Abstract for TR-124

Piperonyl sulfoxide is used to enhance the insecticidal properties of the pyrethrins by inhibiting pyrethrin detoxification enzymes, probably microsomal oxidases, in the insect. Pyrethrins alone produce a transient paralysis, whereas pyrethrins combined with a synergist such as piperonyl sulfoxide are insecticidal.

A bioassay of technical-grade piperonyl sulfoxide 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 sulfoxide in the diet at one of several doses, either 1,500 or 3,000 ppm for the males and either 3,000 or 6,000 ppm for the females, for 105 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 male mice were administered one of two doses, either 350 or 700 ppm, for 104 or 105 weeks. Groups of 50 female mice were initially administered one of two doses, either 700 or 1,400 ppm. Due to excessive weight depression in the dosed female mice, the doses for this sex were reduced after week 20 to 200 and 600 ppm, respectively, and administration of the test chemical at the lower doses was continued for 84 or 85 weeks. The time-weighted average doses for the females were 295 and 754 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 the amount of mean body weight gained were dose related for most or all of thebioassay; the depression in the amount of mean body weight gained was slight, however, in the dosed male rats. Survival of the rats and mice was unaffected by the piperonyl sulfoxide and was 78% or higher 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 the male and female rats and in the female mice, no tumors occurred at incidences that were significantly higher in dosed groups than in control groups.

In the male mice, hepatocellular carcinomas occurred at incidences that were dose related (P<0.001); in direct comparisons, the incidence of these tumors in the high-dose group was significantly higher (P<0.001) than that in the control group (controls 6/18, low-dose 31/50, high-dose 46/50).

It is concluded that under the conditions of this bioassay, technical-grade piperonyl sulfoxide was not carcinogenic for male or female Fischer 344 rats or for female B6C3F1 mice, but was carcinogenic for male B6C3F1 mice, producing an increased incidence of hepatocellular carcinomas.