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Lack of genotoxicity of piperonyl butoxide
W H Butler1, K L Gabriel, F J Preiss
1BIBRA International, Carshalton, Surrey, UK.
Abstract:
The genotoxicity of piperonyl butoxide has been investigated in bacterial mutation assays using tester strains TA98, TA100, TA1535, TA1537 and TA1538. The assays were conducted both with and without metabolic activation. Piperonyl butoxide was tested for mutation with and without metabolic activation in the CHO/HGPRT assay. Chromosomal aberrations were investigated also using Chinese hamster ovary (CHO) cells and effects on DNA were evaluated by in vitro unscheduled DNA synthesis (UDS) test using rat liver primary cell cultures. Piperonyl butoxide was not shown to be genotoxic in any assay system. The data presented supports the view that the liver tumors observed in rodents at dose levels above the maximally tolerated dose (MTD) result from a secondary non-genotoxic mechanism.
Insights
Piperonyl butoxide was not genotoxic in bacterial mutation assays or in mammalian cell assays. Liver tumors in rodents at high doses likely stem from a non-genotoxic mechanism, not DNA damage.
Area of Science:
- Toxicology
- Genetics
- Biochemistry
Background:
- Piperonyl butoxide is a common synergist used in pesticides.
- Rodent studies have shown liver tumors at high doses of piperonyl butoxide.
- The mechanism underlying tumor formation requires clarification.
Purpose of the Study:
- To evaluate the genotoxicity of piperonyl butoxide.
- To determine if piperonyl butoxide causes DNA damage or mutations.
- To investigate the mechanism of liver tumor formation in rodents.
Main Methods:
- Bacterial mutation assays (Ames test) with strains TA98, TA100, TA1535, TA1537, TA1538, with and without metabolic activation.
- Mammalian cell assays: CHO/HGPRT mutation assay and chromosomal aberration assay in Chinese hamster ovary (CHO) cells, with and without metabolic activation.
- In vitro unscheduled DNA synthesis (UDS) test using rat liver primary cell cultures.
Main Results:
- Piperonyl butoxide did not induce mutations in bacterial assays.
- No genotoxic effects were observed in the CHO/HGPRT or chromosomal aberration assays.
- The in vitro UDS test showed no evidence of DNA damage.
- Piperonyl butoxide was not genotoxic in any of the tested systems.
Conclusions:
- Piperonyl butoxide does not exhibit genotoxic potential.
- The liver tumors observed in rodents at high doses are likely due to a secondary, non-genotoxic mechanism.
- These findings suggest piperonyl butoxide's safety profile is not linked to DNA damage.