designed to identify potential hazards from acute exposures. The studies usually employ a single or few high doses over a short time frame. The data are used for the development of appropriate precautionary statements for pesticide product labels. Acute studies identify: • Dermal Toxicity • Eye Irritation • Inhalation Toxicity • Oral Toxicity • Skin Irritation • Skin Sensitization PBO has a low acute toxicity by oral, inhalation and dermal routes. It is minimally irritating to the eyes and skin. It is a dermal sensitizer.

Sub-chronic and Chronic/Carcinogenicity Studies

Sub-chronic and chronic studies examine the toxicity of longer term, repeated exposure to chemicals. They may range from 90 days for sub-chronic studies, to 12-24 months for full lifetime chronic studies, designed to determine potential for carcinogenesis. They are also intended to identify any non-cancer effects as well as a clear No Observable Adverse Effect Level (NOAEL) that is used for risk assessment. Studies conducted on PBO include: • 90 day inhalation toxicology study • 18 month chronic toxicity/carcinogenicity study in mice • 24 month chronic toxicity/carcinogenicity study in rats

NOAELs were derived for PBO from both sub-chronic and chronic studies. These NOAELs are used by EPA to conduct risk assessments for all individual uses of PBO to ensure that all registered products with PBO pose a reasonable certainty of no harm used according to the label directions.

PBO caused an increase in liver tumors in mice that ingested high levels of PBO in the diet for their entire lifetime. The scientific identification and analysis of the key events leading to the formation of the mouse live tumors suggests that the events are not likely to occur in humans.

The EPA rate PBO as a group C carcinogen in humans, possibly carcinogenic.

References