Toxicity Profile for Piperonyl butoxide (1998)

Abstract

Piperonyl butoxide was slightly irritating to the skin and eyes of rabbits, and did not induce skin sensitization in guinea-pigs or rabbits. It was of low acute toxicity to laboratory animals when administered by the oral, dermal or inhalation routes. Whilst the main target organ on repeated oral administration to rats was the liver, other effects included abnormalities in the kidneys, digestive tract, thyroid, blood, and possibly the testes. Other species have been less well studied for the effects of short-term oral dosing, but again the liver appears to be the major target organ. The main effects of inhalation exposure in rats were liver and laryngeal lesions, the latter indicative of irritation. Reproductive studies in mice involving single or repeated oral administration have demonstrated foetotoxicity and malformations at doses that were not overtly toxic to the dams, while a multigeneration study revealed reductions in litter size and weight and pup weight. Oral administration to pregnant rats or rabbits has resulted, in some studies, in malformations, embryotoxicity, foetotoxicity and decreased pup growth, but generally at doses toxic to the parents. Piperonyl butoxide has induced liver tumours in rats and mice (often associated with toxic liver damage) in some long-term feeding studies. It has generally given negative results in a range of genotoxicity tests, including Ames bacterial assays. However, equivocal findings were reported in mice treated by the oral or intraperitoneal routes (in a dominant lethal assay), and in mammalian cells in culture there was evidence of mutagenicity, chromosomal damage and cell transformation.