Piperonyl butoxide is used to enhance the insecticidal properties of the pyrethrins by blocking the pyrethrin detoxification enzymes in the insect. Pyrethrins alone produce a very rapid knockdown of insects followed by substantial recovery, whereas addition of a synergist such as piperonyl butoxide decreases the insecticidal dose of pyrethrin. Piperonyl butoxide is also formulated with synthetic pyrethrin analogues, such as allethrin and tetramethrin.
A bioassay of technical-grade piperonyl butoxide for possible carcinogenicity was conducted by administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice.
Groups of 50 rats of each sex were administered piperonyl butoxide in the diet at one of two doses, either 5,000 or 10,000 ppm, for 107 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at the end of the period of administration of the test chemical.
Groups of 50 mice of each sex were initially administered piperonyl butoxide at one of two doses, either 2,500 or 5,000 ppm. After week 30, the doses for the mice were reduced to 500 and 2,000 ppm, respectively, and administration of the test chemical at the lowered doses was continued for 82 weeks. The time-weighted average doses for the mice were either 1,036 or 2,804 ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving mice were killed at the end of the period of administration of the test chemical.
Mean body weights of dosed groups of rats and mice of each sex were lower than those of corresponding control groups, and the depressions in body weights were dose related. Survival of the rats and mice was unaffected by the piperonyl butoxide and was 80% or greater in all groups at week 90 of the bioassay; thus, sufficient numbers of dosed and control rats and mice of each sex were at risk for the development of late-appearing tumors.
In female rats, lymphomas occurred at incidences that were dose related (P=0.007); in a direct comparison, the incidence of the tumor in the high-dose group was higher (P=0.020) than that in the control group (controls 1/20, low-dose 7/50, high-dose 15/50). However, the incidence of lymphomas, leukemias, and reticuloses in historical-control female Fischer 344 rats at the same laboratory was 19/191 (10%). These historical-control groups include one with an incidence of animals with lymphoma or leukemia of 7/20 (35%) and another with an incidence of 6/20 (30%). Thus, the incidence of lymphomas in the control female rats of the present bioassay may have been abnormally low, and the occurrence of the higher incidence in the dosed groups cannot be clearly related to administration of piperonyl butoxide.
In the male mice, adenomas of the lacrimal gland occurred at incidences that were dose related (P=0.023), but in direct comparisons the incidences in the individual dosed groups were not significantly higher than that in the control group (controls 0/20, low-dose 0/49, high-dose 4/50); thus, the occurrence of this tumor in the male mice was not clearly related to administration of the test chemical.
It is concluded that under the conditions of this bioassay, piperonyl butoxide was not carcinogenic for Fischer 344 rats or B6C3F1 mice.