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Chemosphere Feb 2021Piperonyl butoxide (PBO) is a semisynthetic chemical present in hundreds of pesticide formulations used in agricultural, commercial, and residential settings. PBO acts... (Review)
Review
Piperonyl butoxide (PBO) is a semisynthetic chemical present in hundreds of pesticide formulations used in agricultural, commercial, and residential settings. PBO acts as a pesticide synergist by inhibiting insect cytochrome P450 enzymes and is often present at much higher concentrations than active insecticidal ingredients. PBO was recently discovered to also inhibit Sonic hedgehog (Shh) signaling, a key molecular pathway in embryonic development and in brain and face morphogenesis. Recent animal model studies have shown that in utero PBO exposure can cause overt craniofacial malformations or more subtle neurodevelopmental abnormalities. Related adverse developmental outcomes in humans are etiologically heterogeneous, and, while studies are limited, PBO exposure during pregnancy has been linked to neurodevelopmental deficits. Contextualized in PBO's newly recognized mechanism as a Shh signaling inhibitor, these findings support more rigorous examination of the developmental toxicity of PBO and its potential contribution to etiologically complex human birth defects. In this review, we highlight environmental sources of human PBO exposure and summarize existing animal studies examining the developmental impact of prenatal PBO exposure. Also presented are critical knowledge gaps in our understanding of PBO's pharmacokinetics and potential role in gene-environment and environment-environment interactions that should be addressed to better understand the human health impact of environmental PBO exposure.
Topics: Animals; Embryonic Development; Female; Hedgehog Proteins; Humans; Insecticides; Morphogenesis; Pesticides; Piperonyl Butoxide; Pregnancy
PubMed: 33007564
DOI: 10.1016/j.chemosphere.2020.128414 -
Reproductive Toxicology (Elmsford, N.Y.) Mar 2021A semi-synthetic methylenedioxyphenyl compound piperonyl butoxide (PBO) has been used as a ubiquitous synergist to increase the insecticidal effect of pesticides for...
A semi-synthetic methylenedioxyphenyl compound piperonyl butoxide (PBO) has been used as a ubiquitous synergist to increase the insecticidal effect of pesticides for agricultural and household use. Despite previously demonstrated effects of PBO, the detailed mechanism of PBO in spermatozoa and reproductive toxic effects on male germ cells have not been fully elucidated. Therefore, this study evaluated the effects of PBO on various sperm functions during capacitation and clarified the mechanisms of reproductive toxic effects on male fertility at different concentrations of PBO (0.1, 1, 10, and 100 μM). Sperm motility and kinematics were assessed using computer-assisted sperm analysis and the status of capacitation was evaluated using combined H33258/chlortetracycline (CTC) staining. Intracellular adenosine triphosphate (ATP) and cell viability levels were also measured. In addition, protein kinase A (PKA) activity and protein tyrosine phosphorylation were evaluated. In addition, in vitro fertilization was performed to determine the effects of PBO on cleavage and blastocyst formation rates. We found that PBO significantly decreased sperm motility, kinematics, and acrosome-reacted and capacitated spermatozoa. In addition, PBO suppressed the intracellular ATP levels and directly affected cell viability. Moreover, PBO detrimentally decreased the activation of PKA and altered the levels of tyrosine-phosphorylated proteins. Consequently, cleavage and blastocyst formation rates were significantly reduced in a dose-dependent manner. In line with our observations, the synergist of pesticides PBO may directly and/or indirectly cause disorder in male fertility. Hence, we suggest that careful attention is made to consider reproductive toxicity when using PBO as a synergist.
Topics: Acrosome Reaction; Animals; Cell Survival; Embryonic Development; Female; Fertilization; Infertility, Male; Male; Mice; Mice, Inbred ICR; Pesticide Synergists; Piperonyl Butoxide; Reproduction; Sperm Capacitation; Sperm Motility; Spermatozoa
PubMed: 33515694
DOI: 10.1016/j.reprotox.2021.01.010 -
Journal of Agricultural and Food... Sep 2022As one of the sources of biodiesel, microalgae are expected to solve petroleum shortage. In this study, different concentrations of piperonyl butoxide were added to the...
As one of the sources of biodiesel, microalgae are expected to solve petroleum shortage. In this study, different concentrations of piperonyl butoxide were added to the culture medium to investigate their effects on the growth, pigment content, lipid accumulation, and content of carotenoids in . The results showed that piperonyl butoxide addition significantly decreased the biomass, chlorophyll content, and total carotenoid content but hugely increased the lipid accumulation. With the treatment of 150 ppm piperonyl butoxide combined with 8000 Lux light intensity, the final lipid accumulation and single-cell lipid content were further increased by 21.79 and 76.42% compared to those of the control, respectively. The lipid accumulation in is probably related to the increased expression of in under the action of piperonyl butoxide. The phylogenetic trees of and other oil-rich plants were constructed by multiple sequence alignment of , demonstrating their evolutionary relationship, and the tertiary structure of was predicted. In conclusion, piperonyl butoxide has a significant effect on lipid accumulation in , which provides valuable insights into chemical inducers to enhance biodiesel production in microalgae to solve the problem of diesel shortage.
Topics: Biofuels; Carotenoids; Chlorophyceae; Chlorophyll; Lipids; Microalgae; Petroleum; Phylogeny; Piperonyl Butoxide
PubMed: 36122177
DOI: 10.1021/acs.jafc.2c03006 -
Ecotoxicology and Environmental Safety Jun 1978
Review
Topics: Animals; Biotransformation; Carcinogens, Environmental; Chemical Phenomena; Chemistry; Humans; Mutagens; Pesticide Synergists; Piperonyl Butoxide
PubMed: 398254
DOI: 10.1016/s0147-6513(78)80025-6 -
Scientific Reports Apr 2022Pirimiphos-methyl is a pro-insecticide requiring activation by mosquito cytochrome P450 enzymes to induce toxicity while PBO blocks activation of these enzymes in...
Pirimiphos-methyl is a pro-insecticide requiring activation by mosquito cytochrome P450 enzymes to induce toxicity while PBO blocks activation of these enzymes in pyrethroid-resistant vector mosquitoes. PBO may thus antagonise the toxicity of pirimiphos-methyl IRS when combined with pyrethroid-PBO ITNs. The impact of combining Olyset Plus and PermaNet 3.0 with Actellic 300CS IRS was evaluated against pyrethroid-resistant Anopheles gambiae s.l. in two parallel experimental hut trials in southern Benin. The vector population was resistant to pyrethroids and PBO pre-exposure partially restored deltamethrin toxicity but not permethrin. Mosquito mortality in experimental huts was significantly improved in the combinations of bendiocarb IRS with pyrethroid-PBO ITNs (33-38%) compared to bendiocarb IRS alone (14-16%, p < 0.001), demonstrating an additive effect. Conversely, mortality was significantly reduced in the combinations of pirimiphos-methyl IRS with pyrethroid-PBO ITNs (55-59%) compared to pirimiphos-methyl IRS alone (77-78%, p < 0.001), demonstrating evidence of an antagonistic effect when both interventions are applied in the same household. Mosquito mortality in the combination was significantly higher compared to the pyrethroid-PBO ITNs alone (55-59% vs. 22-26% p < 0.001) showing potential of pirimiphos-methyl IRS to enhance vector control when deployed to complement pyrethroid-PBO ITNs in an area where PBO fails to fully restore susceptibility to pyrethroids.
Topics: Animals; Anopheles; Insecticide Resistance; Malaria; Mosquito Control; Mosquito Vectors; Organothiophosphorus Compounds; Piperonyl Butoxide; Pyrethrins
PubMed: 35478216
DOI: 10.1038/s41598-022-10953-y -
Journal of Medical Entomology Mar 2022Piperonyl butoxide (PBO)-synergized pyrethroid products are widely available for the control of pyrethroid-resistant mosquitoes. To date, no study has examined mosquito...
Piperonyl butoxide (PBO)-synergized pyrethroid products are widely available for the control of pyrethroid-resistant mosquitoes. To date, no study has examined mosquito resistance after pre-exposure to PBO and subsequent enzymatic activity when exposed to PBO-synergized insecticides. We used Culex quinquefasciatus Say (Diptera: Culicidae), an important vector of arboviruses and lymphatic filariasis, as a model to examine the insecticide resistance mechanisms of mosquitoes to PBO-synergized pyrethroid using modified World Health Organization tube bioassays and biochemical analysis of metabolic enzyme expressions pre- and post-PBO exposure. Mosquito eggs and larvae were collected from three cities in Orange County in July 2020 and reared in insectary, and F0 adults were used in this study. A JHB susceptible strain was used as a control. Mosquito mortalities and metabolic enzyme expressions were examined in mosquitoes with/without pre-exposure to different PBO concentrations and exposure durations. Except for malathion, wild strain Cx quinquefasciatus mosquitoes were resistant to all insecticides tested, including PBO-synergized pyrethroids (mortality range 3.7 ± 4.7% to 66.7 ± 7.7%). Wild strain mosquitoes had elevated levels of carboxylesterase (COE, 3.8-fold) and monooxygenase (P450, 2.1-fold) but not glutathione S-transferase (GST) compared to susceptible mosquitoes. When wild strain mosquitoes were pre-exposed to 4% PBO, the 50% lethal concentration of deltamethrin was reduced from 0.22% to 0.10%, compared to 0.02% for a susceptible strain. The knockdown resistance gene mutation (L1014F) rate was 62% in wild strain mosquitoes. PBO pre-exposure suppressed P450 enzyme expression levels by 25~34% and GST by 11%, but had no impact on COE enzyme expression. Even with an optimal PBO concentration (7%) and exposure duration (3h), wild strain mosquitoes had significantly higher P450 enzyme expression levels after PBO exposure compared to the susceptible laboratory strain. These results further demonstrate other studies that PBO alone may not be enough to control highly pyrethroid-resistant mosquitoes due to multiple resistance mechanisms. Mosquito resistance to PBO-synergized insecticide should be closely monitored through a routine resistance management program for effective control of mosquitoes and the pathogens they transmit.
Topics: Animals; Culicidae; Cytochrome P-450 Enzyme System; Insecticide Resistance; Insecticides; Mosquito Control; Mosquito Vectors; Piperonyl Butoxide; Pyrethrins
PubMed: 35050361
DOI: 10.1093/jme/tjab231 -
The Journal of Dermatological Treatment Dec 2023
Topics: Humans; Permethrin; Scabies; Piperonyl Butoxide; Pyrethrins; Insecticides
PubMed: 37526055
DOI: 10.1080/09546634.2023.2242539 -
Archives of Toxicology Oct 2008In order to clarify the possible mechanism of hepatocarcinogenesis induced by piperonyl butoxide, we attempted to identify the transcription factor activated by...
In order to clarify the possible mechanism of hepatocarcinogenesis induced by piperonyl butoxide, we attempted to identify the transcription factor activated by piperonyl butoxide in the male ICR mouse liver. Administration of 0.6% piperonyl butoxide for 24 h elevated the level of liver nuclear proteins that bind to an AP-1 consensus oligonucleotide, and these proteins demonstrated a supershift with the anti-c-Jun antibody. Additionally, immunoblot analysis revealed that piperonyl butoxide induced c-Jun phosphorylation within 8 h of administration, and phosphorylated ATF-2 was detected after 24 h of piperonyl butoxide treatment. Immunohistochemical analysis also demonstrated the presence of phosphorylated ATF-2 in the hepatocyte nuclei of mice fed with 0.6% piperonyl butoxide for 24 h. Furthermore, piperonyl butoxide induced ATF-2 phosphorylation in TLR-3, a mouse immortalized hepatocyte cell line. These results indicated that piperonyl butoxide activated c-Jun and ATF-2 in mouse hepatocytes during the early stage of hepatocarcinogenesis.
Topics: Activating Transcription Factor 2; Animals; Carcinogens; Cell Line; Cell Transformation, Neoplastic; Electrophoretic Mobility Shift Assay; Hepatocytes; Immunohistochemistry; Male; Mice; Mice, Inbred ICR; Phosphorylation; Piperonyl Butoxide; Proto-Oncogene Proteins c-jun; Time Factors; Transcription Factor AP-1
PubMed: 18228000
DOI: 10.1007/s00204-008-0283-0 -
Vector Borne and Zoonotic Diseases... Feb 2020The use of conventional pesticides becomes a complicated issue as more species of insect pests become resistant to them. Nanopesticides suit new approaches in pest...
The use of conventional pesticides becomes a complicated issue as more species of insect pests become resistant to them. Nanopesticides suit new approaches in pest control. Herein, we tested the toxicological efficacy of imidacloprid compared with three of its nanoformulations (IMD01, IMD02, and IMD03) on second and fourth instar of larvae. Furthermore, we assessed the synergistic actions of piperonyl butoxide (PBO) on imidacloprid and its nanoformulations against second and fourth instar of . The nanoformulation (IMD03) was the most potent insecticide (LC = 14, 6, and 2 ng/mL after 24, 48, and 72 h of exposure, respectively), whereas the lowest toxic nanoformulation was IMD01. However, imidacloprid had the lowest toxicity among the tested compounds (LC = 1015, 705, and 621 ng/mL after 24, 48, and 72 h of exposure, respectively). PBO significantly synergized imidacloprid and its nanoformulations. However, the most synergistic effects were on IMD03 and the lowest was imidacloprid itself. Based on our results, nanopesticides are currently the most promising tool to control mosquitoes. However, further semifield and field studies should be done to illustrate the efficacy of imidacloprid and its nanoformulations on mosquitoes.
Topics: Animals; Culex; Insecticides; Larva; Mosquito Control; Nanoparticles; Neonicotinoids; Nitro Compounds; Pesticide Synergists; Piperonyl Butoxide
PubMed: 31408394
DOI: 10.1089/vbz.2019.2474 -
Toxicology and Industrial Health Apr 2019Previous studies reported that piperonyl butoxide (PBO) induces adverse effects on exploratory behaviour in male mice. However, no consistent effects of PBO treatment...
Previous studies reported that piperonyl butoxide (PBO) induces adverse effects on exploratory behaviour in male mice. However, no consistent effects of PBO treatment were observed in female mice. This study aimed to evaluate PBO's neurobehavioral effects in female mice. Female mice were exposed to PBO through diet to provide levels of 0 (control), 0.025%, 0.1%, and 0.4% from 5 to 12 weeks of age, and selected behavioural parameters were measured. The average female body weight showed no significant effect from PBO treatment through the experimental periods. Regarding multiple-T water maze performance at 10 weeks of age, no significant effect caused by PBO treatment was observed. Exploratory behaviour examination of 8-week-old female mice indicated that the average speed declined in a significant dose-related manner, and the longitudinal pattern indicated a significant difference between the control and high-dose groups. For exploratory behaviour examination at 11 weeks of age, the total exploration distance shortened in a significant dose-related manner, and the average speed declined similarly. These longitudinal patterns showed significant differences between the control and high-dose groups. The PBO dose levels in this study produced several adverse effects on exploratory behaviour in female mice.
Topics: Animals; Behavior, Animal; Dose-Response Relationship, Drug; Exploratory Behavior; Female; Maze Learning; Mice; Pesticide Synergists; Piperonyl Butoxide
PubMed: 30871449
DOI: 10.1177/0748233719833272