Piperonyl Butoxide

This review examines piperonyl butoxide (PBO), a pesticide synergist that inhibits insect cytochrome P450 enzymes and is also a recently recognized inhibitor of Sonic hedgehog (Shh) signaling. Animal studies show that in utero PBO exposure causes craniofacial malformations and neurodevelopmental abnormalities. Human studies are limited but suggest links to neurodevelopmental deficits. The authors highlight major knowledge gaps regarding PBO pharmacokinetics and gene‑environment interactions, calling for more rigorous investigation of its developmental toxicity.

Fig. 1 The Sonic hedgehog signaling pathway is susceptible to both genetic and environmental dysregulation. (Rivera-González KS, et al., 2021)

In a cluster randomized trial in Tanzania (48 clusters, 3‑year follow‑up), PBO‑pyrethroid long‑lasting insecticidal nets (LLINs) continued to offer some protection against malaria in the third year, though net usage had dropped to 31‑47%. At 28 months, malaria infection prevalence was lower in PBO‑pyrethroid LLIN groups (69.3% vs. 80.9%; OR 0.45). At 33 months, the effect was weaker in intention‑to‑treat analysis but still significant in per‑protocol (OR 0.34). Mosquito densities were similar between net types. To maximize impact, net re‑distribution cycles should align with LLIN lifespan.

Fig. 2 Anopheles densities per night per house for each vector species, proportion within group also presented in each of the bar chart. (Protopopoff N, et al., 2023)