Lack of genotoxicity of piperonyl butoxide

Butler, W. H.; Gabriel, Karl L.; Preiss, Frederick J.; Osimitz, T G

doi:10.1016/s0165-1218(96)90113-5

Cited by 14 publications

(5 citation statements)

References 25 publications

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“…Galloway et al (1987) investigated a wide range of compounds including PBO in Chinese hamster ovary cells and failed to find chromosome aberrations and sister chromatid exchange in the presence or absence of rat liver S-9. PBO had no effect on Chinese hamster ovary cells in the report of Butler et al (1996), and produced a small increase in sister chromatid exchanges only in the absence of S-9 in the recent study by Tayama (1996). Tayama also concluded that the metabolites of PBO are unlikely to be genotoxic.…”

Section: Genotoxicitymentioning

confidence: 93%

“…While K-ras mutation has been reported in human tumors at various sites (Almoguera et al, 1988;Bos et al, 1987) no such association has been observed in tumors of the rodent liver, the apparent target site of PBO (Maronpot et al, 1995). Butler et al (1996) reported that PBO did not induce unscheduled DNA synthesis in rat hepatocytes. Moreover, Beamand et al (1996) showed a similar negative response to PBO in cultured human hepatocytes.…”

Section: Genotoxicitymentioning

confidence: 99%

“…PBO has shown no evidence of mutagenic activity in a number of bacterial assays involving Salmonella typhimurium, Bacillus subtilis, and Escherichia coli both in the presence or absence of rat liver microsomes (S-9) (Ashwood-Smith et al, 1972;Butler et al, 1996;Ishidate et al, 1984;Kawachi et al, 1980;Moriye et al, 1983;White et al, 1977).…”

Section: Genotoxicitymentioning

confidence: 99%

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The Safety Assessment of Piperonyl Butoxide

Osimitz

2010

Hayes' Handbook of Pesticide Toxicology

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Section: Genotoxicitymentioning

confidence: 93%

Section: Genotoxicitymentioning

confidence: 99%

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The Safety Assessment of Piperonyl Butoxide

Osimitz

2010

Hayes' Handbook of Pesticide Toxicology

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“…The MDBs-safrole, isosafrole, myristicin, sesamin, sesamole, sesamex, among others-are commonly found in human food plants, including carrot, turnip, parsnip, nutmeg, dill, anise, fennel, pepper, and sesame seeds (8). Piperonyl butoxide is a synthetic MDB and is used widely as an insecticide synergist, especially in combination with pyrethroids, primarily for its ability to inhibit CYP-mediated insecticide metabolism (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Differential induction of cytochrome P450 gene expression by 4n-alkyl-methylenedioxybenzenes in primary rat hepatocyte cultures

Sidhu

Marcus

Parkinson

et al. 1998

J. Biochem. Mol. Toxicol.

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A well‐characterized primary rat hepatocyte culture system was used to examine induction patterns of cytochrome 450 gene expression by a series of 4‐n ‐alkyl‐methylenedioxybenzene (MDBs) derivatives. Hepatocytes were treated for 24, 48, or 72 hours with 0–500 μ M of the MDB compounds, and total cellular RNA and protein from each treatment was evaluated by hybridization and immunochemical techniques. Exposure to MDB congeners possessing increasing 4‐n ‐alkyl side‐chain length (C0–C8) resulted in dose‐ and structure‐dependent activation of CYP2B1, 2B2, 3A1, 1A1, and 1A2 gene expression. At equivalent 100 μ M concentrations, the C6 and C8 MDB congeners were more effective than the prototypical inducer phenobarbital (PB) with respect to induction potency of CYP2B1, CYP2B2, and CYP3A1 gene expression. In contrast to PB, longer side‐chain–substituted MDBs effectively induced CYP1A1 and CYP1A2 gene expression, in addition to the CYP2B and CYP3A genes. At equivalent molar concentrations, the catechol derivative of C6‐MDB was ineffective in its ability to induce CYP gene expression, indicating the importance of the intact methylenedioxy bridge in the induction mechanism. Levels of MDB‐inducible CYP2B1 and CYP2B2 mRNA were highly correlated with CYP2B1/2 apoprotein levels, ascertained by immunoblot analysis of cultured hepatocyte S9 fractions. Compared with results from previous in vivo analysis (12), the current data indicate that pharmacodynamic factors may influence MDB induction profiles and that differences in MDB effects on CYP gene expression result depending on distinct structure‐activity relationships. © 1998 John Wiley & Sons, Inc. J Biochem Toxicol 12: 253–262, 1998

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“…Nearly 50% of the amount of PBO produced is distributed for use in indoor residential products (unpublished PBO Task Force data). As a result, humans could potentially be exposed to low levels of PBO from dietary and residential sources.Although PBO has not been extensively studied in humans, several investigations have demonstrated that PBO is not mutagenic in a wide range of short-term tests (White et al., \911;Kawachi et al, 1980; Rosenkrantz et al, 1990;Butler et al, 1996) and that PBO does not induce unscheduled DNA synthesis in cultured human liver slices (Beamand et al, 1996). Occupational and consumer exposure to PBO has not resulted in any significant effects to human health.…”

mentioning

confidence: 99%

Effect of Piperonyl Butoxide on Cell Replication and Xenobiotic Metabolism in the Livers of CD-1 Mice and F344 Rats

et al. 1997

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Male CD-1 mice were fed diets containing 0 (control), 10, 30, 100, and 300 mg/kg/day piperonyl butoxide (PBO) and 0.05% sodium phenobarbital (NaPB) and male F344 rats were fed diets containing 0 (control), 100, 550, 1050, and 1850 mg/kg/day PBO and 0.5% NaPB for periods of 7 and 42 days. In both species PBO and NaPB increased relative liver weight and whereas PBO produced a midzonal (mouse) or periportal/midzonal (rat) hypertrophy, NaPB produced a centrilobular hypertrophy. In the rat, individual cell necrosis was also observed at 42 days after high doses of PBO. Replicative DNA synthesis, assessed as the hepatocyte labeling index following implantation of 7-day osmotic pumps containing 5-bromo-2'-deoxyuridine during Study Days 0-7 and 35-42, was increased in mice given 300 mg/kg/day PBO and NaPB for 7 days and in rats given 550 and 1050 mg/kg/day PBO and NaPB for 7 days and 1050 mg/kg/day PBO for 42 days. While PBO had no effect on body weights in mice, the body weights of rats given 550, 1050, and 1850 mg/kg/day PBO for 42 days were reduced to 92, 89, and 70% of control, respectively. PBO induced microsomal cytochrome P450 content and mixed function oxidase activities in the mouse and rat, although the effects were less marked than those produced by NaPB. In summary, this data demonstrates that PBO can produce liver enlargement in the mouse and the rat which is associated with induction of xenobiotic metabolism, hypertrophy, and hyperplasia. The hepatic effects of PBO in the mouse were similar to but less marked than those produced by NaPB. In the rat high doses of PBO were hepatotoxic and resulted in a marked reduction in body weight Thus while the reported formation of eosinophilic nodules in mouse liver by PBO may occur by a mechanism(s) similar to that of NaPB and other nongenotoxic enzyme inducers, the reported tumor forma-1 Presented in part at the Annual Meeting of the Society of Toxicology, Baltimore, Maryland, March 5-9, 1995, and Anaheim, California, March 10-14, 1996.2 To whom correspondence should be addressed. tion in rats at greater than the maximum tolerated dose is most likely associated with marked enzyme induction in conjunction with a regenerative hyperplasia resulting from PBO-induced hepatOtOxicity. O 1997 Sodtty of Toriralogy.Piperonyl butoxide (a-[2-(2-butoxyethoxy)ethoxy]-4,5-methylenedioxy-2-propyltoluene, PBO) is a commonly used synergist for naturally derived pyrethrins. PBO is registered for applications on a variety of crops (including fruits and vegetables), livestock, lawn and turf, mosquitoes, agricultural premises, food-processing plants, dairies, pets, and residential dwellings. Nearly 50% of the amount of PBO produced is distributed for use in indoor residential products (unpublished PBO Task Force data). As a result, humans could potentially be exposed to low levels of PBO from dietary and residential sources.Although PBO has not been extensively studied in humans, several investigations have demonstrated that PBO is not mutagenic in a wide range of short-term tests (White ...

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Lack of genotoxicity of piperonyl butoxide

Cited by 14 publications

References 25 publications

The Safety Assessment of Piperonyl Butoxide

The Safety Assessment of Piperonyl Butoxide

Differential induction of cytochrome P450 gene expression by 4n-alkyl-methylenedioxybenzenes in primary rat hepatocyte cultures

Effect of Piperonyl Butoxide on Cell Replication and Xenobiotic Metabolism in the Livers of CD-1 Mice and F344 Rats

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