Klaren WD, Hoberman AM, Hauswirth JW. Reproduction and developmental toxicological evaluation of piperonyl butoxide (PBO). Poster presented at Society of Toxicology Annual Meeting, San Diego, CA, March 2022.
Piperonyl Butoxide (PBO) is a widely used and generally accepted pesticidal synergist found in agricultural as well as consumer pest control products. The importance of the use of PBO derives from the ability to maintain insecticidal efficacy while reducing the amount and application of active insecticide ingredients. Recent investigations into the potential reproductive and developmental toxicity of PBO has raised concerns about its use. Specifically, concerns have risen from research related to inhibition of the sonic hedgehog pathway by PBO ultimately leading to downstream developmental effects. As part of the inherent hazard evaluation and regulatory obligations for PBO, an extensive toxicological data set is available to address the proposed concerns. Such a dataset includes studies compliant with good laboratory practices and with EPA testing guidelines. Three studies, used for regulatory submissions and here-to-fore unpublished in full produced by Piperonyl Butoxide Task Force II (PBTFII), investigated the reproductive and developmental potential for PBO: (1) a dietary two-generation reproduction study in rats [0, 300, 1000, 5000 ppm], (2) an oral gavage developmental toxicity study in rats [0, 200, 500, 1000 mg/kg/day], and (3) an oral gavage developmental toxicity study in rabbits [0, 50, 100, 200 mg/kg/day]. Prominent findings from the first study include decreases in body weight across both generations and sexes at the highest dose, 5000 ppm. No effects on reproduction were observed. In the developmental toxicity study in rats decreases in body weight and feed consumption occurred in the dams at >500 mg/kg/day with an increase in urogenital wetness and urine staining at 1000 mg/kg/day. No developmental toxicity was observed. In the rabbit study, no maternal or developmental toxicity was observed. These results support a low potential for reproductive and developmental effects of PBO with the lowest NOAEL of 1000 ppm or 89 and 102 mg/kg/day for males and females, respectively. The peer review publication of these studies is forthcoming and will help place the more recent findings of the potential for reproductive and developmental effects of PBO into the appropriate context.