title: Uranyl nitrate: 91-day toxicity studies in the New Zealand white rabbit.
abstract: These studies were undertaken to derive a lowest-observed-adverse-effect level (LOAEL) in the New Zealand White rabbit following a 91-day exposure to uranium (U, as uranyl nitrate hexahydrate, UN) in drinking water. Males were exposed for 91 days to UN in their drinking water (0.96, 4.8, 24, 120, or 600 mg UN/L). Subsequently, females were similarly exposed for 91 days (4.8, 24, or 600 mg UN/L). Control groups were given tap water (< 0.001 mg U/L). Regular observations were recorded, and urine was collected periodically. Four males showed evidence of Pasteurella multocida infection and were excluded from the study. Following the study, all animals were euthanized, and multiple hematological and biochemical parameters were determined. Necropsies were conducted, and histopathological examination was performed. The hematological and biochemical parameters were not affected in a significant exposure-related manner. Dose-dependent differences consisted of histopathological changes limited primarily to kidney. Changes in renal tubules were characteristic of uranium toxicity. Based on changes in the tubular nuclei, the 91-day LOAEL for males in this study is 0.96 mg UN/L drinking water. The females drank 65% more water than the males, yet appeared to be less affected by the exposure regimen, although they also developed significant tubular nuclear changes in their lowest exposure group, deriving a LOAEL of 4.8 mg UN/L. Tissue uranium residue studies suggested that pharmacokinetic parameters for the males and females differ, possibly accounting for the difference in observed sensitivity to UN. An adverse effect of P. multocida infection cannot be excluded.
authors.affiliation: Environmental and Occupational Toxicology Division, Department of National Health and Welfare, Ottawa, Ontario, Canada.
authors.forename: A P
authors.initials: AP
authors.lastname: Gilman
authors.forename: D C
authors.initials: DC
authors.lastname: Villeneuve
authors.forename: V E
authors.initials: VE
authors.lastname: Secours
authors.forename: A P
authors.initials: AP
authors.lastname: Yagminas
authors.forename: B L
authors.initials: BL
authors.lastname: Tracy
authors.forename: J M
authors.initials: JM
authors.lastname: Quinn
authors.forename: V E
authors.initials: VE
authors.lastname: Valli
authors.forename: M A
authors.initials: MA
authors.lastname: Moss
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D011817:Rabbits; D014018:Tissue Distribution; D014502:Uranyl Nitrate / Q000633:toxicity*
chemical_list: D014502:Uranyl Nitrate