Piperonyl butoxide (PBO) is a pale yellow to light brown liquid[1] organic compound used as an adjuvant component of pesticide formulations for synergy.

Pyrethrum is a type of potent insecticide that kills mosquitoes and other disease-carrying vectors, thereby providing public health benefits, such as preventing malaria.

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.

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).

The United States Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the law that gives United States 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.

United States EPA also evaluates the pesticide to ensure that it will not have unreasonable adverse effects on humans, the environment and non-target species.

Numerous toxicology studies have been conducted over the past 40 years on PBO examining the full range of potential toxic effects.

[19] The Food Quality Protection Act (FQPA) of 1996 required the United States EPA to address the issue of endocrine disruption.

Since the passage of the FQPA, the US EPA has developed a two-tiered endocrine disruptor screening program (EDSP) designed to examine potential effects of substances on the estrogenic, androgenic, and thyroid (EAT) hormone systems in both humans and wildlife.

The purpose of Tier 2 is to determine whether a substance that interacts with the EAT hormone system exerts an adverse effect in humans or wildlife, and to develop a dose-response that, in association with exposure data, can be used to assess risk.

The Piperonyl Butoxide Task Force II, a group of companies that produces or markets PBO-containing products, has conducted all 11 EDSP Tier 1 screens and has submitted all required documentation and study reports.

Under the auspices of the United Nations, the Food and Agriculture Organization/World Health Organization (FAO/WHO) Joint Meeting on Pesticide Residues evaluated the entire body of toxicology of PBO several times since 1965.

[20] PBO has been found to inhibit the Hedgehog signaling pathway, a critical regulator of brain and face development in all vertebrates, via antagonism of the protein Smoothened (SMO).

[21] PBO was found to be capable of causing dose-dependent brain and face malformations in mice exposed during early development, including the rare human birth defect holoprosencephaly.

An epidemiology study found that PBO exposure was correlated with dose-dependent reductions in neurocognitive development in 3-year old children.

While the focus of the NDETF effort was on total-release foggers, a study was also conducted to determine both dispersion (air levels) and deposition (on flooring) of pyrethrins/PBO resulting from the use of a hand held aerosol spray can.

The US EPA, in their re-registration eligibility decision, determined "no risks of concern" existed for householders mixing, loading, handling, or applying PBO-containing products.