to the formation of the mouse liver tumors suggest that the events are not likely to occur in humans. The EPA classifies PBO as a group C carcinogen - "possibly carcinogenic to humans." Under the auspices of the United Nations, the Food and Agriculture Organization/World Health Organization (FAO/WHO) Joint Meeting on Pesticide Residues evaluated the entire body of toxicology of PBO several times since 1965. They concluded that, at doses up to internationally accepted standards for a maximum tolerated dose, PBO is not considered to be carcinogenic in the mouse or rat, thus leading to the conclusion that PBO is not carcinogenic to humans. Developmental Toxicity Studies PBO has been found to inhibit the Hedgehog signaling pathway, a critical regulator of brain and face development in all vertebrates, via antagonism of the protein Smoothened (SMO). PBO was found to be capable of causing dose-dependent brain and face malformations in mice exposed during early development, including the rare human birth defect Holoprosencephaly. Even doses of PBO that did not cause overt holoprosencephaly-associated facial abnormalities were found to cause subtle neuroanatomical defects, for which the cognitive or behavioral consequences are unknown. An epidemiology study found that PBO exposure was correlated with dose-dependent reductions in neurocognitive development in 3-year old children. Animal impacts PBO is moderately to highly toxic to aquatic invertebrates, such as water fleas and shrimp. At lower, long-term doses, water flea reproduction was affected. PBO is highly toxic to amphibians in the tadpole stage. Exposure assessment Given the extensive non-dietary use of PBO, manufacturers of PBO and marketers of PBO-containing products formed the Non-Dietary Exposure Task Force (NDETF) in 1996 to develop a long-term research program to more fully understand the phenomenon of human exposure to insecticides used in the home. Most of the studies were conducted with formulations of pyrethrins/PBO and synthetic pyrethroids/PBO, and focused on the indoor use of fogger and aerosol products. Carpet and vinyl flooring surfaces were selected because of their different physical and chemical properties, and because they represent a significant percentage of the floor coverings used in homes in North America. While the focus of the NDETF effort was on total-release foggers, a study was also conducted to determine both dispersion (air levels) and deposition (on flooring) of pyrethrins/PBO resulting from the use of a hand held aerosol spray can. Potential direct exposure of the user was also measured. Air sampling from the breathing