The objective of this project is to determine the potential toxicity and carcinogenicity of sodium fluoride, methyleugenol, and optionally anthraquinone, by oral routes to Fischer 344 rats and B6C3F1 mice. The basic award for each chemical includes the development of analytical chemistry and dose formulation methods. Once these methods have been adequately developed, toxicity/carcinogenicity studies are to be conducted. Sodium fluoride -- 104-week study is to be conducted, involving seventy male rats, at 3 doses plus controls via dosed water, with interim sacrifices at 26 and 65 weeks. Special studies to be conducted at interim sacrifices include hematology; serum calcium, phosphorus, fluoride and alkaline phosphatase; and bone fluoride. Serum and bone fluoride concentrations are to be measured at terminal sacrifice. Whole body radiographs are to be made for all animals prior to necropsy throughout the study. Methyleugenol -- Toxicokinetic studies are to be conducted first to establish basic toxicokinetic parameters, to determine the extent of bioaccumulation and to determine actual internal doses after a single exposure. A 104-week study is to be conducted, involving fifty- animals/sex/species, at 3 doses plus controls via gavage. An additional 60 rats per sex are to be treated for 26 weeks at one dose for a stop study. Ten of these additional rats per sex are to be sacrificed at 26 weeks and the remainder will continue to seek 014 treated with vehicle only. Toxicokinetic studies are to be conducted during the chronic study to evaluate the effects of long term exposure and age on toxicokinetic parameters. Optional Study of Anthraquinone -- A 13-week study is to be conducted, involving ten animals/sex/species, at 5 doses plus controls via dosed feed. Special studies include hematology, clinical chemistries and urinalysis in rats, hematology in mice; SMVCE in rats and mice; toxicokinetic studies are to be conducted to establish basic toxicokinetic parameters, to determine the extent of bioaccumulation and to determine actual internal doses after a single exposure. 104-week study is to be conducted, involving fifty animals/sex/species, at 3 exposure concentrations plus controls. Toxicokinetic studies are to be conducted during the chronic study to evaluate the effects of long term exposure and age on toxicokinetic parameters.
