Chronic Toxicity/Carcinogenicity Study of Pyrilamine in B6C3F1 Mice

The chronic toxicity and carcinogenicity of pyrilamine maleate were evaluated in B6C3F1 mice by feeding for up to 2 years to groups of 60 male or female mice at dietary levels of 0,150, 750, or 1,500 ppm (as the free base). Up to 12 mice per sex and dose group were killed after 65 weeks for clinical chemistry, hematology, and histopathologic evaluation of control and high-dose animals. Histopathology was performed on all animals that were dead or moribund or lived until the study was terminated at 2 years. Daily exposures to pyrilamine ranged from ∼16 to 176 mg/kg, compared with maximum human exposure of 3 mg/kg. Regarding longevity, pyrilamine-treated male mice tended to survive longer than controls, whereas no differences among treated and control female mice were noted. Body weights did not differ among treated and control male groups, but final body weight average of treated female mice was 6–10% lower than that for controls. Although no dose-response trends were noted in male mice for histopathologic end points, liver /body and liver/ brain weight ratios were significantly greater in high-dose male mice than in controls. Chronic liver inflammation exhibited a positive dose-response trend in female mice, but there was no evidence for a carcinogenic response to pyrilamine by either sex.