Piperonyl butoxide (PBO) is a pale yellow to light brown liquid organic compound used as a synergist component of pesticide formulations. That is, despite having no pesticidal activity of its own, it enhances the potency of certain pesticides such as carbamates, pyrethrins, pyrethroids, and rotenone. It is a semisynthetic derivative of safrole. 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, thus is called a synergist. PBO was first patented in 1947 in the US by Herman Wachs. 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 United States 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- and postharvest 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 used extensively as an ingredient with insecticides to control insect pests in and around the home, in food-handling establishments such as restaurants, and 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). Because of its limited, if any, insecticidal properties, PBO is never used alone. Mechanism of action PBO acts as an insecticide synergist by inhibiting the natural defense mechanisms of the insect, the most important of which is the mixed-function oxidase system, (MFOs) also known as the cytochrome P-450 system. The MFO system is the primary route of detoxification in insects, and causes the oxidative breakdown of insecticides such as pyrethrins and the synthetic pyrethroids - thus when PBO is added, higher